27 results on '"Meyer-Lindenberg, Andreas"'
Search Results
2. Hippocampal and Frontolimbic Function as Intermediate Phenotype for Psychosis: Evidence from Healthy Relatives and a Common Risk Variant in CACNA1C.
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Erk, Susanne, Meyer-Lindenberg, Andreas, Schmierer, Phöbe, Mohnke, Sebastian, Grimm, Oliver, Garbusow, Maria, Haddad, Leila, Poehland, Lydia, Mühleisen, Thomas W., Witt, Stephanie H., Tost, Heike, Kirsch, Peter, Romanczuk-Seiferth, Nina, Schott, Björn H., Cichon, Sven, Nöthen, Markus M., Rietschel, Marcella, Heinz, Andreas, and Walter, Henrik
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MENTAL illness , *PSYCHOSES , *HIPPOCAMPUS (Brain) , *PHENOTYPES , *CALCIUM channels , *CINGULATE cortex , *MAGNETIC resonance imaging - Abstract
Background Variation in CACNA1C has consistently been associated with psychiatric disease in genome-wide association studies. We have previously shown that healthy carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate (pgACC) dysfunction during episodic memory recall. To test whether this brain systems-level abnormality is a potential intermediate phenotype for psychiatric disorder, we studied unaffected relatives of patients with bipolar disorder, major depression, and schizophrenia. Methods The study population comprised 188 healthy first-degree relatives of patients with bipolar disorder ( n = 59), major depression ( n = 73), and schizophrenia ( n = 56) and 110 comparison subjects from our discovery study who were genotyped for rs1006737 and underwent functional magnetic resonance imaging while performing an episodic memory task and psychological testing. Group comparisons were analyzed using SPM8 and PASW Statistics 20. Results Similar to risk allele carriers in the discovery sample, relatives of index patients exhibited hippocampal and pgACC dysfunction as well as increased scores in depression and anxiety measures, correlating negatively with hippocampal activation. Carrying the rs1006737 risk variant resulted in a stronger decrease of hippocampal and pgACC activation in relatives, indicating an additive effect of CACNA1C variation on familial risk. Conclusions Our findings implicate abnormal perigenual and hippocampal activation as a promising intermediate phenotype for psychiatric disease and suggest a pathophysiologic mechanism conferred by a CACNA1C variant being implicated in risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2014
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3. Progress in sensorimotor neuroscience of schizophrenia spectrum disorders: Lessons learned and future directions.
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Hirjak, Dusan, Meyer-Lindenberg, Andreas, Sambataro, Fabio, Fritze, Stefan, Kukovic, Jacqueline, Kubera, Katharina M., and Wolf, Robert C.
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MAGNETIC resonance imaging , *CLINICAL neurosciences , *NEUROSCIENCES , *MOVEMENT disorders , *SCHIZOPHRENIA - Abstract
The number of neuroimaging studies on movement disorders, sensorimotor, and psychomotor functioning in schizophrenia spectrum disorders (SSD) has steadily increased over the last two decades. Accelerated by the addition of the "sensorimotor domain" to the Research Domain Criteria (RDoC) framework in January 2019, neuroscience research on the role of sensorimotor dysfunction in SSD has gained greater scientific and clinical relevance. To draw attention to recent rapid progress in the field, we performed a triennial systematic review (PubMed search from January 1st, 2018 through December 31st, 2020), in which we highlight recent neuroimaging findings and discuss methodological pitfalls as well as challenges for future research. The identified magnetic resonance imaging (MRI) studies suggest that sensorimotor abnormalities in SSD are related to cerebello-thalamo-cortico-cerebellar network dysfunction. Longitudinal and interventional studies highlight the translational potential of the sensorimotor domain as putative biomarkers for treatment response and as targets for non-invasive neurostimulation techniques in SSD. • Sensorimotor neuroscience is growing rapidly. • CTCC dysfunction might lead to sensorimotor abnormalities in SSD. • Sensorimotor neuroscience exhibits diagnostic and therapeutic relevance. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Age-related changes in midbrain dopaminergic regulation of the human reward system.
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Dreher, Jean-Claude, Meyer-Lindenberg, Andreas, Kohn, Philip, and Berman, Karen Faith
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DOPAMINE receptors , *NEURAL receptors , *POSITRON emission tomography , *MAGNETIC resonance imaging , *MESENCEPHALON , *PHARMACOLOGY - Abstract
The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals. a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans. although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and rewardrelated neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[[sup18]F)FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRl) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging. [ABSTRACT FROM AUTHOR]
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- 2008
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5. Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome.
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Meyer-Lindenberg, Andreas, Mervis, Carolyn B., Sarpal, Deepak, Koch, Paul, Steele, Sonya, Kohn, Philip, Marenco, Stefano, Morris, Colleen A., Das, Saumitra, Kippenhan, Shane, Mattay, Venkata S., Weinberger, Daniel R., and Berman, Karen Faith
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WILLIAMS syndrome , *GENES , *PROTEINS , *SYNDROMES in children , *BLOOD circulation , *CHROMOSOMES , *ASPARTIC acid metabolism , *ASPARTIC acid , *COMPARATIVE studies , *HIPPOCAMPUS (Brain) , *MAGNETIC resonance imaging , *RESEARCH methodology , *MEDICAL cooperation , *NERVE tissue proteins , *PHOSPHOTRANSFERASES , *PROTEIN kinases , *RESEARCH , *RESEARCH funding , *POSITRON emission tomography , *TRANSFERASES , *DNA-binding proteins , *EVALUATION research , *CASE-control method - Abstract
Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, in the hippocampal formation (HF). Furthermore, deficits in spatial navigation and long-term memory, major cognitive domains dependent on hippocampal function, have been described in WS. We used multimodal neuroimaging to characterize hippocampal structure, function, and metabolic integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy controls. PET and functional MRI studies showed profound reduction in resting blood flow and absent differential response to visual stimuli in the anterior HF in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of synaptic activity, were reduced. Hippocampal size was preserved, but subtle alterations in shape were present. These data demonstrate abnormalities in HF in WS in agreement with murine models, implicate LIMK1 and CYLN2 in human hippocampal function, and suggest that hippocampal dysfunction may contribute to neurocognitive abnormalities in WS. [ABSTRACT FROM AUTHOR]
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- 2005
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6. Microstructural white matter biomarkers of symptom severity and therapy outcome in catatonia: Rationale, study design and preliminary clinical data of the whiteCAT study.
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Hirjak, Dusan, Brandt, Geva A., Peretzke, Robin, Fritze, Stefan, Meyer-Lindenberg, Andreas, Maier-Hein, Klaus H., and Neher, Peter F.
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WHITE matter (Nerve tissue) , *CATATONIA , *MACHINE learning , *DIFFUSION magnetic resonance imaging , *MAGNETIC resonance imaging - Abstract
The number of magnetic resonance imaging (MRI) studies on neuronal correlates of catatonia has dramatically increased in the last 10 years, but conclusive findings on white matter (WM) tracts alterations underlying catatonic symptoms are still lacking. Therefore, we conduct an interdisciplinary longitudinal MRI study (whiteCAT) with two main objectives: First, we aim to enroll 100 psychiatric patients with and 50 psychiatric patients without catatonia according to ICD-11 who will undergo a deep phenotyping approach with an extensive battery of demographic, psychopathological, psychometric, neuropsychological, instrumental and diffusion MRI assessments at baseline and 12 weeks follow-up. So far, 28 catatonia patients and 40 patients with schizophrenia or other primary psychotic disorders or mood disorders without catatonia have been studied cross-sectionally. 49 out of 68 patients have completed longitudinal assessment, so far. Second, we seek to develop and implement a new method for semi-automatic fiber tract delineation using active learning. By training supportive machine learning algorithms on the fly that are custom tailored to the respective analysis pipeline used to obtain the tractogram as well as the WM tract of interest, we plan to streamline and speed up this tedious and error-prone task while at the same time increasing reproducibility and robustness of the extraction process. The goal is to develop robust neuroimaging biomarkers of symptom severity and therapy outcome based on WM tracts underlying catatonia. If our MRI study is successful, it will be the largest longitudinal study to date that has investigated WM tracts in catatonia patients. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Structural alterations of amygdala and hypothalamus contribute to catatonia.
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Fritze, Stefan, Brandt, Geva A., Kubera, Katharina M., Schmitgen, Mike M., Northoff, Georg, Geiger-Primo, Lena S., Tost, Heike, Meyer-Lindenberg, Andreas, Wolf, Robert C., and Hirjak, Dusan
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CATATONIA , *HYPOTHALAMUS , *LIMBIC system , *AMYGDALOID body , *PSYCHIATRIC rating scales , *MAGNETIC resonance imaging - Abstract
At present, current diagnostic criteria and systems neglect affective symptom expression in catatonia. This potentially serious omission could explain why putative contributions of limbic system structures, such as amygdala, hippocampus or hypothalamus, to catatonia in schizophrenia spectrum disorders (SSD) have been scarcely investigated so far. To determine whether topographical alterations of the amygdala, hippocampus and hypothalamus contribute to catatonia in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-Cat, n = 30) and without (SSD-nonCat, n = 28) catatonia as defined by a Northoff Catatonia Rating Scale (NCRS) total score of ≥3 and =0, respectively, in comparison with healthy controls (n = 20). FreeSurfer v7.2 was used for automated segmentation of the amygdala and its 9 nuclei, hippocampus and its 21 subfields and hypothalamus and its associated 5 subunits. SSD-Cat had significantly smaller anterior inferior hypothalamus, cortical nucleus of amygdala, and hippocampal fimbria volumes when compared to SSD-nonCat. SSD-Cat had significantly smaller amygdala, hippocampus and hypothalamus whole and subunit volumes when compared to healthy controls. In SSD-Cat according to DSM-IV-TR (n = 44), we identified positive correlations between Brief Psychiatric Rating Scale (BPRS) item #2 (reflecting anxiety) and respective amygdala nuclei as well as negative correlation between NCRS behavioral score and hippocampus subiculum head. The lower volumes of respective limbic structures involved in affect regulation may point towards central affective pathomechanisms in catatonia. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Psychomotor slowing in schizophrenia is associated with cortical thinning of primary motor cortex: A three cohort structural magnetic resonance imaging study.
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Fritze, Stefan, Brandt, Geva A., Benedyk, Anastasia, Moldavski, Alexander, Geiger-Primo, Lena S., Andoh, Jamila, Volkmer, Sebastian, Braun, Urs, Kubera, Katharina M., Wolf, Robert C., von der Goltz, Christoph, Schwarz, Emanuel, Meyer-Lindenberg, Andreas, Tost, Heike, and Hirjak, Dusan
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CEREBRAL cortical thinning , *MAGNETIC resonance imaging , *FRONTAL lobe , *DIAGNOSTIC imaging , *MOTOR cortex , *SCHIZOPHRENIA - Abstract
• PANSS G#7 and TMT-B have a surrogate value for psychomotor slowing in SZ. • Primary motor cortex thinning contribute to psychomotor slowing in SZ. • Cortical rather than subcortical regions contribute to psychomotor slowing in SZ. Psychomotor slowing (PS) is characterized by slowed movements and lower activity levels. PS is frequently observed in schizophrenia (SZ) and distressing because it impairs performance of everyday tasks and social activities. Studying brain topography contributing to PS in SZ can help to understand the underlying neurobiological mechanisms as well as help to develop more effective treatments that specifically target affected brain areas. Here, we conducted structural magnetic resonance imaging (sMRI) of three independent cohorts of right-handed SZ patients (SZ#1: n = 72, SZ#2: n = 37, SZ#3: n = 25) and age, gender and education matched healthy controls (HC) (HC#1: n = 40, HC#2: n = 37, HC#3: n = 38). PS severity in the three SZ cohorts was determined using the Positive and Negative Syndrome Scale (PANSS) item #G7 (motor retardation) and Trail-Making-Test B (TMT-B). FreeSurfer v7.2 was used for automated parcellation and segmentation of cortical and subcortical regions. SZ#1 patients showed reduced cortical thickness in right precentral gyrus (M1; p = 0.04; Benjamini-Hochberg [BH] corr.). In SZ#1, cortical thinning in right M1 was associated with PANSS item #G7 (p = 0.04; BH corr.) and TMT-B performance (p = 0.002; BH corr.). In SZ#1, we found a significant correlation between PANSS item #G7 and TMT-B (p = 0.005, ρ =0.326). In conclusion, PANSS G#7 and TMT-B might have a surrogate value for predicting PS in SZ. Cortical thinning of M1 rather than alterations of subcortical structures may point towards cortical pathomechanism underlying PS in SZ. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Effective connectivity during face processing in major depression – distinguishing markers of pathology, risk, and resilience.
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Sacu, Seda, Wackerhagen, Carolin, Erk, Susanne, Romanczuk-Seiferth, Nina, Schwarz, Kristina, Schweiger, Janina I., Tost, Heike, Meyer-Lindenberg, Andreas, Heinz, Andreas, Razi, Adeel, and Walter, Henrik
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MENTAL depression risk factors , *BIOMARKERS , *PREFRONTAL cortex , *TEMPORAL lobe , *FUNCTIONAL connectivity , *FACE perception , *MAGNETIC resonance imaging , *RISK assessment , *COMPARATIVE studies , *MENTAL depression , *RESEARCH funding , *EMOTIONS , *AMYGDALOID body , *PSYCHOLOGICAL resilience , *CAUSAL models - Abstract
Background: Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression. Methods: Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity. Results: MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls. Conclusions: Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Brain structural correlates of upward social mobility in ethnic minority individuals.
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Schweiger, Janina I., Capraz, Necip, Akdeniz, Ceren, Braun, Urs, Ebalu, Tracie, Moessnang, Carolin, Berhe, Oksana, Zang, Zhenxiang, Schwarz, Emanuel, Bilek, Edda, Meyer-Lindenberg, Andreas, and Tost, Heike
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SOCIAL mobility , *MINORITIES , *SOCIAL marginality , *SOCIAL status , *MAGNETIC resonance imaging , *MINORITY stress , *GRAY matter (Nerve tissue) , *JOB stress - Abstract
Purpose: Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system. Methods: To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging. Results: Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group. Conclusion: Our findings extend prior work by pointing to a biological signature of the "allostatic costs" of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Structural alterations in brainstem, basal ganglia and thalamus associated with parkinsonism in schizophrenia spectrum disorders.
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Fritze, Stefan, Harneit, Anais, Waddington, John L., Kubera, Katharina M., Schmitgen, Mike M., Otte, Marie-Luise, Geiger, Lena S., Tost, Heike, Meyer-Lindenberg, Andreas, Wolf, Robert C., and Hirjak, Dusan
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SCHIZOPHRENIA , *MAGNETIC resonance imaging , *BASAL ganglia , *BRAIN stem , *THALAMUS - Abstract
The relative roles of brainstem, thalamus and striatum in parkinsonism in schizophrenia spectrum disorder (SSD) patients are largely unknown. To determine whether topographical alterations of the brainstem, thalamus and striatum contribute to parkinsonism in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-P, n = 35) and without (SSD-nonP, n = 64) parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥ 4 and < 4, respectively, in comparison with healthy controls (n = 20). FreeSurfer v6.0 was used for segmentation of four brainstem regions (medulla oblongata, pons, superior cerebellar peduncle and midbrain), caudate nucleus, putamen and thalamus. Patients with parkinsonism had significantly smaller medulla oblongata (p = 0.01, false discovery rate (FDR)-corrected) and putamen (p = 0.02, FDR-corrected) volumes when compared to patients without parkinsonism. Across the entire patient sample (n = 99), significant negative correlations were identified between (a) medulla oblongata volumes and both SAS total (p = 0.034) and glabella-salivation (p = 0.007) scores, and (b) thalamic volumes and both SAS total (p = 0.033) and glabella-salivation (p = 0.007) scores. These results indicate that brainstem and thalamic structures as well as basal ganglia-based motor circuits play a crucial role in the pathogenesis of parkinsonism in SSD. [ABSTRACT FROM AUTHOR]
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- 2021
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12. Implications of fMRI and genetics for the law and the routine practice of forensic psychiatry.
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Dressing, Harald, Sartorius, Alexander, and Meyer-Lindenberg, Andreas
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FORENSIC psychiatry , *PRACTICE of law , *DELINQUENT behavior , *CRIMINALS , *MAGNETIC resonance imaging - Abstract
This review outlines recent neurobiological findings in humans relevant for the practice of law and forensic psychiatry. We focus on offenders with antisocial personality disorder and on sex offenders. In addition, the impact of risk polymorphisms in monoamine oxidase A (MAO-A), previously related to violence in interaction with the environment, on brain structure and function and on personality traits in healthy persons are presented. While increasing knowledge of functional and structural alterations provides a better understanding of the neurobiological underpinnings of delinquent behaviour, antisocial and violent behaviour arises from a complex pattern of biological, psychological, social and situational factors, precluding a stance of simple biological reductionism. Rather, optimal integration of neurobiological findings requires cooperation among many disciplines such as medicine, criminology, sociology, psychology, politics and neuroscience. [ABSTRACT FROM AUTHOR]
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- 2008
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13. Amygdala functional connectivity in major depression – disentangling markers of pathology, risk and resilience.
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Wackerhagen, Carolin, Veer, Ilya M., Erk, Susanne, Mohnke, Sebastian, Lett, Tristram A., Wüstenberg, Torsten, Romanczuk-Seiferth, Nina Y., Schwarz, Kristina, Schweiger, Janina I., Tost, Heike, Meyer-Lindenberg, Andreas, Heinz, Andreas, and Walter, Henrik
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AMYGDALOID body physiology , *MENTAL depression genetics , *MENTAL depression risk factors , *AMYGDALOID body , *BIOMARKERS , *COMPARATIVE studies , *STATISTICAL correlation , *MENTAL depression , *FACE , *FRONTAL lobe , *MAGNETIC resonance imaging , *MATHEMATICAL models , *PSYCHOLOGY , *PSYCHOLOGICAL resilience , *RISK assessment , *PHENOTYPES , *TASK performance , *FAMILY history (Medicine) , *FUNCTIONAL connectivity - Abstract
Background: Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience. Methods: We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA. Results: Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching. Conclusion: Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Association between pubertal stage at first drink and neural reward processing in early adulthood.
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Boecker‐Schlier, Regina, Holz, Nathalie E., Hohm, Erika, Zohsel, Katrin, Blomeyer, Dorothea, Buchmann, Arlette F., Baumeister, Sarah, Wolf, Isabella, Esser, Günter, Schmidt, Martin H., Meyer‐Lindenberg, Andreas, Banaschewski, Tobias, Brandeis, Daniel, and Laucht, Manfred
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PUBERTY , *ALCOHOL , *ADULT attitudes , *REWARD (Psychology) , *PATHOLOGICAL psychology , *AGE distribution , *ELECTROENCEPHALOGRAPHY , *FRONTAL lobe , *LONGITUDINAL method , *MAGNETIC resonance imaging , *NEUROLOGIC examination , *DELAY discounting (Psychology) - Abstract
Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Cortical surface-based threshold-free cluster enhancement and cortexwise mediation.
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Lett, Tristram A., Waller, Lea, Tost, Heike, Veer, Ilya M., Nazeri, Arash, Erk, Susanne, Brandl, Eva J., Charlet, Katrin, Beck, Anne, Vollstädt‐Klein, Sabine, Jorde, Anne, Kiefer, Falk, Heinz, Andreas, Meyer‐Lindenberg, Andreas, Chakravarty, M. Mallar, and Walter, Henrik
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Threshold-free cluster enhancement (TFCE) is a sensitive means to incorporate spatial neighborhood information in neuroimaging studies without using arbitrary thresholds. The majority of methods have applied TFCE to voxelwise data. The need to understand the relationship among multiple variables and imaging modalities has become critical. We propose a new method of applying TFCE to vertexwise statistical images as well as cortexwise (either voxel- or vertexwise) mediation analysis. Here we present TFCE_mediation, a toolbox that can be used for cortexwise multiple regression analysis with TFCE, and additionally cortexwise mediation using TFCE. The toolbox is open source and publicly available (). We validated TFCE_mediation in healthy controls from two independent multimodal neuroimaging samples ( N = 199 and N = 183). We found a consistent structure-function relationship between surface area and the first independent component (IC1) of the N-back task, that white matter fractional anisotropy is strongly associated with IC1 N-back, and that our voxel-based results are essentially identical to FSL randomise using TFCE (all PFWE<0.05). Using cortexwise mediation, we showed that the relationship between white matter FA and IC1 N-back is mediated by surface area in the right superior frontal cortex ( PFWE < 0.05). We also demonstrated that the same mediation model is present using vertexwise mediation ( PFWE < 0.05). In conclusion, cortexwise analysis with TFCE provides an effective analysis of multimodal neuroimaging data. Furthermore, cortexwise mediation analysis may identify or explain a mechanism that underlies an observed relationship among a predictor, intermediary, and dependent variables in which one of these variables is assessed at a whole-brain scale. Hum Brain Mapp 38:2795-2807, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2017
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16. Dynamic brain network reconfiguration as a potential schizophrenia genetic risk mechanism modulated by NMDA receptor function.
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Braun, Urs, Schäfer, Axel, Bassett, Danielle S., Rausch, Franziska, Schweiger, Janina I., Bilek, Edda, Erk, Susanne, Romanczuk-Seiferth, Nina, Grimm, Oliver, Geiger, Lena S., Haddad, Leila, Otto, Kristina, Mohnke, Sebastian, Heinz, Andreas, Zink, Mathias, Walter, Henrik, Schwarz, Emanuel, Meyer-Lindenberg, Andreas, and Tost, Heike
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SCHIZOPHRENIA , *METHYL aspartate receptors , *NEUROSCIENCES , *MAGNETIC resonance imaging , *PHARMACOLOGY - Abstract
Schizophrenia is increasingly recognized as a disorder of distributed neural dynamics, but the molecular and genetic contributions are poorly understood. Recent work highlights a role for altered N-methyl-D-aspartate (NMDA) receptor signaling and related impairments in the excitation-inhibitory balance and synchrony of large-scale neural networks. Here, we combined a pharmacological intervention with novel techniques from dynamic network neuroscience applied to functional magnetic resonance imaging (fMRI) to identify alterations in the dynamic reconfiguration of brain networks related to schizophrenia genetic risk and NMDA receptor hypofunction.We quantified "network flexibility," a measure of the dynamic reconfiguration of the community structure of time-variant brain networks during working memory performance. Comparing 28 patients with schizophrenia, 37 unaffected first-degree relatives, and 139 healthy controls, we detected significant differences in network flexibility [F(2,196) = 6.541, P = 0.002] in a pattern consistent with the assumed genetic risk load of the groups (highest for patients, intermediate for relatives, and lowest for controls). In an observer-blinded, placebo-controlled, randomized, cross-over pharmacological challenge study in 37 healthy controls, we further detected a significant increase in network flexibility as a result of NMDA receptor antagonism with 120 mg dextromethorphan [F(1,34) = 5.291, P = 0.028]. Our results identify a potential dynamic network intermediate phenotype related to the genetic liability for schizophrenia that manifests as altered reconfiguration of brain networks during working memory. The phenotype appears to be influenced by NMDA receptor antagonism, consistent with a critical role for glutamate in the temporal coordination of neural networks and the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2016
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17. Neural Correlates of the Cortisol Awakening Response in Humans.
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Boehringer, Andreas, Tost, Heike, Haddad, Leila, Lederbogen, Florian, Wüst, Stefan, Schwarz, Emanuel, and Meyer-Lindenberg, Andreas
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HYDROCORTISONE , *ENVIRONMENTAL risk , *MAGNETIC resonance imaging , *PATHOLOGICAL psychology , *NEUROLOGY - Abstract
The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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18. Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state.
- Author
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Rausch, Franziska, Mier, Daniela, Eifler, Sarah, Fenske, Sabrina, Schirmbeck, Frederike, Englisch, Susanne, Schilling, Claudia, Meyer-Lindenberg, Andreas, Kirsch, Peter, and Zink, Mathias
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BRAIN physiology , *MENTAL illness risk factors , *ACADEMIC medical centers , *COGNITION disorders , *STATISTICAL correlation , *DECISION making , *FISHER exact test , *MAGNETIC resonance imaging , *PSYCHOLOGICAL tests , *QUESTIONNAIRES , *RESEARCH funding , *SCHIZOPHRENIA , *STATISTICS , *T-test (Statistics) , *STATISTICAL power analysis , *DATA analysis , *CASE-control method , *DATA analysis software , *DESCRIPTIVE statistics - Abstract
Background: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning -- the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS). Methods: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making. Results: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage. Limitations: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not pre-psychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam. Conclusion: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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19. Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia.
- Author
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Schirmbeck, Frederike, Mier, Daniela, Esslinger, Christine, Rausch, Franziska, Englisch, Susanne, Eifler, Sarah, Meyer-Lindenberg, Andreas, Kirsch, Peter, and Zink, Mathias
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BRAIN physiology , *CEREBRAL cortex , *OBSESSIVE-compulsive disorder , *ANALYSIS of covariance , *ANTIPSYCHOTIC agents , *CHI-squared test , *GOODNESS-of-fit tests , *MAGNETIC resonance imaging , *PSYCHOLOGICAL tests , *RESEARCH funding , *T-test (Statistics) , *WECHSLER Adult Intelligence Scale , *EFFECT sizes (Statistics) , *DESCRIPTIVE statistics , *MANN Whitney U Test , *MENTAL illness risk factors ,DRUG therapy for schizophrenia - Abstract
Background: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive-compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations: The main limitation of this study is its cross-sectional design. Conclusion: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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20. A cross-over study of effects on the hypothalamus-pituitary-adrenal (HPA) axis and the sympathoadrenergic system in magnetic field strength exposure from 0 to 7 T.
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Gilles, Maria, Paslakis, Georgios, Heinrich, Angela, Szostek, Anne, Meyer, Patric, Nees, Frauke, Rauschenberg, Jaane, Gröbner, Jens, Krumm, Bertram, Semmler, Wolfhard, Flor, Herta, Meyer-Lindenberg, Andreas, and Deuschle, Michael
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HYPOTHALAMIC-pituitary-adrenal axis , *MAGNETIC resonance imaging , *ADRENERGIC mechanisms , *HYDROCORTISONE , *MAGNETIC fields - Abstract
The concept of stress is relevant to magnetic resonance imaging (MRI) examination in various ways. First, levels of stress to staff and patients have not been quantified in ultra-high magnetic fields. Second, research is increasingly interested in experimentally defining regional brain activity during stress. It is therefore important to know whether exposure to the ultra-high static magnetic fields per se might also lead to neurohormonal responses in the hypothalamus-pituitary-adrenal axis and the sympathoadrenal systems. In the present blinded case cross-over study with 41 healthy participants, we measured cortisol not only before and after but also during static magnetic field exposure in MRI scanners. Measures of catecholamines before and after exposure were also part of the study protocol. Using three different field strengths (1.5, 3 and 7 T) and a mock scanner (0 T), we examined whether not only the MRI procedure but also the static magnetic field per se has an influence on the neuroendocrine responses. We found no significant differences in the course of cortisol or catecholamine concentrations between the different static magnetic fields. Our study suggests that the results of MRI studies using stress-paradigms are not influenced by the static magnetic field itself. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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21. Hierarchical Organization of Human Cortical Networks in Health and Schizophrenia.
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Bassett, Danielle S., Bullmore, Edward, Verchinski, Beth A., Mattay, Venkata S., Weinberger, Daniel R., and Meyer-Lindenberg, Andreas
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SCHIZOPHRENIA , *DEPERSONALIZATION , *PSYCHOSES , *MAGNETIC resonance imaging , *MEDICAL imaging systems , *DIAGNOSTIC imaging - Abstract
The complex organization of connectivity in the human brain is incompletely understood. Recently, topological measures based on graph theory have provided a new approach to quantify large-scale cortical networks. These methods have been applied to anatomical connectivity data on nonhuman species, and cortical networks have been shown to have small-world topology, associated with high local and global efficiency of information transfer. Anatomical networks derived from cortical thickness measurements have shown the same organizational properties of the healthy human brain, consistent with similar results reported in functional networks derived from resting state functional magnetic resonance imaging (MRI) and magnetoencephalographic data. Here we show, using anatomical networks derived from analysis of inter-regional covariation of gray matter volume in MRI data on 259 healthy volunteers, that classical divisions of cortex (multimodal, unimodal, and transmodal) have some distinct topological attributes. Although all cortical divisions shared nonrandom properties of small-worldness and efficient wiring (short mean Euclidean distance between connected regions), the multimodal network had a hierarchical organization, dominated by frontal hubs with low clustering, whereas the transmodal network was assortative. Moreover, in a sample of 203 people with schizophrenia, multimodal network organization was abnormal, as indicated by reduced hierarchy, the loss of frontal and the emergence of nonfrontal hubs, and increased connection distance. We propose that the topological differences between divisions of normal cortex may represent the outcome of different growth processes for multimodal and transmodal networks and that neurodevelopmental abnormalities in schizophrenia specifically impact multimodal cortical organization. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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22. Abnormal amygdala activation profile in pedophilia.
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Sartorius, Alexander, Ruf, Matthias, Kief, Christine, Demirakca, Traute, Bailer, Josef, Ende, Gabriele, Henn, Fritz A., Meyer-Lindenberg, Andreas, and Dressing, Harald
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AMYGDALOID body , *NEUROSCIENCES , *PEDOPHILIA , *MAGNETIC resonance imaging , *MENTAL health - Abstract
Despite considerable public interest research in neurobiological correlates of pedophilia is scarce. Since amygdala activation is central for emotional valuation, arousal, and salience, we investigated the activation profile of this structure in 10 male subjects with pedophilia (exclusively attracted to boys), all convicted sex-offenders and sentenced to forensic psychiatric treatment along with ten male heterosexual matched controls. We used a sexually non-explicit functional Magnetic Resonance Imaging (fMRI) paradigm with images of men, women, boys or girls randomly embedded in neutral target/non-target geometrical symbols. We applied statistical parametric mapping (SPM2) and SPSS 14 for image processing and analysis. While controls activated significantly less to pictures of children compared to adults, the activation profile was reversed in subjects with pedophilia, who exhibited significantly more activation to children than adults. The highest activation was observed for boys in the patient group, and for women in control participants. Our data show enhanced activation to children’s pictures even in an incidental context and suggest the provocative hypothesis that a normally present mechanism for reduced emotional arousal for children relative to adults is reversed in pedophilia, suggesting a neural substrate associated with deviant sexual preference in this condition. More extensive research in this field would be of benefit for both the victims and the offenders. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
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23. Know Your Place: Neural Processing of Social Hierarchy in Humans
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Zink, Caroline F., Tong, Yunxia, Chen, Qiang, Bassett, Danielle S., Stein, Jason L., and Meyer-Lindenberg, Andreas
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MAGNETIC resonance imaging , *CEREBRAL cortex , *BEHAVIOR analysts , *HEALTH - Abstract
Summary: Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health. [Copyright &y& Elsevier]
- Published
- 2008
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24. Dysfunctional Prefrontal Regional Specialization and Compensation in Schizophrenia.
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Hao-Yang Tan, Sust, Steven, Buckholtz, Joshua W., Mattay, Venkata S., Meyer-Lindenberg, Andreas, Egan, Michael F., Weinberger, Daniel R., and Callicott, Joseph H.
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SCHIZOPHRENIA , *PSYCHOSES , *PEOPLE with schizophrenia , *SHORT-term memory , *MAGNETIC resonance imaging , *PSYCHIATRY - Abstract
Objective: It has been suggested that in healthy persons higher-order cognitive processing engaged by incremental working memory load hierarchically employs more dorsal than ventral prefrontal resources in healthy individuals. Given that working memory performance is impaired in schizophrenia, especially at higher executive loads, the authors investigated how this prefrontal functional organization might be altered in disease, independent of performance deficits, Method: Using N-back working memory functional magnetic resonance imaging (fMRI) data, the authors studied 15 patients with schizophrenia and 26 healthy comparison subjects. Subgroups based on median performance accuracy at 2-back were analyzed; high performers included eight schizophrenia patients and 14 comparison subjects, and low performers included seven patients and 12 comparison subjects. Results: High-performing but not low-performing comparison subjects responded to incremental working memory executive load with disproportionately greater dorsal but not ventral prefrontal cortex activation, which also predicted performance accuracy. In the high- and low-performing patient groups, incremental working memory load caused a disproportionate increase in ventral but not dorsal prefrontal cortex activation relative to the respective comparison group, which also correlated with accuracy. Functional connectivity between the ventral prefrontal cortex and posterior parietal cortex was relatively greater in patients, whereas comparison subjects had greater functional connectivity between the dorsal prefrontal cortex and posterior parietal cortex. Conclusions: The hierarchical organization of the prefrontal cortex may be compromised in schizophrenia, resulting in loss of functional specialization and integration at the dorsal prefrontal cortex and in compensatory activation from the ventral prefrontal cortex, which may ultimately affect working memory and executive cognition. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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25. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia.
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Callicott, Joseph H., Straub, Richard E., Pezawas, Lukas, Egan, Michael F., Mattay, Venkata S., Hariri, Ahmad R., Verchinski, Beth A., Meyer-Lindenberg, Andreas, Balkissoon, Rishi, Kolachana, Bhaskar, Goldberg, Terry E., and Weinbergert, Daniel R.
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SCHIZOPHRENIA , *GENE expression , *HIPPOCAMPUS (Brain) , *MAGNETIC resonance imaging , *GENETIC polymorphisms , *DIAGNOSTIC imaging - Abstract
Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with schizophrenia in a family-based sample (P = 0.002). A common nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated with schizophrenia (P = 0004). Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes. In addition to overtransmission in schizophrenia, the Ser allele was associated with altered hippocampal structure and function in healthy subjects, including reduced hippocampal gray matter volume and altered engagement of the hippocampus during several cognitive tasks assayed with functional magnetic resonance imaging. These convergent data suggest that allelic variation within DISC1, either at Ser704Cys or haplotypes monitored by it, increases the risk for schizophrenia and that the mechanism of this effect involves structural and functional alterations in the hippocampal formation. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
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26. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume?
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Lemaitre, Herve, Goldman, Aaron L., Sambataro, Fabio, Verchinski, Beth A., Meyer-Lindenberg, Andreas, Weinberger, Daniel R., and Mattay, Venkata S.
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MORPHOMETRICS , *PREFRONTAL cortex , *BRAIN imaging , *THICKNESS measurement , *MOLECULAR structure , *AGE factors in disease , *REGRESSION analysis - Abstract
Abstract: Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. [Copyright &y& Elsevier]
- Published
- 2012
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27. Increased Medial Orbitofrontal and Amygdala Activation: Evidence for a Systems-Level Endophenotype of Bipolar I Disorder.
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Linke, Julia, King, Andrea Victoria, Rietschel, Marcella, Strohmaier, Jana, Hennerici, Michael, Gass, Achim, Meyer-Lindenberg, Andreas, and Wessa, Michèle
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AMYGDALOID body , *BIPOLAR disorder , *MAGNETIC resonance imaging , *DRUG utilization , *MOTIVATION (Psychology) - Abstract
Objective: Bipolar I disorder is highly heritable, but endophenotypes of the disorder mediating genetic risk are only beginning to be defined. The authors investigate state- and trait-related neural mechanisms related to motivation in euthymic bipolar patients and unaffected first-degree relatives of bipolar patients to define the status of motivational processing as a neural systems-level endophenotype. Method: Our study comprised two samples; the first consisted of 19 euthymic bipolar patients and 19 matched comparison subjects, and the second included 22 relatives and 22 matched comparison subjects. Motivational processing was assessed with a probabilistic reversal learning task during event-related functional MRI. Data were analyzed using a region-of-interest approach restricting analysis to the medial and lateral orbitofrontal cortex, the amygdala, the anterior cingulate cortex, and the striatum. Results: The authors observed increased activation in response to reward and reward reversal contingencies in the left medial orbitofrontal cortex in patients with bipolar disorder and in the right medial orbitofrontal cortex in their relatives. Activation of the amygdala in response to reward reversal was increased in patients and relatives. In response to reward, activation of the amygdala was greater only in relatives, but there was a significant negative correlation between medication and amygdala activation in patients. Conclusions: These results identify increased activity of the orbitofrontal cortex and the amygdala, related to heightened sensitivity to reward and deficient prediction error signal, as a candidate endophenotype of bipolar disorder. The results support a role of motivational processing in the risk architecture of bipolar disorder and identify a new systems-level therapeutic target for the illness. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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