Tiffany C. Ho

The COVID-19 pandemic and its associated lockdowns were an unprecedented source of stress, with striking adverse effects on adolescents’ mental health but relatively unknown effects on important aspects of neurobiological functioning. Using data from 154 adolescents (age M ± SD = 16.2 ± 1.1 years; range = 13.9–19.4) drawn from an ongoing longitudinal study and assessed either before or after the pandemic, we compared the pre-pandemic and post-pandemic groups on three key stress-sensitive biological systems: the hypothalamic-pituitary-adrenal (HPA) axis, immune response, and neural responses to affective stimuli. We found that compared to those assessed before the pandemic, adolescents assessed post-lockdown had significantly lower total cortisol production, elevated levels of systemic inflammation, and reduced neural activation in the prefrontal cortex during affective processing (pseudo-F(1,3250) = 7.43, p = 0.006). These findings suggest that, for adolescents, the experience of the pandemic was associated with significant disruptions in multiple biological systems that are sensitive to stress that might have enduring adverse developmental effects.

Childhood maltreatment (CM), encompassing abuse and neglect, affects over two-thirds of the general population and increases risk for stress-related psychopathology, including major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). The extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM, however, is uncertain. Here, we analyzed CM and 3D structural brain MRI data from 3,711 participants in the ENIGMA MDD and PTSD Working Groups (25 sites; 33.3±13.0 years; 59.9% female). Normative modeling estimated deviation z-scores for 14 subcortical volumes (SV), 68 cortical thickness (CT), and 68 surface area (SA) measures, capturing differences from population norms. Transdiagnostic associations between CM and brain deviation scores were evaluated within each sex and age cohort. In young adults (ages 18-35), abuse was associated with larger volumes in thalamus and pallidum, thinner isthmus cingulate and middle frontal regions, and thicker medial orbitofrontal cortex; there were no significant effects in pediatric (≤18 years) participants. The strongest effects were observed in young female adults (|β|=.07-.22, q<.05): greater abuse and neglect were correlated with smaller hippocampus and putamen volumes, thinner entorhinal cortex, and smaller SA in fusiform/inferior parietal regions, and with larger SA in orbitofrontal and occipital cortices. In males, abuse had widespread effects on CT and SA (|β|=.1-.18, q<.05); effects for neglect were minimal. Our findings of age- and sex-specific instantiations of CM on brain morphometry highlight the importance of developmental context in understanding how adverse experiences shape neurobiological vulnerability to MDD and PTSD.

Magnetic resonance imaging has provided pathophysiological insights into adolescent depression but is a relatively inaccessible technology. Generating scalable indicators of depression that are informed by neuroscience is therefore critical for providing solutions that allow us to detect and treat this devastating disorder. In this preregistered study, we investigated whether passively acquired smartphone-based language usage represents such an indicator of depression and explored whether the neural correlates of depression mediate or moderate this association. Forty adolescents (ages 14–18 years) with ( n = 26) and without ( n = 14) depression completed clinical assessments and a resting-state fMRI scan, prior to downloading a passive mobile sensing app to their smartphones. Linguistic features derived from over 1.2 million words (319,364 messages) across all smartphone apps were used to examine word usage patterns. Independent components analysis followed by dual regression was used to derive intrinsic networks commonly associated with depression: central executive network (CEN), default mode network (DMN), and salience network (SN). Depression was associated with more negative emotion word usage and fewer future-focus word usage on a daily basis (all ps < 0.05). Higher depressive symptoms and brain networks DMN and CEN were associated with greater first-person pronoun usage (all p s < 0.04). Accounting for CEN connectivity amplified the positive association between depressive symptoms and first-person pronoun usage. Lower SN–CEN connectivity moderated the association between depression and negative emotion word usage. Depression in adolescents is associated with naturalistic language usage during smartphone activities and may represent neurocognitive biases that are candidate treatment targets for interventions.