Introduction The hypothalamus-pituitary–adrenal (HPA) axis plays an important role in regulating behavior, neuroplastic responses to the environment during childhood and adolescent development, and highly implicated in stress-related mental disorders. However, due to the small size of hypothalamic structures and the limited availability of automated segmentation tools, there are relatively few neuroimaging studies examining hypothalamic involvement in mental health in human populations. Using a semi-automated segmentation approach, we conducted an exploratory study examining associations between hypothalamic volume and mental health-related behaviors in typically developing youth. Methods T1-weighted magnetic resonance imaging (MRI) scans and behavioral measures Behavioral Assessment System for Children-2 Parent Report Scale (BASC-2 PRS) were collected from 71 youth (aged 6–16 years). T1-weighted MRI data were quality checked and processed, and hypothalamic volumes semi-automatically delineated. Left, right and total hypothalamus volumes were tested across age using linear mixed effects models, as well as tested separately for associations with clinical T scores using a general linear model. Results Left ( T = −2.0; p = 0.04) and total ( T = −2.6, p = 0.01) hypothalamic volume decreased with age. A trend-level association was observed between left hypothalamic volume and adaptability scores ( T = 1.8; p = 0.08), which did not reach conventional statistical significance. No significant associations were observed for internalizing or externalizing scores. Conclusion Decreased ability to adapt to one’s environment may be a predictor of mental illness. In this exploratory study, we observed significantly decreasing hypothalamus volume across this age range. There was a trend-level association between hypothalamic volume and adaptability, suggesting that structural variation in this region may be relevant to stress-related functioning in youth. However, this finding should be interpreted cautiously and requires replication in larger, longitudinal samples.
Todd et al. (Tue,) studied this question.