Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up.

BACKGROUND: Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy. METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients. RESULTS: Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively. CONCLUSION: These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.

Abnormalities of structural covariance of insular subregions in drug-naïve OCD patients.

The insula plays a significant role in the neural mechanisms of obsessive-compulsive disorder. Previous studies have identified functional and structural abnormalities in insula in obsessive-compulsive disorder patients. The predictive coding model in the context of interoception can explain the psychological and neuropathological manifestations observed in obsessive-compulsive disorder. The model is based on the degree of laminar differentiation of cerebral cortex. The interindividual differences in a local measure of brain structure often covary with interindividual differences in other brain regions. We investigated the anatomical network involving the insula in a drug-naïve obsessive-compulsive disorder sample. We recruited 58 obsessive-compulsive disorder patients and 84 matched health controls. The cortical thickness covariance maps between groups were compared at each vertex. We also evaluated the modulation of Yale-Brown Obsessive-Compulsive Scale scores and obsessive-compulsive disorder duration on thickness covariance. Our findings indicated that the thickness covariance seeded from granular and dysgranular insula are different compared with controls. The duration and severity of obsessive-compulsive disorder can modulate the thickness covariance of granular and dysgranular insula with posterior cingulate cortex and rostral anterior cingulate cortex. Our results revealed aberrant insular structural characteristics and cortical thickness covariance in obsessive-compulsive disorder patients, contributing to a better understanding of the involvement of insula in the pathological mechanisms underlying obsessive-compulsive disorder.

Altered brain functional network topology in Obsessive-Compulsive Disorder: A comparison of patients with varying severity of depressive symptoms and the impact on psychosocial functioning.

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with psychosocial impairment, which can be exacerbated by depressive symptoms. In this study, we employed graph theory analysis to investigate the association among neuroimaging, clinical features, and psychosocial functioning in OCD patients, with a specific focus on the differential impact of depressive symptoms. METHODS: 216 OCD patients were divided into two subgroups based on depressive symptoms. Resting-state functional MRI data were acquired from a subset of 106 OCD patients along with 77 matched healthy controls (HCs). We analyzed the topological characteristics of the entire brain and the cognition-related subnetworks and performed Pearson correlation analyses to further explore the relationship with psychosocial functioning. RESULTS: OCD patients with more severe depressive symptoms exhibited greater impairment across all dimensions of psychosocial functioning. Graph theory analysis revealed more pronounced reductions in network efficiency within the entire brain, the default mode network (DMN), and the cingulo-opercular network (CON) among patients with non or mild depressive symptoms. Lower nodal efficiency and degree centrality of the right superior temporal gyrus (STG) were found in OCD patients and these variables were positively correlated with psychosocial functioning impairment. CONCLUSIONS: This study revealed that the presence of depressive symptoms generally exacerbated psychosocial functioning impairment in OCD patients. Abnormalities in the functional integration of the entire brain, the DMN, and the CON in OCD patients may comprise the basis of cognitive deficits, while dysfunction of the right STG may affect the psychosocial functioning through its role in emotion, intention perception, and insight.

Shared genetics of psychiatric disorders and type 2 diabetes:a large-scale genome-wide cross-trait analysis.

BACKGROUND: Individuals with psychiatric disorders have elevated rates of type 2 diabetes comorbidity. Although little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetics and causal link between different type 2 diabetes and psychiatric disorders. METHODS: We conducted a large-scale genome-wide cross-trait association study(GWAS) to investigate genetic overlap between type 2 diabetes and anorexia nervosa, attention deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. By post-GWAS functional analysis, we identify variants genes expression in various tissues. Enrichment pathways, potential protein interaction and mendelian randomization also provided to research the relationship between type 2 diabetes and psychiatric disorders. RESULTS: We discovered that type 2 diabetes and psychiatric disorders had a significant correlation. We identified 138 related loci, 32 were novel loci. Post-GWAS analysis revealed that 86 differentially expressed genes were located in different brain regions and peripheral blood in type 2 diabetes and related psychiatric disorders. MAPK signaling pathway plays an important role in neural development and insulin signaling. In addition, there is a causal relationship between T2D and mental disorders. In PPI analysis, the central genes of the DEG PPI network were FTO and TCF7L2. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics andpotential causal links between type 2 diabetes and related psychiatric disorders, suggesting potential new biological functions in common among them.

Obsessive-Compulsive Disorder and Metabolic Disorders: Overview and Future Perspective.

ABSTRACT: Obsessive-compulsive disorder (OCD) has a bidirectional relationship with metabolic disorders. The purposes of this review are to decipher the links between OCD and metabolic disorders and to explore the etiological mechanism of OCD in metabolism, which may aid in early identification of and tailored interventions for OCD and metabolic disorders.

Shared genetics between classes of obesity and psychiatric disorders: A large-scale genome-wide cross-trait analysis.

AIMS: Epidemiological studies demonstrate an association between classes of obesity and psychiatric disorders, although little is known about shared genetics and causality of association. Thus, we aimed to investigate shared genetics and causal link between different classes of obesity and psychiatric disorders. METHODS: We used genome-wide association study (GWAS) summary data range from 9725 to 500,199 sample sizes of European descent, conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between the classes of obesity and anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. We conducted transcriptome-wide association study analysis (TWAS) to identified variants regulated gene expression in those related disorders. Finally, pathway enrichment analysis to identified major pathways. RESULTS: In the combined analysis, we replicated 211 previously reported loci and discovered 58 novel independent loci that were associated with all three classes of obesity and related psychiatric disorders. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, circulatory, adipose, digestive, respiratory, and nervous systems, such as DCC, NEGR1, INO80E. Mendelian randomization analyses suggested that there may be a two-way or one-way causal relationship between obesity and psychiatric disorders. CONCLUSION: This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between classes of obesity and psychiatric disorders (attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, major depressive disorder, schizophrenia, and obsessive-compulsive disorder). Such shared genetics suggests potential new biological functions in common among them.

Functional Connectivity within the Frontal-Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. RESULTS: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. CONCLUSIONS: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal-striatal network, which distinguishes OCD from washing OCD.