Hypothalamic volume is associated with dysregulated sleep in autistic and non-autistic young children.

Difficulty initiating or maintaining sleep is common among autistic individuals and co-occurs with internalizing and externalizing symptoms. This study tested associations between subcortical regions implicated in sleep processes and measures of dysregulated sleep initiation/maintenance in autistic and non-autistic 2- to 4-year-olds. The role of co-occurring externalizing and internalizing symptoms in these associations was also evaluated. Participants included 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds who completed magnetic resonance imaging. A subscale of items from the Children's Sleep Habits Questionnaire, previously shown to be reliable across both autistic and non-autistic children, was used to measure dysregulated sleep initiation/maintenance. Externalizing and internalizing symptoms were evaluated using the Child Behavior Checklist-Preschool. Associations between volumes for nine subcortical structures known to be implicated in sleep were separately modeled. Mediation analyses explored whether such associations could be accounted for by externalizing or internalizing symptoms. Smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. Externalizing (but not internalizing) problems partially mediated this association. Findings implicate the right hypothalamus in sleep initiation and maintenance issues for both autistic and non-autistic young children, supporting prior evidence of its central role in sleep regulation.Lay AbstractDifficulty initiating or maintaining sleep is common among autistic individuals and often goes alongside difficulties regulating emotions and behavior during the day. Although there is a body of research suggesting that subcortical brain regions, including a brain region known as the hypothalamus, play important roles regulating sleep, few studies have examined whether this extends to young autistic children. Using data from a sample of 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds, we examined whether size of subcortical brain regions implicated in sleep processes is associated with difficulties initiating and/or maintaining sleep. In addition, we examined whether daytime behaviors and emotions were also implicated in these associations. We found that smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. This relationship remained evident even after accounting for externalizing behaviors and emotions like anger that were also associated with both the hypothalamus and dysregulated sleep initiation/maintenance. The strength of association between right hypothalamus volumes and dysregulated sleep initiation/maintenance was similar for autistic and non-autistic children. These findings suggest that for both young autistic and non-autistic children, the hypothalamus plays unique roles in regulating both sleep and externalizing behaviors. For managing sleep initiation and maintenance difficulties in clinical practice, the findings underscore the importance of considering environmental (e.g. not having a regular bedtime routine) and neurobiological factors, for both autistic and non-autistic young children.