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1. Association of in utero HIV exposure with child brain structure and language development: a South African birth cohort study

Author: Catherine J. Wedderburn, Shunmay Yeung, Sivenesi Subramoney, Jean-Paul Fouche, Shantanu H. Joshi, Katherine L. Narr, Andrea M. Rehman, Annerine Roos, Diana M. Gibb, Heather J. Zar, Dan J. Stein, and Kirsten A. Donald
Subjects: HIV, Antiretroviral therapy, Brain structure, Neurodevelopment, Language, Magnetic resonance imaging, Medicine
Abstract: Abstract Background There is a growing population of children with in utero HIV exposure who are at risk of poor neurodevelopmental outcomes despite avoiding HIV infection. However, the underlying neurobiological pathways are not understood and neuroimaging studies are lacking. We aimed to investigate the cortical brain structure of children who are HIV-exposed and uninfected (HEU) compared to HIV-unexposed (HU) children and to examine the relationship with neurodevelopment. Methods The Drakenstein Child Health birth cohort study enrolled pregnant women from a high HIV prevalence area in South Africa with longitudinal follow-up of mother–child pairs. High-resolution magnetic resonance imaging scans from 162 children (70 HEU; 92 HU) were acquired at 2–3 years of age. All HEU children were born to mothers taking antiretroviral therapy. Measures of brain structure (cortical thickness and surface area) in the prefrontal cortex regions were extracted from T1-weighted images and compared between groups using multivariate analysis of variance and linear regression. Child development, assessed using the Bayley Scales of Infant and Toddler Development-III, was correlated with cortical structure, and mediation analyses were performed. Results Analyses demonstrated an association between HIV exposure and cortical thickness across the prefrontal cortex (p = 0.035). Children who were HEU had thicker cortices in prefrontal regions, with significantly greater cortical thickness in the medial orbitofrontal cortex (mOFC) bilaterally compared to HU children (3.21 mm versus 3.14 mm, p = 0.009, adjusted effect size 0.44 [95% CI 0.12 to 0.75]). Estimates held across multiple sensitivity analyses. There were no group differences in cortical surface area. Language scores, which were lower in HEU versus HU children (81.82 versus 86.25, p = 0.011, effect size − 0.44 [95% CI − 0.78 to − 0.09]), negatively correlated with prefrontal cortical thickness in both groups. Cortical thickness in the mOFC mediated the relationship between HIV exposure and poor language outcomes (Sobel test p = 0.032). Conclusions In this cohort study, exposure to HIV during pregnancy was associated with altered cortical structure in early life. Our findings indicate that differences in cortical thickness development in the prefrontal region in children who are HEU may be a pathway leading to language impairment. Longitudinal studies are needed to determine the lasting impact.
Published: 2024
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2. Motivation levels and white matter microstructure in children living with HIV

Author: Catherine J. Wedderburn, Tatum Sevenoaks, Jean-Paul Fouche, Nicole J. Phillips, Stephen D. Lawn, Dan J. Stein, and Jacqueline Hoare
Subjects: Motivation, Apathy, HIV, Children, Diffusion tensor imaging, Medicine, Science
Abstract: Abstract Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children’s Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6–16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p
Published: 2024
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3. Maternal perinatal depression and child brain structure at 2-3 years in a South African birth cohort study

Author: Jennifer A. Pellowski, Catherine J. Wedderburn, Nynke A. Groenewold, Annerine Roos, Sivenesi Subramoney, Nadia Hoffman, Jean-Paul Fouche, Shantanu H. Joshi, Roger P. Woods, Katherine L. Narr, Heather J. Zar, Kirsten A. Donald, and Dan J. Stein
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2–3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6–10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = −74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = −78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.
Published: 2023
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4. The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Author: Cees J. Weeland, Selina Kasprzak, Niels T. de Joode, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Srinivas Balachander, Nerisa Banaj, Nuria Bargallo, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Vilde Brecke, Silvia Brem, Carolina Cappi, Yuqi Cheng, Kang Ik K. Cho, Daniel L. C. Costa, Sara Dallaspezia, Damiaan Denys, Goi Khia Eng, Sónia Ferreira, Jamie D. Feusner, Martine Fontaine, Jean-Paul Fouche, Rachael G. Grazioplene, Patricia Gruner, Mengxin He, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Hao Hu, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Minah Kim, Kathrin Koch, Yoo Bin Kwak, Jun Soo Kwon, Luisa Lazaro, Chiang-shan R. Li, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Jose M. Menchón, Luciano Minnuzi, Pedro Silva Moreira, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Ana E. Ortiz, Jose C. Pariente, John Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y. C. Janardhan Reddy, Daniela Rodriguez-Manrique, Yuki Sakai, Eiji Shimizu, Venkataram Shivakumar, Helen Blair Simpson, Noam Soreni, Carles Soriano-Mas, Nuno Sousa, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, Jumpei Takahashi, Tais Tanamatis, Jinsong Tang, Anders Lillevik Thorsen, David Tolin, Ysbrand D. van der Werf, Hein van Marle, Guido A. van Wingen, Daniela Vecchio, G. Venkatasubramanian, Susanne Walitza, Jicai Wang, Zhen Wang, Anri Watanabe, Lidewij H. Wolters, Xiufeng Xu, Je-Yeon Yun, Qing Zhao, ENIGMA OCD Working Group, Tonya White, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, and Chris Vriend
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (
Published: 2022
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5. A longitudinal and qualitative analysis of caregiver depression and quality of life in the Cape Town adolescent antiretroviral cohort

Author: Tatum Sevenoaks, Jean-Paul Fouche, Bulelwa Mtukushe, Nicole Phillips, Sarah Heany, Landon Myer, Heather J. Zar, Dan J. Stein, and Jacqueline Hoare
Subjects: Caregiver depression, HIV infection, Adolescent, Mental health, Quality of life, Mental healing, RZ400-408
Abstract: Background: This study aimed to investigate depression and quality of life longitudinally in caregivers of adolescents with perinatally acquired HIV (PHIV) enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). Methods: Depression, socioeconomic factors and quality of life were assessed in caregivers (n = 121) at baseline and 36 months follow-up using the Centers for Epidemiological Studies Depression Scale (CESD), the Family Resources Scale (FRS), Family Support Scale (FSS), and the World Health Organization's Quality of Life Scale (WHOQoL). Internalizing and externalizing behaviors in PHIV adolescents were assessed using the Child Behaviour Checklist (CBCL). Qualitative analysis was conducted to highlight key concerns raised by caregivers in caring for PHIV adolescents. Results: CESD was significantly lower at follow-up compared to baseline (p = 0.001), with FRS (p = 0.003) and WHOQoL physical health (p = 0.038) significantly higher at follow-up. Higher CESD scores were predicted by increased CBCL internalizing (baseline: p = 0.002; follow-up: p = 0.021) and externalizing behavior (baseline: p = 0.010; follow-up: p = 0.015) in PHIV adolescents and decreased WHOQoL physical health (baseline: p = 0.001; follow-up: p = 0.016) and WHOQoL overall quality of life (baseline: p = 0.003; follow-up: p = 0.019). Higher WHOQoL Total Score was predicted by lower CESD scores (baseline: p
Published: 2022
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6. Shape analysis of subcortical structures in obsessive‐compulsive disorder and the relationship with comorbid anxiety, depression, and medication use: A meta‐analysis by the OCD Brain Imaging Consortium

Author: Jean‐Paul Fouche, Nynke A. Groenewold, Tatum Sevenoaks, Sarah Heany, Christine Lochner, Pino Alonso, Marcelo C. Batistuzzo, Narcis Cardoner, Christopher R. K. Ching, Stella J. deWit, Boris Gutman, Marcelo Q. Hoexter, Neda Jahanshad, Minah Kim, Jun Soo Kwon, David Mataix‐Cols, Jose M. Menchon, Euripedes C. Miguel, Takashi Nakamae, Mary L. Phillips, Jesus Pujol, Yuki Sakai, Je‐Yeon Yun, Carles Soriano‐Mas, Paul M. Thompson, Kei Yamada, Dick J. Veltman, Odile A. vanden Heuvel, and Dan J. Stein
Subjects: anxiety, depression, gray matter, magnetic resonance imaging, neuroimaging, obsessive‐compulsive disorder, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Objective Neuroimaging studies of obsessive‐compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients. Methods Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta‐analysis utilizing the ENIGMA‐Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape. Results There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co‐morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls. Conclusions The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape.
Published: 2022
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7. White matter microstructure and its relation to clinical features of obsessive–compulsive disorder: findings from the ENIGMA OCD Working Group

Author: Fabrizio Piras, Federica Piras, Yoshinari Abe, Sri Mahavir Agarwal, Alan Anticevic, Stephanie Ameis, Paul Arnold, Nerisa Banaj, Núria Bargalló, Marcelo C. Batistuzzo, Francesco Benedetti, Jan-Carl Beucke, Premika S. W. Boedhoe, Irene Bollettini, Silvia Brem, Anna Calvo, Kang Ik Kevin Cho, Valentina Ciullo, Sara Dallaspezia, Erin Dickie, Benjamin Adam Ely, Siyan Fan, Jean-Paul Fouche, Patricia Gruner, Deniz A. Gürsel, Tobias Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Mariangela Iorio, Anthony James, Y. C. Janardhan Reddy, Christian Kaufmann, Kathrin Koch, Peter Kochunov, Jun Soo Kwon, Luisa Lazaro, Christine Lochner, Rachel Marsh, Akiko Nakagawa, Takashi Nakamae, Janardhanan C. Narayanaswamy, Yuki Sakai, Eiji Shimizu, Daniela Simon, Helen Blair Simpson, Noam Soreni, Philipp Stämpfli, Emily R. Stern, Philip Szeszko, Jumpei Takahashi, Ganesan Venkatasubramanian, Zhen Wang, Je-Yeon Yun, ENIGMA OCD Working Group, Dan J. Stein, Neda Jahanshad, Paul M. Thompson, Odile A. van den Heuvel, and Gianfranco Spalletta
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p
Published: 2021
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8. Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study

Author: Catherine J. Wedderburn, Sivenesi Subramoney, Shunmay Yeung, Jean-Paul Fouche, Shantanu H. Joshi, Katherine L. Narr, Andrea M. Rehman, Annerine Roos, Jonathan Ipser, Frances C. Robertson, Nynke A. Groenewold, Diana M. Gibb, Heather J. Zar, Dan J. Stein, and Kirsten A. Donald
Subjects: Neuroimaging, Children, Africa, Cortical surface area, Cortical thickness, Cognition, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2–3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2–3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation.
Published: 2020
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9. Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder

Author: Janna Marie Bas-Hoogendam, Henk van Steenbergen, J. Nienke Pannekoek, Jean-Paul Fouche, Christine Lochner, Coenraad J. Hattingh, Henk R. Cremers, Tomas Furmark, Kristoffer N.T. Månsson, Andreas Frick, Jonas Engman, Carl-Johan Boraxbekk, Per Carlbring, Gerhard Andersson, Mats Fredrikson, Thomas Straube, Jutta Peterburs, Heide Klumpp, K. Luan Phan, Karin Roelofs, Dick J. Veltman, Marie-José van Tol, Dan J. Stein, and Nic J.A. van der Wee
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n=174) and healthy control (HC)-participants (n=213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. Keywords: Social anxiety disorder, Structural MRI, Voxel-based morphometry, Gray matter, Mega-analysis, Striatum
Published: 2017
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10. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Premika S. W. Boedhoe, Martijn W. Heymans, Lianne Schmaal, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Anna Calvo, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Valentina Ciullo, Sara Dallaspezia, Damiaan Denys, Jamie D. Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, Patricia Gruner, Gregory L. Hanna, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Neda Jahanshad, Anthony James, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Jun Soo Kwon, Luisa Lazaro, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Astrid Morer, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Seiji Nishida, Erika L. Nurmi, Joseph O'Neill, John Piacentini, Fabrizio Piras, Federica Piras, Y. C. Janardhan Reddy, Tim J. Reess, Yuki Sakai, Joao R. Sato, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Michael C. Stevens, Philip R. Szeszko, David F. Tolin, Guido A. van Wingen, Ganesan Venkatasubramanian, Susanne Walitza, Zhen Wang, Je-Yeon Yun, ENIGMA-OCD Working-Group, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, and Jos W. R. Twisk
Subjects: neuroimaging, MRI, IPD meta-analysis, mega-analysis, linear mixed-effect models, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses.Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods.Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models.Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
Published: 2019
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11. Cortical thickness across the lifespan

Author: Simon E. Fisher, Eveline A. Crone, Dominik Grotegerd, Jilly Naaijen, Anders M. Dale, Sean N. Hatton, Ramona Baur-Streubel, Anthony A. James, Daniel Brandeis, Andrew J. Kalnin, Andreas Reif, Hans-Jörgen Grabe, Pieter J. Hoekstra, Lars Nyberg, Fleur M. Howells, Moji Aghajani, Randy L. Buckner, Daniel A. Rinker, Steven G. Potkin, Dennis van 't Ent, Rachel M. Brouwer, Sophia Frangou, Yang Wang, Nhat Trung Doan, Theodore D. Satterthwaite, Christine Lochner, Geraldo F. Busatto, Lars T. Westlye, Lara M. Wierenga, Calhoun Vd, Henry Brodaty, Carles Soriano-Mas, Annette Conzelmann, Christian K. Tamnes, Julian N. Trollor, Nicholas G. Martin, Neeltje E.M. van Haren, René S. Kahn, Irina Lebedeva, Philip Asherson, Suzanne C. Swagerman, John A. Joska, Theophilus N. Akudjedu, Kang Sim, Lachlan T. Strike, Patricia Gruner, Brenna C. McDonald, Thomas Frodl, Edith Pomarol-Clotet, Víctor Ortiz-García de la Foz, Margaret J. Wright, Norbert Hosten, Jean-Paul Fouche, Bernd Weber, Salvador Sarró, Wei Wen, Dag Alnæs, Greig I. de Zubicaray, Iris E. C. Sommer, Marise W. J. Machielsen, Knut Schnell, Dara M. Cannon, Paola Fuentes-Claramonte, Josiane Bourque, Andreas Meyer-Lindenberg, Anton Albajes-Eizagirre, Sarah Hohmann, Erin W. Dickie, Theo G.M. van Erp, Micael Andersson, Paul Pauli, Thomas Espeseth, Heather C. Whalley, Victoria Chubar, Ruben C. Gur, Tomohiro Nakao, Xavier Caseras, Alessandro Bertolino, Ignacio Martínez-Zalacaín, Katharina Wittfeld, Erick J. Canales-Rodríguez, David C. Glahn, Neda Jahanshad, Jiyang Jiang, Katie L. McMahon, Stefan Borgwardt, Erlend S. Dørum, Jaap Oosterlaan, Won Hee Lee, Alan Breier, Steven Williams, Aristotle N. Voineskos, Bernard Mazoyer, Jordan W. Smoller, Nancy C. Andreasen, Ilya M. Veer, Tiffany M. Chaim-Avancini, Sophie Maingault, Paul M. Thompson, Eco J. C. de Geus, Luisa Lázaro, Giulio Pergola, Efstathios Papachristou, Beng-Choon Ho, David Mataix-Cols, Esther Walton, Ben J. Harrison, Dirk J. Heslenfeld, Pablo Najt, Helena Fatouros-Bergman, Derrek P. Hibar, Gunter Schumann, Raymond Salvador, Lieuwe de Haan, Henry Völzke, Joaquim Radua, Henk Temmingh, Lianne Schmaal, Martine Hoogman, Daniel H. Wolf, Georg C. Ziegler, Marieke Klein, Barbara Franke, Erik G. Jönsson, Laura Koenders, Stefan Ehrlich, Oliver Gruber, Ingrid Agartz, Kun Yang, Ryota Kanai, Sarah Baumeister, Colm McDonald, Annabella Di Giorgio, Amanda Worker, Anne Uhlmann, Marcus V. Zanetti, Danai Dima, Matthew D. Sacchet, Sarah E. Medland, Aurora Bonvino, Benedicto Crespo-Facorro, Jan Egil Nordvik, Joshua L. Roffman, Yannis Paloyelis, Jessica A. Turner, T. P. Klyushnik, Christopher G. Davey, Rachel E. Gur, Ian B. Hickie, Christopher R.K. Ching, Jonna Kuntsi, Tobias Banaschewski, Chaim Huyser, Amirhossein Modabbernia, John D. West, Fabrice Crivello, Núria Bargalló, Patricia J. Conrod, Nic J.A. van der Wee, Mauricio H. Serpa, Thomas H. Wassink, Kathryn I. Alpert, Dick J. Veltman, Andrew J. Saykin, Genevieve McPhilemy, Perminder S. Sachdev, Vincent P. Clark, Ian H. Gotlib, Susanne Erk, Henrik Walter, Dennis van den Meer, Simon Cervenka, Oliver Grimm, Andrew M. McIntosh, Alexander Tomyshev, Francisco X. Castellanos, Bernd Kramer, Klaus-Peter Lesch, Odile A. van den Heuvel, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Terry L. Jernigan, Yulyia Yoncheva, Anouk den Braber, Jim Lagopoulos, Maria J. Portella, Ole A. Andreassen, Gaelle E. Doucet, Avram J. Holmes, Nynke A. Groenewold, Pedro G.P. Rosa, Hilleke E. Hulshoff Pol, Sanne Koops, José M. Menchón, Jan K. Buitelaar, Dan J. Stein, Dorret I. Boomsma, Lei Wang, C.A. Hartman, Pascual Sánchez-Juan, Andreas Heinz, European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Karolinska Schizophrenia Project (KaSP), Ontwikkelingspsychologie (Psychologie, FMG), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Epidemiology and Data Science, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Brain Imaging, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Biological Psychology, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, and APH - Personalized Medicine
Subjects: Male, Aging, Neurologi, Audiology, Trajectories, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], Child, Research Articles, Cerebral Cortex, Psychiatry, Aged, 80 and over, Radiological and Ultrasound Technology, Fractional polynomial, 05 social sciences, Radiology, Nuclear Medicine & Medical Imaging, 1. No poverty, Cognition, Middle Aged, Cerebral cortex, Regression, 3. Good health, Escorça cerebral, Neurology, Radiology Nuclear Medicine and imaging, Healthy individuals, Child, Preschool, anatomy & histology [Cerebral Cortex], Female, Analysis of variance, Anatomy, Life Sciences & Biomedicine, Trajectorie, Research Article, Neuroinformatics, Adult, medicine.medical_specialty, Adolescent, Human Development, Clinical Neurology, BF, Neuroimaging, Biology, Development, 050105 experimental psychology, Psykiatri, Cortical thickness, 03 medical and health sciences, Young Adult, Neuroimaging genetics, Envelliment, medicine, Humans, trajectories, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, development, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Brain morphometry, aging, Neurosciences, cortical thickness, Cross-Sectional Studies, RC0321, Neurology (clinical), Neurosciences & Neurology, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)
Published: 2022

12. Greater male than female variability in regional brain structure across the lifespan

Author: Erick J. Canales-Rodríguez, Hans J. Grabe, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Daniel Brandeis, Yang Wang, Henry Brodaty, Ruben C. Gur, Iris E. C. Sommer, Paul M. Thompson, Knut K. Kolskår, Christopher G. Davey, Dick J. Veltman, Eco J. C. de Geus, Tobias Banaschewski, Greig I. Zubicaray, Xavier Caseras, Sarah Baumeister, Raquel E. Gur, Vincent P. Clark, Maria J. Portella, Simon E. Fisher, Christopher R.K. Ching, Lars T. Westlye, Laura Koenders, Vince D. Calhoun, Carles Soriano-Mas, Nicholas G. Martin, Stefan Ehrlich, Fleur M. Howells, Catharina A. Hartman, Matthew D. Sacchet, Ole A. Andreassen, Josiane Bourque, Fabrice Crivello, Annette Conzelmann, Jaap Oosterlaan, Brenna C. McDonald, Gaelle E. Doucet, Avram J. Holmes, José M. Menchón, Danai Dima, Moji Aghajani, Joshua L. Roffman, Steven Williams, Lei Wang, David Mataix-Cols, Philip R. Szeszko, Bernd Weber, Tiril P. Gurholt, Sarah Hohmann, Ian H. Gotlib, Patricia Gruner, Anthony C. James, Paul Pauli, Lara M. Wierenga, Andrew M. McIntosh, Andrew J. Kalnin, Jim Lagopoulos, Henrik Walter, Andreas Reif, Andrew Simmons, Norbert Hosten, Pieter J. Hoekstra, Aristotle Voineskos, Alexander Tomyshev, Anton Albajes-Eizagirre, Jean-Paul Fouche, Dara M. Cannon, Ignacio Martínez‐Zalacaín, Geneviève Richard, Theophilus N. Akudjedu, David C. Glahn, Patricia J. Conrod, Ben J. Harrison, Alan Anticevic, Martine Hoogman, Francisco X. Castellanos, Bernd Kramer, Neda Jahanshad, Lieuwe de Haan, Dennis van der Meer, John D. West, Alan Breier, Jordan W. Smoller, P. G. P. Rosa, Katharina Wittfeld, Dan J. Stein, Jiyang Jiang, Jilly Naaijen, Christine Lochner, Dorret I. Boomsma, Alessandro Bertolino, Marise W. J. Machielsen, Hilleke E. Hulshoff Pol, Henry Völzke, Christian K. Tamnes, Ingrid Agartz, Georg C. Ziegler, Marieke Klein, Lars Nyberg, Perminder S. Sachdev, Philip Asherson, I.M. Veer, Sean N. Hatton, Núria Bargalló, Annabella Di Giorgio, Henk Temmingh, John A. Joska, Odile A. van den Heuvel, Wei Wen, Eveline A Crone, Kang Sim, Kathryn I. Alpert, Dennis van 't Ent, Jan K. Buitelaar, Joaquim Radua, Julian N. Trollor, B Mazoyer, Chaim Huyser, H. C. Whalley, Irina Lebedeva, Erin W. Dickie, Marcus Vinicus Zanetti, Stefan Borgwardt, Theodore D. Satterthwaite, Daniel H Wolf, Sophia I. Thomopoulos, Giulio Pergola, Luisa Lazaro, Ramona Baur-Streubel, Beathe Haatveit, Yannis Paloyelis, Ian B. Hickie, Jonna Kuntsi, Sophia Frangou, R. Salvador, Geraldo F. Busatto, Margaret J. Wright, Aurora Bonvino, Edith Pomarol-Clotet, Anouk den Braber, Lachlan T. Strike, Phil Lee, Anne Uhlmann, Yuliya N. Yoncheva, Mauricio H. Serpa, Dag Alnæs, Paola Fuentes-Claramonte, Katie L. McMahon, Andrew J. Saykin, Genevieve McPhilemy, Tiffany M. Chaim-Avancini, Sophie Maingault, Barbara Franke, Colm McDonald, Rachel M. Brouwer, Salvador Sarró, Department of Psychology, Education and Child Studies, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, AMS - Ageing & Vitality, AMS - Sports, APH - Personalized Medicine, Cognitive Psychology, Clinical Neuropsychology, IBBA, Karolinska Schizophrenia Project (KaSP) Consortium, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Amsterdam Neuroscience, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Pediatric surgery, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, Netherlands Twin Register (NTR), SEGMENTATION, Vulnerability, Disease, HM, 0302 clinical medicine, Anàlisi de variància, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], sexual characteristics, Analysis of variance, nuclear magnetic resonance imaging, Cervell, Research Articles, Cerebral Cortex, Sex Characteristics, Radiological and Ultrasound Technology, 05 social sciences, Brain, clinical trial, Brain Structure, Magnetic Resonance Imaging, Early life, Adolescence, medicine.anatomical_structure, Neurology, Cerebral cortex, Healthy individuals, X-CHROMOSOME, anatomy & histology [Cerebral Cortex], Evolution of the brain, Female, Anatomy, Neurovetenskaper, Research Article, Radiology, Nuclear Medicine and Medical Imaging, Neuroinformatics, SEX-DIFFERENCES, diagnostic imaging, brain, Human Development, BF, Neuroimaging, SURFACE-AREA, Evolució del cervell, Regional area, Biology, MULTISAMPLE, 050105 experimental psychology, brain cortex, 03 medical and health sciences, CEREBRAL-CORTEX, Sex differences, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, human, ddc:610, Cortical surface, GENERAL INTELLIGENCE, diagnostic imaging [Brain], METAANALYSIS, biological variation, HUMAN HIPPOCAMPUS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], physiology [Biological Variation, Population], Neurosciences, Gender, Brain Cortical Thickness, multicenter study, Biological Variation, Population, Diferències entre sexes, physiology, RC0321, Radiologi och bildbehandling, Neurology (clinical), anatomy & histology [Brain], 170 000 Motivational & Cognitive Control, 030217 neurology & neurosurgery, anatomy and histology, meta analysis, physiology [Human Development], Demography
Abstract: Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

13. Shape analysis of subcortical structures in obsessive-compulsive disorder and the relationship with comorbid anxiety, depression, and medication use:A meta-analysis by the OCD Brain Imaging Consortium

Author: Jean‐Paul Fouche, Nynke A. Groenewold, Tatum Sevenoaks, Sarah Heany, Christine Lochner, Pino Alonso, Marcelo C. Batistuzzo, Narcis Cardoner, Christopher R. K. Ching, Stella J. de Wit, Boris Gutman, Marcelo Q. Hoexter, Neda Jahanshad, Minah Kim, Jun Soo Kwon, David Mataix‐Cols, Jose M. Menchon, Euripedes C. Miguel, Takashi Nakamae, Mary L. Phillips, Jesus Pujol, Yuki Sakai, Je‐Yeon Yun, Carles Soriano‐Mas, Paul M. Thompson, Kei Yamada, Dick J. Veltman, Odile A. van den Heuvel, Dan J. Stein, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Behavioral Neuroscience, Magnetic resonance imaging, Depression, Obsessive-compulsive disorder, Brain, Humans, Neuroimaging, Subcortical, Comorbidity, Anxiety, Gray matter
Abstract: Neuroimaging studies of obsessive-compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients. Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta-analysis utilizing the ENIGMA-Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape. There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co-morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls. The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape. There is a paucity of literature on subcortical shape in OCD patients. In this multi-site meta-analysis there was no significant difference in shape between OCD patients and controls, however abnormalities in both shape thickness and surface area were found for medicated OCD patients with comorbid anxiety and depression compared to healthy controls.
Published: 2022

14. Early structural brain development in infants exposed to HIV and antiretroviral therapy in utero in a South African birth cohort

Author: Catherine J. Wedderburn, Nynke A. Groenewold, Annerine Roos, Shunmay Yeung, Jean‐Paul Fouche, Andrea M. Rehman, Diana M. Gibb, Katherine L. Narr, Heather J. Zar, Dan J. Stein, and Kirsten A. Donald
Subjects: Male, child development, brain structure, antiretroviral therapy, Public Health, Environmental and Occupational Health, Infant, Newborn, Brain, Infant, HIV Infections, Infectious Diseases, Breast Feeding, newborn infant, Pregnancy, HIV exposure, Humans, magnetic resonance imaging, Birth Cohort, Female, Prospective Studies, Pregnancy Complications, Infectious, Research Articles, Research Article
Abstract: Introduction There is a growing population of children who are HIV‐exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV‐unexposed (HU). Methods Magnetic resonance imaging using a T2‐weighted sequence was undertaken in a subgroup of infants aged 2–6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother–child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio‐economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure. Results One hundred forty‐six infants (40 HEU; 106 HU) with high‐resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p < 0.05) compared to HU infants. There were no group differences in other subcortical volumes (all p > 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (
Published: 2022

15. Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART

Author: Sarah J. Heany, Heather J. Zar, Jacqueline Hoare, Landon Myer, Dan J. Stein, Jean-Paul Fouche, and Nicole Phillips
Subjects: Pediatrics, medicine.medical_specialty, Health (social science), Adolescent, Population, CBCL, HIV Infections, Toxicology, Corpus callosum, Biochemistry, Article, White matter, Behavioral Neuroscience, South Africa, Fractional anisotropy, Medicine, Humans, education, Child Behavior Checklist, Child, education.field_of_study, business.industry, Brain, General Medicine, medicine.anatomical_structure, Cross-Sectional Studies, Diffusion Tensor Imaging, Mental Health, Neurology, Child, Preschool, Cohort, business, Neurocognitive
Abstract: Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host–virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV + alcohol) (n = 26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV + alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV + alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV + alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV + alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV + alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV + alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV + alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.
Published: 2021

16. Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure

Author: Roger P. Woods, Shantanu H. Joshi, Catherine J. Wedderburn, Annerine Roos, Heather J. Zar, Kirsten A. Donald, Katherine L. Narr, Sivenesi Subramoney, Dan J. Stein, and Jean-Paul Fouche
Subjects: Male, animal structures, Uncinate fasciculus, Physiology, White matter integrity, Development, Toxicology, Article, White matter, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Fractional anisotropy, medicine, Humans, Pharmacology (medical), Prenatal tobacco exposure, 030212 general & internal medicine, Risk factor, Pharmacology, business.industry, Fornix, Brain, White Matter, Psychiatry and Mental health, Stria terminalis, medicine.anatomical_structure, Diffusion Tensor Imaging, Child, Preschool, Prenatal Exposure Delayed Effects, Corticospinal tract, Prenatal alcohol exposure, Anisotropy, Female, Nerve Net, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Highlights • Prenatal alcohol exposure alters white matter integrity in 2–3-year-old children. • Effects of prenatal alcohol exposure on white matter integrity persist. • Co-exposure of alcohol and tobacco amplify white matter alterations in motor tracts., Background Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2–3-year-old children. Methods Children (n = 83, 30–37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored. Results Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls. Conclusion Widespread altered white matter microstructural integrity at 2–3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function.
Published: 2021

17. Childhood Trauma and Mental Health in the Cape Town Adolescent Antiretroviral Cohort

Author: Heather J. Zar, Jean-Paul Fouche, Tatum Sevenoaks, Jacqueline Hoare, Nicole Phillips, Dan J. Stein, Landon Myer, and Sarah J. Heany
Subjects: 050103 clinical psychology, medicine.medical_specialty, business.industry, media_common.quotation_subject, Public health, 05 social sciences, CTQ tree, Stigma (botany), Anger, Critical Care and Intensive Care Medicine, medicine.disease, Mental health, Emergency Medicine, Medicine, Attention deficit hyperactivity disorder, Anxiety, 0501 psychology and cognitive sciences, Original Article, medicine.symptom, business, Psychological abuse, 050104 developmental & child psychology, media_common, Clinical psychology
Abstract: This study aimed to assess the association of childhood trauma, stressful life events and HIV stigma with mental health in South African adolescents from the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Childhood Trauma Questionnaire, Life Events Questionnaire and the HIV Stigma Scale for South African Adolescents Living with HIV was used to assess childhood trauma, stressful life events and stigma in adolescents living with perinatally acquired HIV and healthy controls enrolled in the CTAAC. These measures were associated with mental health outcomes including the Beck-Youth Inventories, Child Behaviour Checklist, Columbian Impairment Scale, Childrens Motivation Scale, Conners Scale for Attention Deficit Hyperactivity Disorder using Pearson correlations and self-reported alcohol use, using Spearman-rank correlation. 63.7% of adolescents reported at least one childhood trauma on the CTQ. Significant associations were reported between CTQ measures and Beck-Youth Inventories. Emotional abuse was associated with anxiety, anger, depression and disruptive behaviour. Emotional neglect was associated with poor self-concept and disruptive behaviour. LEQ total score was significantly associated with Beck-Youth Inventories including anxiety, depression, anger and disruptive behaviour scales. HIV stigma was significantly associated with Beck-Youth Inventories including depression, anger and disruptive behaviour. Childhood trauma, stressful life events and HIV stigma in South African adolescents are associated with anxiety, depression, anger, disruptive-behaviour and poor self-concept. This study highlights the importance of enquiring about exposure to a variety of traumas, particularly those commonly experienced by South African adolescents. In addition, it is important to understand the impact of trauma exposure on each individuals mental health and functioning.
Published: 2021

18. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Tiffany M. Chaim-Avancini, Suzanne C. Swagerman, Sophie Maingault, Mauricio H. Serpa, Kang Sim, Patricia Gruner, Dara M. Cannon, Esther Walton, Gunter Schumann, Christopher R.K. Ching, Simon E. Fisher, Tomohiro Nakao, Nhat Trung Doan, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Ilya M. Veer, Lieuwe de Haan, Paul Pauli, Derrek P. Hibar, Kun Yang, Dan J. Stein, Dominik Grotegerd, Víctor Ortiz-García de la Foz, Daniel Brandeis, Sarah Baumeister, Xavier Caseras, Fabrice Crivello, Vincent P. Clark, Maria J. Portella, Salvador Sarró, Dorret I. Boomsma, Henry Völzke, Daniel H. Wolf, Lianne Schmaal, Yannis Paloyelis, Barbara Franke, Matthew D. Sacchet, Anne Uhlmann, Yulyia Yoncheva, Ole A. Andreassen, Erick J. Canales-Rodríguez, Ingrid Agartz, Anouk den Braber, Colm McDonald, Edith Pomarol-Clotet, Anders M. Dale, Calhoun Vd, David Mataix-Cols, Ignacio Martínez-Zalacaín, Joshua L. Roffman, Andrew J. Kalnin, Anton Albajes-Eizagirre, Andreas Reif, Won Hee Lee, Gaelle E. Doucet, Hans-Jörgen Grabe, Pieter J. Hoekstra, Avram J. Holmes, Theophilus N. Akudjedu, Ian H. Gotlib, Fleur M. Howells, Andrew J. Saykin, Genevieve McPhilemy, Moji Aghajani, David C. Glahn, Rachel M. Brouwer, Núria Bargalló, Knut Schnell, Katharina Wittfeld, Thomas Frodl, Josiane Bourque, Ryota Kanai, Raymond Salvador, Sean N. Hatton, Terry L. Jernigan, Helena Fatouros-Bergman, Oliver Grimm, Marise W. J. Machielsen, Victoria Chubar, Henk Temmingh, Andrew M. McIntosh, Georg C. Ziegler, Marieke Klein, T. P. Klyushnik, Iris E. C. Sommer, Heather C. Whalley, Rachel E. Gur, Alan Breier, Jordan W. Smoller, Kathryn I. Alpert, Dick J. Veltman, Neda Jahanshad, Sophia Frangou, Jiyang Jiang, Jessica A. Turner, Eveline A. Crone, Thomas Espeseth, Alexander Tomyshev, Christine Lochner, Anthony A. James, Aristotle N. Voineskos, Julian N. Trollor, Efstathios Papachristou, Beng-Choon Ho, Pablo Najt, Christian K. Tamnes, Geraldo F. Busatto, Stefan Borgwardt, Andreas Meyer-Lindenberg, Philip Asherson, Francisco X. Castellanos, Bernd Kramer, Jim Lagopoulos, Marcus V. Zanetti, Joaquim Radua, John A. Joska, Giulio Pergola, Nynke A. Groenewold, Erlend S. Dørum, Henrik Walter, Jan Egil Nordvik, Alessandro Bertolino, Wei Wen, Klaus-Peter Lesch, Ian B. Hickie, Pedro G.P. Rosa, Randy L. Buckner, Daniel A. Rinker, Hilleke E. Hulshoff Pol, Steven G. Potkin, Odile A. van den Heuvel, Nancy C. Andreasen, Sanne Koops, Amanda Worker, Susanne Erk, Lei Wang, Norbert Hosten, Jean-Paul Fouche, Dennis van 't Ent, Jonna Kuntsi, Dennis van den Meer, Simon Cervenka, C.A. Hartman, Nicholas G. Martin, Carles Soriano-Mas, Neeltje E.M. van Haren, Pascual Sánchez-Juan, Andreas Heinz, Brenna C. McDonald, Thomas H. Wassink, José M. Menchón, Katie L. McMahon, Jan K. Buitelaar, Sarah E. Medland, Aurora Bonvino, Patricia J. Conrod, Nic J.A. van der Wee, Paul M. Thompson, Micael Andersson, Perminder S. Sachdev, Lars Nyberg, Eco J. C. de Geus, Ramona Baur-Streubel, Lachlan T. Strike, Dag Alnæs, Paola Fuentes-Claramonte, Ben J. Harrison, Martine Hoogman, Lars T. Westlye, Annette Conzelmann, Annabella Di Giorgio, Benedicto Crespo-Facorro, Sarah Hohmann, Jilly Naaijen, Yang Wang, Henry Brodaty, Greig I. de Zubicaray, Laura Koenders, Ruben C. Gur, Stefan Ehrlich, Danai Dima, Christopher G. Davey, Tobias Banaschewski, Amirhossein Modabbernia, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Theodore D. Satterthwaite, René S. Kahn, Margaret J. Wright, Jaap Oosterlaan, Steven Williams, Bernard Mazoyer, Lara M. Wierenga, Bernd Weber, Luisa Lázaro, Irina Lebedeva, Erin W. Dickie, Chaim Huyser, John D. West, Theo G.M. van Erp, National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Karolinska Schizophrenia Project (KaSP), Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, APH - Personalized Medicine, Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, diagnostic imaging [Corpus Striatum], Physiology, Hippocampus, Edat, Morfologia (Biologia), Lateral ventricles, anatomy & histology [Corpus Striatum], 0302 clinical medicine, Thalamus, 130 000 Cognitive Neurology & Memory, Basal ganglia, diagnostic imaging [Amygdala], Child, Cervell, Research Articles, diagnostic imaging [Hippocampus], Aged, 80 and over, Radiological and Ultrasound Technology, Putamen, Radiology, Nuclear Medicine & Medical Imaging, 05 social sciences, ENIGMA, Multisi, Brain, Middle Aged, Amygdala, 3. Good health, Neurology, Child, Preschool, Brain size, Female, Anatomy, Life Sciences & Biomedicine, Neurovetenskaper, Research Article, Neuroinformatics, Adult, Adolescent, anatomy & histology [Hippocampus], Human Development, multisite, BF, Neuroimaging, Nucleus accumbens, Biology, Brain morphometry, Morphology (Biology), 050105 experimental psychology, Young Adult, 03 medical and health sciences, Age, Longitudinal trajectories, brain morphometry, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, anatomy & histology [Thalamus], Aged, diagnostic imaging [Thalamus], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Neurosciences, Corpus Striatum, nervous system, anatomy & histology [Amygdala], RC0321, Neurosciences & Neurology, longitudinal trajectories, Neurology (clinical), 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.
Published: 2021

19. Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Author: Robert H. Paul, Jaroslaw Harezlak, Beau M. Ances, Hei Lam, Adam J. Woods, Joga Chaganti, Joshua Faskowitz, Cecilia M. Shikuma, Jasmina Boban, Xavier Pennec, Jodi M. Heaps-Woodruff, Thomas Ernst, Charles H. Hinkin, Andrew J. Levine, Beau K. Nakamoto, Ronald A. Cohen, Eric C. Porges, Neda Jahanshad, Bruce J. Brew, Jacqueline Hoare, Taylor Kuhn, Christine Lebrun-Frenay, Meng Law, Dan J. Stein, Paul M. Thompson, Lucette A. Cysique, Bradford A. Navia, Vikash Gupta, Talia M. Nir, Matteo Vassallo, Victor Valcour, Linda Chang, Lydiane Mondot, John A. Joska, April D. Thames, Jintanat Ananworanich, Jean-Paul Fouche, Kalpana J. Kallianpur, Christopher R.K. Ching, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Cape Town, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Novi Sad, University of New South Wales [Sydney] (UNSW), University of Maryland School of Medicine, University of Maryland System, Neuroscience Research Australia (NeuRA), Indiana State University, Missouri Institute of Mental Health [St. Louis] (MIMH), University of Missouri [St. Louis], University of Missouri System-University of Missouri System, University of California [Los Angeles] (UCLA), University of California, University of Hawai'i [Honolulu] (UH), Monash University [Melbourne], Hôpital Pasteur [Nice] (CHU), Department of Neurology [UCLA], University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Universitaire de Nice (CHU Nice), Tufts University School of Medicine [Boston], Université Côte d'Azur (UCA), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), McKnight Brain Institute [Gainesville] (UF|MBI), University of Florida [Gainesville] (UF), University of California [San Francisco] (UCSF), Centre Hospitalier de Cannes, University of Missouri School of Medicine, University of Missouri System, University of California (UC), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), and University of California [San Francisco] (UC San Francisco)
Subjects: Cart, Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, Putamen, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunosuppression, Amygdala, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neuroimaging, Internal medicine, Statistical significance, medicine, business, Viral load, Neurocognitive, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: BackgroundHuman immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure.MethodsData were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance.FindingsLower current CD4+ count was associated with smaller hippocampal (β= 20.3 mm3per 100 cells/mm3;p= 0.0001) and thalamic volumes (β= 29.3;p= 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes (β= 65.1;p= 0.0009). On average, a dVL was associated with smaller hippocampal (Cohen’sd= 0.24;p= 0.0003) and amygdala volumes (d= 0.18;p= 0.0058).InterpretationIn HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health.FundingThis work was supported, in part, by NIH grant U54 EB020403.Research in ContextEvidence before this studyHIV type-1 infection can be managed with antiretroviral therapy, however neurocognitive impairment persists even in treated HIV+ individuals. Given the challenges associated with standardized cognitive testing, there is a need to identify quantitative markers of central nervous system impairment. A number of neuroimaging studies have reported brain abnormalities in HIV-infected patients; however, prior studies investigating associations between CD4+ T-cell count or HIV viral load and subcortical brain volume report variable effect sizes and regional distributions of effects, limiting the generalizability of the conclusions drawn to date. We have conducted a literature search for reports in English language journals published until June 2019, using the following search terms: HIV AND subcortical AND neuroimaging AND brain AND viral load AND RNA AND CD4. After removing studies that were not applicable, there were 30 studies investigating CD4+ T-cell count and viral load associations with subcortical brain structure.Added value of the studyThe aim of the current study was to investigate structural brain associations with two biomarkers universally used to monitor immune function and treatment response, namely plasma RNA viral load and CD4+ T-cell counts. Prior analyses have been performed in smaller, heterogeneous cohorts, but by combining data across cohorts, we can identify consistent associations between brain volume and indicators of HIV infection across cohorts. The ENIGMA-HIV Working Group was established to identify common neurobiological signatures of the HIV-infected brain by harmonizing data analysis from HIV neuroimaging studies worldwide. The value of this dataset is that it is well-powered and representative of many HIV+ people living in the cART era.Implications of all the available evidenceOur results provide robust evidence that despite demographic and clinical heterogeneity among HIV-infected individuals, brain abnormalities are consistently linked to HIV viral load and immunosuppression. This supports the importance of achieving viral suppression and immune system restoration in maintaining brain health in people living with HIV. The vulnerability of limbic regions, found in this study, extends beyond the classically implicated regions of the basal ganglia; this suggests that these regions remain an important target of cART era HIV research, especially given their heightened vulnerability to age-associated atrophy and neurodegeneration.
Published: 2021

20. Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

Author: Dan J. Stein, Christopher R.K. Ching, Taylor Kuhn, Kalpana J. Kallianpur, Vikash Gupta, Paul M. Thompson, Joshua Faskowitz, Neda Jahanshad, Bradford A. Navia, Thomas Ernst, Xavier Pennec, Ronald A. Cohen, Cecilia M. Shikuma, Bruce J. Brew, Jean-Paul Fouche, Hei Y. Lam, Christine Lebrun-Frenay, Lauren E. Salminen, Jaroslaw Harezlak, Wesley Surento, Beau M. Ances, Lydiane Mondot, Eric C. Porges, Beau K. Nakamoto, Linda Chang, April D. Thames, Adam J. Woods, Matteo Vassallo, Talia M. Nir, John A. Joska, Jasmina Boban, Jodi M. Heaps-Woodruff, Charles H. Hinkin, Meng Law, Jintanat Ananworanich, Robert H. Paul, Lucette A. Cysique, Jacqueline Hoare, Joga Chaganti, Andrew J. Levine, Victor Valcour, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of Cape Town, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), University of Amsterdam [Amsterdam] (UvA), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Novi Sad, St. Vincent’s Clinical School [Sydney, Australia], UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW)-University of New South Wales [Sydney] (UNSW), University of Maryland School of Medicine, University of Maryland System, University of Hawai'i [Honolulu] (UH), University of New South Wales [Sydney] (UNSW), Indiana University [Bloomington], Indiana University System, Missouri Institute of Mental Health [St. Louis] (MIMH), University of Missouri [St. Louis], University of Missouri System-University of Missouri System, University of California [Los Angeles] (UCLA), University of California, Monash University [Melbourne], Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Tufts University School of Medicine [Boston], E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), McKnight Brain Institute [Gainesville] (UF|MBI), University of Florida [Gainesville] (UF), Southern California University of Health Sciences, University of California [San Francisco] (UCSF), Centre Hospitalier de Cannes, University of Missouri System, Global Health, University of California (UC), Southern California University of Health Sciences (SCU), and University of California [San Francisco] (UC San Francisco)
Subjects: Adult, Male, Cart, medicine.medical_specialty, Cross-sectional study, Population, HIV Infections, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Young adult, education, Aged, Original Investigation, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, education.field_of_study, business.industry, Research, Brain, General Medicine, Middle Aged, Viral Load, Magnetic Resonance Imaging, CD4 Lymphocyte Count, 3. Good health, Online Only, Cross-Sectional Studies, Infectious Diseases, Meta-analysis, Brain size, Female, business, Neurocognitive, Viral load, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Key Points Question Are HIV plasma markers that are universally used to monitor immune function and treatment response associated with subcortical brain volumes in clinically and demographically heterogeneous HIV-infected individuals? Findings In this cross-sectional study of 1203 HIV-infected adults, lower current CD4+ T-cell counts were associated with smaller hippocampal and thalamic volumes independent of treatment status, although in the subset of participants not receiving treatment, they were associated with smaller putamen volumes. Across all participants, detectable viral load was associated with smaller hippocampal volumes, but in the subset of participants receiving HIV treatment, detectable viral load was also associated with smaller amygdala volumes. Meaning In a heterogeneous population of HIV-infected individuals, volumes of structures in the limbic system were consistently associated with plasma markers., Importance Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P, This cross-sectional study examines structural brain associations with CD4+ T-cell count and viral load in HIV-positive individuals taking and not taking combination antiretroviral therapy.
Published: 2021

21. A diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals

Author: Jacqueline, Hoare, Jenny, Westgarth-Taylor, Jean-Paul, Fouche, Bruce, Spottiswoode, Robert, Paul, Kevin, Thomas, Dan, Stein, and John, Joska
Published: 2012
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22. ENIGMA and global neuroscience:A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Frank G. Hillary, Esther Walton, Gunter Schumann, Sophia I. Thomopoulos, Patricia J. Conrod, Nic J.A. van der Wee, Daqiang Sun, Charlotte A.M. Cecil, Robin Bülow, Henry Völzke, Rachel M. Brouwer, Yann Chye, Katrina L. Grasby, Ingrid Agartz, Bernhard T. Baune, Josselin Houenou, Simon E. Fisher, Mark S. Shiroishi, Daan van Rooij, Miguel E. Rentería, Yanli Zhang-James, Courtney A. Filippi, Stephen V. Faraone, Sara Bertolín, Elisabeth A. Wilde, Eus J.W. Van Someren, Christopher R.K. Ching, Iliyan Ivanov, Barbara Franke, Derrek P. Hibar, Tiffany C. Ho, Hilleke E. Hulshoff Pol, Norbert Hosten, Ilya M. Veer, Daniel Garijo, Jean-Paul Fouche, Inga K. Koerte, Hans J. Grabe, Carles Soriano-Mas, Lianne Schmaal, Brenda Bartnik-Olson, Amanda K. Tilot, Sinead Kelly, Ysbrand D. van der Werf, Anderson M. Winkler, Henrik Walter, Hugh Garavan, Max A. Laansma, Agnes B. McMahon, Laura K.M. Han, Natalia Shatokhina, Scott Mackey, David F. Tate, Jason L. Stein, Thomas Frodl, Tiril P. Gurholt, Carrie E. Bearden, Katharina Wittfeld, Carrie R. McDonald, Andrew R. Mayer, Yolanda Gil, Jun Soo Kwon, Tomas Hajek, Jan K. Buitelaar, Moji Aghajani, Bhim M. Adhikari, Premika S.W. Boedhoe, Graeme Fairchild, Maria Jalbrzikowski, Alexander Olsen, Carolien G.F. de Kovel, Talia M. Nir, Mojtaba Zarei, Karen Caeyenberghs, Dirk J.A. Smit, Fabio Macciardi, Jeanne Leerssen, Margaret J. Wright, Eduard T. Klapwijk, Elena Pozzi, Lisa T. Eyler, Abraham Nunes, Sanjay M. Sisodiya, Clyde Francks, Emily L. Dennis, Rajendra A. Morey, Pauline Favre, Sophia Frangou, Boris A. Gutman, Merel Postema, Ida E Sønderby, Ian H. Harding, Julio E. Villalon-Reina, Sook-Lei Liew, Peter Kochunov, Celia van der Merwe, Je-Yeon Yun, David C. Glahn, Stefan Ehrlich, George A Karkashadze, Jian Chen, Nils Opel, Tianye Jia, Peristera Paschou, Xiangzhen Kong, Marieke Klein, Leyla Namazova-Baranova, Sylvane Desrivières, Danai Dima, Masoud Tahmasian, Dennis Hernaus, Sven C. Mueller, Gemma Modinos, Guido van Wingen, Ulrike Lueken, Ole A. Andreassen, Jonathan D. Rohrer, Lauren E. Salminen, Laura A. Berner, Eileen Luders, Georg Homuth, Stephane A. De Brito, Martine Hoogman, Federica Piras, Carrie Esopenko, Laura S van Velzen, Janna Marie Bas-Hoogendam, Udo Dannlowski, Mark W. Logue, Willem B Bruin, André Aleman, Sarah E. Medland, Neeltje E.M. van Haren, Theo G.M. van Erp, Sean N. Hatton, Laurena Holleran, Gary Donohoe, Alexander P. Lin, Rebecca C. Knickmeyer, Leonardo Tozzi, Fabrizio Pizzagalli, Kevin Hilbert, Sonja M C de Zwarte, Dick J. Veltman, Gianfranco Spalletta, Daniel S. Pine, Tim Hahn, Pratik Mukherjee, Alexander Teumer, Joanna Bright, Andre Altmann, Neda Jahanshad, James H. Cole, Arielle R. Baskin-Sommers, Odile A. van den Heuvel, Dan J. Stein, Vladimir Zelman, Lei Wang, Ronald A. Cohen, Joseph O' Neill, David Baron, Fabrizio Piras, Robert R. Althoff, Nynke A. Groenewold, Philipp G. Sämann, Christopher D. Whelan, Jessica A. Turner, Janita Bralten, Guohao Zhang, Paul M. Thompson, and Netherlands Institute for Neuroscience (NIN)
Subjects: DISORDER, Scientific community, Review Article, bepress|Life Sciences|Neuroscience and Neurobiology, 0302 clinical medicine, SCHIZOPHRENIA, Medicine and Health Sciences, GENETIC INFLUENCES, ENDOPHENOTYPE CONCEPT, Cervell, VOLUMES, RISK, Psychiatry, 0303 health sciences, 05 social sciences, Brain, Genomics, Magnetic Resonance Imaging, WORKING, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Eating disorders, Dissociative identity disorder, Biometris, Neurology, Conduct disorder, Schizophrenia, Major depressive disorder, Anxiety, medicine.symptom, Psychology, Neuroinformatics, Neuroimaging, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, lcsh:RC321-571, Neurologia, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, MEGA-ANALYSIS, medicine, Life Science, Humans, 0501 psychology and cognitive sciences, ddc:610, Psiquiatria, Bipolar disorder, diagnostic imaging [Brain], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, bepress|Life Sciences|Neuroscience and Neurobiology|Other Neuroscience and Neurobiology, Biological Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genetics [Depressive Disorder, Major], Reproducibility of Results, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, PsyArXiv|Neuroscience, PsyArXiv|Neuroscience|Other Neuroscience and Neurobiology, RC0321, HERITABILITY ANALYSIS, Autism, Psychiatric disorders, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.
Published: 2020

23. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

Author: Jonathan P. Shock, Erika L. Nurmi, Francesco Benedetti, Gianfranco Spalletta, Anthony C. James, Damiaan Denys, Jose C. Pariente, Ignacio Martínez-Zalacaín, Yanni Liu, Paulo Marques, Joseph O'Neill, Ganesan Venkatasubramanian, Benjamin A. Ely, Noam Soreni, Tobias U. Hauser, Michael C. Stevens, Masaru Kuno, Kate D. Fitzgerald, Je-Yeon Yun, Stephanie H. Ameis, John Piacentini, Yuki Sakai, Kang Ik K. Cho, Kathrin Koch, Luciano Minuzzi, Fabrizio Piras, Hao Hu, Chaim Huyser, Philip R. Szeszko, Gerd Kvale, Zhen Wang, Luke Taylor, Jean Paul Fouche, Marcelo Q. Hoexter, Francesca Assogna, Odile A. van den Heuvel, Rachel Marsh, Carles Soriano-Mas, Alan Anticevic, David Mataix-Cols, Eiji Shimizu, Fern Jaspers-Fayer, Rajat M. Thomas, Yoshinari Abe, Pedro Moreira, Norbert Kathmann, Astrid Morer, Rosa Calvo, Guido van Wingen, João Ricardo Sato, Egill A. Fridgeirsson, Chris Perriello, Janardhanan C. Narayanaswamy, Anushree Bose, Pedro Morgado, Oana G. Rus-Oswald, Akiko Nakagawa, Silvia Brem, Luisa Lazaro, Dan J. Stein, Paul D. Arnold, Yoshiyuki Hirano, Premika S.W. Boedhoe, Emily R. Stern, Irene Bollettini, Sara Dallaspezia, Lianne Schmaal, Federica Piras, Willem B Bruin, José M. Menchón, Jan K. Buitelaar, Christian Kaufmann, Christine Lochner, Yuqi Cheng, Brian P. Brennan, H. Blair Simpson, David F. Tolin, Daan van Rooij, Pino Alonso, Iliyan Ivanov, S. Evelyn Stewart, Paul M. Thompson, Takashi Nakamae, Deniz A. Gürsel, Paul Zhutovsky, Jan C. Beucke, Jamie D. Feusner, Patricia Gruner, Tomohiro Nakao, Y.C. Janardhan Reddy, Jun Soo Kwon, Graduate School, ANS - Compulsivity, Impulsivity & Attention, APH - Global Health, APH - Mental Health, Adult Psychiatry, Child Psychiatry, Bruin, Willem B., Taylor, Luke, Thomas, Rajat M., P Shock, Jonathan, Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C., Boedhoe, Premika S. W., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P., K Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A., Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Gürsel, Deniz A., Hauser, Tobias U., Hirano, Yoshiyuki, Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Soo Kwon, Jun, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Moreira, Pedro S., Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., O’Neill, Joseph, Pariente, Jose C., Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Janardhan Reddy, Y. C., Rus-Oswald, Oana G., Sakai, Yuki, Sato, João R., Schmaal, Lianne, Shimizu, Eiji, Blair Simpson, H., Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Evelyn Stewart, S., Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Consortium, ENIGMA-OCD, Thompson, Paul M., van den Heuvel, Odile A., Stein, Dan J., van Wingen, Guido A., Netherlands Institute for Neuroscience (NIN), ENIGMA-OCD Working Group, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry
Subjects: Obsessive-Compulsive Disorder, Multivariate analysis, Disease, Neuroimaging biomarkers, 0302 clinical medicine, Obsessive-compulsive disorder, Medicine, Psychology, Prefrontal cortex, screening and diagnosis, medicine.diagnostic_test, Biochemical markers, Brain, Serious Mental Illness, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Detection, Mental Health, Marcadors bioquímics, Public Health and Health Services, Biomedical Imaging, Clinical psychology, medicine.drug, medicine.medical_specialty, Clinical Sciences, MEDLINE, Neuroimaging, Article, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, Obsessive compulsive, Clinical Research, Internal medicine, Medical imaging, Diagnostic biomarker, Humans, Clinical significance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Fluoxetine, business.industry, Neurosi obsessiva, Neurosciences, Magnetic resonance imaging, Diagnostic markers, 030227 psychiatry, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Obsessive compulsive disorder, ENIGMA-OCD Working Group, business, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract: ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic resonance imaging (MRI) studies have provided evidence for structural abnormalities in distinct brain regions, but effect sizes are small and have limited clinical relevance. To investigate whether individual patients can be distinguished from healthy controls, we performed multivariate analysis of structural neuroimaging data from the ENIGMA-OCD consortium.MethodWe included 46 data sets with neuroimaging and clinical data from adult (≥18 years) and pediatric (1images from 2,304 OCD patients and 2,068 healthy controls were analyzed using standardized processing to extract regional measures of cortical thickness, surface area and subcortical volume. Machine learning classification performance was tested using cross-validation, and possible effects of clinical variables were investigated by stratification.ResultsClassification performance for OCD versus controls using the complete sample with different classifiers and cross-validation strategies was poor (AUC—0.57 (standard deviation (SD)=0.02;Pcorr=0.19) to 0.62 (SD=0.03;Pcorrcorr>.99) to 0.54 (SD=0.08;Pcorr>.99)). In contrast, good classification performance (>0.8 AUC) was achieved within subgroups of patients split according to their medication status.ConclusionsParcellated structural MRI data do not enable good distinction between patients with OCD and controls. However, classifying subgroups of patients based on medication status enables good identification at the individual subject level. This underlines the need for longitudinal studies on the short- and long-term effects of medication on brain structure.
Published: 2020

24. Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study

Author: Jonathan C Ipser, Shunmay Yeung, Heather J. Zar, Andrea M. Rehman, Diana M. Gibb, Frances Robertson, Annerine Roos, Jean-Paul Fouche, Sivenesi Subramoney, Catherine J. Wedderburn, Kirsten A. Donald, Katherine L. Narr, Nynke A. Groenewold, Dan J. Stein, and Shantanu H. Joshi
Subjects: Male, medicine.medical_specialty, Cognitive Neuroscience, Context (language use), Neuroimaging, Cortical surface area, 050105 experimental psychology, Article, Cortical thickness, lcsh:RC321-571, Cohort Studies, 03 medical and health sciences, South Africa, 0302 clinical medicine, Physical medicine and rehabilitation, Child Development, Cognition, medicine, Cognitive development, Humans, 0501 psychology and cognitive sciences, Toddler, Children, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Resting state fMRI, medicine.diagnostic_test, business.industry, 05 social sciences, Brain, Magnetic resonance imaging, Magnetic Resonance Imaging, Neurology, Child, Preschool, Africa, Female, business, Neurocognitive, 030217 neurology & neurosurgery
Abstract: Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2–3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2–3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ≥0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation., Highlights • MRI data are challenging to acquire in the early years of life. • Paediatric MRI without sedation is feasible in sub-Saharan Africa, with 77% success. • The Drakenstein Child Health study has novel MRI data of South African children. • Morphological features of the cortex associate with neurocognitive development. • Structure-cognition relationships in heteromodal association regions at 2–3 years.
Published: 2020

25. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders:Findings from the ENIGMA ADHD, ASD, and OCD working groups

Author: Pedro Moreira, Ruth O'Gorman Tuura, Mara Cercignani, Philip Aherson, Maria Jalbrzikowski, Kate D. Fitzgerald, Declan G. Murphy, Bernd Kardatzki, Christine Ecker, David F. Tolin, Fern Jaspers-Fayer, Pedro Morgado, Juan Carlos Soliva Vila, Kang Ik K. Cho, Kathrin Koch, Timothy J. Silk, Philip R. Szeszko, Thomas Frodl, Mara Parellada, Shlomi Haar, Eileen Daly, Bob Oranje, Anouk Schrantee, Leyla Namazova-Baranova, Joseph A. King, Beatriz Luna, Silvia Brem, Eric Earl, Alasdair Vance, Michela Tosetti, Christine Deruelle, Ramona Baur-Streubel, Jackie Fitzgerald, Kirsten O'Hearn, Michael C. Stevens, Yoshiyuki Hirano, J. Antoni Ramos-Quiroga, Erika L. Nurmi, Kaylita Chantiluke, Joseph O'Neill, Kerstin Kohls, Olga Puig, Devon Shook, Clodagh M. Murphy, Gustavo Sudre, Marlene Behrmann, Jaap Oosterlaan, Tinatin Gogberashvili, Lianne Schmaal, Carles Soriano-Mas, Liesbeth Hoekstra, Ignacio Martínez-Zalacaín, Noam Soreni, Marcel P. Zwiers, Paulo Mattos, Gregor Kohls, Andreas J. Fallgatter, Tiffany M. Chaim-Avancini, Alexander Baranov, S. Evelyn Stewart, Sara Dallaspezia, Gianfranco Spalletta, Jonna Kuntsi, Lizanne J. S. Schweren, Joel T. Nigg, Leanne Tamm, Premika S.W. Boedhoe, Adriana Di Martino, Jane McGrath, Marcelo C. Batistuzzo, Norbert Skokauskas, Filippo Muratori, John Piacentini, Jean-Paul Fouche, Sarah Baumeister, Alan Anticevic, Neil A. Harrison, Christine M. Freitag, Pedro G.P. Rosa, Stephen V. Faraone, Ana Cubillo, David Mataix-Cols, Yuki Sakai, Stefan Ehrlich, Eileen Oberwelland Weiss, Fabrizio Piras, Dirk J. Heslenfeld, Je-Yeon Yun, Paul Pauli, Catharina A. Hartman, Ganesan Venkatasubramanian, Janardhanan C. Narayanaswamy, Charles B Malpas, Jan C. Beucke, José M. Menchón, Egill A. Fridgeirsson, Margot J. Taylor, Mauricio Moller Martinho, H. Blair Simpson, Jan K. Buitelaar, Gerd Kvale, Ivanei E. Bramati, Aki Tsuchiyagaito, Susanne Walitza, Irene Bollettini, Jeffery N. Epstein, Anders M. Dale, Thomas Ethofer, Terry L. Jernigan, David Coghill, Rachel Marsh, Andreas Reif, Astri J. Lundervold, Pieter J. Hoekstra, Oana Georgiana Rus, Damiaan Denys, Gregory L. Wallace, Matt C. Gabel, Hazel McCarthy, Sarah Hohmann, Rosa Nicolau, Stephanie H. Ameis, Neda Jahanshad, Takashi Nakamae, Xin Feng, Emily R. Stern, Georg G. von Polier, Yanni Liu, Paulo Marques, Anushree Bose, Hao Hu, Sara Lera-Miguel, Deniz A. Gürsel, Jochen Seitz, Jos W. R. Twisk, Mario Rodrigues Louzã, Clare Kelly, Annette Conzelmann, Alysa E. Doyle, Odile A. van den Heuvel, Anthony A. James, Chris Perriello, Joost Janssen, Damien A. Fair, Norbert Kathmann, Francisco X. Castellanos, Paul D. Arnold, Oscar Vilarroya, Geraldo F. Busatto, Federica Piras, Pino Alonso, Akiko Nakagawa, Sarah Durston, Lena Schwarz, Mitul A. Mehta, Dan J. Stein, Celso Arango, Daan van Rooij, Ilan Dinstein, Anastasia Christakou, Klaus-Peter Lesch, Kerstin J. Plessen, Jennifer Fedor, Yolanda Vives-Gilabert, Ilaria Gori, Louise Gallagher, Brian P. Brennan, Yuqi Cheng, Barbara Franke, Sabin Khadka, Stephanie E. Novotny, Martine Hoogman, Georgii Karkashadze, Georg C. Ziegler, Yuliya N. Yoncheva, Rosa Calvo, Thomas Wolfers, Marcelo Q. Hoexter, Benjamin A. Ely, Masaru Kuno, Alessandra Retico, Yoshinari Abe, Geoffrey B. Hall, Tobias Banaschewski, Anatoly Anikin, Christine Lochner, Astrid Morer, Guido van Wingen, Jan Haavik, Joseph Biederman, Luisa Lázaro, Francesco Benedetti, Fengfeng Zhou, Guillaume Auzias, Daniel Brandeis, Dmitry Kapilushniy, Katya Rubia, Philip Shaw, Christian Kaufmann, Sara Calderoni, Marcus V. Zanetti, Anastasia Solovieva, Zhen Wang, Francesca Assogna, Jamie D. Feusner, Chaim Huyser, Fernanda Tovar-Moll, Theo G.M. van Erp, Y.C. Janardhan Reddy, Jun Soo Kwon, Yannis Paloyelis, Anna Calvo, Patricia Gruner, Kathrin C. Zierhut, Liesbeth Reneman, Tomohiro Nakao, Janita Bralten, Marie F. Høvik, Mark A. Bellgrove, Maarten Mennes, Paul M. Thompson, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Epidemiology and Data Science, Pediatric surgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Boedhoe, Premika S W, van Rooij, Daan, Hoogman, Martine, Twisk, Jos W R, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobia, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thoma, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thoma, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, Kardatzki, Bernd, Karkashadze, Georgii, Kathmann, Norbert, Kaufmann, Christian, Kelly, Clare, Khadka, Sabin, King, Joseph A, Koch, Kathrin, Kohls, Gregor, Konrad, Kerstin, Kuno, Masaru, Kuntsi, Jonna, Kvale, Gerd, Kwon, Jun Soo, Lázaro, Luisa, Lera-Miguel, Sara, Lesch, Klaus-Peter, Hoekstra, Liesbeth, Liu, Yanni, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, Malpas, Charles B, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mattos, Paulo, Mccarthy, Hazel, Mcgrath, Jane, Mehta, Mitul A, Menchón, José M, Mennes, Maarten, Martinho, Mauricio Moller, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan G M, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Namazova-Baranova, Leyla, Narayanaswamy, Janardhanan C, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Nurmi, Erika L, Weiss, Eileen Oberwelland, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, O'Neill, Joseph, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yanni, Parellada, Mara, Pauli, Paul, Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Puig, Olga, Ramos-Quiroga, J Antoni, Reddy, Y C Janardhan, Reif, Andrea, Reneman, Liesbeth, Retico, Alessandra, Rosa, Pedro G P, Rubia, Katya, Rus, Oana Georgiana, Sakai, Yuki, Schrantee, Anouk, Schwarz, Lena, Schweren, Lizanne J S, Seitz, Jochen, Shaw, Philip, Shook, Devon, Silk, Tim J, Simpson, H Blair, Skokauskas, Norbert, Soliva Vila, Juan Carlo, Solovieva, Anastasia, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Sudre, Gustavo, Szeszko, Philip R, Tamm, Leanne, Taylor, Margot J, Tolin, David F, Tosetti, Michela, Tovar-Moll, Fernanda, Tsuchiyagaito, Aki, van Erp, Theo G M, van Wingen, Guido A, Vance, Alasdair, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Wallace, Gregory L, Wang, Zhen, Wolfers, Thoma, Yoncheva, Yuliya N, Yun, Je-Yeon, Zanetti, Marcus V, Zhou, Fengfeng, Ziegler, Georg C, Zierhut, Kathrin C, Zwiers, Marcel P, Thompson, Paul M, Stein, Dan J, Buitelaar, Jan, Franke, Barbara, van den Heuvel, Odile A, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, and APH - Mental Health
Subjects: Male, Research Report, Obsessive-Compulsive Disorder, Frontal cortex, Systems Analysis, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Hippocampal formation, Audiology, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Child, Obsessive-compulsive disorder (OCD), ComputingMilieux_MISCELLANEOUS, Intelligence quotient, Psychopathology, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, ABNORMALITIES, ENIGMA, Organ Size, 3. Good health, Psychiatry and Mental health, Autism spectrum disorder, Brain size, Cohort, Female, MRI, Adult, medicine.medical_specialty, CORTEX, Adolescent, DEFICIT HYPERACTIVITY DISORDER, Human Development, Neuroimaging, behavioral disciplines and activities, Article, 03 medical and health sciences, FIELD-STRENGTH, mental disorders, medicine, MEGA-ANALYSIS, Attention deficit hyperactivity disorder, Humans, Cortical surface, Structural MRI, Attention Deficit Disorder with Hyperactivity, Cerebrum, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, medicine.disease, 030227 psychiatry, VOXEL, Autism, business, 030217 neurology & neurosurgery
Abstract: ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.
Published: 2020

26. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author: Xiang-Zhen Kong, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Francesca Assogna, Justin T. Baker, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Benjamin A. Ely, Jamie Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, David C. Glahn, Patricia Gruner, Deniz A. Gürsel, Tobias U. Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Anthony James, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Masaru Kuno, Gerd Kvale, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Sarah E. Medland, José M. Menchón, Luciano Minuzzi, Pedro S. Moreira, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O'Neill, Jose C. Pariente, Chris Perriello, John Piacentini, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Oana Georgiana Rus-Oswald, Yuki Sakai, Joao R. Sato, Lianne Schmaal, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Aki Tsuchiyagaito, Daan van Rooij, Guido A. van Wingen, Ganesan Venkatasubramanian, Zhen Wang, Je-Yeon Yun, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Clyde Francks, Alan Anticevic, Nerisa Banaj, Nuria Bargalló, Daniel Brandeis, Geraldo F. Busatto, Anna Calvo, Valentina Ciullo, Froukje E. de Vries, Stella J. de Wit, Erin Dickie, Renate Drechsler, Madalena Esteves, Andrea Falini, Yu Fang, Martijn Figee, Martine Fontaine, Geoff Hall, Sayo Hamatani, Gregory L. Hanna, Bjarne Hansen, Keisuke Ikari, Neda Jahanshad, Ricardo Magalhães, Yasutaka Masuda, Koji Matsumoto, James T. McCracken, Euripedes C. Miguel, Jin Narumoto, Seiji Nishida, Sara Poletti, Tim Reess, Eiji Shimizu, Nuno Sousa, Jumpei Takahashi, Jinsong Tang, Anders Lillevik Thorsen, Ysbrand D. van der Werf, Dick J. Veltman, Daniela Vecchio, Susanne Walitza, Anri Watanabe, Jian Xu, Xiufeng Xu, Kei Yamada, Tokiko Yoshida, Mojtaba Zarei, Qing Zhao, Cong Zhou, ENIGMA-OCD Working Group, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, Kong, X. -Z., Boedhoe, P. S. W., Abe, Y., Alonso, P., Ameis, S. H., Arnold, P. D., Assogna, F., Baker, J. T., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Bose, A., Brem, S., Brennan, B. P., Buitelaar, J., Calvo, R., Cheng, Y., Cho, K. I. K., Dallaspezia, S., Denys, D., Ely, B. A., Feusner, J., Fitzgerald, K. D., Fouche, J. -P., Fridgeirsson, E. A., Glahn, D. C., Gruner, P., Gursel, D. A., Hauser, T. U., Hirano, Y., Hoexter, M. Q., Hu, H., Huyser, C., James, A., Jaspers-Fayer, F., Kathmann, N., Kaufmann, C., Koch, K., Kuno, M., Kvale, G., Kwon, J. S., Lazaro, L., Liu, Y., Lochner, C., Marques, P., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Medland, S. E., Menchon, J. M., Minuzzi, L., Moreira, P. S., Morer, A., Morgado, P., Nakagawa, A., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E. L., O'Neill, J., Pariente, J. C., Perriello, C., Piacentini, J., Piras, F., Pittenger, C., Reddy, Y. C. J., Rus-Oswald, O. G., Sakai, Y., Sato, J. R., Schmaal, L., Simpson, H. B., Soreni, N., Soriano-Mas, C., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Szeszko, P. R., Tolin, D. F., Tsuchiyagaito, A., van Rooij, D., van Wingen, G. A., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Anticevic, A., Banaj, N., Bargallo, N., Brandeis, D., Busatto, G. F., Calvo, A., Ciullo, V., de Vries, F. E., de Wit, S. J., Dickie, E., Drechsler, R., Esteves, M., Falini, A., Fang, Y., Figee, M., Fontaine, M., Hall, G., Hamatani, S., Hanna, G. L., Hansen, B., Ikari, K., Jahanshad, N., Magalhaes, R., Masuda, Y., Matsumoto, K., Mccracken, J. T., Miguel, E. C., Narumoto, J., Nishida, S., Poletti, S., Reess, T., Shimizu, E., Sousa, N., Takahashi, J., Tang, J., Thorsen, A. L., van der Werf, Y. D., Veltman, D. J., Vecchio, D., Walitza, S., Watanabe, A., Xu, J., Xu, X., Yamada, K., Yoshida, T., Zarei, M., Zhao, Q., Zhou, C., Thompson, P. M., Stein, D. J., van den Heuvel, O. A., Francks, C., Netherlands Institute for Neuroscience (NIN), Universidade do Minho, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, Obsessive-Compulsive Disorder, Mega-analysis, Mega-analysi, media_common.quotation_subject, Thalamus, Medicina Básica [Ciências Médicas], Audiology, Asymmetry, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, mental disorders, medicine, Image Processing, Computer-Assisted, Obsessive-compulsive disorder, Brain asymmetry, Humans, Child, Biological Psychiatry, Depression (differential diagnoses), media_common, Brain Mapping, Science & Technology, medicine.diagnostic_test, business.industry, Laterality, Neurosi obsessiva, Brain, Magnetic resonance imaging, Cerebral cortex, Magnetic Resonance Imaging, humanities, Escorça cerebral, 030104 developmental biology, Meta-analysis, Ciências Médicas::Medicina Básica, Pallidum, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Accepted Manuscript, BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -20.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD., This research was funded by the Max Planck Society (Germany). Additional funding was from the Japan Society for the Promotion of Science (KAKENHI Grant No. 18K15523 [to YA], KAKENHI Grant No. 16K04344 [to YH], KAKENHI Grant Nos. 16K19778 and 18K07608 [to TNakam], and KAKENHI Grant No. 26461762 [to AN]); the Carlos III Health Institute (Grant No. PI14/00419 [to PA], Grant No. PI040829 cofunded by European Regional Development Fund [to LL], Grant No. FI17/00294 [to IM-Z], Grant No. PI16/00950 [to JMM], and Grant Nos. CPII16/00048, PI13/01958, and PI16/00889 cofunded by European Regional Development Funds [to CS-M]); the Ontario Mental Health Foundation (Research Training Fellowship [to SHA]); Alberta Innovates Translational Health Chair in Child and Youth Mental Health (to PDA), the Ontario Brain Institute (to PDA); the National Institute of Mental Health (Grant No. K23MH104515 [to JTB], Grant No. K23-MH092397 [to BPB], Grant No. K23MH082176 [to KDF), Grant No. R21MH101441 [to RM], Grant No. R01MH081864 [to JO and JP], and Grant No. R01MH085900 [to JO and JF], Grant No. R21MH093889 [to HBS]); Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant No. 2011/21357–9 [to MCB], Grant No. 2011/21357–9 [to GFB], Grant No. 2011/21357–9 [to MQH], and Grant No. 2011/21357–9 [to ECM]); the Swiss National Science Foundation (Grant No. 320030_130237 [to SB; principal investigator, Susanne Walitza]); the Hartmann Müller Foundation (Grant No. 1460 [to SB]); the David Judah Fund at the Massachusetts General Hospital (to BPB); EU FP7 Project TACTICS (Grant No. 278948 [to JB]); the National Natural Science Foundation of China (Grant No. 81560233 [to YC] and Grant No. 81371340 [to ZW]); the International OCD Foundation (Grant No. K23 MH115206 [to PG]); the Wellcome Sir Henry Dale Fellowship (Grant No. 211155/Z/18/Z [to TUH]); the Jacobs Foundation (to TUH); the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator Grant No. 27023 [to TUH]); the Agency for Medical Research and Development (Grant No. JP18dm0307002 [to YH]); the Michael Smith Foundation for Health Research (to FJ-F); the Federal Ministry of Education and Research of Germany (Grant No. BMBF-01GW0724 [to NK]); the Deutsche Forschungsgemeinschaft (Grant No. KO 3744/7–1 [to KK]); the Helse Vest Health Authority (Grant Nos. 911754 and 911880 [to GK]); the Norwegian Research Council (Grant No. HELSEFORSK 243675 [to GK]); the Marató TV3 Foundation (Grant Nos. 01/2010 and 091710 [to LL]); the Agency for Management of University and Research Grants (Grant No. 2017 SGR 881 [to LL] and 2017 SGR 1247 from the Generalitat de Catalunya [to JMM]); Fundação para a Ciência e a Tecnologia (Grant No. PDE/BDE/113604/2015 from the PhD-iHES Program [to RM], Grant No. PDE/BDE/113601/2015 from the PhD-iHES Program [to PSM]); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (Grant Nos. 22591262, 25461732, and 16K10253 [to TNakao]); the Government of India Department of Science and Technology (DST INSPIRE Faculty Grant No. -IFA12-LSBM-26 [to JCN] and Grant No. SR/S0/HS/0016/2011 [to YCJR]); the Government of India Department of Biotechnology (Grant No. BT/06/IYBA/2012 [to JCN] and Grant No. BT/PR13334/Med/30/259/2009 [to YCJR]); the New York State Office of Mental Health (to HBS); the Italian Ministry of Health (Grant No. RC13-14-15-16A [to GS]); the National Center for Advancing Translational Sciences (Grant No. UL1TR000067/KL2TR00069 [to ERS]); the Canadian Institutes of Health Research (to SES); the Michael Smith Foundation for Health Research (to SES); the British Columbia Provincial Health Services Authority (to SES); the Netherlands Organization for Scientific Research (Grant No. NWO/ZonMW Vidi 917.15.318 [to GAvW]); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z [to GV]); the Shanghai Key Laboratory of Psychotic Disorders (Grant No. 13dz2260500 [to ZW]).
Published: 2020

27. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD

Author: Federica Piras, Christine Lochner, Jan C. Beucke, José M. Menchón, Philip R. Szeszko, Hao Hu, Janardhanan C. Narayanaswamy, Damiaan Denys, Guido van Wingen, Yanni Liu, Luisa Lazaro, Jean Paul Fouche, Marcelo Queiroz Hoexter, Y. C.Janardhan Reddy, Silvia Brem, Paul D. Arnold, Sara Dallaspezia, Keisuke Ikari, Neda Jahanshad, Qing Zhao, Kang Ik Cho, Norbert Kathmann, Gianfranco Spalletta, Yuqi Cheng, Susanne Walitza, Derrek P. Hibar, Dan J. Stein, Christopher Pittenger, Odile A. van den Heuvel, Yoshinari Abe, Anushree Bose, David Mataix-Cols, Ganesan Venkatasubramanian, Je Yeon Yun, Ignacio Martínez-Zalacaín, Xiufeng Xu, João Ricardo Sato, Noam Soreni, Premika S.W. Boedhoe, Luciano Minuzzi, Carles Soriano-Mas, David F. Tolin, Kate D. Fitzgerald, Christian Kaufmann, Rachel Marsh, H. Blair Simpson, Fabrizio Piras, Zhen Wang, Michael C. Stevens, Lianne Schmaal, Marcelo C. Batistuzzo, Takashi Nakamae, Paul M. Thompson, Stephanie H. Ameis, Gregory L. Hanna, Irene Bollettini, Chaim Huyser, Kathrin Koch, Jun Soo Kwon, Mónica Giménez, Anna Calvo, Francesco Benedetti, Patricia Gruner, Jian Xu, Tomohiro Nakao, Universitat de Barcelona, Other departments, ANS - Amsterdam Neuroscience, Adult Psychiatry, Boedhoe, Premika S. W., Schmaal, Lianne, Abe, Yoshinari, Ameis, Stephanie H., Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik, Dallaspezia, Sara, Denys, Damiaan, Fitzgerald, Kate D., Fouche, Jean-Paul, Giménez, Mònica, Gruner, Patricia, Hanna, Gregory L., Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Jahanshad, Neda, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Liu, Yanni, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Y. C. Janardhan, Sato, Joao R., Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stevens, Michael C., Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Van Wingen, Guido A., Xu, Jian, Xu, Xiufeng, Yun, Je-Yeon, Zhao, Qing, Thompson, Paul M., Stein, Dan J., Van Den Heuvel, Odile A., Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Netherlands Institute for Neuroscience (NIN)
Subjects: Obsessive-Compulsive Disorder, FreeSurfer, Audiology, Pediatrics, Hippocampus, 0302 clinical medicine, Neurodevelopmental disorder, Thalamus, Obsessive-compulsive disorder, Young adult, Child, Psychiatry, Pediatria, medicine.diagnostic_test, Healthy subjects, Organ Size, Middle Aged, Control subjects, Magnetic Resonance Imaging, Psychiatry and Mental health, Psychiatry and Mental Health, Mega analysis, Psychology, Human, Adult, medicine.medical_specialty, Adolescent, Neuroimaging, Globus Pallidus, behavioral disciplines and activities, Article, Malalts, 03 medical and health sciences, Young Adult, Hippocampu, mental disorders, medicine, Humans, Thalamu, Sick, Neurosi obsessiva, Globus Pallidu, Magnetic resonance imaging, Voxel-based morphometry, medicine.disease, 030227 psychiatry, Structural MRI, 030217 neurology & neurosurgery
Abstract: Objective: structural brain imaging studies in obsessive compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta and mega-analyses of data from OCD sites worldwide. Method: T-1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results: the meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. Conclusions: the results indicate different patterns of sub cortical abnormalities in pediatric and adult OCD patients. The patlidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.
Published: 2017

28. White Matter Microstructure and its Relation to Clinical Features of Obsessive-Compulsive Disorder: Findings from the ENIGMA OCD Working Group

Author: Marcelo C. Batistuzzo, Jan C. Beucke, Marcelo Q. Hoexter, Rachel Marsh, Stephanie H. Ameis, Jumpei Takahashi, Jun Soo Kwon, Paul D. Arnold, Silvia Brem, Yoshinari Abe, Philipp Stämpfli, Premika S.W. Boedhoe, Benjamin Adam, Núria Bargalló, Sara Dallaspezia, Anthony A. James, Anna Calvo, Yoshiyuki Hirano, Patricia Gruner, Dan J. Stein, Noam Soreni, Eiji Shimizu, Gianfranco Spalletta, Akiko Nakagawa, Kang Ik K. Cho, Kathrin Koch, Daniela Simon, Fabrizio Piras, Ganesan Venkatasubramanian, Zhen Wang, Sri Mahavir Agarwal, Yuki Sakai, Philip R. Szeszko, Irene Bollettini, Emily R. Stern, Christian Kaufmann, Siyan Fan, Jean-Paul Fouche, Federica Piras, Tobias U. Hauser, Neda Jahanshad, Christine Lochner, Paul M. Thompson, Janardhanan C. Narayanaswamy, Mariangela Iorio, Janardhan Y. C. Reddy, Alan Anticevic, Odile A. van den Heuvel, Peter Kochunov, Erin W. Dickie, Je Yeon Yun, Luisa Lázaro, Francesco Benedetti, Takashi Nakamae, Deniz A. Gürsel, and Helen Blair Simpson
Subjects: medicine.medical_specialty, business.industry, Audiology, Age and sex, White matter microstructure, White matter, medicine.anatomical_structure, Group differences, Obsessive compulsive, Fractional anisotropy, Cohort, medicine, business, Diffusion MRI
Abstract: ImportanceMicrostructural alterations in cortico-subcortical connections are thought to be present in Obsessive-Compulsive Disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities.ObjectiveTo investigate microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date.Design, Setting, and ParticipantsIn this cross-sectional case-control magnetic resonance study, we investigated diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA-OCD Working Group.Main Outcomes and MeasuresWe extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics.ResultsAdult OCD patients showed significant FA reduction in the sagittal stratum (d=-0.21, z=-3.21, p=0.001) and posterior thalamic radiation (d=-0.26, z=-4.57, pConclusions and RelevanceMicrostructural alterations in projection and association fibers to posterior brain regions were found in adult OCD, and related to disease course and medication status. Such results are relevant to models positing deficits in connectivity as a crucial mechanism in OCD.KEY POINTSQuestionDo patients with Obsessive-Compulsive Disorder (OCD) show white matter microstructural alterations, and are these alterations related to clinical features?FindingsData from 19 sites of the ENIGMA-OCD Consortium were included, involving 700 adult patients and 645 adult controls, 174 pediatric patients and 144 pediatric controls. Diffusion tensor imaging data were meta-analyzed using a harmonized data processing and analysis protocol. Adult, but not pediatric, patients showed alterations in the sagittal stratum and posterior thalamic radiation; sagittal stratum differences were associated with clinical features.MeaningMicrostructural abnormalities found in adult but not in the pediatric cohort, are related to illness duration and medication status.
Published: 2019
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29. Methane-flow system within the Nyegga pockmark field, offshore mid-Norway

Author: Stéphanie Dupré, Jean-Paul Foucher, Catherine Pierre, Carole Decker, Graham Westbrook, Stephan Ker, Karine Olu, Jean-Pierre Donval, Jean-Luc Charlou, Marie-Madeleine Blanc-Valleron, and Hervé Nouzé
Subjects: Norwegian margin, gas chimneys, pockmarks, seeps, authigenic carbonates, chemosynthesis-based communities, Science
Abstract: We investigated fluid seepage within the Nyegga pockmark field (600–900 m water depths) off mid-Norway from Remotely Operated Vehicle dives at the so-called CNE sites (CNE01 to CNE17). The seafloor morphology of some of these features corresponds to pockmarks and adjacent ridges, with the latter being the focus of present seepage activity. These structures are underlain by chimneys above a gas-charged zone with, in some cases, a substantial body of hydrate-invaded sediment (down to 1.3 s in two-way travel time at CNE03). Present-day methane-rich fluid seepage through the seabed is indicated by chemosynthetic fauna, in particular Siboglinidae polychaetes (Oligobrachia haakonmobiensis webbi and Sclerolinum contortum), microbial mats and associated Rissoidae gastropod (Alvania sp.) grazers, and confirmed by measured in situ bottom-water methane anomalies, up to 2,130 nL/L. No free-gas bubble emissions were observed or acoustically identified. The presence of authigenic carbonates reveals past seepage with very low δ13C values (down to −58‰) indicating that the major source of carbon was methane carried by the venting fluids. The ages of major periods of methane venting are provided by vesicomyid bivalve shells (Isorropodon nyeggaensis) present in two sedimentary layers, 14,930 and 15,500 14C yr BP (ca. 17,238 and 17,952 cal yr BP), respectively, corresponding to the time of Melt Water Pulse IA. The seafloor morphology and pattern of seepage -chemosynthetic fauna and microbial mat distribution and dissolved methane concentration-are remarkably heterogeneous. Pore-water chemistry profiles in a gravity core taken only 40 m from major seepage sites indicate no seepage and anaerobic methane oxidation at a sub-bottom depth of about 2 m. Present-day seepage from the studied pockmark-chimney fluid-flow system charged with gas hydrate is dominated by the advection of methane solution in pore water. Some of this methane could result from the dissolution of hydrate in the chimney, most of which would have formed during an earlier period (post-LGM times) of history of the chimney, when it was venting free gas. However, the presence of free gas beneath this chimney is probably why the water entering the chimney is already saturated with methane and the process of hydrate formation in the chimney continues today.
Published: 2023
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30. Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder

Author: P.L. Remijnse, Takashi Nakamae, Joon Hwan Jang, Wi Hoon Jung, Dan J. Stein, Marta Subirà, Pino Alonso, Marcelo Q. Hoexter, Jean-Paul Fouche, Damiaan Denys, Lizanne J. S. Schweren, Mary L. Phillips, Kei Yamada, Na Young Shin, David Mataix-Cols, Kenji Fukui, João Ricardo Sato, Yuki Sakai, Christine Lochner, Jesus Pujol, Marta Cano, Narcís Cardoner, Sung Nyun Kim, Carles Soriano-Mas, E. C. Miguel, Danielle C. Cath, Dick J. Veltman, Stella J. de Wit, Odile A. van den Heuvel, Jin Narumoto, Jun Soo Kwon, José M. Menchón, Geraldo F. Busatto, Seiji Nishida, Universitat de Barcelona, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Anatomy and neurosciences, Other departments, and Adult Psychiatry
Subjects: Adult, Male, Aging, Obsessive-Compulsive Disorder, Caudate nucleus, Ventromedial prefrontal cortex, Statistical parametric mapping, Amygdala, 03 medical and health sciences, Malalties del sistema nerviós, 0302 clinical medicine, Limbic system, Neuroimaging, Functional neuroimaging, medicine, Image Processing, Computer-Assisted, Limbic System, Obsessive-compulsive disorder, Humans, Pharmacology (medical), Psiquiatria, Biological Psychiatry, Psychiatry, Sex Characteristics, Putamen, Neurosi obsessiva, Nervous system Diseases, Organ Size, Magnetic Resonance Imaging, 030227 psychiatry, Neostriatum, Psychiatry and Mental health, Compulsive behavior, medicine.anatomical_structure, Cross-Sectional Studies, Linear Models, Female, Psychology, Conducta compulsiva, Neuroscience, 030217 neurology & neurosurgery, Research Paper
Abstract: Background: Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive–compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored.Methods: We performed a mega-analysis pooling structural MRI scans from the Obsessive–compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software.Results: Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex.Limitations: This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres.Conclusion: Our results provide evidence for structural network–level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders.
Published: 2016

31. Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings

Author: Edward P. Riley, Roger P. Woods, Kirsten A. Donald, Heather J. Zar, Jonathan C Ipser, Dan J. Stein, Nastassja Koen, Katherine L. Narr, Annerine Roos, Fleur M. Howells, Bharat B. Biswal, and Jean-Paul Fouche
Subjects: Male, Blood Oxygen Level-Dependent, Medicine (miscellaneous), Audiology, Toxicology, Somatosensory system, Functional Laterality, Cohort Studies, Alcohol Use and Health, Substance Misuse, 0302 clinical medicine, Thalamus, Pregnancy, Neural Pathways, Psychology, Intrinsic Brain Activity, Pediatric, Blood-oxygen-level dependent, medicine.diagnostic_test, Substance Abuse, Brain, Magnetic Resonance Imaging, Alcoholism, Psychiatry and Mental health, Fetal Alcohol Spectrum Disorders, Prenatal Exposure Delayed Effects, Neurological, Resting-State MRI, Biomedical Imaging, Mental health, Female, Brainstem, Clinical psychology, medicine.medical_specialty, Alcohol Drinking, Intellectual and Developmental Disabilities (IDD), Clinical Sciences, Basic Behavioral and Social Science, Lateralization of brain function, Article, 03 medical and health sciences, Alcohol Exposure, Clinical Research, Functional neuroimaging, Behavioral and Social Science, medicine, Humans, Conditions Affecting the Embryonic and Fetal Periods, Functional MRI, Fetal Alcohol Spectrum Disorders (FASD), Functional Neuroimaging, Neurosciences, Infant, Newborn, Infant, Magnetic resonance imaging, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, Brain Disorders, 030227 psychiatry, Functional imaging, Neostriatum, Pregnancy Complications, Case-Control Studies, Multivariate Analysis, 030217 neurology & neurosurgery, Brain Stem
Abstract: Background Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Methods Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Results Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Conclusions Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.
Published: 2016

32. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author: Derek W. Morris, Carles Soriano-Mas, Tomáš Paus, Henrik Walter, Dick J. Veltman, Yuqi Cheng, Benjamin S. Aribisala, Anna Cattrell, Hilleke E. Hulshoff Pol, Vatche G. Baboyan, Simon E. Fisher, Michael N. Smolka, Saskia P. Hagenaars, Sarah Jurk, Roberto Roiz-Santiañez, Nicholas G. Martin, Lars T. Westlye, Odile A. van den Heuvel, Lucija Abramovic, Jan Egil Nordvik, Guillén Fernández, Jürgen Gallinat, Je Yeon Yun, Benson Mwangi, Ignacio Martínez-Zalacaín, Bernd Kraemer, Gareth J. Barker, José M. Menchón, Marie-Laure Paillère Martinot, Zhen Wang, Jan K. Buitelaar, Jean-Luc Martinot, Herve Lemaitre, Aiden Corvin, Henry Brodaty, Thomas Wolfers, Silvia Brem, Christine Lochner, Derrek P. Hibar, Susanne Walitza, Susana Muñoz Maniega, Premika S.W. Boedhoe, Nathalie Tzourio-Mazoyer, Uli Bromberg, Sonja M C de Zwarte, Dan J. Stein, Mark E. Bastin, Clyde Francks, Tobias U. Hauser, Sinead Kelly, Hugh Garavan, Omar Mothersill, Gary Donohoe, Neda Jahanshad, Greig I. de Zubicaray, Yoshinari Abe, Roel A. Ophoff, Christian Büchel, Esther Walton, Pieter J. Hoekstra, Nils Opel, Gunter Schumann, Jian Xu, Dara M. Cannon, Elena Shumskaya, Ingrid Agartz, Bernhard T. Baune, A. Marten H. Onnink, Tomohiro Nakao, Rosa Ayesa-Arriola, David Mataix-Cols, Sylvane Desrivières, Klaus-Peter Lesch, Paul Pauli, Wei Wen, Nora C. Vetter, Martine Hoogman, Ganesan Venkatasubramanian, Miguel E. Rentería, Ole A. Andreassen, Penny A. Gowland, Ian J. Deary, Patricia J. Conrod, Nicola J. Armstrong, Masaki Fukunaga, Vince D. Calhoun, Volker Arolt, Dimitri Papadopoulos Orfanos, Benedicto Crespo-Facorro, Lachlan T. Strike, Natalie A. Royle, Joanna M. Wardlaw, Sarah E. Medland, Annette Conzelmann, Andrea Gonzalez Suarez, Arun L.W. Bokde, Ryota Hashimoto, Robert Whelan, Michelle Luciano, Pascual Sánchez-Juan, Neeltje E.M. van Haren, Hao Hu, Luise Poustka, Jun Soo Kwon, Hans J. Grabe, Andreas Heinz, Katharina Wittfeld, Michael Gill, Erik G. Jönsson, Frauke Nees, Perminder S. Sachdev, Oliver Gruber, David C. Glahn, Chaim Huyser, Anushree Bose, Herta Flor, Janardhan Y. C. Reddy, Bernd Ittermann, John Blangero, Dennis van der Meer, Andre F. Marquand, Xiufeng Xu, Tulio Guadalupe, Dominik Grotegerd, Jessica A. Turner, Annerine Roos, Tobias Banaschewski, Theo G.M. vanErp, Jean-Paul Fouche, Paul M. Thompson, Alejandro Arias-Vasquez, Christopher D. Whelan, Maria del C. Valdés Hernández, Eric Artiges, Janardhanan C. Narayanaswaamy, Thomas Espeseth, Bernard Mazoyer, Katie L. McMahon, Erlend S. Dørum, Samantha J. Brooks, Samuel R. Mathias, Vincent Frouin, Fleur M. Howells, Barbara Franke, Colm McDonald, Jingjing Zhao, Daniella Vuletic, Nhat Trung Doan, Harald Kugel, Lianne Schmaal, Marcel P. Zwiers, Fabrice Crivello, Anne Uhlmann, Karen A. Mather, René S. Kahn, Roberto Toro, Stefan Ehrlich, Udo Dannlowski, Jair C. Soares, Takashi Nakamae, Margaret J. Wright, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Child Psychiatry, Other departments, ANS - Complex Trait Genetics, International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], Yale University [New Haven], Department of Psychiatry and Human Behavior, University of California [Irvine] (UCI), University of California-University of California, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Department of Psychiatry, Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan, University Medical Center [Utrecht], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University of Oslo (UiO), Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Mental Health Sciences Unit, University College of London [London] (UCL), Adolescent psychopathology and Medicine, CHU Cochin [AP-HP], Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Southern California (USC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg], Centre for Neuroimaging Sciences, Institute of Psychiatry, King‘s College London, University of Adelaide, The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, Texas], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, VU University Medical Center [Amsterdam], National Institute of Mental Health and Neurosciences [Bagalore, India], Hospital of the University of Pennsylvania, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Dementia Collaborative Research Centre, University of New South Wales [Sydney] (UNSW), Centre for Healthy Brain Ageing, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Institute of Psychiatry, Psychology & Neuroscience, King's College London, Center for disease control, China (Chinese CDC), Center for Disease Control, China, Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Germany, Tübingen, Würzburg, Germany, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), School of Psychology, University of Queensland, University of Queensland [Brisbane], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), sans affiliation, Universität Mannheim [Mannheim], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Division of Cerebral Integration National Institute for Physiological Sciences Okazaki Japan, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Calgary, Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], University Clinic for Child and Adolescent Psychiatry (UCCAP), University of Zürich [Zürich] (UZH), University Medical Center Groningen [Groningen] (UMCG), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], MetaCase [Jyväskylä], Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Department of Psychiatry & Behavioral Science Seoul National University College of Medicine Seoul Republic of Korea, Université de Cergy Pontoise (UCP), Université Paris-Seine, Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Medstar Research Institute, Neuroimagerie en psychiatrie (U1000), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Imperial College London, Centre for Advanced Imaging, Queensland Institute of Medical Research, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Universitat de Barcelona (UB), National University of Ireland [Galway] (NUI Galway), Climate Change Unit [Ispra], JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC)-European Commission - Joint Research Centre [Ispra] (JRC), Sunnaas Rehabilitation Hospital HT Nesodden Norway, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University-McGill University, Texas A&M University [College Station], QIMR Berghofer Medical Research Institute, Universiteit van Amsterdam (UvA), Centre for Healthy Brain Ageing [Sydney], The University of Sydney, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Göttingen Zentrum Geowissenschaften, Georg-August-Universität Göttingen, Technische Universität Dresden (TUD), Instituto de Geociências, Universidade de Brasília, Magnetic Resonance Imaging, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa, Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], University of York [York, UK], Centre for Cognitive Ageing & Cognitive Epidemiology, Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands, University of Twente [Netherlands], Berlin School of Mind and Brain [Berlin], Humboldt Universität zu Berlin, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Computational and Applied Mathematics [Houston], Rice University [Houston], Department of Physics [Kowloon], Hong Kong University of Science and Technology (HKUST), University College Dublin [Dublin] (UCD), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University of Missouri [Columbia], University of Missouri System, Mechanics surfaces and materials processing (MSMP), École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Department of Genetics, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Dpt of Psychiatry [New Haven], Yale University School of Medicine, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Radboud University [Nijmegen], Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg] = Heidelberg University, Texas Biomedical Research Institute [San Antonio, TX], University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Radboud University [Nijmegen], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Sans affiliation, Universität Mannheim, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universität Zürich [Zürich] = University of Zurich (UZH), Seoul National University [Seoul] (SNU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Georg-August-University = Georg-August-Universität Göttingen, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Twente, Humboldt University Of Berlin, Centre épigénétique et destin cellulaire (EDC), Department of Physics [Hong Kong University of Science and Technology], University of Missouri [Columbia] (Mizzou), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Yale School of Medicine [New Haven, Connecticut] (YSM), Hal, GIN, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Georg-August-University [Göttingen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, International Max Planck Research School for Language Sciences ( IMPRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, Department of Psychiatry Yale School of Medicine New Haven USA, University of California [Irvine] ( UCI ), Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), University College of London [London] ( UCL ), Centro de Investigación Biomédica en Red de Salud Mental ( CIBERSAM ), Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, University of Southern California, Marina del Rey, CA, USA, The University of Adelaide, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India, Hospital of the University of Pennsylvania, University of New South Wales [Sydney] ( UNSW ), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), King's College, Center for disease control, China ( Chinese CDC ), GIN - IMN UMR 5293 CNRS CEA Université de Bordeaux, Institut des Maladies Neurodégénératives [Bordeaux] ( IMN ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Institut national de la recherche agronomique [Jouy en Josas] ( INRA Jouy en Josas ), Department of Psychology, University of Oslo, Oslo 0373, Norway, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Charite-Universitatsmedizin Berlin [Berlin], University of Nottingham, UK ( UON ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, (UCCAP) University of Zurich Zurich Switzerland, University Medical Center Groningen, University of Groningen, Karolinska University Hospital (Solna), Université de Cergy Pontoise ( UCP ), Bonn Universität [Bonn], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Universitat de Barcelona ( UB ), National University of Ireland [Galway] ( NUI Galway ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ) -European Commission - Joint Research Centre [Ispra] ( JRC ), University Medical Center Utrecht-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], Universiteit van Amsterdam ( UvA ), The University of Sydney [Sydney], Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Technische Universität Dresden ( TUD ), Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Hong Kong University of Science and Technology ( HKUST ), University College Dublin [Dublin] ( UCD ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, University of Missouri-Columbia, Mechanics surfaces and materials processing ( MSMP ), North Carolina State University [Raleigh] ( NCSU ), and Yale School of Medicine
Subjects: Male, Aging, Planum temporale, Caudate nucleus, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Subcortical brain asymmetry, Functional Laterality, Behavioral Neuroscience, 0302 clinical medicine, pathology [Aging], ddc:150, 130 000 Cognitive Neurology & Memory, Basal ganglia, YOUNG-ADULTS, Brain asymmetry, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Handedness, Original Research, Sex Characteristics, Age, Enigma, Heritability, Meta-analysis, Sex, Putamen, 05 social sciences, Brain, Human brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, AMYGDALA VOLUME, Psychiatry and Mental health, genetics [Functional Laterality], Globus pallidus, medicine.anatomical_structure, Neurology, BASAL GANGLIA VOLUMES, Radiology Nuclear Medicine and imaging, genetics [Aging], [ SCCO.NEUR ] Cognitive science/Neuroscience, CAUDATE-NUCLEUS, Female, Psychology, Sex characteristics, MRI, Neuroinformatics, Adult, Adolescent, Cognitive Neuroscience, Clinical Neurology, BF, HAND PREFERENCE, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Quantitative Trait, Heritable, Meta-Analysis as Topic, medicine, Journal Article, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, diagnostic imaging [Brain], Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, TOURETTE-SYNDROME, [SCCO.NEUR] Cognitive science/Neuroscience, PLANUM TEMPORALE, NORMAL INDIVIDUALS, HEMISPHERIC-DIFFERENCES, nervous system, RC0321, Neurology (clinical), Neuroscience, anatomy & histology [Brain], 030217 neurology & neurosurgery
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders. Electronic supplementary material The online version of this article (doi:10.1007/s11682-016-9629-z) contains supplementary material, which is available to authorized users.
Published: 2016

33. Diffusion Tensor Imaging in Anxiety Disorders

Author: Elliot Ayling, Nic J.A. van der Wee, Moji Aghajani, and Jean-Paul Fouche
Subjects: Generalized anxiety disorder, Internalizing disorders, behavioral disciplines and activities, White matter, Neural Pathways, medicine, Obsessive-compulsive disorder, Humans, Social anxiety disorder, Panic disorder, Post-traumatic stress disorder, Social anxiety, Brain, Structural integrity, medicine.disease, Psychiatry and Mental health, medicine.anatomical_structure, Diffusion tensor imaging, nervous system, DTI, Trait anxiety, Anxiety, medicine.symptom, Psychology, Neurocircuitry, Mri findings, Clinical psychology, Diffusion MRI, Anxiety disorders
Abstract: Diffusion tensor imaging (DTI) can be used to examine the structural integrity of regional white matter and to map white matter tracts. DTI studies have been performed in several psychiatric disorders, especially in those for which a developmental or a neuropsychiatric component was postulated. Thus far, the use of DTI has been very limited in panic disorder, social anxiety disorder, and generalized anxiety disorder, and somewhat more extensive in post-traumatic stress disorder and obsessive-compulsive disorder. In most anxiety disorders, the results of DTI studies are in line with other structural and functional MRI findings and can be interpreted within the frameworks of existing models for the neurocircuitry of the various disorders. DTI findings could further enrich neurobiological models for anxiety disorders, although replication is often warranted, and studies in pediatric populations are lagging behind remarkably.
Published: 2012

34. The neural correlates of intimate partner violence in women

Author: Jean-Paul Fouche, B. Vythilingum, Sandra Marais, E. Jordaan, Bruce S Spottiswoode, Dan J. Stein, S. J. Flegar, Department of Public Health and Family Medicine, and Faculty of Health Sciences
Subjects: Adult, Rural Population, Domestic Violence, medicine.medical_specialty, Corpus callosum, Poison control, Neuroimaging, Hippocampus, Nerve Fibers, Myelinated, behavioral disciplines and activities, White matter, South Africa, Young Adult, mental disorders, Fractional anisotropy, Injury prevention, Image Processing, Computer-Assisted, medicine, Humans, Psychiatry, Brain Mapping, Brain, Organ Size, social sciences, Hippocampal volume, Intimate partner violence, Magnetic Resonance Imaging, Psychiatry and Mental health, Diffusion Magnetic Resonance Imaging, Sexual Partners, medicine.anatomical_structure, Anisotropy, Domestic violence, Female, Psychology, Diffusion MRI
Abstract: Objective: To examine hippocampal volume and white matter tracts in women with and without intimate partner violence (IPV). Method: Nineteen women with IPV exposure in the last year, and 21 women without IPV exposure in the last year underwent structural magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) sequences. Additional data on alcohol use and presence of psychiatric disorder was collected. Differences in fractional anisotropy (FA) between the two groups were examined, using a statistical model that included demographic measures, alcohol use and psychiatric disorder. Results: IPV subjects did not demonstrate significantly different hippocampal volumes compared to subjects without recent IPV. FA was, however, significantly reduced in the body of the corpus callosum of IPV subjects. Adjusting for age, alcohol use, smoking and psychiatric diagnosis did not change the significance of the result. Conclusion: Data on hippocampal volume in IPV are inconsistent, perhaps reflecting the fact that multiple factors influence this measure. Reduced FA in the body of the corpus callosum in IPV suggests altered integrity of this white matter tract; additional work is needed to address the underlying mechanisms and clinical correlates of this finding. Key Words: Corpus callosum; Hippocampal volume; Intimate partner violence; Neuroimaging
Published: 2011

35. Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort

Author: Nynke A. Groenewold, Catherine J. Wedderburn, Jennifer A. Pellowski, Jean-Paul Fouché, Liza Michalak, Annerine Roos, Roger P. Woods, Katherine L. Narr, Heather J. Zar, Kirsten A. Donald, and Dan J. Stein
Subjects: Magnetic resonance imaging, Brain morphometry, Prenatal stress, Depressive disorders, Child development, Sex differences, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Several studies have reported enlarged amygdala and smaller hippocampus volumes in children and adolescents exposed to maternal depression. It is unclear whether similar volumetric differences are detectable in the infants’ first weeks of life, following exposure in utero. We investigated subcortical volumes in 2-to-6 week old infants exposed to antenatal maternal depression (AMD) from a South African birth cohort. Methods: AMD was measured with the Beck Depression Inventory 2nd edition (BDI-II) at 28–32 weeks gestation. T2-weighted structural images were acquired during natural sleep on a 3T Siemens Allegra scanner. Subcortical regions were segmented based on the University of North Carolina neonatal brain atlas. Volumetric estimates were compared between AMD-exposed (BDI-II ⩾ 20) and unexposed (BDI-II
Published: 2022
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36. Structure and Drivers of Cold Seep Ecosystems

Author: Jean-Paul Foucher, Graham K. Westbrook, Antje Boetius, Silvia Ceramicola, Stéphanie Dupré, Jean Mascle, Jürgen Mienert, Olaf Pfannkuche, Catherine Pierre, and Daniel Praeg
Subjects: HERMES, hydrocarbon seeps, biological hotspot, marine biodiversity, seabed mapping, authigenic carbonate, chemosynthetic communities, Oceanography, GC1-1581
Abstract: Submarine hydrocarbon seeps are geologically driven "hotspots" of increased biological activity on the seabed. As part of the HERMES project, several sites of natural hydrocarbon seepage in the European seas were investigated in detail, including mud volcanoes and pockmarks, in study areas extending from the Nordic margin, to the Gulf of Cádiz, to the Mediterranean and Black seas. High-resolution seabed maps and the main properties of key seep sites are presented here. Individual seeps show ecosystem zonation related to the strength of the methane flux and distinct biogeochemical processes in surface sediments. A feature common to many seeps is the formation of authigenic carbonate constructions. These constructions exhibit various morphologies ranging from large pavements and fragmented slabs to chimneys and mushroom-shaped mounds, and they form hard substrates colonized by fixed fauna. Gas hydrate dissociation could contribute to sustain seep chemosynthetic communities over several thousand years following large gas-release events.
Published: 2009

37. Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV

Author: Heather J. Zar, Samantha J. Brooks, Sarah J. Heany, Jacqueline Hoare, Dan J. Stein, Nicole Phillips, Jean-Paul Fouche, and Landon Myer
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Brain activity and meditation, Anti-HIV Agents, Hippocampus, BF, HIV Infections, Audiology, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Virology, medicine, Cingulum (brain), Humans, Child, medicine.diagnostic_test, business.industry, Working memory, Putamen, Brain, Cognition, Magnetic Resonance Imaging, Infectious Disease Transmission, Vertical, 030104 developmental biology, Memory, Short-Term, Neurology, RC0321, Female, Neurology (clinical), Functional magnetic resonance imaging, business, Insula, 030217 neurology & neurosurgery
Abstract: There is evidence of HIV affecting cognitive functioning across age groups, with adult studies showing related deficits in frontostriatal and hippocampal regional activity. Additionally, delayed initiation of antiretroviral treatment (ART) has been associated with poorer cognitive outcomes in HIV-infected youth. Little is known, however, of the neural correlates underlying such cognitive deficits in youth populations. We investigated maintenance working memory-related brain activity in South African HIV-infected youth and controls, and the effect of ART initiation age on underlying structures. Sixty-four perinatally infected youth (ages 9-12) and 20 controls (ages 9-13) underwent functional magnetic resonance imaging (fMRI) while completing 1-back and 0-back blocks of the N-back task. At an uncorrected p value threshold of 0.001, the HIV-infected group showed decreased activation in the left superior temporal gyrus, pre- and postcentral gyri, insula, and putamen as well as bilateral hippocampus, and mid cingulum. The HIV patients with delayed ART initiation showed less activation during processing conditions in the mid cingulum; left inferior parietal gyrus; and right inferior frontal, bilateral thalamic, and superior temporal regions. When these regions were tested for structural differences, the mid cingulum and right inferior frontal gyrus, insula, and thalamus were found to have less cortical thickness, surface area, or volume in the group with delayed ART initiation. Regional differences between HIV-infected youth and controls noted in the N-back task are consistent with impairments in structures involved in maintenance working memory. These data support earlier ART initiation in perinatally infected individuals.

38. Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres.

Author: Fouche JP, du Plessis S, Hattingh C, Roos A, Lochner C, Soriano-Mas C, Sato JR, Nakamae T, Nishida S, Kwon JS, Jung WH, Mataix-Cols D, Hoexter MQ, Alonso P, de Wit SJ, Veltman DJ, Stein DJ, and van den Heuvel OA
Subjects: Adult, Cerebral Cortex diagnostic imaging, Female, Hippocampus diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Obsessive-Compulsive Disorder diagnostic imaging, Cerebral Cortex pathology, Hippocampus pathology, Obsessive-Compulsive Disorder pathology
Abstract: Background: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness., Aims: To investigate alterations in cortical thickness and subcortical volume in OCD., Method: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken., Results: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group × age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls., Conclusions: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group × age interaction effects may be the result of altered neuroplasticity., (© The Royal College of Psychiatrists 2017.)
Published: 2017
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39. A diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals.

Author: Hoare J, Westgarth-Taylor J, Fouche JP, Spottiswoode B, Paul R, Thomas K, Stein D, and Joska J
Subjects: AIDS Dementia Complex pathology, AIDS Dementia Complex physiopathology, AIDS Dementia Complex psychology, Adolescent, Adult, Case-Control Studies, Female, HIV Seropositivity physiopathology, HIV Seropositivity psychology, Humans, Male, Memory Disorders physiopathology, Memory Disorders virology, Nerve Fibers, Myelinated metabolism, South Africa, Young Adult, Diffusion Tensor Imaging methods, HIV Seropositivity pathology, Memory Disorders pathology, Nerve Fibers, Myelinated pathology
Abstract: HIV-associated prospective memory (ProM) impairment has emerged, in earlier studies as a significant predictor of medication management and independence in activities of daily living. The relationship between ProM and white matter integrity in HIV has not previously been investigated. Participants, including 128 HIV-infected individuals and 32 healthy controls, were assessed using a comprehensive neuropsychological evaluation and both objective and subjective measures of ProM. Diffusion tensor imaging (DTI) was utilized to investigate the relationship of white matter integrity to ProM in a randomly selected subsample of 40 HIV positive subjects, using a whole brain voxel-based approach to define fractional anisotrophy (FA) and mean diffusion (MD). Total prospective memory was significantly poorer in the HIV positive group when compared with healthy controls (p = 0.023). Time-based ProM was poorer in the HIV group compared to healthy controls both without prompts (p = 0.001) and with prompts (p = 0.001). Poor Total ProM score correlated with performance on neuropsychological tests of executive functioning, information processing speed, learning, and working memory (p < 0.05). Those HIV positive participants with poor ProM had significantly decreased FA in the regions of superior corona radiata (p = 0.0035), the corpus collosum (p = 0.006) and the cingulum (p = 0.0033) when compared to those who were HIV positive with good ProM. This study reinforces the importance of ProM assessment in HIV.
Published: 2012
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