Abstract
The prefrontal deficits in psychiatric disorders have been investigated using functional neuroimaging tools; however, no studies have tested the related characteristics across psychiatric disorders considering various demographic and clinical confounders. We analyzed 1558 functional brain measurements using a functional near-infrared spectroscopy during a verbal fluency task from 1200 participants with three disease spectra [196 schizophrenia, 189 bipolar disorder (BPD), and 394 major depressive disorder (MDD)] and 369 healthy controls along with demographic characteristics (age, gender, premorbid IQ, and handedness), task performance during the measurements, clinical assessments, and medication equivalent doses (chlorpromazine, diazepam, biperiden, and imipramine) in a consistent manner. The association between brain functions and demographic and clinical variables was tested using a general linear mixed model (GLMM). Then, the direction of relationship between brain activity and symptom severity, controlling for any other associations, was estimated using a model comparison of structural equation models (SEMs). The GLMM showed a shared functional deficit of brain activity and a schizophrenia-specific delayed activity timing in the prefrontal cortex (false discovery rate-corrected p < 0.05). Comparison of SEMs showed that brain activity was associated with the global assessment of functioning scores in the left inferior frontal gyrus opercularis (IFGOp) in BPD group and the bilateral superior temporal gyrus and middle temporal gyrus, and the left superior frontal gyrus, inferior frontal gyrus triangularis, and IFGOp in MDD group. This cross-disease large-sample neuroimaging study with high-quality clinical data reveals a robust relationship between prefrontal function and behavioral outcomes across three major psychiatric disorders.
Highlights
Mental illness is a common disease that around 20% of the general population encounter through their lives (Kessler, Chiu, Demler, Merikangas, & Walters, 2005)
Linear or quadratic age effects were found in brain activity of the bilateral superior temporal gyrus (STG), right inferior frontal gyrus triangularis (IFGTr), and left middle temporal gyrus (MTG) (Fig. 2a, and online Supplementary Tables S7 and S8)
The present study investigated the relationship between the characteristics of hemoglobin changes during a phonological verbal fluency task (VFT) using Functional near-infrared spectroscopy (fNIRS) and a wide range of demographic and clinical variables in a large sample size including multiple disease spectra
Summary
Mental illness is a common disease that around 20% of the general population encounter through their lives (Kessler, Chiu, Demler, Merikangas, & Walters, 2005). Previous neuroimaging studies have reported that cognitive deficits in schizophrenia were associated with volumetric and functional alterations in the PFC (Koike, Nishimura, Takizawa, Yahata, & Kasai, 2013; Weinberg et al, 2016). These alterations were seen in other psychiatric disorders including bipolar disorder (BPD) and major depressive disorder (MDD), suggesting a shared dysfunction across diseases (Barch & Sheffield, 2014; Kinou et al, 2013; Suto, Fukuda, Ito, Uehara, & Mikuni, 2004). This cross-disease large-sample neuroimaging study with high-quality clinical data reveals a robust relationship between prefrontal function and behavioral outcomes across three major psychiatric disorders
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