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Set-shifting-related basal ganglia deformation as a novel familial marker of obsessive-compulsive disorder.

ABSTRACT: The symptoms of obsessive-compulsive disorder (OCD) are suggestive of cognitive rigidity, and previous work identified impaired flexible responding on set-shifting tasks in such patients. The basal ganglia are central to habit learning and are thought to be abnormal in OCD, contributing to inflexible, rigid habitual patterns of behaviour. Here, we demonstrate that increased cognitive inflexibility, indexed by poor performance on the set-shifting task, correlated with putamen morphology, and that patients and their asymptomatic relatives had common curvature abnormalities within this same structure. The association between the structure of the putamen and the extradimensional errors was found to be significantly familial in OCD proband-relative pairs. The data implicate changes in basal ganglia structure linked to cognitive inflexibility as a familial marker of OCD. This may reflect a predisposing heightened propensity toward habitual response patterns and deficits in goal-directed planning.

SUBMITTER: Isobe M

PROVIDER: S-EPMC7613037 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Changes in Volume of Subregions Within Basal Ganglia in Obsessive-Compulsive Disorder: A Study With Atlas-Based and VBM Methods.

Project description:BackgroundThe role of basal ganglia in the pathogenesis of obsessive-compulsive disorder (OCD) remains unclear. The studies on volume changes of basal ganglia in OCD commonly use the VBM method; however, the Atlas-based method used in such research has not been reported. Atlas-based method has a lower false positive rate compared with VBM method, thus having advantages partly.ObjectivesThe current study aimed to detect the volume changes of subregions within basal ganglia in OCD using Atlas-based method to further delineate the precise neural circuitry of OCD. What is more, we explored the influence of software used in Atlas-based method on the volumetric analysis of basal ganglia and compared the results of Atlas-based method and regularly used VBM method.MethodsWe analyzed the brain structure images of 37 patients with OCD and 41 healthy controls (HCs) using the VBM method, Atlas-based method based on SPM software, or Freesurfer software to find the areas with significant volumetric variation between the two groups, and calculated the effects size of these areas.ResultsVBM analysis revealed a significantly increased volume of bilateral lenticular nucleus in patients compared to HCs. In contrast, Atlas-based method based on Freesurfer revealed significantly increased volume of left globus pallidus in patients, and the largest effect size of volumetric variation was revealed by Freesurfer analysis.ConclusionsThis study showed that the volume of bilateral lenticular nucleus significantly increased in patients compared to HCs, especially left globus pallidus, which was in accordance with the previous findings. In addition, Freesurfer is better than SPM and a good choice for Atlas-based volumetric analysis of basal ganglia.

| S-EPMC9251343 | biostudies-literature

Obsessive-compulsive disorder.

Project description:Obsessive-compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the 'obsessive-compulsive and related disorders', a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive-behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.

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Project description:Background: Obsessive-compulsive disorder (OCD) is a heterogeneous illness, and emerging evidence suggests that different symptom dimensions may have distinct underlying neurobiological mechanisms. We aimed to look for familial patterns in the occurrence of these symptom dimensions in a sample of families with at least two individuals affected with OCD. Methods: Data from 153 families (total number of individuals diagnosed with DSM-5 OCD = 330) recruited as part of the Accelerator Program for Discovery in Brain Disorders using Stem Cells (ADBS) was used for the current analysis. Multidimensional Item Response Theory (IRT) was used to extract dimensional scores from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) checklist data. Using linear mixed-effects regression models, intra-class correlation coefficients (ICC), for each symptom dimension, and within each relationship type were estimated. Results: IRT yielded a four-factor solution with Factor 1 (Sexual/Religious/Aggressive), Factor 2 (Doubts/Checking), Factor 3 (Symmetry/Arranging), and Factor 4 (Contamination/Washing). All except for Factor 1 were found to have significant ICCs, highest for Factor 3 (0.41) followed by Factor 4 (0.29) and then Factor 2 (0.27). Sex-concordant dyads were found to have higher ICC values than discordant ones, for all the symptom dimensions. No major differences in the ICC values between parent-offspring and sib-pairs were seen. Conclusions: Our findings indicate that there is a high concordance of OCD symptom dimensions within multiplex families. Symptom dimensions of OCD might thus have significant heritability. In view of this, future genetic and neurobiological studies in OCD should include symptom dimensions as a key parameter in their analyses.

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Project description:Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.

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Disrupted cortical network as a vulnerability marker for obsessive-compulsive disorder.

Project description:Morphological alterations of brain structure are generally assumed to be involved in the pathophysiology of obsessive–compulsive disorder (OCD). Yet, little is known about the morphological connectivity properties of structural brain networks in OCD or about the heritability of those morphological connectivity properties. To better understand these properties, we conducted a study that defined three different groups: OCD group with 30 subjects, siblings group with 19 subjects, and matched controls group with 30 subjects. A structural brain network was constructed using 68 cortical regions of each subject within their respective group (i.e., one brain network for each group). Both small-worldness and modularity were measured to reflect the morphological connectivity properties of each constructed structural brain network. When compared to the matched controls, the structural brain networks of patients with OCD indeed exhibited atypical small-worldness and modularity. Specifically, small-worldness showed decreased local efficiency, and modularity showed reduced intra-connectivity in Module III (default mode network) and increased interconnectivity between Module I (executive function) and Module II (cognitive control/spatial). Intriguingly, the structured brain networks of the unaffected siblings showed similar small-worldness and modularity as OCD patients. Based on the atypical structural brain networks observed in OCD patients and their unaffected siblings, abnormal small-worldness and modularity may indicate a candidate endophenotype for OCD.

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Project description:BACKGROUND:There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined. METHOD:We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression. RESULTS:Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation. CONCLUSIONS:OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression.

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Project description:Obsessive-compulsive disorder (OCD) has been seen to run in families and genetics help to understand its heritability. In this review, we summarize older studies which focused on establishing the familial nature of OCD, including its various dimensions of symptoms, and we focus on recent findings from studies using both the candidate gene approach and genome-wide association study (GWAS) approach. The family studies and twin studies establish the heritability of OCD. Candidate gene approaches have implicated genes in the serotonergic, glutamatergic, and dopaminergic pathways. GWAS has not produced significant results possibly due to the small sample size. Newer techniques such as gene expression studies in brain tissue, stem cell technology, and epigenetic studies may shed more light on the complex genetic basis of OCD.

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