Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder

Abstract

Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments.

Neural Correlates of Suicidality in Adolescents with Major Depression: Resting‐State Functional Connectivity of the Precuneus and Posterior Cingulate Cortex

“…This study represents an expanded sample that includes data from both medicated and unmedicated participants with MDD that have been published previously (Cullen et al., , ; Hall et al., ; Klimes‐Dougan et al., ; Musgrove et al., ; Sommerfeldt et al., ). Relative to the earliest publication by Cullen et al.…”

Cortico‐limbic connectivity in MAOA‐L carriers is vulnerable to acute tryptophan depletion

“…This is in line with the lowered DMN activity under reduced 5‐HT metabolism [Scharinger et al, ] and tighter coupling to limbic activity. Indeed in patients with depression, the DMN activity during resting state was found to extend further into the limbic system [Sheline et al, ], and was restored to normal levels after increasing 5‐HT availability [Cullen et al, ].…”

Neuroimaging Biomarkers for Predicting Treatment Response and Recurrence of Major Depressive Disorder

“…The association between increased RSFC in the striatum and treatment resistance to both SSRIs and SNRIs was reported [57]. Treatment response was associated with high RSFC between the amygdala and right medial and middle frontal cortices; however, it was also associated with low RSFC between the amygdala, right posterior cingulate cortex, and right precuneus [58]. Therefore, these results are largely inconsistent among studies.…”