Distinct and Shared Endophenotypes of Neural Substrates in Bipolar and Major Depressive Disorders.

Toshio Matsubara,Mami Nakashima,Yoshifumi Watanabe,Koji Matsuo,Naofumi Matsunaga,Kazuteru Egashira,Matakazu Furukawa,Masayuki Nakano,Toshio Watanuki,Kenichiro Harada,Huiguang He

doi:10.1371/journal.pone.0168493

Abstract

Little is known about disorder-specific biomarkers of bipolar disorder (BD) and major depressive disorder (MDD). Our aim was to determine a neural substrate that could be used to distinguish BD from MDD. Our study included a BD group (10 patients with BD, 10 first-degree relatives (FDRs) of individuals with BD), MDD group (17 patients with MDD, 17 FDRs of individuals with MDD), and 27 healthy individuals. Structural and functional brain abnormalities were evaluated by voxel-based morphometry and a trail making test (TMT), respectively. The BD group showed a significant main effect of diagnosis in the gray matter (GM) volume of the anterior cingulate cortex (ACC; p = 0.01) and left insula (p < 0.01). FDRs of individuals with BD showed significantly smaller left ACC GM volume than healthy subjects (p < 0.01), and patients with BD showed significantly smaller ACC (p < 0.01) and left insular GM volume (p < 0.01) than healthy subjects. The MDD group showed a tendency toward a main effect of diagnosis in the right and left insular GM volume. The BD group showed a significantly inverse correlation between the left insular GM volume and TMT-A scores (p < 0.05). Our results suggest that the ACC volume could be a distinct endophenotype of BD, while the insular volume could be a shared BD and MDD endophenotype. Moreover, the insula could be associated with cognitive decline and poor outcome in BD.

Highlights

Differentiating between a diagnosis of bipolar disorder (BD) and major depressive disorder (MDD) is of clinical importance, as 69% of individuals with BD are misdiagnosed with MDD [1]
Twin studies have demonstrated decreased hippocampal volumes in first-degree relatives (FDRs) of individuals with BD and MDD, as compared to healthy control subjects [25,26]. These results suggest that brain volumetric abnormalities reflect the vulnerability of FDRs and may reveal candidate endophenotypes for BD and MDD
Our current study revealed a reduction in the gray matter (GM) volume in the anterior cingulate cortex (ACC) of patients with BD and FDRs of individuals with BD, but not in patients with MDD or in FDRs of individuals with MDD

Summary

Introduction

Differentiating between a diagnosis of bipolar disorder (BD) and major depressive disorder (MDD) is of clinical importance, as 69% of individuals with BD are misdiagnosed with MDD [1]. These errors cause harmful consequences for patients with BD, such as inappropriate medication prescription, drug-induced switching of the mood phase, and a poor prognosis. Disorders” carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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