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Depression recurrence is debilitating, and there is a pressing need to develop clinical tools that detect the re-emergence of symptoms with the aim of bridging patients to treatment before recurrences. At baseline, remitted depressed adults (n=22) and healthy controls (n=24) were administered clinical interviews and completed self-report symptom measures. Then, smartphone apps were installed on personal smartphones to acquire geolocation data over 21 days and ecological momentary assessment of positive and negative affect during the initial 14-day period. Compared with healthy controls, remitted depressed adults exhibited reduced circadian routine (regularity of one’s daily routine) and lower average daily distance traveled. Further, reduced distance traveled associated with greater daily negative affect after controlling for depression severity; however, this effect was not more pronounced among remitted adults. A LASSO regression indicated that a linear combination of circadian routine, average distance traveled, and baseline depression severity classified remitted depressed individuals with 72% accuracy; outperforming models restricted to either geolocation or clinical measures alone. Mobile sensing approaches hold enormous promise to improve clinical care for depressive disorders. Although barriers remain, leveraging technological advancements related to real-time monitoring can improve treatment for depressed patients and potentially, reduce high rates of recurrence.

Background Neurobiological measures may inform our understanding of individual differences in adolescents’ general risk for and resilience to depressive symptoms, including during the COVID-19 pandemic. We tested a developmental model linking variation in amygdala–subgenual anterior cingulate cortex (sgACC) resting-state connectivity to perceived parenting experiences earlier in adolescence, to concurrent depressive symptoms before the pandemic, and to subsequent depressive symptoms during the pandemic. Methods We used data from a longitudinal study that included three waves (N = 214 adolescents; ages 9–15 years at time 1 [T1], 11–17 years at T2, and 12–19 years during the pandemic at T3). We assessed positive parenting (warm and supportive) (T1), depressive symptoms (T1 to T3), and functional connectivity between the sgACC and basolateral (BLA) and centromedial amygdala (T1 and T2). We modeled associations among earlier positive parenting, amygdala–sgACC connectivity, and depressive symptoms before and during the pandemic. Results Less positive parenting at T1 was associated prospectively with stronger BLA–sgACC connectivity at T2 (β = −0.22) over and above the effect of BLA–sgACC connectivity at T1. Stronger BLA–sgACC connectivity, in turn, was associated with heightened depressive symptoms, both before the pandemic (r = 0.21) and during the pandemic (β = 0.19; independent of the effect of pre-pandemic symptoms). Conclusions Adolescents who experience less positive parenting may develop a pattern of BLA–sgACC connectivity that increases their risk for mental health problems. BLA–sgACC connectivity may be associated with depressive symptoms in general, including during periods of heightened risk for adolescents, such as the pandemic.

Sleep health tends to worsen during adolescence, partially due to pubertal-related changes that, in combination with social and psychological factors, can lead to long-lasting impairments in sleep health and affective functioning. Discrepant findings between subjective and objective measures of sleep in relation to affect have been reported in studies of adults; however, few investigations have assessed both subjective and objective sleep quality in a single sample, and fewer have examined this in the context of pubertal development. We aimed to (1) characterise pubertal associations with subjective sleep satisfaction, objective sleep efficiency, and objective and subjective sleep duration in adolescents; (2) examine the longitudinal association between daily affect and sleep metrics; and (3) test whether pubertal stage moderated this association. Eighty-nine participants (64% female, ages 13-20) completed an ecological momentary assessment (EMA) and actigraphy protocol. Independent of age, advanced pubertal stage was associated with lower subjective sleep satisfaction but not with objective sleep indices. Subjective sleep satisfaction was associated with within-person trajectories of negative affect, but not with positive affect. Pubertal stage and sleep satisfaction did not interact to predict within-day negative or positive affect. These findings are consistent with previous reports showing that objective and subjective sleep health are associated differently with puberty, and that subjective sleep health is associated with daily affect. Pubertal stage may be a more important indicator of subjective sleep quality in adolescence than is chronological age, most likely due to hormonal changes and psychological adjustment to the physical changes associated with the pubertal transition.

Background Suicidal ideation (SI) typically emerges during adolescence but is challenging to predict. Given the potentially lethal consequences of SI, it is important to identify neurobiological and psychosocial variables explaining the severity of SI in adolescents. Methods In 106 participants (59 female) recruited from the community, we assessed psychosocial characteristics and obtained resting-state fMRI data in early adolescence (baseline: aged 9-13 years). Across 250 brain regions, we assessed local graph theory-based properties of interconnectedness: local efficiency, eigenvector centrality, nodal degree, within-module z-score, and participation coefficient. Four years later (follow-up: ages 13-19 years), participants self-reported their SI severity. We used least absolute shrinkage and selection operator (LASSO) regressions to identify a linear combination of psychosocial and brain-based variables that best explain the severity of SI symptoms at follow-up. Nested-cross-validation yielded model performance statistics for all LASSO models. Results A combination of psychosocial and brain-based variables explained subsequent severity of SI (R2 = .55); the strongest was internalizing and externalizing symptom severity at follow-up. Follow-up LASSO regressions of psychosocial-only and brain-based-only variables indicated that psychosocial-only variables explained 55% of the variance in SI severity; in contrast, brain-based-only variables performed worse than the null model. Conclusions A linear combination of baseline and follow-up psychosocial variables best explained the severity of SI. Follow-up analyses indicated that graph theory resting-state metrics did not increase the prediction of the severity of SI in adolescents. Attending to internalizing and externalizing symptoms is important in early adolescence; resting-state connectivity properties other than local graph theory metrics might yield a stronger prediction of the severity of SI.

The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents’ mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13–19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.

Suicide is a leading cause of death, and presently, there is no definitive clinical indicator of future suicide behaviors. Anhedonia, a transdiagnostic symptom reflecting diminished ability to experience pleasure, has recently emerged as a risk factor for suicidal thoughts and behaviors (STBs). This overview, therefore, has the following aims. First, prior research relating anhedonia to STBs will be reviewed, with a particular focus on clarifying whether anhedonia is more closely associated with suicidal thoughts versus behaviors. Second, the National Institute of Mental Health's Research Domain Criteria Positive Valence Systems provide a useful heuristic to probe anhedonia across different units of analysis, including clinical symptoms, behaviors, neural mechanisms, and molecular targets. Accordingly, anhedonia-related constructs linked to STBs will be detailed as well as promising next steps for future research. Third, although anhedonia is not directly addressed in leading suicide theories, this review will provide potential inroads to explore anhedonia within diathesis-stress and interpersonal suicide frameworks. Last, novel approaches to treat anhedonia as a means of reducing STBs will be examined.

Background: Neurobiological measures may serve as predictive markers of risk for and resilience to depressive symptoms during the COVID-19 pandemic. We tested a developmental model linking variation in amygdala–subgenual anterior cingulate cortex (sgACC) resting-state connectivity both to earlier experiences in the family environment and to subsequent vulnerability to depressive symptoms during the pandemic.Methods: We used data from a longitudinal study that included three waves (N=214 adolescents; ages 9-15 years at Time 1 (T1), 11-17 years at Time 2 (T2), and 12-19 years during the pandemic at Time 3 [T3]). We assessed parental warmth (T1), depressive symptoms (T1 to T3), and functional connectivity between the sgACC and basolateral (BLA) and centromedial amygdala (CMA) (T1 and T2). We modeled associations among early parental warmth, amygdala–sgACC connectivity, and depressive symptoms before and during the pandemic.Results: Less parental warmth was associated prospectively with stronger BLA–sgACC connectivity approximately two years later (=-.23, p=.021) over and above the effect of BLA–sgACC connectivity at T1. Stronger BLA–sgACC connectivity, in turn, was associated with heightened depressive symptoms, both before (r=.21, p=.031) and during the pandemic (=.22, p=.031; independent of the effect of pre-pandemic symptoms). Conclusion: Adolescents who experience less parental warmth may develop a pattern of BLA–sgACC connectivity that increases their risk for mental health problems during the pandemic. BLA–sgACC connectivity in early to middle adolescence may be a predictive marker of risk for depressive symptoms in general and specifically during periods of heightened stress.

Highlights • We tested the impact of early life stress (ELS) on age-white matter (WM) relations. • Higher ELS youth showed greater age-WM associations in several tracts. • These tracts connected frontal regions with limbic, occipital, and parietal regions. • Older youth with higher ELS showed a negative uncinate-internalizing association. • More mature uncinate morphometry may be adaptive in ELS-exposed adolescents., Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9–14) to assess lifetime exposure to stress and objective cumulative ELS severity. We used diffusion-weighted imaging to measure WM fixel-based morphometry and tested the effects of age and ELS on WM fiber density and cross-section (FDC), and associations between WM FDC and internalizing problems. Age was positively associated with FDC in all WM tracts; greater ELS severity was related to stronger age-WM associations in several association tracts connecting the frontal lobes with limbic, parietal, and occipital regions, including bilateral superior and inferior longitudinal and uncinate fasciculi (UF). Among older adolescents with greater ELS severity, a higher UF FDC was associated with fewer internalizing problems. Greater ELS severity predicted more mature WM morphometry in tracts implicated in emotion regulation and cognitive processing. More phenotypically mature UF WM may be adaptive against internalizing psychopathology in adolescents exposed to ELS.

BackgroundSuicidal ideation (SI) typically emerges during adolescence but is challenging to predict. Given the consequences of SI, it is important to identify neurobiological and psychological predictors of SI in adolescents in order to improve strategies to prevent suicide.MethodsIn 109 participants (61 female), we assessed psychological characteristics and obtained resting-state fMRI data in early adolescence (ages 9-13). Using graph theoretical methods, we assessed local network properties across 250 brain regions by computing measures of nodal interconnectedness: local efficiency, eigenvector centrality, nodal degree, within-module z-score, and participation coefficient. Four years later (ages 13-17), participants self-reported their SI severity. We used LASSO regression to identify a linear combination of the most important psychological, environmental, and brain-based predictors of future SI severity.ResultsThe LASSO analysis identified a combination of 10 predictors of future SI severity (R2=0.23). Severity of internalizing symptoms at baseline was the strongest predictor; the remaining 9 predictors were brain-based, including nodal degree of the inferior frontal gyrus, precentral gyrus, fusiform gyrus, and inferior temporal gyrus; within-module degree of the substantia nigra and inferior parietal lobe; eigenvector centrality of the subgenual cingulate gyrus; participation coefficient of the caudal cingulate gyrus and medial amygdala.ConclusionsOur findings suggest that combining network properties and earlier internalizing symptoms may improve prediction of later SI, compared to prior symptoms and other sociodemographic variables alone. Research should validate the clinical utility of these markers as predictors of suicidal thoughts.

Background Early pubertal maturation has been posited to be a biopsychosocial risk factor for the onset of internalizing psychopathology in adolescence; further, early-maturing youths exhibit heightened reactivity to stressful events. School closures and enforced social distancing, as well as health and financial uncertainties, during the COVID-19 pandemic are expected to adversely affect mental health in youths, particularly adolescents who are already at risk for experiencing emotional difficulties. The executive control network (ECN) supports cognitive processes required to successfully navigate novel challenges and regulate emotions in stressful contexts. Methods We examined whether functional coherence of the ECN, measured using resting-state functional magnetic resonance imaging 5 years before the pandemic (T1), is a neurobiological marker of resilience to increases in the severity of internalizing symptoms during COVID-19 in adolescents who were in more advanced stages of puberty at T1 relative to their same-age peers (N = 85, 49 female). Results On average, participants reported an increase in symptoms from the 3 months before pandemic to the 2 most recent weeks during the pandemic. We found that early-maturing youths exhibited greater increases in internalizing symptoms during the pandemic if their ECN coherence was low; in contrast, relative pubertal stage was not associated with changes in internalizing symptoms in adolescents with higher ECN coherence at T1. Conclusions These findings highlight the role of the functional architecture of the brain that supports executive functioning in protecting against risk factors that may exacerbate symptoms of internalizing psychopathology during periods of stress and uncertainty.