T10. HERITABILITY OF AMYGDALA ACTIVITY AND ITS GENOME WIDE ASSOCIATION WITH THE SCHIZOPHRENIA RISK LOCUS OF MIR137

It is well known that heritability plays a prominent role in risk for schizophrenia, and that this brain disorder is crucially characterized by emotional symptoms. Less known is how heritability shapes brain activity during emotion processing and whether this brain phenotype is also associated with genetic variation increasing risk for schizophrenia. Here, we implemented a multi-step, data-driven approach in order to assess the relevance of the link between heritability, genetic variation, and schizophrenia for brain activity during emotion processing

Involvement of the IL-6 Signaling Pathway in the Anti-Anhedonic Effect of the Antidepressant Agomelatine in the Chronic Mild Stress Model of Depression

Neuroinflammation has emerged as an important factor in the molecular underpinnings of major depressive disorder (MDD) pathophysiology and in the mechanism of action of antidepressants. Among the inflammatory mediators dysregulated in depressed patients, interleukin (IL)-6 has recently been proposed to play a crucial role. IL-6 activates a signaling pathway comprising the JAK/STAT proteins and characterized by a specific negative feedback loop exerted by the cytoplasmic protein suppressor of cytokine signalling-3 (SOCS3). On these bases, here, we explored the potential involvement of IL-6 signaling in the ability of the antidepressant drug agomelatine to normalize the anhedonic-like phenotype induced in the rat by chronic stress exposure. To this aim, adult male Wistar rats were subjected to the chronic mild stress (CMS) paradigm and chronically treated with vehicle or agomelatine. The behavioral evaluation was assessed by the sucrose consumption test, whereas molecular analyses were performed in the prefrontal cortex. We found that CMS was able to stimulate IL-6 production and signaling, including SOCS3 gene and protein expression, but the SOCS3-mediated feedback-loop inhibition failed to suppress the IL-6 cascade in stressed animals. Conversely, agomelatine treatment normalized the stress-induced decrease in sucrose consumption and restored the negative modulation of the IL-6 signaling via SOCS3 expression and activity. Our results provide additional information about the pleiotropic mechanisms that contribute to agomelatine’s therapeutic effects

Impact of SARS-CoV-2 outbreak on heart and lung transplant: a patient-perspective survey

The risk of COVID-19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID-19 and the impact of the SARS-CoV-2 outbreak on the personal hygiene and expectations of in heart and lung transplant recipients

Heritability of amygdala reactivity to angry faces and its replicable association with the schizophrenia risk locus ofmiR-137

Background: Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia. Methods: We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI). Results: We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, p < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the miR-137 locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (p = 0.03). Limitations: The limited sample size available for GWAS analyses may require further replication of results. Conclusion: Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for miR-137 in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to miR-137

Personal resources and depression in schizophrenia: The role of self-esteem, resilience and internalized stigma

Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives

Background: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relativeâ\u80\u93control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probandsâ\u80\u99 scores. Methods: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probandsâ\u80\u99 MCCB scores predicted REL neurocognitive performance. Results: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. Conclusions: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors