Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action.

Frailty syndrome is defined as extreme stress vulnerability and decreased potential to adapt. The elderly and chronically ill patients are affected mostly. This condition increases the risk of adverse health outcomes as infections, falls, delirium, institutionalization, progression of comorbidities and mortality. The pathophysiological mechanism is a complex immune and neuroendocrine dysregulation. According to the phenotype model, frailty presents when three of the followings occur: weakness, exhaustion, slowness, weight loss and decreased activity, while cumulative model counts the number of health deficits. Aging, frailty, dementia and depression are independent clinical entities; they may present separately but may also potentiate each other. Hence most of the frailty scales assess the physical, mental and social dimensions as well. Mild or moderate frailty is potentially reversible with an individualised caring plan. Given short, easy-to-use screening tools, risk groups can be identified in the primary care and referred to a specialised team for further treatment. Here the authors summarise the literature of a re-discovered, current clinical phenomena, frailty syndrome, focusing on the practical issues in primary care. Orv. Hetil., 2014, 155(49), 1935–1951.