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2. Eye-tracking measurement of attention bias to social threat among youth: A replication and extension study

Author

Meghan E. Byrne, Sara Kirschner, Anita Harrewijn, Rany Abend, Amit Lazarov, Lucrezia Liuzzi, Katharina Kircanski, Simone P. Haller, Yair Bar-Haim, and Daniel S. Pine

Subjects
Attention bias, Eye-tracking, Youth, Anxiety, Irritability, Negative affect, Mental healing, RZ400-408, Psychiatry, RC435-571
Abstract

Attentional bias to social threat cues has been linked to heightened anxiety and irritability in youth. Yet, inconsistent methodology has limited replication and led to mixed findings. The current study aims to 1) replicate and extend two previous pediatric studies demonstrating a relationship between negative affectivity and attentional bias to social threat and 2) examine the test-retest reliability of an eye-tracking paradigm among a subsample of youth. Attention allocation to negative versus non-negative emotional faces was measured using a free-viewing eye-tracking task among youth (N = 185 total, 60 % female, Mage = 13.10 years, SDage = 2.77) with three face-pair conditions: happy-angry, neutral-disgust, sad-happy. Replicating procedures of two previous studies, linear mixed-effects models compared attention bias between children with anxiety disorders and healthy controls. Bifactor analysis was used to parse shared versus unique facets of general negative affectivity (i.e., anxiety, irritability), which were then examined in relation to attention bias. Test-retest reliability of the bias-index was estimated among a subsample of youth (N = 36). No significant differences in attention allocation or bias emerged between anxiety and healthy control groups. While general negative affectivity across the sample was not associated with attention bias, there was a positive relationship for anxiety and irritability on duration of attention allocation toward negative faces. Test-retest reliability for attention bias was moderate (r = 0.50, p

Published
2024
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4. Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Author

Bruin, Willem B., Zhutovsky, Paul, van Wingen, Guido A., Bas-Hoogendam, Janna Marie, Groenewold, Nynke A., Hilbert, Kevin, Winkler, Anderson M., Zugman, Andre, Agosta, Federica, Åhs, Fredrik, Andreescu, Carmen, Antonacci, Chase, Asami, Takeshi, Assaf, Michal, Barber, Jacques P., Bauer, Jochen, Bavdekar, Shreya Y., Beesdo-Baum, Katja, Benedetti, Francesco, Bernstein, Rachel, Björkstrand, Johannes, Blair, Robert J., Blair, Karina S., Blanco-Hinojo, Laura, Böhnlein, Joscha, Brambilla, Paolo, Bressan, Rodrigo A., Breuer, Fabian, Cano, Marta, Canu, Elisa, Cardinale, Elise M., Cardoner, Narcís, Cividini, Camilla, Cremers, Henk, Dannlowski, Udo, Diefenbach, Gretchen J., Domschke, Katharina, Doruyter, Alexander G. G., Dresler, Thomas, Erhardt, Angelika, Filippi, Massimo, Fonzo, Gregory A., Freitag, Gabrielle F., Furmark, Tomas, Ge, Tian, Gerber, Andrew J., Gosnell, Savannah N., Grabe, Hans J., Grotegerd, Dominik, Gur, Ruben C., Gur, Raquel E., Hamm, Alfons O., Han, Laura K. M., Harper, Jennifer C., Harrewijn, Anita, Heeren, Alexandre, Hofmann, David, Jackowski, Andrea P., Jahanshad, Neda, Jett, Laura, Kaczkurkin, Antonia N., Khosravi, Parmis, Kingsley, Ellen N., Kircher, Tilo, Kostic, Milutin, Larsen, Bart, Lee, Sang-Hyuk, Leehr, Elisabeth J., Leibenluft, Ellen, Lochner, Christine, Lui, Su, Maggioni, Eleonora, Manfro, Gisele G., Månsson, Kristoffer N. T., Marino, Claire E., Meeten, Frances, Milrod, Barbara, Jovanovic, Ana Munjiza, Mwangi, Benson, Myers, Michael J., Neufang, Susanne, Nielsen, Jared A., Ohrmann, Patricia A., Ottaviani, Cristina, Paulus, Martin P., Perino, Michael T., Phan, K. Luan, Poletti, Sara, Porta-Casteràs, Daniel, Pujol, Jesus, Reinecke, Andrea, Ringlein, Grace V., Rjabtsenkov, Pavel, Roelofs, Karin, Salas, Ramiro, Salum, Giovanni A., Satterthwaite, Theodore D., Schrammen, Elisabeth, Sindermann, Lisa, Smoller, Jordan W., Soares, Jair C., Stark, Rudolf, Stein, Frederike, Straube, Thomas, Straube, Benjamin, Strawn, Jeffrey R., Suarez-Jimenez, Benjamin, Sylvester, Chad M., Talati, Ardesheer, Thomopoulos, Sophia I., Tükel, Raşit, van Nieuwenhuizen, Helena, Werwath, Kathryn, Wittfeld, Katharina, Wright, Barry, Wu, Mon-Ju, Yang, Yunbo, Zilverstand, Anna, Zwanzger, Peter, Blackford, Jennifer U., Avery, Suzanne N., Clauss, Jacqueline A., Lueken, Ulrike, Thompson, Paul M., Pine, Daniel S., Stein, Dan J., van der Wee, Nic J. A., Veltman, Dick J., and Aghajani, Moji

Published
2024
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7. Risk factors for unexpected infant death among very premature infants in France

Author

Cécile, Dubois, Pétronela, Rachieru-Sourisseau, Estelle, Darviot, Alain, De Broca, Clémence, Mougey, Adèle, Schiby, Julia, Pauls-Barsanti, Adeline, Robelin, Stéphane, Rioualen, Anne-Laure, Duigou, Mathilde, Granjon, Anne-Sophie, Trentesaux, Djamel, Sebbouh, Assia, Smail, Noella, Lode, Stéphanie, Perez-Martin, Anne-Pascale, Michard-Lenoir, Adbelihah, Tahir, Christine, Laguille, Delphine, Brouet, Camille, Le Stradic, Béatrice, Kugener, Alice, Cartallas, Patricia, Garcia-Meric, Inge, Harrewijn, Odile, Pidoux, Bénédicte, Vrignaud, Anne, Borsa-Dorion, Mickael, Afanetti, Caroline, Robin, Marie, Lebeau, Mariana, Englender, Célin, Farges, Juliette, Raghani, Maëlle, Monnier, Hugues, Patural, Audrey, Breining, Alexandre, Pupin, Gilles, Duthoit, Lucile, Barnet, Blandine, Cabaret, Yasmine, Plee, Aurélien, Galerne, Camille, Aupiais, Morgane, Dubourg, Marie, Kieffer, Blandine, Muanza, Guen, Christèle Gras Le, Bourneuf, Anne-Laure, Pabic, Estelle Le, de Visme, Sophie, Levieux, Karine, and Pladys, Patrick

Published
2024
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8. Inconsistency Between Pictures on Baby Diaper Packaging in Europe and Safe Infant Sleep Recommendations

Author

de Visme, Sophie, Korevaar, Daniel A., Gras-Le Guen, Christèle, Flamant, Alix, Bevacqua, Martina, Stanzelova, Anna, Trinh, Nhung T.H., Ciobanu, Dalia-Alexandra, Carvalho, Ana Araújo, Kyriakoglou, Ifigeneia, Fuentes, Maria, Refes, Yacine, Briand-Huchet, Elisabeth, Sellier, Anne-Laure, Harrewijn, Inge, Cohen, Jérémie F., and Chalumeau, Martin

Published
2024
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9. Assessing the Degree of Ecological Validity of Your Study: Introducing the Multidimensional Assessment of Research in Context (MARC) Tool

Author

Naumann, Sandra, Byrne, Michelle L., de la Fuente, Alethia, Harrewijn, Anita, Nugiel, Tehila, Rosen, Maya, van Atteveldt, Nienke, and Matusz, Pawel J.

Abstract

In cognitive neurosciences, fundamental principles of mental processes and functional brain organization have been established with highly controlled tasks and testing environments. Recent technical advances allowed the investigation of these functions and their brain mechanisms in naturalistic settings. The diversity in those approaches have been recently (Matusz, P. J., Dikker, S., Huth, A. G., & Perrodin, C. (2019). Are we ready for real-world neuroscience? "Journal of Cognitive Neuroscience," 31(3), 327-338. doi:10.1162/jocn_e_01276) classified via a three-category cycle, including "controlled laboratory," "partially naturalistic laboratory," and "naturalistic real-world research." Based on this model, we developed the Multidimensional Assessment of Research in Context (MARC) tool to easily delineate the approach researchers have taken in their study. MARC provides means to describe the degree of ecological validity for each component of a study (e.g., sample, stimuli, measures, etc.), and the study's location on the cycle. The tool comprises seven questions concerning a study's characteristics. It outputs a summary of those and a compass plot, which can be used for presentations, preregistration, grant proposals, and papers. It aims to improve drawing conclusions across studies and raise awareness about the generalizability of research findings.

Published
2022
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11. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author

Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.

Published
2023
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14. Gender-Differentiated Emotion Socialization: Evoked by Child Behaviors, Parents' Neural Responses Toward Gender-Stereotype Violations, or Both?

Author

Portengen, Christel M., Harrewijn, Anita, van Baar, Anneloes L., and Endendijk, Joyce J.

Subjects
*BRAIN physiology, *HOME care services, *FEAR, *STEREOTYPES, *DIVERSITY & inclusion policies, *SADNESS, *SEX distribution, *GENDER-neutral language, *ELECTROENCEPHALOGRAPHY, *ANGER, *EMOTIONS, *PARENT attitudes, *DESCRIPTIVE statistics, *SOCIALIZATION, *CHILD behavior
Abstract

SYNOPSIS: Objective. During early childhood, gender-specific trajectories of behavior and emotional development become more prominent. However, it remains unclear whether parents' gender-differentiated socialization is evoked by children's own behaviors and emotions, processes within parents, or both. This study examined whether parents' gender labeling of emotional characters could be predicted by (1) their children's behavior and emotional expressions, (2) parents' neural responses to gender-stereotype violations and confirmations by their own children, or (3) both. Design. Home visits were conducted with 71 families consisting of a father, mother, and a daughter and son aged 3–6 years. Electroencephalographic measurements were obtained from parents while they passively viewed pictures of their daughter and son combined with gender-typed behavior and emotional expression words. Mothers' and fathers' use of gender labels was coded while they read a picture book to their daughter and son in which gender-neutral child characters displayed sadness, fear, and anger. Children's gender-typed behavior and emotional expressions were measured through parent-reports on the Brief Symptom Checklist. Results. No relations were found between parents' use of gender labels and parents' neural processing of gender-stereotype confirmations and violations or children's behavior and emotional expressions. Conclusions. Parents' neural processing and children's emotion and behavioral expressions did not affect parents' use of gender labels. Parents were more likely to label pictures of sad children as "girl" than as "boy," but this difference could not be predicted from either parent-centered or child-centered factors. [ABSTRACT FROM AUTHOR]

Published
2025
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16. Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

Author

Anita Harrewijn, Elise M. Cardinale, Nynke A. Groenewold, Janna Marie Bas-Hoogendam, Moji Aghajani, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Savannah Gosnell, Ramiro Salas, Andrea P. Jackowski, Pedro M. Pan, Giovanni A. Salum, Karina S. Blair, James R. Blair, Mira Z. Hammoud, Mohammed R. Milad, Katie L. Burkhouse, K. Luan Phan, Heidi K. Schroeder, Jeffrey R. Strawn, Katja Beesdo-Baum, Neda Jahanshad, Sophia I. Thomopoulos, Randy Buckner, Jared A. Nielsen, Jordan W. Smoller, Jair C. Soares, Benson Mwangi, Mon-Ju Wu, Giovana B. Zunta-Soares, Michal Assaf, Gretchen J. Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rachel Berta, Erica Tamburo, Rebecca B. Price, Gisele G. Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza Jovanovic, Bianca A. V. Alberton, Brenda Benson, Gabrielle F. Freitag, Courtney A. Filippi, Andrea L. Gold, Ellen Leibenluft, Grace V. Ringlein, Kathryn E. Werwath, Hannah Zwiebel, André Zugman, Hans J. Grabe, Sandra Van der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L. Balderston, Monique Ernst, Christian Grillon, Lilianne R. Mujica-Parodi, Helena van Nieuwenhuizen, Hugo D. Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Tali M. Ball, Gregory A. Fonzo, Martin P. Paulus, Murray B. Stein, Raquel E. Gur, Ruben C. Gur, Antonia N. Kaczkurkin, Bart Larsen, Theodore D. Satterthwaite, Jennifer Harper, Michael Myers, Michael T. Perino, Chad M. Sylvester, Qiongru Yu, Ulrike Lueken, Dick J. Veltman, Paul M. Thompson, Dan J. Stein, Nic J. A. Van der Wee, Anderson M. Winkler, and Daniel S. Pine

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Published
2021
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20. Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy

Author

Abend, Rany, Bajaj, Mira A., Harrewijn, Anita, Matsumoto, Chika, Michalska, Kalina J., Necka, Elizabeth, Palacios-Barrios, Esther E., Leibenluft, Ellen, Atlas, Lauren Y., and Pine, Daniel S.

Subjects
Physiological aspects, Research, Threat (Psychology) -- Research, Adolescent anxiety -- Research, Neuroanatomy -- Research, Neurological research, Prefrontal cortex -- Physiological aspects, Anxiety in youth -- Research, Anxiety in teenagers -- Research
Abstract

Introduction Anticipation of threat engages conserved neural circuitry that has evolved to facilitate defensive behaviours; (1-3) perturbations in this circuitry could generate excessive anticipatory response, a core element of pathological [...], Background: Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. Methods: Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat- anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. Results: Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05). Limitations: Limitations included the modest sample size and the cross-sectional design. Conclusion: These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Published
2021
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34. Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

Author

Haller, Simone P., Linke, Julia O., Grassie, Hannah L., Jones, Emily L., Pagliaccio, David, Harrewijn, Anita, White, Lauren K., Naim, Reut, Abend, Rany, Mallidi, Ajitha, Berman, Erin, Lewis, Krystal M., Kircanski, Katharina, Fox, Nathan A., Silverman, Wendy K., Kalin, Ned H., Bar-Haim, Yair, and Brotman, Melissa A.

Subjects
COGNITIVE therapy, ANXIETY disorders, CHILD patients, PEDIATRIC therapy, FUNCTIONAL magnetic resonance imaging, AT-risk youth
Abstract

Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT. Unmedicated youths diagnosed with an anxiety disorder underwent 12 weeks of CBT as part of two randomized clinical trials testing the efficacy of adjunctive computerized cognitive training. Across both trials, participants completed a threat-processing task during functional MRI before and after treatment. Age-matched healthy comparison youths completed two scans over the same time span. The mean age of the samples was 13.20 years (SD=2.68); 41% were male (youths with anxiety disorders, N=69; healthy comparison youths, N=62). An additional sample including youths at temperamental risk for anxiety (N=87; mean age, 10.51 years [SD=0.43]; 41% male) was utilized to test the stability of anxiety-related neural differences in the absence of treatment. Whole-brain regional activation changes (thresholded at p<0.001) were examined using task-based blood-oxygen-level-dependent response. Before treatment, patients with an anxiety disorder exhibited altered activation in fronto-parietal attention networks and limbic regions relative to healthy comparison children across all task conditions. Fronto-parietal hyperactivation normalized over the course of treatment, whereas limbic responses remained elevated after treatment. In the at-risk sample, overlapping clusters emerged between regions showing stable associations with anxiety over time and regions showing treatment-related changes. Activation in fronto-parietal networks may normalize after CBT in unmedicated pediatric anxiety patients. Limbic regions may be less amenable to acute CBT effects. Findings from the at-risk sample suggest that treatment-related changes may not be attributed solely to the passage of time. [ABSTRACT FROM AUTHOR]

Published
2024
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36. ASSESSMENT OF MASONRY ARCH BRIDGES WITH A SHALLOW OR PILE FOUNDATION

Author

Harrewijn, T., Lantinga, C., and Vergoossen, R.

Subjects
Wooden foundation piles, Residual lifetime, Masonry arch bridge, NLFEA, Foundation Reuse, Assessment, Proof-loading, PLAXIS
Abstract

This paper is about the assessment of masonry arch bridges in the Netherlands, whether or not founded on wooden foundation piles. A large part of the public road network in old city centres is still formed by masonry arch bridges crossing the canals. The general question of the local authorities is: “Can these masonry arch bridges withstand motorised traffic including busses and occasionally heavy trucks?” Nonlinear finite element analysis in PLAXIS is applied for the assessment of the failure behaviour of the masonry structure and its shallow or pile foundation. The structural limits are related to cracking, continuous deformations and instability. A proof-loading of a real bridge increased the reliability of the calculation methodology. With NLFEA it can be demonstrated that these historic bridges still meet the current loads from heavy motorised traffic. With a quick scan method based on the MEXE theory, a large group of arches can be quickly classified, so the assessment with NLFEA can start with the riskiest objects. In many cases lifetime extension of these bridges is possible, whether or not by strengthening the superstructure. This means that the shallow foundation or pile foundation is reused., Paper presentation

Published
2023
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37. Development of Neural Mechanisms Underlying Threat Processing: Associations With Childhood Social Reticence and Adolescent Anxiety

Author

Anita Harrewijn, Sonia G. Ruiz, Rany Abend, Simone P. Haller, Anni R. Subar, Caroline Swetlitz, Emilio A. Valadez, Melissa A. Brotman, Gang Chen, Andrea Chronis-Tuscano, Ellen Leibenluft, Yair Bar-Haim, Nathan A. Fox, Daniel S. Pine, and Clinical Psychology

Subjects
SDG 3 - Good Health and Well-being, General Medicine
Abstract

Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety. Methods: In this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27). Results: A significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala–dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety. Conclusions: These findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.

Published
2023

38. ANXIETY? STAY AWAY FROM ME!

Author

van der Hoek, Dinand, Muller, Kirsten S., de Zwart, Elize, Pittig, Andre, Harrewijn, Anita, and Wong, Alex H. K.

Subjects
ANXIETY, STUTTERING, EMOTIONS
Abstract

Have you ever felt anxious? How do you usually react when you are afraid of something? Anxiety is a normal feeling that everyone gets from time to time. Since it is an unpleasant feeling, people often try to avoid situations that make them feel that way. For example, skipping school because you have to give a presentation in front of the whole class. Some people can feel too much anxiety. Anxiety makes them nauseous, and they might start to stutter. In our work, we would like to discuss "avoidance of learned fear". In this article, we will explore anxious feelings and whether people tend to avoid things they are anxious about. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Why Do Some Children Become Very Anxious?

Author

Rachel Bernstein, Jordan Galbraith, Devi Lakhlani, Isaac Morales, George A. Buzzell, Ranjan Debnath, Ellen Leibenluft, Daniel S. Pine, Nathan A. Fox, and Anita Harrewijn

Subjects
General Medicine
Abstract

While it is normal to be scared of things, some children are so scared that it disrupts their lives. This is called an anxiety disorder. To help children with anxiety disorders, we need to know how anxiety disorders start. From other research we knew that toddlers who avoid new situations are more likely to become anxious later in life. They are more likely, which does not mean they all become more anxious, just some of them. We wanted to know if brain activity could predict which children would become anxious. We studied avoidance in toddlers and invited them back as preteens. We studied their brains while they were resting and while they were making mistakes in front of somebody else. We found that brain responses to mistakes predicted which avoidant toddlers became very anxious as preteens. This helps us understand who might develop anxiety, so that we can help!

Published
2022
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42. WHAT TOOLS ARE IN YOUR COPING TOOLBOX?

Author

Kapoğlu, Naz, Kärkkäinen, Dalila Ruiz Y, Tapio, Laura, Haar, Sam B. ter, Hertog, Marianne den, Huijgen, Rowan, Harrewijn, Anita, Godor, Brian P., and Hallen, Ruth Van der

Subjects
TOOLBOXES, CHOICE (Psychology), ADAPTABILITY (Personality), STRESS management
Abstract

This article explores the concept of coping and the different strategies people use to manage difficult situations. Coping involves finding ways to deal with tough feelings or situations, and individuals may respond differently based on their own coping toolbox. The article discusses three main types of coping strategies: problem-focused coping, emotion-focused coping, and avoidant coping. It also highlights that coping strategies are learned and influenced by upbringing and the people around us. The article concludes by mentioning that coping is not unique to humans, as even plants have their own coping strategies to manage difficult environmental conditions. [Extracted from the article]

Published
2023
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43. Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety

Author

Rany Abend, Sonia G. Ruiz, Mira A. Bajaj, Anita Harrewijn, Julia O. Linke, Lauren Y. Atlas, Anderson M. Winkler, and Daniel S. Pine

Subjects
Neurophysiology and neuropsychology, Endocrine and Autonomic Systems, Physiology, QP351-495, Neurosciences. Biological psychiatry. Neuropsychiatry, Fear, Anxiety, Amygdala, Biochemistry, Anticipation, Cellular and Molecular Neuroscience, Endocrinology, Cortex, Neurology. Diseases of the nervous system, Original Research Article, RC346-429, Molecular Biology, Threat, RC321-571
Abstract

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety. 50 pediatric anxiety patients and healthy-comparisons (33 females) completed an instructed threat-anticipation task whereby cues signaled delivery of painful (threat) or non-painful (safety) thermal stimulation. Temporal changes in skin-conductance indexed anxiety effects on anticipatory responding as function of threat imminence. Multivariate network analyses of resting-state functional connectivity data from a subsample were used to identify intrinsic-function correlates of anticipatory-response dynamics, within a specific, distributed network derived from translational research on defensive responding. By considering threat imminence, analyses revealed specific anxiety effects. Importantly, pathological anxiety was associated with excessive deployment of anticipatory physiological response as threat, but not safety, outcomes became more imminent. Magnitude of increase in threat-anticipatory physiological responses corresponded with magnitude of intrinsic connectivity within a cortical-subcortical circuit. Moreover, more severe anxiety was associated with stronger associations between anticipatory physiological responding and connectivity that ventromedial prefrontal cortex showed with hippocampus and basolateral amygdala, regions implicated in animal models of anxiety. These findings link basic and clinical research, highlighting variations in intrinsic function in conserved defensive circuitry as a potential pathophysiological mechanism in anxiety., Highlights • We translate animal insight on fear dynamics into human research on anxiety. • Patients and controls completed threat anticipation task and resting-state scan. • We observed aberrant threat-anticipatory physiological response dynamics in anxiety. • Aberrant dynamics in anxiety linked to cortical-subcortical intrinsic function. • Findings link basic, clinical research; highlight potential pathophysiological mechanism.

Published
2022

44. ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Author

Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., Agosta, F., Ahs, F., An, I., Alberton, B. A. V., Andreescu, C., Asami, T., Assaf, M., Avery, S. N., Nicholas, L., Balderston, Barber, J. P., Battaglia, M., Bayram, A., Beesdo-Baum, K., Benedetti, F., Berta, R., Bjorkstrand, J., Blackford, J. U., Blair, J. R., Karina, S., Blair, Boehme, S., Brambilla, P., Burkhouse, K., Cano, M., Canu, E., Cardinale, E. M., Cardoner, N., Clauss, J. A., Cividini, C., Critchley, H. D., Udo, Dannlowski, Deckert, J., Demiralp, T., Diefenbach, G. J., Domschke, K., Doruyter, A., Dresler, T., Erhardt, A., Fallgatter, A. J., Fananas, L., Brandee, Feola, Filippi, C. A., Filippi, M., Fonzo, G. A., Forbes, E. E., Fox, N. A., Fredrikson, M., Furmark, T., Ge, T., Gerber, A. J., Gosnell, S. N., Grabe, H. J., Grotegerd, D., Gur, R. E., Gur, R. C., Harmer, C. J., Harper, J., Heeren, A., Hettema, J., Hofmann, D., Hofmann, S. G., Jackowski, A. P., Andreas, Jansen, Kaczkurkin, A. N., Kingsley, E., Kircher, T., Kosti c, M., Kreifelts, B., Krug, A., Larsen, B., Lee, S. -H., Leehr, E. J., Leibenluft, E., Lochner, C., Maggioni, E., Makovac, E., Mancini, M., Manfro, G. G., Mansson, K. N. T., Meeten, F., Michalowski, J., Milrod, B. L., Muhlberger, A., Lilianne, R., Mujica-Parodi, Munjiza, A., Mwangi, B., Myers, M., Igor Nenadi, C., Neufang, S., Nielsen, J. A., Oh, H., Ottaviani, C., Pan, P. M., Pantazatos, S. P., Martin, P., Paulus, Perez-Edgar, K., Penate, W., Perino, M. T., Peterburs, J., Pfleiderer, B., Phan, K. L., Poletti, S., Porta-Casteras, D., Price, R. B., Pujol, J., Andrea, Reinecke, Rivero, F., Roelofs, K., Rosso, I., Saemann, P., Salas, R., Salum, G. A., Satterthwaite, T. D., Schneier, F., Schruers, K. R. J., Schulz, S. M., Schwarzmeier, H., Seeger, F. R., Smoller, J. W., Soares, J. C., Stark, R., Stein, M. B., Straube, B., Straube, T., Strawn, J. R., Suarez-Jimenez, B., Boris, Suchan, Sylvester, C. M., Talati, A., Tamburo, E., Tukel, R., van den Heuvel, O. A., Van der Auwera, S., van Nieuwenhuizen, H., van Tol, M. -J., van Velzen, L. S., Bort, C. V., Vermeiren, R. R. J. M., Visser, R. M., Volman, I., Wannemuller, A., Wendt, J., Werwath, K. E., Westenberg, P. M., Wiemer, J., Katharina, Wittfeld, M. -J., Wu, Yang, Y., Zilverstand, A., Zugman, A., Zwiebel, H. L., Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., ENIGMA-anxiety working, Group, Filippi, M, and UCL - SSH/IPSY - Psychological Sciences Research Institute

Subjects
Córtex pré-frontal, Review Article, Anxiety, Prefrontal cortex, Specific phobia, 0302 clinical medicine, limbic system, magnetic resonance imaging, Multicenter Studies as Topic, genetics, Review Articles, prefrontal cortex, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, Social anxiety, amygdala, Amygdala, Anxiety Disorders, Transtornos de ansiedade, Neurology, multicentric network, Anatomy, medicine.symptom, Psychology, Neurovetenskaper, Clinical psychology, endocrine system, Generalized anxiety disorder, brain, Neuroimaging, Sistema límbico, 050105 experimental psychology, 03 medical and health sciences, Global mental health, Limbic system, Magnetic resonance imaging, Imatges per ressonància magnètica, medicine, Genetics, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Neuroimagem, Psykologi (exklusive tillämpad psykologi), Panic disorder, neurosciences, Imageamento por ressonância magnética, Tonsila do cerebelo, medicine.disease, anxiety disorders, Genética, Psychology (excluding Applied Psychology), Ansietat, Neurology (clinical), Working group, 030217 neurology & neurosurgery, Anxiety disorders
Abstract

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Published
2020
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46. Brain characteristics associated with anxiety disorders

Author

Groenewold, N.A., Bas-Hoogendam, J.M., Aghajani, M., Hilbert, K., Zugman, A., Fullana, M.A., Harrewijn, A., Cardinale, E.M., Roelofs, E., Laansma, M.A., Velzen, L.S. van, Thomopoulos, S.I., Jahanshad, N., Winkler, A.M., Thompson, P.M., Veltman, D.J., Lueken, U., Pine, D.S., Stein, D.J., and Wee, N.J.A. van der

Published
2021

49. Attention bias to negative versus non-negative faces is related to negative affectivity in a transdiagnostic youth sample

Author

Simone P. Haller, Anita Harrewijn, Katharina Kircanski, Rany Abend, Chika Matsumoto, Elise M. Cardinale, Mira A. Bajaj, Melissa A. Brotman, Reut Naim, Caitlin Stavish, Kelly Dombek, and Clinical Psychology

Subjects
Male, Adolescent, Anxiety, Attentional bias, Irritability, Article, Negative affectivity, Attentional Bias, 03 medical and health sciences, 0302 clinical medicine, Treatment targets, Pediatric anxiety, medicine, Humans, Child, Biological Psychiatry, Anxiety Disorders, Irritable Mood, 030227 psychiatry, Psychiatry and Mental health, Child, Preschool, Female, medicine.symptom, Arousal, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

This study identified a shared pathophysiological mechanism of pediatric anxiety and irritability. Clinically, anxiety and irritability are common, co-occurring problems, both characterized by high-arousal negative affective states. Behaviorally, anxiety and irritability are associated with aberrant threat processing. To build on these findings, we examined eye-tracking measures of attention bias in relation to the unique and shared features of anxiety and irritability in a transdiagnostic sample of youth (n = 97, 58% female, Mage = 13.03, SDage = 2.82). We measured attention bias to negative versus non-negative emotional faces during a passive viewing task. We employed bifactor analysis to parse the unique and shared variance of anxiety and irritability symptoms from self- and parent-report questionnaires. Negative affectivity is the derived latent factor reflecting shared variance of anxiety and irritability. We found that higher negative affectivity was associated with looking longer at negative versus non-negative faces, reflecting a shared mechanism of anxiety and irritability. This finding suggests that modification of elevated attention to negative emotional faces may represent a common potential treatment target of anxiety and irritability.

Published
2021

50. Cortical and subcortical brain structure in generalized anxiety disorder : findings from 28 research sites in the ENIGMA-Anxiety Working Group

Author

Harrewijn, Anita, Pine, Daniel S., Salum Junior, Giovanni Abrahão, and Manfro, Gisele Gus

Subjects
Transtornos de ansiedade, Córtex cerebral
Abstract

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This megaanalysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Published
2021

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