Developmental Change in Amygdala Reactivity During Adolescence: Effects of Family History of Depression and Stressful Life Events

Abstract

Objective Though heightened amygdala reactivity is observed in patients with major depression, two critical gaps in our knowledge remain. First, it is unclear whether heightened amygdala reactivity is a premorbid vulnerability or consequence of the disorder. Second, it is unknown how and when this neural phenotype develops. The objective of this study was to address these gaps by evaluating developmental change in threat-related amygdala reactivity in adolescents at high or low risk for depression based on family history, before the onset of disorder. Method Adolescents (initially aged 11–15 years) completed an fMRI paradigm that elicited threat-related amygdala reactivity at baseline and again 2 years later. After quality control, data from 232 adolescents at Wave 1 and 197 adolescents at Wave 2 were available. Longitudinal data (meeting quality control at both waves) were available for 157 of these participants. Change in amygdala reactivity was assessed as a function of family history of depression and stressful life event severity. Results Threat-related amygdala reactivity increased with age in those with a positive family history regardless of the severity of life stress reported, and in adolescents with a negative family history when they reported relatively severe life stress. Critically, these changes in amygdala reactivity with age occurred in the absence of clinical disorder or increases in depressive symptoms. Conclusions These results suggest that heightened amygdala reactivity emerges during adolescence prior to the development of depression as a function of familial risk or, in the absence of familial risk, stressful life events.

Prefrontal brain responsiveness to negative stimuli

“…42 On the other hand, altered functioning of the OFC has been shown during reward processing in firstdegree relatives of patients with MDD. 43 However, these findings must not be regarded as contradictive to the present results; rather, they refer to the complex role of the OFC in different conditions in terms of diverging signalling during different paradigms, such as emotional face matching or reward processing.…”

“…It could point to a certain degree of heterogeneity between different brain regions in ventromedial functioning in individuals at risk for MDD. Also, one has to keep in mind that in contrast to the study by Swartz and colleagues, 43 which investigated neural responses in adolescents, participants of the present study were adults (mean age 37.12 ± 12.95 years), which generally might be regarded as an obstacle in a direct comparison of results from samples of different age groups. More in-depth research regarding this opposing pattern of signalling in the ventromedial network is needed before firm conclusions can be drawn.…”

The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank

“…Second, developmental aspects are represented as changes to the domains of functioning over time. For example, there appear to be important effects of exposure to early adversity on stress hormone levels (Heim et al, 2008;Lopez-Duran et al, 2009;Rao et al, 2010) and development of certain brain regions (Dannlowski et al, 2012;Lupien et al, 2011;Swartz et al, 2015;Whittle et al, 2011). These environmental and developmental influences can thus be added to the RDoC matrix to allow for a better understanding of the association between a given domain of functioning (e.g.…”

Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later

“…A few recent studies are beginning to suggest that amygdala reactivity to emotional facial expression is predictive of depression over time. For example, prediction has been found across a yearlong span in a community sample enriched for familial history of depression (Swartz et al, 2015) and in the presence of stressful life events (Swartz et al, 2014), as well as across an 8-month period in response to treatment, in a clinically depressed sample (Canli et al, 2005). Beyond these few studies; however, this literature has been largely cross-sectional, i.e.…”