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Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., Design, Setting, and Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., Main Outcomes and Measures: Interregional profiles of group difference in cortical thickness between cases and controls., Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., Conclusions and Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Anxiety disorders are associated with enhanced error-related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN-anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10-19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression., (© 2018 Wiley Periodicals, Inc.)

Objective: Abnormal engagement of the posterior medial frontal cortex (pMFC) occurs during performance monitoring in obsessive-compulsive disorder (OCD), including in pediatric patients. Yet, the development of pMFC function in OCD-affected youth remains poorly understood., Method: A total of 69 patients with pediatric OCD and 72 healthy controls (HC), 8 to 19 years of age, were scanned during the Multisource Interference Task (MSIT). The effects of group, age, performance, and interactions on pMFC response to errors and interference were tested in the region of interest [ROI]) and whole-brain analyses. Secondary analyses considered bilateral anterior insula/frontal operculum (aI/fO), given the contribution of these regions with pMFC to a cingulo-opercular network (CON) for task control (e.g., error and interference processing)., Results: Error-related pMFC activity was greater for OCD patients than for HC, increased with age in OCD patients, but decreased with age in HC. Greater pMFC activation associated with better performance in HC but not OCD patients. In the patients, greater pMFC activation to errors was associated with lower OCD severity. Altered error-related activation and performance associations were also observed in the right aI/fO in OCD patients, whereas the left aI/fO response to interference was associated with lower OCD severity., Conclusion: Atypical increase in error-related pMFC activation with age in pediatric OCD suggests altered development of pMFC function during the early course of illness. Greater pMFC activation with better performance in HC, and with age and lower symptom severity in OCD patients, suggests an adaptive function of heightened pMFC response to errors that could be further enhanced (e.g., via cognitive training) to improve outcomes in OCD from the early course of illness., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken., Method: T 1 -weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume., Results: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33., Conclusions: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

Anxiety disorders are among the earliest emerging disorders and most common mental health problem across the lifespan. A common characteristic of individuals with anxiety is poor attentional and cognitive control. Therefore, researchers are interested in how cognitive functioning relates to anxiety in young children. In particular, research has demonstrated associations between anxiety and electrophysiological markers of cognitive control skills such as the error-related negativity (ERN). The nature of the anxiety-ERN relationship is not well understood, however. The purpose of the present study was to examine: 1) the association between the ERN and diagnostically-defined symptoms of different anxiety disorders; and 2) the extent to which disorder-specific symptoms of anxiety moderated the association between ERN and behavioral performance on a Go/No-Go task in a sample of 139 children 5-8 years of age (70 females and 69 males). Results suggest that more separation anxiety disorder (SAD) symptoms are associated with a smaller ΔERN, even after controlling for other anxiety disorder symptoms. Children with more SAD symptoms showed higher error rates and failed to exhibit the expected association between ΔERN and behavioral performance, suggesting ineffective error-monitoring in young children with SAD problems.

Socio-emotional processing is an essential part of development, and age-related changes in its neural correlates can be observed. The late positive potential (LPP) is a measure of motivated attention that can be used to assess emotional processing; however, changes in the LPP elicited by emotional faces have not been assessed across a wide age range in childhood and young adulthood. We used an emotional face matching task to examine behavior and event-related potentials (ERPs) in 33 youth aged 7-19 years old. Younger children were slower when performing the matching task. The LPP elicited by emotional faces but not control stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the P1) decreased with age for both faces and shapes, suggesting increased efficiency of early visual processing. Results indicate age-related attenuation in emotional processing that may stem from greater efficiency and regulatory control when performing a socio-emotional task., (© 2015 Wiley Periodicals, Inc.)

Background: Patients with obsessive-compulsive disorder (OCD) show abnormal functioning in ventral frontal brain regions involved in emotional/motivational processes, including anterior insula/frontal operculum (aI/fO) and ventromedial frontal cortex (VMPFC). While OCD has been associated with an increased neural response to errors, the influence of motivational factors on this effect remains poorly understood., Methods: To investigate the contribution of motivational factors to error processing in OCD and to examine functional connectivity between regions involved in the error response, functional magnetic resonance imaging data were measured in 39 OCD patients (20 unmedicated, 19 medicated) and 38 control subjects (20 unmedicated, 18 medicated) during an error-eliciting interference task where motivational context was varied using monetary incentives (null, loss, and gain)., Results: Across all errors, OCD patients showed reduced deactivation of VMPFC and greater activation in left aI/FO compared with control subjects. For errors specifically resulting in a loss, patients further hyperactivated VMPFC, as well as right aI/FO. Independent of activity associated with task events, OCD patients showed greater functional connectivity between VMPFC and regions of bilateral aI/FO and right thalamus., Conclusions: Obsessive-compulsive disorder patients show greater activation in neural regions associated with emotion and valuation when making errors, which could be related to altered intrinsic functional connectivity between brain networks. These results highlight the importance of emotional/motivational responses to mistakes in OCD and point to the need for further study of network interactions in the disorder., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)