Disruption of resting-state functional connectivity of right posterior insula in adolescents and young adults with major depressive disorder

Abstract

Background: The neural basis of Major Depressive Disorder (MDD) which is a clinical syndrome characterized by emotional and cognitive impairments is poorly understood. Accumulating evidence has suggested that the insula is an important substrate underlying the mechanism of MDD. This study aimed to examine the disrupted resting-state brain regional function in insula and to further investigate the associated resting-state functional connectivity (rs-FC) of insula underlie the MDD in adolescents and young adults.

Methods: We employed 3.0T resting-state functional magnetic resonance imaging (rs-fMRI) to acquire data from 76 adolescents and young adults with MDD and 44 age and sex matched healthy control subjects. We employed a regional Amplitude of Low-Frequency Fluctuation (ALFF) analysis to explore local intrinsic neural oscillation alterations in insula and an ALFF-based functional connectivity (FC) approach to detect the potential changes in remote connectivity with insula in adolescents and young adults with MDD.

Results: By applying ALFF analysis, significantly decreased activities were detected in bilateral insula, and in particular in right anterior insular gyrus (MNI; ROI1: 42, 24, -3), right posterior insular gyrus (Montreal Neurological Institute, MNI; ROI2: 36, -9, 15) and left anterior insular gyrus (MNI; ROI3: -36, 12, 9) in patients with MDD compared to the healthy controls (p < 0.05, 1000 permutations, TFCE corrected). With ROI2 as the seed in the subsequent ALFF-based rs-FC analysis, patients with MDD were observed to have significantly reduced FC with bilateral middle occipital gyrus, lingual gyrus, calcarine, postcentral gyrus, precentral gyrus, supramarginal area, superior temporal gyrus and middle cingulate gyrus as compared to the healthy controls (p < 0.05, 1000 permutations, TFCE corrected). No significant differences of FC were detected between the patients and healthy controls when using ROI1 and ROI3 as the seeds. We found no correlations between ALFF or rs-FC values and the severity of depression as estimated by Hamilton Depression Rating Scale (HAM-D).

Limitations: Clinical information were limited and no significant correlations were found between imaging variables and HAM-D scores, which reduces the power to interpret the present findings. A cross-sectional design was employed in this study so that it is not possible to know whether the abnormal ALFF or altered brain FC of insula reflects a state or trait effect in young people with MDD.

Conclusions: This study highlights the regional/network interaction abnormalities of insula in adolescents and young adults with MDD, and could provide further insight into understanding the neural pathomechanism of MDD in young patients.

Keywords: Amplitude of low-frequency fluctuation; Functional connectivity; Insula; Major depressive disorder; Resting-state functional magnetic resonance imaging.