Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

Haiyang Geng,Fei Wang,Lingtao Kong,Yanqing Tang,Xiaowei Jiang,Miao Chang,Qian Zhou,Songbai Li,Gaolang Gong,Feng Wu,Yifang Zhou

doi:10.1371/journal.pone.0148345

Abstract

BackgroundEvidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.MethodsDiffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified.ResultsCompared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.ConclusionsFirst-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

Highlights

Adolescent major depressive disorder (MDD) is associated with increased risk of suicide, behavior disorders and long-term functional impairment into adulthood[1,2]
There was no significant correlation between the fornix Fractional anisotropy (FA) and the strength of functional connectivity within the adolescent MDD group
First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in healthy controls (HC) in the prefrontal cortex (PFC)-hippocampus neural circuitry

Summary

Introduction

Adolescent major depressive disorder (MDD) is associated with increased risk of suicide, behavior disorders and long-term functional impairment into adulthood[1,2]. As white matter fiber tracts structural connecting brain regions into neural circuits, diffusion tensor imaging (DTI), an MRI technique detecting white matter microstructure integrity in vivo, has been used to explore white matter abnormalities relevant to the neurobiology of MDD. Our previous DTI study demonstrated abnormalities in the superior longitudinal fasciculus within DLPFC as well as middle frontal white matter in the early stage of MDD[22], suggesting that disrupted structural connectivity of frontal-limbic neural circuits may play an important role in the pathophysiology of MDD. This study investigates the potential disruptions in prefrontalhippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure

Methods

Results

Conclusion