Dataset Information

Impaired left amygdala resting state functional connectivity in subthreshold depression individuals.

ABSTRACT: Subthreshold depression (StD) affects people who experience clinically relevant depressive symptoms, which does not meet the diagnostic criteria for major depressive disorder (MDD). StD represents an ideal model for understanding the pathophysiological mechanisms of depression. Impaired emotion processing is a core feature of depression; careful investigation is required to better understand the neural correlates of emotion processing in depressed populations. In the current study, we explored whether the resting-state functional connectivity of the amygdala, a hub that taps a wide range of brain areas involved in emotion processing, is altered in individuals with StD when compared with healthy controls. Resting-state imaging data was collected from 59 individuals with StD and 59 age- and gender-matched controls. We found that the resting-state functional connectivity of the left amygdala with the cognitive control network and the left insula was significantly lower in people with StD than that in healthy controls. Such association was not observed in the right amygdala. Furthermore, functional connectivity strength between the left amygdala and the left precuneus was positively associated with depressive symptoms in individuals with StD. Our findings are in line with those reported in subjects with MDD, which may assist in further elucidating the pathophysiological mechanisms of depression, and contribute to the development of tailored treatments for individuals with StD who are at high risk of developing MDD.

SUBMITTER: Peng X

PROVIDER: S-EPMC7560839 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Impaired left amygdala resting state functional connectivity in subthreshold depression individuals.

Peng Xiaoling X Lau Way K W WKW Wang Chanyu C Ning Lingfang L Zhang Ruibin R

Scientific reports 20201014 1

Subthreshold depression (StD) affects people who experience clinically relevant depressive symptoms, which does not meet the diagnostic criteria for major depressive disorder (MDD). StD represents an ideal model for understanding the pathophysiological mechanisms of depression. Impaired emotion processing is a core feature of depression; careful investigation is required to better understand the neural correlates of emotion processing in depressed populations. In the current study, we explored w ...[more]

PMID: 33057046

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Project description:ImportanceMajor depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships.ObjectiveTo examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions.Design, setting, and participantsA cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses.Main outcomes and measuresUsing a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala.ResultsAdolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls.Conclusions and relevanceImpaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

Project description:During adolescence, considerable social and biological changes occur that interact with functional brain maturation, some of which are sex-specific. The amygdala is one brain area that has displayed sexual dimorphism, specifically in socio-affective (superficial amygdala [SFA]), stress (centromedial amygdala [CMA]), and learning and memory (basolateral amygdala [BLA]) processing. The amygdala has also been implicated in mood and anxiety disorders which display sex-specific features, most prominently observed during adolescence. Using functional magnetic resonance imaging (fMRI), the present study examined the interaction of age and sex on resting state functional connectivity (RSFC) of amygdala sub-regions, BLA and SFA, in a sample of healthy adolescents between the ages 10 and 16 years (n = 122, 71 boys). Whole-brain, voxel-wise partial correlation analyses were conducted to determine RSFC of bilateral BLA and SFA seed regions, created using the Eickhoff-Zilles maximum probability maps based on cytoarchitectonic mapping and FMRIB's Integrated Registration and Segmentation Tool (FIRST). Monte Carlo simulation was implemented to correct for multiple comparisons (threshold of 53 contiguous voxels with a z-value ≥ 2.25). Results indicated that with increasing age, there was a corresponding decrease in RSFC between both amygdala sub-regions and parieto-occipital cortices, with a concurrent increase in RSFC with medial prefrontal cortex (mPFC). Specifically, boys and girls demonstrated increased coupling of mPFC and left and right SFA with age, respectively; however, neither sex showed increased connectivity between mPFC and BLA, which could indicate relative immaturity of fronto-limbic networks that is similar across sex. A dissociation in connectivity between BLA- and SFA-parieto-occipital RSFC emerged, in which girls had weaker negative RSFC between SFA and parieto-occipital regions and boys had weaker negative RSFC of BLA and parieto-occipital regions with increased age, both standing in contrast to adult patterns of amygdala sub-regional RSFC. The present findings suggest relative immaturity of amygdala sub-regional RSFC with parieto-occipital cortices during adolescence, with unique patterns in both sexes that may support memory and socio-affective processing in boys and girls, respectively. Understanding the underlying normative functional architecture of brain networks associated with the amygdala during adolescence may better inform future research of the neural features associated with increased risk for internalizing psychopathology.

Dataset Information

Impaired left amygdala resting state functional connectivity in subthreshold depression individuals.

Publications

Impaired left amygdala resting state functional connectivity in subthreshold depression individuals.

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