Inverse association between slow-wave sleep and low-grade inflammation in children and adolescents with major depressive disorder.

OBJECTIVE: To investigate the relationship between both self-reported and objective sleep variables and low-grade inflammation in children and adolescents with major depressive disorder (MDD) of moderate to severe symptom severity. METHODS: In this cross-sectional study, we examined twenty-nine children and adolescents diagnosed with MDD and twenty-nine healthy controls (HC). Following a one-week actigraphy assessment, comprehensive sleep evaluations were conducted, including a one-night sleep EEG measurement and self-reported sleep data. Plasma high-sensitivity C-reactive protein (hsCRP) was employed as a marker to assess low-grade inflammation. RESULTS: No significant difference in hsCRP levels was observed between participants with MDD and HC. Furthermore, after adjusting for sleep difficulties, hsCRP exhibited no correlation with the severity of depressive symptoms. In HC, levels of hsCRP were not linked to self-reported and objective sleep variables. In contrast, depressed participants showed a significant correlation between hsCRP levels and increased subjective insomnia severity (Insomnia Severity Index; r = 0.41, p < 0.05), increased time spent in the N2 sleep stage (r = 0.47, p < 0.01), and decreased time spent in slow-wave sleep (r = - 0.61, p < 0.001). Upon additional adjustments for body mass index, tobacco use and depression severity, only the inverse association between hsCRP and time spent in slow-wave sleep retained statistical significance. Moderation analysis indicated that group status (MDD vs. HC) significantly moderates the association between slow-wave sleep and hsCRP. CONCLUSION: Our findings suggest that alterations in the architecture of slow-wave sleep may have a significant influence on modulating low-grade inflammatory processes in children and adolescents with MDD.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case-control study.

PURPOSE: Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status. METHODS: This is a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13-17 years. We assessed depression severity using the Children's Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire. RESULTS: SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) µg/L) and controls (32.5 (22.6, 48.3) µg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls. CONCLUSION: Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Sleep disturbance, but not depression severity, is associated with inflammation in children and adolescents.

STUDY OBJECTIVES: We aimed to examine the association between self-rated and clinician-rated sleep disturbances and C-reactive protein (CRP), an objective marker of inflammation, in pediatric depression. METHODS: Two hundred fifty-six children and adolescents (15.2 ± 1.6 y, 72.3% female) with moderate to severe symptoms of depression participated in the study. Sleep disturbances were assessed by self-reports (Insomnia Severity Index) and clinician ratings (Kiddie-Schedule for Affective Disorder and Schizophrenia), inflammation by plasma CRP levels. RESULTS: Higher levels of CRP correlated positively with clinician-rated middle insomnia and hypersomnia. After adjusting for control variables (body mass index, tobacco, alcohol, stress, age, sex, antidepressants, sleep medication, depression severity), regression models confirmed the significant association of clinician-rated hypersomnia and middle insomnia symptoms with elevated CRP levels. In the adjusted regression models, other clinician-rated manifestations of sleep disturbance (eg, initial insomnia) and insomnia self-ratings were not significantly associated with CRP. Body mass index correlated positively with CRP, but body mass index had no mediating effect on the associations between sleep disturbances and CRP. We did not find an association between depression severity, assessed by the Children's Depression Rating Scale-Revised, and CRP. CONCLUSIONS: Results of the present study indicate a significant association of hypersomnia and middle insomnia symptoms with CRP in pediatric depression, not linked to alterations in the body mass index. CITATION: Strumberger MA, Häberling I, Emery S, et al. Sleep disturbance, but not depression severity, is associated with inflammation in children and adolescents. J Clin Sleep Med. 2023;19(10):1775-1784.