Faculty Bibliography
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96
Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Importance/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:Interregional profiles of group difference in cortical thickness between cases and controls. Results/UNASSIGNED: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/UNASSIGNED: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.
PMCID:7450410
PMID: 32857118
ISSN: 2168-6238
CID: 4650132
Insula Functional Connectivity During Urge Suppression in Obsessive-Compulsive Disorder [Meeting Abstract]
ISI:000645683800577
ISSN: 0006-3223
CID: 5309812
Neural Mechanisms of Symptom Dimensions During Provocation in Obsessive-Compulsive Disorder [Meeting Abstract]
ISI:000645683800868
ISSN: 0006-3223
CID: 5309822
Interoception and Obsessive-Compulsive Disorder: A Review of Current Evidence and Future Directions
Disrupted interoceptive processes are present in a range of psychiatric conditions, and there is a small but growing body of research on the role of interoception in obsessive-compulsive disorder (OCD). In this review, we outline dimensions of interoception and review current literature on the processing of internal bodily sensations within OCD. Investigations in OCD utilizing objective measures of interoception are limited and results mixed, however, the subjective experience of internal bodily sensations appears to be atypical and relate to specific patterns of symptom dimensions. Further, neuroimaging investigations suggest that interoception is related to core features of OCD, particularly sensory phenomena and disgust. Interoception is discussed in the context of treatment by presenting an overview of existing interventions and suggesting how modifications aimed at better targeting interoceptive processes could serve to optimize outcomes. Interoception represents a promising direction for multi-method research in OCD, which we expect, will prove useful for improving current interventions and identifying new treatment targets.
PMCID:8424053
PMID: 34512412
ISSN: 1664-0640
CID: 4998522
Urges-For-Action in OCD: Blink Suppression Failure Relates to Clinical Heterogeneity [Meeting Abstract]
ISI:000645683800317
ISSN: 0006-3223
CID: 5309802
Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters
No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
PMID: 33033241
ISSN: 2158-3188
CID: 4645762
Dimensions of interoception in obsessive-compulsive disorder
Interoceptive sensibility (IS) refers to the subjective experience of perceiving and being aware of one's internal body sensations, and is typically evaluated using self-report questionnaires or confidence ratings. Here we evaluated IS in 81 patients with OCD and 76 controls using the Multidimensional Scale of Interoceptive Awareness (MAIA), which contains 8 subscales assessing adaptive and maladaptive responses to sensation. Compared to controls, OCD patients showed hyperawareness of body sensations. Patients also demonstrated a more maladaptive profile of IS characterized by greater distraction from and worry about unpleasant sensations, and reduced tendency to experience the body as safe and trustworthy. These findings were independent of medication status and comorbidities in the patient group. Correlational analyses showed that subscales of the MAIA were differentially associated with OCD symptom dimensions. These findings indicate that patients with OCD show abnormality of IS that is independent of confounding factors related to medication and comorbidities and associated with different OCD symptom dimensions. Future work would benefit from examining neural correlates of these effects and evaluating whether dimensions of IS are impacted by treatments for the disorder.
PMCID:7665060
PMID: 33194538
ISSN: 2211-3649
CID: 4671322
Reward function as an outcome predictor in youth with mood and anxiety symptoms
BACKGROUND:Adolescent depression varies considerably in the course. However, there are no biobehavioral predictors of illness trajectories, and follow-up studies in depressed youth are sparse. Here we sought to examine whether reward function would predict future clinical outcomes in adolescents with depressive symptoms. We utilized the reward flanker fMRI task to assess brain function during distinct reward processes of anticipation, attainment and positive prediction error (PPE, i.e. receiving uncertain rewards). METHODS:Subjects were 29 psychotropic-medication-free participants with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two adolescents (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined symptom severity as predictors for follow-up clinical outcomes. Whole-brain analyses examined the relationships between neural reward processes and follow-up outcomes. RESULTS:Clinically, anhedonia, but not irritability, predicted future depression and suicidal ideations. Among reward processes, only neural activation during PPE was correlated with future depression and anhedonia severity. Specifically, activation in the left angular gyrus-a component of default mode network-was associated with future depression, while activation in the dorsal anterior cingulate, operculum and left insula-key regions within the salience and pain networks-was associated with future anhedonia, even when controlling baseline anhedonia. LIMITATIONS/CONCLUSIONS:Small sample size and variability in follow-up intervals limit the generalizability of conclusions. CONCLUSIONS:This research suggests the anhedonia and reward dysfunction may predict a worse course in adolescent depression. The adolescents with anhedonia should be monitored more carefully for a longer period.
PMID: 33010568
ISSN: 1573-2517
CID: 4626442
Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups
OBJECTIVE:Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS:-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS:No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS:The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
PMID: 32539527
ISSN: 1535-7228
CID: 4484542
Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium
BACKGROUND:Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS:We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS:In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS:The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
PMID: 31178097
ISSN: 1873-2402
CID: 3929742
