Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia.

The long lapse between the presumptive origin of schizophrenia (SCZ) during early development and its diagnosis in late adolescence has hindered the study of crucial neurodevelopmental processes directly in living patients. Dopamine, a neurotransmitter consistently associated with the pathophysiology of SCZ, participates in several aspects of brain development including pruning of neuronal extensions. Excessive pruning is considered the cause of the most consistent finding in SCZ, namely decreased brain volume. It is therefore possible that patients with SCZ carry an increased susceptibility to dopamine's pruning effects and that this susceptibility would be more obvious in the early stages of neuronal development when dopamine pruning effects appear to be more prominent. Obtaining developing neurons from living patients is not feasible. Instead, we used Monocyte-Derived-Neuronal-like Cells (MDNCs) as these cells can be generated in only 20 days and deliver reproducible results. In this study, we expanded the number of individuals in whom we tested the reproducibility of MDNCs. We also deepened the characterization of MDNCs by comparing its neurostructure to that of human developing neurons. Moreover, we studied MDNCs from 12 controls and 13 patients with SCZ. Patients' cells differentiate more efficiently, extend longer secondary neurites and grow more primary neurites. In addition, MDNCs from medicated patients expresses less D1R and prune more primary neurites when exposed to dopamine. Haloperidol did not influence our results but the role of other antipsychotics was not examined and thus, needs to be considered as a confounder.

Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review.

Despite the existence of many preclinical studies, scientific evidence is lacking on the clinical use of alpha-lipoic acid (ALA) for central nervous system disorders. Therefore, we aimed at revising the literature concerning the use of ALA for the treatment of psychiatric and neurological conditions and to point out what is missing for the introduction of this antioxidant to this purpose. For this systematic review we performed a search using PubMed and SCOPUS databases with the following keywords: "alpha-Lipoic Acid AND central nervous system OR psychiatric disorders OR neurological disorders OR mood disorders OR anxiety OR psychosis OR Alzheimer OR Parkinson OR stroke". The total number of references found after automatically and manually excluding duplicates was 1061. After primary and secondary screening 32 articles were selected. Regarding psychiatric disorders, the studies of ALA in schizophrenia are advanced being ALA administration related to the improvement of schizophrenia symptoms and side effects of antipsychotic medication. In neurological disorders, ALA as a supplement was effective in the prevention of Alzheimer disease progression. For stroke, the use of the supplement ALAnerv® (containing 300 mg ALA) presented important results, since it was observed a reversal of clinical parameters and oxidative imbalance in these patients. For other neurological conditions, such as encephalopathy, multiple sclerosis, traumatic brain injury, mitochondrial disorders and migraine, the results are still preliminary. Overall, there is a need of well-designed clinical trials to enhance the clinical evidences of ALA effects for the treatment of neurological and psychiatric conditions.

Naltrexone in the Treatment of Broadly Defined Behavioral Addictions: A Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Broadly defined behavioral addiction is a conceptual framework including behaviors characterized by loss of control and continuation despite significant negative consequences. Broadly defined behavioral addictions share many similarities with substance use disorders. As naltrexone is one of the most studied treatment for substance use disorders, we conducted a meta-analysis of randomized placebo-controlled trials (RCT) assessing the effectiveness of naltrexone in the treatment of broadly defined behavioral addictions. METHOD: We conducted a literature search and selection, up to January 1, 2017, according to previously set inclusion criteria. The selected trials underwent a quality assessment before data extraction and statistical analysis, which used fixed and random effects models. Standardized mean differences (SMD) were calculated using Hedge's adjusted g. RESULTS: A total of 6 RCTs (n = 356) were included. Of these, 3 assessed naltrexone effectiveness in the treatment of pathological gambling, and 3 tested its benefits in broadly defined behavioral addictions other than pathological gambling (kleptomania, trichotillomania, and impulsive compulsive disorders). The meta-analysis of the whole sample resulted in a statistically significant score improvement under naltrexone versus placebo (fixed effect model: SMD = -0.27, 95% CI [-0.51 to -0.03], z = 2.23; p = 0.025). CONCLUSION: The results of our meta-analysis suggest a beneficial effect of naltrexone in the treatment of broadly defined behavioral addictions.

De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.

Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.

Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.

Incidence and outcomes of COVID-19 first wave pandemic in a French nursing home with residents suffering from severe mental illnesses.

During the first wave of COVID-19, nearly 50% of France's fatalities occurred in nursing homes. Older people with mental health disorders are considered to be more prone to infections when epidemics arise. To test this hypothesis, we conducted a retrospective descriptive and comparative study of the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a cohort of elderly residents with or without severe mental illness (SMI) living in a French nursing home facility. This was done during the first lockdown from March 17th until May 11th, 2020. Our study included 72 participants of 75 residents, of whom 58 contracted COVID-19, 14 developed a severe form requiring hospitalisation, and 14 died. The disease was significantly less frequent in residents with SMI 15(62%) than those without SMI 43 (89.6%). In regression analysis, a higher level of autonomy was significantly associated with a lower disease incidence. Once contracted, residents with or without SMI differed significantly neither on morbidity nor mortality. The period of survival did not either significantly differ between the two groups. As a potential explanation, we suggested that pathological social withdrawal added to stigmatisation could have protected SMI residents from contracting the disease.