Reduced fronto-amygdalar connectivity in adolescence is associated with increased depression symptoms over time

Abstract

Depression is common among adolescents, affecting greater than 12% of youth in a given year. Studies have shown aberrant amygdala connectivity in depressed adolescents, compared with controls; however, no studies have examined whether these abnormalities precede and heighten risk for depressive symptom expression. This study used resting state functional connectivity (RSFC) magnetic resonance imaging to examine neurobiological markers of escalating depression symptoms in adolescents (ages 12–16 years; free from psychopathology at baseline). Of a large sample of adolescents, 18 showed ≥ 1 S.D. increase in depression scale t-scores over time (“escalators”; time to escalation ranging from 6 to 54 months in follow up) and were matched and compared to 19 youth showing stable CDI scores over time (“controls”). Whole-brain analyses on baseline RSFC data using an amygdala seed region-of-interest (ROI) showed that controls had greater RSFC, relative to escalators, between the right amygdala and left inferior frontal and supramarginal gyrus and right mid-cingulate cortex. Additionally, relative to escalators, control youth had less RSFC between the left amygdala and cerebellum. Findings suggest a possible neurobiological marker of increasing depressive symptoms during adolescence, characterized in part by reduced fronto-limbic connectivity, suggesting a premorbid deficiency in top-down emotional regulation.

Neural connectivity biotypes: associations with internalizing problems throughout adolescence

“…The original GIMME algorithm is well-suited for connectivity analyses of 5-15 ROIs (Gates & Molenaar, 2012). We selected the same 15 ROIs examined by Price, Lane, et al (2017), given that these regions have been implicated previously in neuroimaging studies of internalizing symptoms (Burkhouse et al, 2019;Geng et al, 2016;Scheuer et al, 2017). Similar to Price, Lane, et al (2017), 8 mm radius spherical masks were applied around peak coordinates of (1) CCN regions including dACC, bilateral posterior parietal cortex (PPC), and left dlPFC; (2) VAN nodes including bilateral nucleus accumbens (Nacc), bilateral anterior insula, bilateral ventrolateral PFC (VLPFC), bilateral amygdala, and subgenual ACC (sgACC); and (3) DMN regions including posterior cingulate cortex (PCC) and perigenual ACC (pgACC) (coordinates for all ROIs are included in Supplemental Material).…”

Restructuring of amygdala subregion apportion across adolescence

“…All participants were right-handed and free of neurological, 114 neurodevelopmental, and/or psychological diagnoses. Detailed exclusionary criteria can be found 115 elsewhere (Alarcon et al, 2015;Scheuer et al, 2017;Morales et al, 2018). 116…”

Convergent neurobiological predictors of emergent psychopathology during adolescence

“…Additionally, smaller volumes and thinner prefrontal cortices (Brumback et al, ; Cheetham et al, ; Foland‐Ross et al, ; Kuhn et al, ; Squeglia et al, ) and reduced prefrontal activation during tasks involving rewarding and emotional stimuli (Buchel et al, ; Jin et al, ; Jones et al, ; Kujawa et al, ) and executive control (Heitzeg et al, ; Mahmood et al, ; Norman et al, ) also appear to be associated with the onset, escalation, and persistence of adolescent psychopathology. Lastly, reduced functional connectivity both within limbic regions (Connolly et al, ), and between limbic and prefrontal regions (Camchong et al, ; Scheuer et al, ; Strikwerda‐Brown et al, ), as well as smaller indices of white matter maturation (i.e., fractional anisotropy) in tracts serving limbic and frontal regions (Chung et al, ; Huang et al, ) may serve as a risk marker for greater psychopathological symptoms.…”

“…First, in unmedicated adolescents with major depressive disorder, reduced functional connectivity between the amygdala and insula at baseline was associated with greater increases in depressive symptoms 3 months later (Connolly et al, ). Furthermore, baseline asymptomatic adolescents who showed a significant increase in depression symptoms at follow up (between 6 and 54 months) had reduced baseline connectivity between the amygdala and the inferior frontal, supramarginal and mid‐cingulate gyri at baseline, when compared to adolescents who showed no change in depressive symptoms (Scheuer et al, ). Lastly, in healthy adolescents, a decrease in functional connectivity between the subgenual anterior cingulate cortex and the dorsal medial prefrontal cortex, posterior cingulate cortex, angular gyrus and middle temporal gyrus, between baseline and follow‐up (average of 2 years) was associated with higher depressive symptoms at follow‐up (Strikwerda‐Brown et al, ).…”