From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Etiology of cardiovascular disease in patients with schizophrenia: current perspectives

Murat Emul,1 Tevfik Kalelioglu21Department of Psychiatry, Medical School of Cerrahpasa, Istanbul University, 2Department of Psychiatry, Bakirkoy Mental Health Research and Training Hospital, Istanbul, TurkeyAbstract: Cardiovascular morbidity and mortality are important problems among patients with schizophrenia. A wide spectrum of reasons, ranging from genes to the environment, are held responsible for causing the cardiovascular risk factors that may lead to shortening the life expectancy of patients with schizophrenia. Here, we have summarized the etiologic issues related with the cardiovascular risk factors in schizophrenia. First, we focused on heritable factors associated with cardiovascular disease and schizophrenia by mentioning studies about genetics–epigenetics, in the first-episode or drug-naïve patients. In this context, the association and candidate gene studies about metabolic disturbances in schizophrenia are reviewed, and the lack of the effects of epigenetic/posttranscriptional factors such as microRNAs is mentioned. Increased rates of type 2 diabetes mellitus and disrupted metabolic parameters in schizophrenia are forcing clinicians to struggle with metabolic syndrome parameters and related issues, which are also the underlying causes for the risk of having cardiometabolic and cardiovascular etiology. Second, we summarized the findings of metabolic syndrome-related entities and discussed the influence of the illness itself, antipsychotic drug treatment, and the possible disadvantageous lifestyle on the occurrence of metabolic syndrome (MetS) or diabetes mellitus. Third, we emphasized on the risk factors of sudden cardiac death in patients with schizophrenia. We reviewed the findings on the arrhythmias such as QT prolongation, which is a risk factor for Torsade de Pointes and sudden cardiac death or P-wave prolongation that is a risk factor for atrial fibrillation. For example, the use of antipsychotics is an important reason for the prolongation of QT and some other cardiac autonomic dysfunctions. Additionally, we discussed relatively rare issues such as myocarditis and cardiomyopathy, which are important for prognosis in schizophrenia that may have originated from the use of antipsychotic medication. In conclusion, we considered that the studies and awareness about physical needs of patients with schizophrenia are increasing. It seems logical to increase cooperation and shared care between the different health care professionals to screen and treat cardiovascular disease (CVD)-risk factors, MetS, and diabetes in patients with psychiatric disorders, because some risk factors of MetS or CVD are avoidable or at least modifiable to decrease high mortality in schizophrenia. We suggested that future research should focus on conducting an integrated system of studies based on a holistic biopsychosocial evaluation.Keywords: antipsychotic, cardiovascular risk, MetS, miRNA, QTc, schizophreni

Clozapine use in two women with schizophrenia during pregnancy

Stabilized patients who receive clozapine may wish to have children; but studies on pregnant women receiving clozapine treatment are limited. In this study, we report on clozapine use during pregnancy in two women. The first woman ( Case 1) had two deliveries while she was receiving clozapine treatment for schizophrenia. Both her deliveries were term, uncomplicated vaginal deliveries, and the clozapine dose was reduced throughout pregnancy. The second woman ( Case 2) developed schizophrenia after her first child was born. She became pregnant after clozapine initiation. She delivered twins by term, uncomplicated vaginal delivery. In our cases, no specific risks for the mothers and their children can be attributed to the use of clozapine. Physicians must be aware of the changes in fertility induced by prolactin-sparing drugs. Mothers who receive clozapine treatment should not be advised to breastfeed their children