Ventrolateral prefrontal hemodynamic responses in autism spectrum disorder with and without depression.

Yoshiyuki Hirano,Toshiyuki Ohtani,Chihiro Sutoh,Manabu Sakakibara,Eiji Shimizu,Fumiyo Oshima,Akio Wakabayashi

doi:10.1371/journal.pone.0256780

Abstract

In clinical settings, autism spectrum disorder (ASD) with comorbid depression is often difficult to diagnose, and should be considered in treatment. However, to our knowledge, no functional imaging study has examined the difference between ASD adolescents with and without comorbid depression. We aimed to compare the characteristics and prefrontal brain function of ASD with and without depression in order to identify a biological marker that can be used to detect the difference. Twenty-eight drug-naïve adolescents with ASD (14 ASD with and 14 ASD without depression) and 14 age- and gender-matched adolescents with typical development were evaluated using several variables. These included intelligence quotient, autism quotient, depression severity using the Beck Depression Inventory 2nd edition (BDI-II), and level of social functioning using the Social Adaptation Self-evaluation Scale (SASS). In addition, frontotemporal hemodynamic responses during a verbal fluency task (VFT) were measured using functional near-infrared spectroscopy (fNIRS). The ASD group, including both of the ASD with and ASD without depression groups, showed smaller hemodynamic responses than the typical development group in portions of the left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the VFT. Moreover, the smaller hemodynamic responses in the right VLPFC during the VFT in the ASD group were associated with the worse BDI-II and SASS scores. Furthermore, the ASD with depression group showed smaller hemodynamic responses in the right VLPFC during the VFT than the ASD without depression group in a direct comparison. Adolescents with ASD showed reduced activation in broad frontotemporal regions during a cognitive task compared with those with typical development. More specifically, the right VLPFC activation reflected the level of self-estimated depression and social functioning in the ASD subjects, and could be used to discriminate between ASD adolescents with and without depression.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior [1]
Comparison of frontotemporal activation between the two ASD groups (i.e. ASD+D and ASD-D) and the typical development (TD) group revealed that both ASD groups exhibited significantly reduced activation in the broad frontotemporal regions including left dorsolateral prefrontal cortex (DLPFC), bilateral ventrolateral prefrontal cortex (VLPFC) and anterior part of the temporal cortex (aTC) during the verbal fluency task (VFT)
Within the two ASD groups, activation in the right VLPFC during the VFT in the ASD+D group was reduced compared to the ASD-D group

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and interaction, as well as restricted and repetitive patterns of behavior [1]. Depression is common among individuals with ASD, and social functioning and depression may be intimately intertwined in ASD [2]. A recent meta-analysis suggested that individuals with ASD are approximately four times more likely to experience depression than the general population, and elevated depression rates in ASD are associated with increasing age (40.2% in adult samples vs 7.7% in samples < 18 years old) and average-to-above average IQ (52.8% vs 12.2% when mean IQ is below average) [3]. Depression is common in people with ASD, for adolescents and those with average or greater intelligence; university students may be a at-risk population. The co-occurrence of depression can exacerbate impairments associated with ASD (e.g., diminished social adaptive functioning) [4, 5]

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