Abnormal Amygdala Resting-State Functional Connectivity in Adolescent Depression

Abstract

IMPORTANCE Major 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.OBJECTIVE To 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 RELEVANCE Impaired 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.

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression

“…Antidepressants reduce DMN hyperconnectivity in depressed patients to levels comparable with healthy control participants , and reductions in prefrontal connectivity correlate with symptom improvement (Wang et al, 2015). In adolescents with depression, altered connectivity has been reported between the amygdala and prefrontal cortex (Cullen et al, 2014), as well as between the amygdala and the anterior cingulate cortex (Connolly et al, 2013;Ho et al, 2014). Our findings build upon the prior literature on the DMN and depression by demonstrating that individuals at high familial risk for MDD have increased DMN connectivity.…”

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

“…Similar to recent work [Aghajani et al, 2016; Cullen et al, 2014; Roy et al, 2013], post‐hoc analyses examined the effects of comorbidity and substance use on trait‐specific iFC patterns (i.e., patterns that we elaborate on in the Discussion). As such, employing FSL's FEATquery tool on individual participant's connectivity maps, subject‐level connectivity measures (i.e., mean Z‐ values) were first extracted from clusters of brain regions that exhibited trait‐specific iFC with amygdala subregions in our group‐level analysis (clusters depicted in Fig.…”

Individual Differences in Adult Reading Are Associated with Left Temporo-parietal to Dorsal Striatal Functional Connectivity

“…Several regions that are typically anticorrelated with the left IPL, including anterior cingulate, post-central gyrus, right hippocampus, and precuneus, are less anticorrelated or positively correlated in RD readers across reading and resting tasks (Schurz et al 2014). While interpretation of differences in negative connectivity can be more challenging, findings involving negative connectivity in RD, psychiatric (Cullen et al 2014;Stegmayer et al 2014), and neurodevelopmental disorders (Jung et al 2014) suggest that variability in negative connectivity may be an important predictor of symptoms and warrants further research.…”