4 research outputs found
Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients
Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication
Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatmentāresistant depression
Ā© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives. https://creativecommons.org/licenses/by-nc-nd/4.0/Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to firstāline therapeutic options, resulting in treatmentāresistant bipolar depression (BāTRD). Esketamine, the Sāenantiomer of ketamine, has recently been approved for treatmentāresistant depression (TRD), but no data are available on its use in BāTRD. Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in BāTRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in BāTRD, focusing on the average risk of an affective switch. Methods: Thirtyāfive BāTRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (MontgomeryāAsberg Depression Rating Scale/MADRS, Hamiltonādepression scale/HAMāD, Hamiltonāanxiety scale/HAMāA) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with BāTRD and TRD. Esketamine showed a greater anxiolytic action in subjects with BāTRD than in those with TRD. Improvement in depressive symptoms was not associated with treatmentāemergent affective switch. Conclusions: Our results supported the effectiveness and tolerability of esketamine in a realāworld population of subjects with BāTRD. The low risk of manic switch in BāTRD patients confirmed the safety of this treatment.Peer reviewe