Regulation of oxytocin receptor gene expression in obsessive-compulsive disorder: a possible role for the microbiota-host epigenetic axis.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. RESULTS: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. CONCLUSIONS: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies.

In Search for Biomarkers in Obsessive-Compulsive Disorder: New Evidence on Saliva as a Practical Source of DNA to Assess Epigenetic Regulation.

BACKGROUND: Brain-Derived Neurotrophic Factor (BDNF) is a promising candidate biomarker in both the development and aetiology of different neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). Most of the studies in the field have been carried out in blood cells, including peripheral blood mononucleated cells (PBMCs), although DNA of high quality can be easily isolated from saliva. OBJECTIVE: The objective of this study was to evaluate the epigenetic regulation of the BDNF gene in the saliva of a clinical sample of OCD patients in order to assess this source as an alternative to blood. METHODS: We first analyzed DNA methylation levels at BDNF in the saliva of subjects suffering from OCD (n= 50) and healthy controls (n=50). Then, we compared these data with the results previously obtained for the same genomic region in blood samples from the same patients and controls (CTRL). RESULTS: Our preliminary data showed a significant reduction of 5mC levels at BDNF gene (OCD: 1.23 ± 0.45; CTRL: 1.85 ± 0.64; p < 0.0001) and a significant correlation between DNA methylation in PBMCs and saliva (Spearman r = 0.2788). CONCLUSION: We support the perspective that saliva could be a possible, reliable source, and a substitute for blood, in search of epigenetic biomarkers in OCD.

Intrapersonal and Social Factors for Problematic Internet Use among Students during the COVID-19 Pandemic.

BACKGROUND: During the lockdown due to COVID-19, Internet use may become more frequent in students, with possible negative consequences on mental health. In this emergency situation, variables such as depression, anxiety and external locus of control could be related to a Problematic Internet Use; on the other hand, self-esteem, internal locus of control, self-efficacy, and social support can play the role of protective factors for Problematic Internet Use. The present survey aims to verify the impact of these intrapersonal and social factors on Problematic Internet Use in college and High School students during the COVID-19 pandemic through a web-based cross-sectional study. SUBJECTS AND METHODS: 191 students from Lombardy, one of the Italian Regions among the most affected by the COVID-19 pandemic, were included in the study. An online questionnaire has been administered during the first Italian period of forced lockdown. A logistic regression analysis was performed to assess intrapersonal and social factors as predictors of Problematic Internet Use. RESULTS: Analysis highlighted a higher risk of Problematic Internet Use (5.77 times more) in males compared to females. Individuals with high external locus of control and severe depression have respectively 6.56 and 2.84 times more the risk of presenting Problematic Internet Use. In contrast, social support, self-efficacy, and self-esteem were negatively related to Problematic Internet Use. In total sample, the percentage of Problematic Internet Use was high (55.5%). CONCLUSIONS: An increasing use of the Internet has been observed during lockdown, leading to a progressive increase in the diffusion of Problematic Internet Use. Gender, depression and external locus of control emerge as risk factors for Problematic Internet Use, while social support, self-efficacy and self-esteem represent protective factors. The current research identifies some intrapersonal and social factors in an epidemic context for which the development of effective behavioural, supportive and/or educational interventions would be appropriate.

Structured Evaluation of Rehabilitation Programs Outcomes in Psychiatry: Application of a Recovery-Centered Model.

Rehabilitation is oriented to psychiatric patients' recovery through specific techniques and structured projects, not yet fully standardized, carried out in territorial services. This study aims to apply an operational structured outcome indicator model (hospitalizations, continuity of care, LAI treatment adherence, working support) through a recovery-centered model in a rehabilitation community in Milan. This observational-retrospective study included 111 patients from a University High Assistance Rehabilitation Community (C.R.A.) based in Milan. Psychopathological and psychosocial functioning was evaluated with Kennedy Axis V, Brief Psychiatric Rating Scale (BPRS), Life Skills Profile (LSP), AR module of the VADO scale. Statistical analyses were performed using SPSS software version 19. Student t test and Wilcoxon Test were used to analyze quantitative variables, while McNemar test for qualitative variables. The minimum level of significance was set at 0.05 (p <0.05). The results showed that CRA rehabilitation program led to significant improvement in global functioning in terms of hospitalization reduction; improved continuity of care; stable adherence to psychopharmacological treatment with Long Acting Injectable (LAI) antipsychotics; stable employment maintenance during the year following discharge from the CRA. This study confirmed the utility of a structured outcome indicator model and highlighted its feasibility in daily clinical context of a rehabilitative community. Our results supported the effectiveness of a community-based rehabilitation program to improve individual functioning and clinical stability. However, further studies are required to better achieve the development of a recovery-oriented rehabilitation model and rigorously define an outcomes evaluation model.

Peripheral Biomarkers in DSM-5 Anxiety Disorders: An Updated Overview.

Anxiety disorders are prevalent and highly disabling mental disorders. In recent years, intensive efforts focused on the search for potential neuroimaging, genetic, and peripheral biomarkers in order to better understand the pathophysiology of these disorders, support their diagnosis, and characterize the treatment response. Of note, peripheral blood biomarkers, as surrogates for the central nervous system, represent a promising instrument to characterize psychiatric disorders, although their role has not been extensively applied to clinical practice. In this report, the state of the art on peripheral biomarkers of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) Anxiety Disorders is presented, in order to examine their role in the pathogenesis of these conditions and their potential application for diagnosis and treatment. Available data on the cerebrospinal fluid and blood-based biomarkers related to neurotransmitters, neuropeptides, the hypothalamic-pituitary-adrenal axis, neurotrophic factors, and the inflammation and immune system are reviewed. Despite the wide scientific literature and the promising results in the field, only a few of the proposed peripheral biomarkers have been defined as a specific diagnostic instrument or have been identified as a guide in the treatment response to DSM-5 Anxiety Disorders. Therefore, further investigations are needed to provide new biological insights into the pathogenesis of anxiety disorders, to help in their diagnosis, and to tailor a treatment.