Association Between Major Depressive Disorder and Sleep Disturbances Through Inflammation in Adolescents

Abstract

Background: Although approximately 13% of adolescents suffer from Major Depressive Disorder (MDD), and many adolescents have reported sleep disturbances, the relationship between sleep disturbances and MDD in adolescents is poorly understood. Thus, our objective was to study how adolescent MDD was related to sleep disturbances in a crosssectional study, and the potential role of inflammation linking adolescent MDD to sleep disturbances. Methods: Ninety-two female and male, African American and White, adolescents aged 15 to 18 years completed the study. Adolescents were diagnosed with MDD according to the Diagnostic and Statistical Manual of Mental Disorders-5 as confirmed by the MINI International Diagnostic Interview. The severity of depression was assessed using the Quick Inventory of Depressive Symptomatology. Sleep disturbance was measured using the Pediatric Sleep Questionnaires (PSQ). Blood sample was collected from each participant for measuring the inflammatory factors. Results: Compared with the controls (n=39), adolescents with MDD (n=53) had greater PSQ scores (0.32 ± 0.02 vs. 0.10 ± 0.02). In adolescents with MDD, PSQ scores were correlated with the severity of depressive symptoms (r=0.31, p<0.05). In addition, tumor necrosis factor-a levels were greatly elevated in the MDD group (2.4 ± 0.1 vs. 1.8 ± 0.1 pg/ml) compared with the controls. Severity of depressive symptoms was best predicted by PSQ scores, medications, and childhood experiences. Conclusions: Sleep disturbance measured by the PSQ is associated with severe depressive symptoms in adolescents, and one potential pathway may be through elevated tumor necrosis factor-a. Further research is warranted to probe a cause and effect relationship among sleep disturbances, MDD, and chronic inflammation.

Cytokine alterations in pediatric internalizing disorders: Systematic review and exploratory multi-variate meta-analysis

“…We were also unable to find an association with basal IL-6 levels and pediatric internalizing disorders. This is supported by cross-sectional studies that continue to report equivocal ( Gariup et al, 2015 ; Henje-Blom et al, 2012 ; Li et al, 2022 ; Peters et al, 2019 , 2021 ) or null findings in pediatric samples investigating IL-6 ( Byrne et al, 2013 ; Calarge et al, 2019 ; Freed et al, 2019 ; Gabbay et al, 2009a , 2009b ; Gomes et al, 2021 ; Oztürk et al, 2020 ; Petrov et al, 2018 ; Reddy et al, 2020 ). However, some evidence has shown an association between depressive symptoms and longitudinal increases in IL-6 throughout early childhood and adolescence ( Chu et al, 2019 ; Kautz et al, 2020 ).…”

“… BMI associated with current depression after adjusting for raised CRP longitudinally at age 9 and 18. Quality Rating: Moderate Reddy et al, 2020 * USA Clinical (outpatient) and Community 15-18y MINI v.6 (DSM-V) MDD Co-morbidity: Not specified IL-6, TNF-α, IL-8 IL-10 ↑ TNF-α in MDD vs HC. Positive correlation between sleep quality and hyperactivity scores and TNF-α.TNF-α indirect link between MDD and sleep disturbance in adolescents.…”

“…However, some evidence has shown an association between depressive symptoms and longitudinal increases in IL-6 throughout early childhood and adolescence ( Chu et al, 2019 ; Kautz et al, 2020 ). Previous research has identified several variables that are influential in IL-6 levels in children and adolescents that may be responsible for the diversity of findings observed, including disturbed sleep ( Fernandez-Mendoza et al, 2017 ; Toenders et al, 2022 ; Reddy et al, 2020 ), adiposity ( Chiang et al, 2017 ; McInnis et al, 2014 ; Petrov et al, 2018 ), childhood trauma ( Li et al, 2022 ; Miller et al, 2009 ; Peters et al, 2019 ; Russel et al, 2019 ), executive functioning ( Peters et al, 2019 ; Starr et al, 2016 ), emotional perception ( Peters et al, 2021 ) and psycho-social stress ( Colak Sivri et al 2018 ; Flouri et al, 2019 ; Slavich et al, 2015 ). Many of the studies included in this meta-analysis did not account for these influential variables and therefore, in this study, we were unable to explore these potential mediating relationships.…”

“…TNF-α is produced by macrophages in the initial inflammatory response against pathogens and cytotoxicity ( Peters et al, 2019 ). It has also been implicated in homeostatic regulation of synaptic plasticity (e.g., learning and memory) ( Moriarity et al, 2019 ), sleep ( Reddy et al, 2020 ), appetite ( Himmerich et al, 2019 ), and body temperature ( Mills et al, 2013 ). It has been speculated that TNF-α may be mediating the link between somatic depressive symptoms and treatment refraction in pediatric internalizing disorders ( Amitai et al, 2016 , 2020 ; Toenders et al, 2022 ).…”

“…Cytokines that were “not detected” or indicated that they were below the set immunoassay detection threshold were not included ( Byrne et al, 2013 ; Gariup et al, 2015 ). Cytokine measurements for IL-6, IL-8 and IL-10 were not available for Reddy et al, (2020) . There was one study that did not respond to contact and reported their statistics in medians and interquartile ranges ( Pallavi et al, 2015 ).…”