Sleep in children and adolescents with major depressive disorder: associations with low-grade inflammation and omega-3 polyunsaturated fatty acids

The present cumulative dissertation aimed to investigate the association between sleep and low-grade inflammation in children and adolescents diagnosed with major depressive disorder (MDD) and to explore potential associations between Omega-3 polyunsaturated fatty acids (n-3 PUFAs) and sleep in pediatric MDD. The aim of the first manuscript was to investigate the associations between sleep disturbances and plasma levels of high-sensitivity C-reactive protein (hsCRP), an indicator of low-grade inflammation, in a sample of 256 children and adolescents with MDD of moderate to severe symptom severity. The results indicated a significant association between clinician-rated hypersomnia and middle insomnia symptoms with hsCRP in pediatric depression, not linked to alterations in body mass index. The second manuscript aimed to examine the link between both objectively measured and self-reported sleep parameters and low-grade inflammation, indicated by hsCRP, in a younger population. Comprehensive sleep assessments were conducted, including a single-night sleep electroencephalogram (EEG) recording, self-reported sleep data, and actigraphy measurements. To further clarify the potential influence of depression on the relationship between sleep and inflammation, two distinct groups were included: one group of children and adolescents diagnosed with MDD exhibiting moderate to severe symptoms of depression (n = 29), and a control group of healthy peers (n = 29). In the MDD group, the results indicated an inverse association between hsCRP levels and time spent in slow-wave sleep (SWS), suggesting that alterations in the architecture of SWS might play a significant role in modulating low-grade inflammatory processes in pediatric MDD. In the third manuscript, potential associations between n-3 PUFAs and sleep in pediatric depression were investigated. Self-reported and objectively assessed sleep data, along with red blood cell levels of n-3 PUFAs, were collected from 29 children and adolescents with MDD and 30 healthy controls. The findings indicated a significant association between higher levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), and increased total sleep time in children and adolescents diagnosed with MDD. Differences between eicosapentaenoic acid (EPA) and DHA in their associations with sleep outcomes suggest a more significant role for DHA in modulating sleep-related processes in pediatric MDD.