Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive-compulsive disorder.

Though several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype. A total of 200 individuals with OCD were genotyped using the TaqMan assay. All participants were assessed using the Mini International Neuropsychiatric Interview and the Yale-Brown Obsessive-Compulsive Scale, and their response to serotonin reuptake inhibitors (SRIs) was evaluated over naturalistic treatment and follow-up. After correcting for multiple comparisons, the G allele at rs6662980 was found to be associated with contamination and washing symptoms (p = .003). Logistic regression analysis also showed that presence of the G allele predicted poor response to SRIs (odds ratio [OR] = 2.473, 95% confidence interval [1.157, 5.407], p = .021). Interaction between presence of the G allele and the Contamination and Washing factor score predicted greater SRI resistance (OR = 3.654, [2.761, 4.547], p = .004). We conclude that specific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to SRIs, may be affected by variations in the SAPAP3 gene. Limitations of the study are the lack of a dimensional measure for assessing OCD symptoms, the evaluation of treatment response over naturalistic follow-up, and that only a single locus in the SAPAP3 gene was examined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cell cycle abnormality is a cellular phenotype in OCD.

Abnormal indices of cell cycle regulation have been reported in multiple psychiatric disorders. Though reports specific to Obsessive Compulsive Disorder (OCD) are scant, numerous studies have highlighted partly common underlying biology in psychiatric disorders, cell cycle regulation being one such process. In this study, we therefore aimed to explore cell cycle in OCD. To the best of our knowledge, this is the first study to investigate these effects in OCD. We also evaluated the effect of in vitro fluoxetine, commonly used serotonin reuptake inhibitor (SRI) in OCD patients, on cell cycle regulation. The effects of both disease (OCD) and treatment (SRI) were assessed using lymphoblastoid cell lines (LCLs), derived from OCD patients and healthy controls, as a model system. LCLs were treated with 10µM of fluoxetine for 24 h, and the percentage of cells in each phase of the cell cycle was determined by flow cytometry. We observed a lower proportion of cells in the G2/M phase in OCD cases than controls. The findings suggest that cell cycle dysregulation could be peripheral cellular phenotype for OCD. Among cases, all of whom had been systematically characterized for SRI treatment response, LCLs from non-responders to SRI treatment had a lower proportion of cells in G2/M phase than responders.

Does retinoic acid reverse cell cycle dysregulation in Alzheimer's disease lymphocytes?

Aberrant re-entry of neurons into cell cycle appears to be an early event in Alzheimer's disease (AD) and targeting this dysregulation may have therapeutic potential. We have examined whether cell cycle dysregulation in AD can be detected using patient and control derived B-lymphocytes. Cell cycle analysis using flow cytometry demonstrated that cell cycle dysregulation occurs in AD lymphocytes, with a significant difference in the distribution of cells in G0/G1, S and G2/M phases of cell cycle as compared to control lymphocytes. Using global gene expression analysis by RNA sequencing and cell cycle analysis, we examined the role of Retinoic Acid (RA), a candidate molecule predicted to be of therapeutic potential in cell cycle dysregulation associated with AD. CCND1, CCNE2, E2F transcription factors which are known to be dysregulated in AD were among the 32 genes that showed differential expression in response to RA treatment thus suggesting a protective role of RA. However, the cell cycle analysis demonstrated that RA did not reverse the cellular phenotype in AD lymphocytes. This suggests that though RA might have a protective role by influencing the expression of cell cycle genes, it might not be able to arrest abnormal re-entry into cell cycle.