Abnormal Neuronal Differentiation and Mitochondrial Dysfunction in Hair Follicle-Derived Induced Pluripotent Stem Cells of Schizophrenia Patients

The study investigated schizophrenia as a neurodevelopmental disorder by reprogramming hair follicle keratinocytes from three schizophrenia patients and two controls into induced pluripotent stem cells (iPSCs) and differentiating them into neuronal lineages. Schizophrenia-derived dopaminergic neurons showed impaired differentiation, while glutamatergic neurons failed to mature. Additionally, mitochondrial dysfunction was observed, including impaired respiration, sensitivity to dopamine-induced inhibition, dissipation of mitochondrial membrane potential, and disrupted mitochondrial network structure. These findings suggested that abnormalities in neural differentiation and mitochondrial function might be interconnected and relevant to the neurodevelopmental processes in schizophrenia.