A Different Outlook at Psychiatric and Neurological Diseases: Brain Somatic Mutations Are Implicated in Schizophrenia

Abstract

In a groundbreaking article in the current issue of Biological Psychiatry, Kim et al. (1) present results of deep whole exome sequencing in the brain (the dorsolateral prefrontal cortex) and peripheral tissues from 27 patients with schizophrenia and 31 age-matched control subjects, discovering 286 somatic single nucleotide variations in postmortem brains and 340 variations in peripheral tissues. Independent ultradeep targeted amplicon sequencing was used for validation. Glutamatergic synapse, dopaminergic synapse, and long-term potentiation pathways were affected by the newly identified somatic mutations including the GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B) protein.