The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00213-020-05597-7.Rationale: 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. Objective: 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. Methods: A randomized double-blind crossover study assessed the effects of single dose escitalopram (20mg) 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 hours after oral administration of the pharmacological challenge / placebo, and compared across and within groups using a mixed model ANOVA. Results: On 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 x 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). Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD, and that this constitutes a behavioral 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.Peer reviewe

Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

BackgroundThe unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.MethodOCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.ResultsEFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).ConclusionsSymmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders

A Review of the Diagnosis and Management of Hoarding Disorder

Hoarding disorder (HD) is a severe psychiatric and public health problem characterized by extreme challenges with discarding possessions and severe acquisition resulting in excessive clutter that impairs daily functioning and may cause substantial health and safety risks. Over the past 20 years, research on HD has grown substantially and lead to its recent designation in the DSM-5 as a discrete disorder. The key features of the cognitive behavioral etiological model of hoarding include core vulnerabilities, information processing deficits, cognitions and meaning of possessions, and emotionally driven reinforcement patterns. This model has served as the theoretical foundation for efficacious, specialized cognitive behavioral treatment (CBT) for hoarding and validated hoarding assessment measures. The individual manualized CBT treatment has been adapted for delivery through various modalities (e.g., group, web-based, self-help), populations (e.g., geriatric), and providers (e.g., clinicians, peer support, case managers). While CBT is associated with significant reductions in hoarding severity, clinical levels of hoarding symptoms persist for greater than half of treatment completers; thus, more efficacious treatments need to be developed. Further research is necessary to elucidate components of the CBT model and their interaction, in order to inform treatment targets. Although research on pharmacological treatments for HD is in the nascent stages and extant results are somewhat mixed, future studies may assess medication as a standalone treatment or combined with CBT. Family-focused hoarding interventions may also be important given that persons with hoarding behaviors may have limited insight and motivation and its negative effects on the family. Current data indicate a cost-effective and coordinated response that combines community-based and individualized interventions for hoarding may be optimal in order to (1) reach the broadest group of clients with hoarding (e.g., beyond those who voluntarily seek treatment), (2) maximize incentives and motivation through housing, health services, and safety laws, (3) enhance communication and coordination between diverse teams of providers, (4) provide sustainable comprehensive services in a stepped care approach, and (5) reduce stigma