Striatal correlates of Bayesian beliefs in self-efficacy in adolescents and their relation to mood and autonomy: a pilot study.

Major depressive disorder often originates in adolescence and is associated with long-term functional impairment. Mechanistically characterizing this heterogeneous illness could provide important leads for optimizing treatment. Importantly, reward learning is known to be disrupted in depression. In this pilot fMRI study of 21 adolescents (16-20 years), we assessed how reward network disruption impacts specifically on Bayesian belief representations of self-efficacy (SE-B) and their associated uncertainty (SE-U), using a modified instrumental learning task probing activation induced by the opportunity to choose, and an optimal Hierarchical Gaussian Filter computational model. SE-U engaged caudate, nucleus accumbens (NAcc), precuneus, posterior parietal and dorsolateral prefrontal cortex (PFWE < 0.005). Sparse partial least squares analysis identified SE-U striatal activation as associating with one's sense of perceived choice and depressive symptoms, particularly anhedonia and negative feelings about oneself. As Bayesian uncertainty modulates belief flexibility and their capacity to steer future actions, this suggests that these striatal signals may be informative developmentally, longitudinally and in assessing response to treatment.

Keeping up with the kids: the value of co-production in the study of irritability in youth depression and its underlying neural circuitry.

Irritability is a core symptom of adolescent depression, characterized by an increased proneness to anger or frustration. Irritability in youth is associated with future mental health problems and impaired social functioning, suggesting that it may be an early indicator of emotion regulation difficulties. Adolescence is a period during which behavior is significantly impacted by one's environment. However, existing research on the neural basis of irritability typically use experimental paradigms that overlook the social context in which irritability occurs. Here, we bring together current findings on irritability in adolescent depression and the associated neurobiology and highlight directions for future research. Specifically, we emphasize the importance of co-produced research with young people as a means to improve the construct and ecological validity of research within the field. Ensuring that our research design and methodology accurately reflect to lives of young people today lays a strong foundation upon which to better understand adolescent depression and identify tractable targets for intervention.

Puberty differentially predicts brain maturation in male and female youth: A longitudinal ABCD Study.

Research has demonstrated associations between pubertal development and brain maturation. However, existing studies have been limited by small samples, cross-sectional designs, and inconclusive findings regarding directionality of effects and sex differences. We examined the longitudinal temporal coupling of puberty status assessed using the Pubertal Development Scale (PDS) and magnetic resonance imaging (MRI)-based grey and white matter brain structure. Our sample consisted of 8896 children and adolescents at baseline (mean age = 9.9) and 6099 at follow-up (mean age = 11.9) from the Adolescent Brain and Cognitive Development (ABCD) Study cohort. Applying multigroup Bivariate Latent Change Score (BLCS) models, we found that baseline PDS predicted the rate of change in cortical thickness among females and rate of change in cortical surface area for both males and females. We also found a correlation between baseline PDS and surface area and co-occurring changes over time in males. Diffusion tensor imaging (DTI) analyses revealed correlated change between PDS and fractional anisotropy (FA) for both males and females, but no significant associations for mean diffusivity (MD). Our results suggest that pubertal status predicts cortical maturation, and that the strength of the associations differ between sex. Further research spanning the entire duration of puberty is needed to understand the extent and contribution of pubertal development on the youth brain.

Cognitive Function in People With Familial Risk of Depression.

Importance: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span. Objective: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Design, Setting, and Participants: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022. Exposures: Family history (across 1 or 2 prior generations) and polygenic risk of depression. Main Outcomes and Measures: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons. Results: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were -0.55 (95% CI, -1.49 to 0.38) in TGS, -0.09 (95% CI, -0.15 to -0.03) in ABCD, -0.16 (95% CI, -0.31 to -0.01) in Add Health, and -0.10 (95% CI, -0.13 to -0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models. Conclusions and Relevance: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span.

The role of brain structure in the association between pubertal timing and depression risk in an early adolescent sample (the ABCD Study®): A registered report.

BACKGROUND: Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear. METHODS: The current registered report examined associations between pubertal timing (indexed via perceived pubertal development), brain structure (cortical and subcortical metrics, and white matter microstructure) and depressive symptoms in a large sample (N = âˆ¼5000) of adolescents (aged 9-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We used three waves of follow-up data when the youth were aged 10-11 years, 11-12 years, and 12-13 years, respectively. We used generalised linear-mixed models (H1) and structural equation modelling (H2 & H3) to test our hypotheses. HYPOTHESES: We hypothesised that earlier pubertal timing at Year 1 would be associated with increased depressive symptoms at Year 3 (H1), and that this relationship would be mediated by global (H2a-b) and regional (H3a-g) brain structural measures at Year 2. Global measures included reduced cortical volume, thickness, surface area and sulcal depth. Regional measures included reduced cortical thickness and volume in temporal and fronto-parietal areas, increased cortical volume in the ventral diencephalon, increased sulcal depth in the pars orbitalis, and reduced fractional anisotropy in the cortico-striatal tract and corpus callosum. These regions of interest were informed by our pilot analyses using baseline ABCD data when the youth were aged 9-10 years. RESULTS: Earlier pubertal timing was associated with increased depressive symptoms two years later. The magnitude of effect was stronger in female youth and the association remained significant when controlling for parental depression, family income, and BMI in females but not in male youth. Our hypothesised brain structural measures did not however mediate the association between earlier pubertal timing and later depressive symptoms. CONCLUSION: The present results demonstrate that youth, particularly females, who begin puberty ahead of their peers are at an increased risk for adolescent-onset depression. Future work should explore additional biological and socio-environmental factors that may affect this association so that we can identify targets for intervention to help these at-risk youth.

A practical guide for researchers and reviewers using the ABCD Study and other large longitudinal datasets.

As the largest longitudinal study of adolescent brain development and behavior to date, the Adolescent Brain Cognitive Development (ABCD) Study® has provided immense opportunities for researchers across disciplines since its first data release in 2018. The size and scope of the study also present a number of hurdles, which range from becoming familiar with the study design and data structure to employing rigorous and reproducible analyses. The current paper is intended as a guide for researchers and reviewers working with ABCD data, highlighting the features of the data (and the strengths and limitations therein) as well as relevant analytical and methodological considerations. Additionally, we explore justice, equity, diversity, and inclusion efforts as they pertain to the ABCD Study and other large-scale datasets. In doing so, we hope to increase both accessibility of the ABCD Study and transparency within the field of developmental cognitive neuroscience.

Brain structural associations with depression in a large early adolescent sample (the ABCD study®).

BACKGROUND: Depression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However, most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention. METHODS: Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018. FINDINGS: We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen's d = -0⋅018 to -0⋅041, ß = -0·019 to -0⋅057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute ß = 0⋅048 to 0⋅169). INTERPRETATION: Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology. FUNDING: Wellcome Trust (References: 104036/Z/14/Z and 220857/Z/20/Z) and the Medical Research Council (MRC, Reference: MC_PC_17209).