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Aberrant rich club organization in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

ABSTRACT: Recent studies suggested that the rich club organization promoting global brain communication and integration of information, may be abnormally increased in obsessive-compulsive disorder (OCD). However, the structural and functional basis of this organization is still not very clear. Given the heritability of OCD, as suggested by previous family-based studies, we hypothesize that aberrant rich club organization may be a trait marker for OCD. In the present study, 32 patients with OCD, 30 unaffected first-degree relatives (FDR) and 32 healthy controls (HC) underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). We examined the structural rich club organization and its interrelationship with functional coupling. Our results showed that rich club and peripheral connection strength in patients with OCD was lower than in HC, while it was intermediate in FDR. Finally, the coupling between structural and functional connections of the rich club, was decreased in FDR but not in OCD relative to HC, which suggests a buffering mechanism of brain functions in FDR. Overall, our findings suggest that alteration of the rich club organization may reflect a vulnerability biomarker for OCD, possibly buffered by structural and functional coupling of the rich club.

SUBMITTER: Peng Z

PROVIDER: S-EPMC8430383 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleObsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation.ObjectiveThe study aimed to investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD, and healthy controls.MethodsA randomized double-blind cross-over study assessed the effects of single-dose escitalopram (20 mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD, and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 h after oral administration of the pharmacological challenge/placebo and compared across and within groups using a mixed model analysis of variance.ResultsOn the outcome measure of interest, i.e., the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59) = 3.1; p = 0.052), with patients (least square (LS) mean 1.43; standard error [SE] 0.06; 95% confidence interval (CI), 1.31-1.55) and their relatives (LS mean 1.46; SE 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean 1.26; SE 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group × treatment interaction (F(2, 58) = 2.8, p = 0.069), with post hoc tests showing (i) patients (p = 0.009; LS mean difference 0.23; SE 0.08) and relatives (p = 0.03; LS mean difference 0.22; SE 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p = 0.013; LS mean difference 0.1; SE 0.04), but not other groups (both p > 0.1; controls: LS mean difference - 0.03; SE 0.04; relatives: LS mean difference 0.02; SE 0.05).ConclusionOur findings are consistent with a view that there is impaired executive planning in OCD and that this constitutes a behavioural endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.

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Aberrant rich club organization in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.

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