Distinct brain network features predict internalizing and externalizing traits in children and adults.

Internalizing and externalizing traits are two distinct classes of behaviors in psychiatry. However, whether shared or unique brain network features predict internalizing and externalizing behaviors in children and adults remain poorly understood. Using a sample of 2262 children from the Adolescent Brain Cognitive Development (ABCD) study and 752 adults from the Human Connectome Project (HCP), we show that network features predicting internalizing and externalizing behavior are, at least in part, dissociable in children, but not in adults. In ABCD children, traits within internalizing and externalizing behavioral categories are predicted by more similar network features concatenated across task and resting states than those between different categories. We did not observe this pattern in HCP adults. Distinct network features predict internalizing and externalizing behaviors in ABCD children and HCP adults. These data reveal shared and unique brain network features accounting for individual variation within broad internalizing and externalizing categories across developmental stages.

Brain-Based Predictions of Psychiatric Illness-Linked Behaviors Across the Sexes.

BACKGROUND: Individual differences in functional brain connectivity can be used to predict both the presence of psychiatric illness and variability in associated behaviors. However, despite evidence for sex differences in functional network connectivity and in the prevalence, presentation, and trajectory of psychiatric illnesses, the extent to which disorder-relevant aspects of network connectivity are shared or unique across the sexes remains to be determined. METHODS: In this work, we used predictive modeling approaches to evaluate whether shared or unique functional connectivity correlates underlie the expression of psychiatric illness-linked behaviors in males and females in data from the Adolescent Brain Cognitive Development Study (N = 5260; 2571 females). RESULTS: We demonstrate that functional connectivity profiles predict individual differences in externalizing behaviors in males and females but predict internalizing behaviors only in females. Furthermore, models trained to predict externalizing behaviors in males generalize to predict internalizing behaviors in females, and models trained to predict internalizing behaviors in females generalize to predict externalizing behaviors in males. Finally, the neurobiological correlates of many behaviors are largely shared within and across sexes: functional connections within and between heteromodal association networks, including default, limbic, control, and dorsal attention networks, are associated with internalizing and externalizing behaviors. CONCLUSIONS: Taken together, these findings suggest that shared neurobiological patterns may manifest as distinct behaviors across the sexes. Based on these results, we recommend that both clinicians and researchers carefully consider how sex may influence the presentation of psychiatric illnesses, especially those along the internalizing-externalizing spectrum.

Associations Between Prenatal Cannabis Exposure and Childhood Outcomes: Results From the ABCD Study.

Importance: In light of increasing cannabis use among pregnant women, the US Surgeon General recently issued an advisory against the use of marijuana during pregnancy. Objective: To evaluate whether cannabis use during pregnancy is associated with adverse outcomes among offspring. Design, Setting, and Participants: In this cross-sectional study, data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development Study, which recruited 11 875 children aged 9 to 11 years, as well as a parent or caregiver, from 22 sites across the United States between June 1, 2016, and October 15, 2018. Exposure: Prenatal cannabis exposure prior to and after maternal knowledge of pregnancy. Main Outcomes and Measures: Symptoms of psychopathology in children (ie, psychotic-like experiences [PLEs] and internalizing, externalizing, attention, thought, and social problems), cognition, sleep, birth weight, gestational age at birth, body mass index, and brain structure (ie, total intracranial volume, white matter volume, and gray matter volume). Covariates included familial (eg, income and familial psychopathology), pregnancy (eg, prenatal exposure to alcohol and tobacco), and child (eg, substance use) variables. Results: Among 11 489 children (5997 boys [52.2%]; mean [SD] age, 9.9 [0.6] years) with nonmissing prenatal cannabis exposure data, 655 (5.7%) were exposed to cannabis prenatally. Relative to no exposure, cannabis exposure only before (413 [3.6%]) and after (242 [2.1%]) maternal knowledge of pregnancy were associated with greater offspring psychopathology characteristics (ie, PLEs and internalizing, externalizing, attention, thought and, social problems), sleep problems, and body mass index, as well as lower cognition and gray matter volume (all |ß| > 0.02; all false discovery rate [FDR]-corrected P < .03). Only exposure after knowledge of pregnancy was associated with lower birth weight as well as total intracranial volume and white matter volumes relative to no exposure and exposure only before knowledge (all |ß| > 0.02; all FDR-corrected P < .04). When including potentially confounding covariates, exposure after maternal knowledge of pregnancy remained associated with greater PLEs and externalizing, attention, thought, and social problems (all ß > 0.02; FDR-corrected P < .02). Exposure only prior to maternal knowledge of pregnancy did not differ from no exposure on any outcomes when considering potentially confounding variables (all |ß| < 0.02; FDR-corrected P > .70). Conclusions and Relevance: This study suggests that prenatal cannabis exposure and its correlated factors are associated with greater risk for psychopathology during middle childhood. Cannabis use during pregnancy should be discouraged.

No associations in preregistered study of youth depression and functional connectivity of fronto-parietal and default mode networks.

Adolescence is characterized by vulnerability to the onset of major depressive disorder (MDD). The goal of this preregistered study was to assess neural correlates of depression symptoms in young adolescents, both cross-sectionally and longitudinally. The default mode network (DMN) is believed to support internal attention towards self-referential thoughts, while the fronto-parietal network (FPN) is theorized to support cognitive control and regulation of attention. As MDD diagnosis has been associated with heightened connectivity within DMN regions and diminished connectivity within FPN regions relative to healthy controls, our study builds upon group-difference analyses by using dimensional measures of depression severity. Our preregistered hypotheses were that within-DMN functional connectivity would be positively associated with concurrent depression severity, while within-FPN functional connectivity would be negatively associated with concurrent depression severity. Preregistered analyses also examined between DMN-FPN connectivity as an alternative predictor variable, and assessed the longitudinal associations between all three functional connectivity measures and change in depression severity over three subsequent waves. Multiple regression models tested cross-sectional analyses and hierarchical linear models tested longitudinal analyses. One hundred and twenty-four youth completed a resting state functional MRI. Their depression severity was assessed at the time of the scan and at three follow-up sessions. None of the predictor variables were associated with concurrent depression severity, nor with the slope of depression symptom trajectories in longitudinal analyses. These negative results add to extant cross-sectional studies, and may inform future investigations of brain correlates of depression psychopathology in youth.