Next-generation sequencing analysis of multiplex families with atypical psychosis

Tatsushi Okayama,Hiroki Kikuyama,Hiroshi Yoneda,Yasuyuki Hashiguchi,Tetsufumi Kanazawa

doi:10.1038/s41398-018-0272-x

Abstract

Atypical psychosis (similar to acute and transient psychotic disorder, brief psychotic disorder) is highly heritable, but the causal genes remain unidentified. We conducted whole-genome sequencing on multiplex Japanese families with atypical psychosis. The patient group of interest shows acute psychotic features including hallucinations, delusions, and catatonic symptoms while they often show good prognosis after the onset. In addition to the next-generation analysis, HLA typing has been conveyed to check the similarity with autoimmune disease, such as systemic lupus erythematosus (SLE). Shared causal polymorphisms in the Deleted in Colorectal Carcinoma, Netrin 1 receptor (DCC) gene were found in one multiplex family with three patients, and variants in the RNA 3′-Terminal Phosphate Cyclase (RTCA) and One Cut Homeobox 2 (ONECUT2) genes were found to be shared in seven patients. Next-generation sequencing analysis of the MHC region (previously suggested to be a hot region in atypical psychosis) using HLA typing (HLA-DRB1) revealed a common vulnerability with SLE (systemic lupus erythematosus) among five patients. This finding demonstrates the shared etiology between psychotic symptoms and autoimmune diseases at the genetic level. Focusing on a specific clinical phenotype is key for elucidating the genetic factors that underlie the complex traits of psychosis.

Highlights

Atypical psychosis is a taxonomic name that has been used by Japanese psychiatrists since Dr Mitsuda advocated its use[1]
Eight loci out of them were located within intronic or 3′-UTR regions of the genes shown in Table 1 and Fig. 2, no functional variants being found in this analysis
This era has generated significant scientific breakthroughs, including the following findings: (1) no single genetic variant (SNP/CNV) explains the entire etiology of SZ or bipolar disorder (BD); (2) these two disorders exhibit high genetic overlap; and (3) broadly defined phenotypes require larger sample sizes for causal gene detection, no evidence exists for finding such a gene in the future

Summary

Introduction

Atypical psychosis is a taxonomic name that has been used by Japanese psychiatrists since Dr Mitsuda advocated its use[1]. Atypical psychosis patients are classified as having brief psychotic disorders (298.8)[2] or acute and transient psychotic disorders (F23)[3] in the current nosological system. As experienced by those with these disorders, patients with atypical psychoses experience acute onset and hallucinations and/or mood disturbances during the acme phase. Patients with this disorder worsen periodically but can live normal lives after these brief exacerbations and may not remember the experience.

Methods

Results

Conclusion