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.

Resting state functional magnetic imaging (fMRI) is a novel means to examine functional brain networks. It allows investigators to identify functional networks defined by distinct, spontaneous signal fluctuations. Resting state functional connectivity (RSFC) studies examining child and adolescent psychiatric disorders are being published with increasing frequency, despite concerns about the impact of motion on findings. Here we review important RSFC findings on typical brain development and recent publications of child and adolescent psychiatric disorders. We close with a summary of the major findings and current strengths and limitations of RSFC studies.

The management of nonsuicidal self-injurious behavior is a common focus of clinical care, particularly in the treatment of adolescents and young adults. Increased recognition of this problem has led to proposed criteria for future study in DSM-5, which may be beneficial in advancing the field. Clinical care may be fruitfully informed by an understanding of the neurodevelopmental underpinnings of this behavior. The authors discuss the current status of neurobiological research related to nonsuicidal self-injury with a focus on the key dimension of emotion regulation. A case is presented to illustrate the critical points. Preliminary empirical evidence suggests disturbances in neurobiological systems relevant to emotion regulation. Disturbances involve engagement of limbic brain regions and frontal regulatory brain regions that may evolve over time. Additionally, disturbances are observed in serotonin and physiological response systems relevant to emotion regulation. Treatment with serotonin reuptake inhibitors may be most beneficial in combination with dialectical behavioral therapy to address safety, build self-soothing strategies to enhance emotion regulation, and reduce interpersonal sensitivity. Delineation of the neurobiological markers that reflect successful treatment response will help in the identification of new avenues for research and the development of personalized treatments for adolescents with nonsuicidal self-injury.

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