Sleep dysfunction mediates the relationship between hypothalamic-insula connectivity and anxiety-depression symptom severity bidirectionally in young adults.

BACKGROUND: The hypothalamus plays a crucial role in regulating sleep-wake cycle and motivated behavior. Sleep disturbance is associated with impairment in cognitive and affective functions. However, how hypothalamic dysfunction may contribute to inter-related sleep, cognitive, and emotional deficits remain unclear. METHODS: We curated the Human Connectome Project dataset and investigated how hypothalamic resting state functional connectivities (rsFC) were associated with sleep dysfunction, as evaluated by the Pittsburgh Sleep Quality Index (PSQI), cognitive performance, and subjective mood states in 687 young adults (342 women). Imaging data were processed with published routines and evaluated with a corrected threshold. We examined the inter-relationship amongst hypothalamic rsFC, PSQI score, and clinical measures with mediation analyses. RESULTS: In whole-brain regressions with age and drinking severity as covariates, men showed higher hypothalamic rsFC with the right insula in correlation with PSQI score. No clusters were identified in women at the same threshold. Both hypothalamic-insula rsFC and PSQI score were significantly correlated with anxiety and depression scores in men. Further, mediation analyses showed that PSQI score mediated the relationship between hypothalamic-insula rsFC and anxiety/depression symptom severity bidirectionally in men. CONCLUSIONS: Sleep dysfunction is associated with negative emotions and hypothalamic rsFC with the right insula, a core structure of the interoceptive circuits. Notably, anxiety-depression symptom severity and altered hypothalamic-insula rsFC are related bidirectionally by poor sleep quality. These findings are specific to men, suggesting potential sex differences in the neural circuits regulating sleep and emotional states that need to be further investigated.

Gray matter volumetric correlates of attention deficit and hyperactivity traits in emerging adolescents.

Previous research has demonstrated reduction in cortical and subcortical, including basal ganglia (BG), gray matter volumes (GMV) in individuals with attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition that is more prevalent in males than in females. However, the volumetric deficits vary across studies. Whether volumetric reductions are more significant in males than females; to what extent these neural markers are heritable and relate to cognitive dysfunction in ADHD remain unclear. To address these questions, we followed published routines and performed voxel-based morphometry analysis of a data set (n = 11,502; 5,464 girls, 9-10 years) curated from the Adolescent Brain Cognition Development project, a population-based study of typically developing children. Of the sample, 634 and 2,826 were identified as monozygotic twins and dizygotic twins/siblings, respectively. In linear regressions, a cluster in the hypothalamus showed larger GMV, and bilateral caudate and putamen, lateral orbitofrontal and occipital cortex showed smaller GMVs, in correlation with higher ADHD scores in girls and boys combined. When examined separately, boys relative to girls showed more widespread (including BG) and stronger associations between GMV deficits and ADHD scores. ADHD traits and the volumetric correlates demonstrated heritability estimates (a2) between 0.59 and 0.79, replicating prior findings of the genetic basis of ADHD. Further, ADHD traits and the volumetric correlates (except for the hypothalamus) were each negatively and positively correlated with N-back performance. Together, these findings confirm volumetric deficits in children with more prominent ADHD traits. Highly heritable in both girls and boys and potentially more significant in boys than in girls, the structural deficits underlie diminished capacity in working memory and potentially other cognitive deficits in ADHD.

Gray matter volumetric correlates of dimensional impulsivity traits in children: Sex differences and heritability.

Previous research investigated the cerebral volumetric correlates of impulsivity largely in moderate-sized samples and few have examined the distinct correlates of dimensions of impulsivity, sex differences, or heritability of the correlates. Here, we performed voxel-based morphometry analysis of data (n = 11,474; 5,452 girls, 9-10 years) curated from the Adolescent Brain Cognition Development project. In a linear regression with all five UPPS-P subscores as regressors and age in months, total intracranial volume, study site, and scanner model as covariates, higher levels of lack of premeditation, and sensation seeking were correlated with larger cortical and subcortical gray matter volumes (GMVs). In contrast, higher positive urgency was correlated with smaller GMVs in many of the same regions. The dimensional impulsivity traits also involved distinct volumetric correlates, with, for instance, sensation seeking and positive urgency specifically implicating bilateral caudate head/mid-cingulate cortex and bilateral lateral orbitofrontal cortex/left precentral gyrus, respectively. Boys relative to girls scored higher in all impulsivity dimensions. Girls relative to boys showed significantly stronger positive and negative correlations between sensation seeking and insula, putamen, and inferior frontal gyrus (IFG) GMVs and between positive urgency and cingulate cortex, insula, and IFG GMVs, respectively. With a subsample of twins, the dimensional impulsivity traits were weakly to moderately heritable in both girls and boys, and the GMV correlates were highly heritable in girls and boys combined. These findings collectively suggest shared and nonshared as well as sex differences in the cerebral volumetric bases of dimensional impulsivity traits and may facilitate research of externalizing psychopathology in children.

Sex Differences in Depression and Sleep Disturbance as Inter-Related Risk Factors of Diabetes.

Objectives: Previous studies identified depression and sleep disturbance as risk factors for diabetes. Sleep disturbance and depression are known to be inter-related. Further, women relative to men are more prone to depression. Here, we investigated how depression and sleep disturbance may jointly influence the risk of diabetes and the effects of sex on these influences. Methods: Using the data of 21,229 participants from the 2018 National Health Interview Survey, we performed multivariate logistic regression with diabetes diagnosis as the dependent variable, sex, self-reported frequency of weekly depression and nightly sleep duration, and their interactions with sex as independent variables, and age, race, income, body mass index and physical activity as covariates. We employed Bayesian and Akaike Information criteria to identify the best model, evaluated the accuracy of the model in predicting diabetes using receiver operating characteristic analysis, and computed the odds ratios of these risk factors. Results: In the two best models, depression frequency and sleep hours interact with sex in determining the diagnosis of diabetes, with higher depression frequency and nightly duration of sleep longer or shorter than 7 to 8 hours associated with higher likelihood of diabetes. The two models both predicted diabetes at an accuracy (area under the receiver operating characteristic curve) of 0.86. Further, these effects were stronger in men than in women at each depression and sleep level. Conclusions: Depression and sleep inter-relatedly rather than independently contributes to diabetes. Depression and sleep hours associate with diabetes more significantly in men than in women. The current findings indicate a sex-dependent relationship between depression, sleep disturbance and diabetes risk and add to a growing body of evidence linking mental and physical health.

Gray matter volumetric correlates of behavioral activation and inhibition system traits in children: An exploratory voxel-based morphometry study of the ABCD project data.

Approach and avoidance represent two fundamental behavioral traits that develop early in life. Previous studies have examined the neural correlates of approach and avoidance traits in adults and adolescents. Here, using the data set of the Adolescent Brain Cognition Development project, we investigated the structural cerebral bases of behavioral activation system (BAS) and behavioral inhibition system (BIS) in children. We employed voxel-based morphometry to examine how gray matter volumes (GMV) related specifically to BAS and BIS traits in 11,542 children (5491 girls, age 9-10 years) with 648 and 2697 identified as monozygotic twins (MZ) and dizygotic twins/siblings (DZ), respectively. After accounting for the BIS score, higher BAS scores (residuals) were positively correlated with the GMV of the ventral striatum (VS), and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability (h2) of 0.8463. Higher BAS scores were negatively correlated with the GMV of bilateral visual, lateral orbitofrontal, temporal, and inferior frontal cortex, as well as the precuneus. Higher BIS (after accounting for BAS) scores were negatively correlated with the GMVs of the ventral caudate and bilateral putamen/pallidum, hypothalamus, and right anterior insula, and the correlation was stronger in MZ than in DZ and unrelated children, with a heritability of 0.8848. A cluster in the VS showed positive and negative correlation with the BAS and BIS scores, respectively. These findings suggest shared and distinct cerebral volumetric bases of the BAS and BIS traits in children. Whereas both traits have a strong genetic basis, the BAS relative to BIS appears to be more amenable to environmental influences. These findings add to the literature of developmental neuroscience and may help identify genetic risk factors of externalizing and internalizing psychopathology.

Social anxiety, posterior insula activation, and autonomic response during self-initiated action in a Cyberball game.

BACKGROUND: An earlier study characterized the neural correlates of self-initiated actions in a Cyberball game in healthy individuals. It remains unclear how social anxiety may influence these neural processes. METHODS: We examined regional activations to self-initiated actions in 25 adults with low and 25 with high social anxiety (LA and HA, respectively). Skin conductance was recorded concurrently with fMRI. We followed published routines in the analyses of imaging and skin conductance data. RESULTS: We hypothesized that HA as compared to LA individuals would demonstrate increased cortical limbic activations during self-initiated actions (tossing or T > receiving or R trials, to control for motor activities) in social exclusion (EX) vs. fair game (FG) scenario. At a corrected threshold, HA as compared with LA group showed increases in bilateral posterior insula activation during T vs. R trials in EX as compared to FG. Further, HA as compared to LA showed higher skin conductance response to tossing trials during EX as compared to FG. LIMITATIONS: With a limited sample size, we did not examine potential sex effects. Further, we cannot rule out the effects of depression on the findings. CONCLUSIONS: Together, the results suggest that individuals with more severe social anxiety engaged the somatosensory insula to a greater extent and exhibited higher physiological arousal when initiating ball toss during social exclusion in the Cyberball game. Posterior insula response to self-initiated action may represent a biomarker of social anxiety. It remains to be investigated whether interventions to decrease physiological arousal may alleviate social anxiety.

Cerebral responses to self-initiated action during social interactions.

Social interaction involves self-initiated actions that engage subjective awareness of one's own volition. Individuals with social communication needs or social anxiety find it particularly difficult to initiate social interactions. However, extant studies have not specifically addressed how perceived exclusion may influence self-initiated actions during social interaction. As a first step to address this question, we scanned 24 healthy adults participating in a Cyberball game with two fictive players. By contrasting events of observing, receiving, and initiating ball toss during a scenario of fair game (FG) and of exclusion (EX), we examined the neural correlates of self-initiated action during social interactions. Behaviorally, participants were faster in catching but slower in tossing the ball in EX compared with FG, suggesting a burden during self-initiated actions during social exclusion. Tossing versus receiving (or observing) engaged higher activity during EX than FG in the precuneus and angular gyrus, regions that have been widely implicated in theory of mind processing and social emotions. Across subjects these cortical activities correlated positively with the difference between EX and FG in the percentage of trials where participants tossed the ball back to the same player (r = 0.69, p < 0.001). Together, the results suggested that, in healthy adults, social exclusion encumbered and engaged higher posterior cortical activations during self-initiated actions. The findings may facilitate future research of neural markers of social behavioral disorders.