Profiling risk for depressive disorder by circuit, behavior and self-report measures of emotion function

Major depressive disorder (MDD) is characterized by maladaptions in affective brain circuitry and in emotion regulation. It remains unknown whether these maladaptions characterize first-degree relatives of probands who are unaffected yet have a higher risk of developing MDD.

Participants were 72 unaffected first-degree relatives of probands with MDD and 66 matched non-relative controls. We investigated brain circuit function and self-reported emotion regulation strategies for reappraisal and suppression. During functional magnetic resonance imaging, we probed circuitry relevant to both negative and positive valence systems using facial expressions signaling potential threat, sadness and happiness, presented under both conscious and subliminal viewing conditions. We compared groups using a statistically controlled region of interest (ROI) approach including the amygdala, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also used a data-driven cluster analytic approach for characterizing the relatives by their brain function profiles.

As a group, relatives were distinguished by hyper-reactivity of the pregenual ACC during subliminal viewing of threat-related expressions but hypo-activation of the amygdala, insula and dorsal ACC during explicit viewing of the same threat-related expressions and sadness. When considered individually, this brain function profile characterized two-thirds of relatives, and these relatives were also less likely to use reappraisal to regulate negative emotion.

The design was cross-sectional and therefore does not provide direct evidence as to the trait- (versus state-) like profile observed in relatives.

Familial risk for MDD may involve a disruption to the normal recruitment of neural circuits for appraising salient emotions, both implicit and explicit. Interventions targeting reappraisal strategies for regulating negative emotion may serve to buffer this risk.