title: IL-1β and BDNF are associated with improvement in hypersomnia but not insomnia following exercise in major depressive disorder.
abstract: Given the role of sleep in the development and treatment of major depressive disorder (MDD), it is becoming increasingly clear that elucidation of the biological mechanisms underlying sleep disturbances in MDD is crucial to improve treatment outcomes. Sleep disturbances are varied and can present as insomnia and/or hypersomnia. Though research has examined the biological underpinnings of insomnia in MDD, little is known about the role of biomarkers in hypersomnia associated with MDD. This paper examines biomarkers associated with changes in hypersomnia and insomnia and as predictors of improvements in sleep quality following exercise augmentation in persons with MDD. Subjects with non-remitted MDD were randomized to augmentation with one of two doses of aerobic exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. The four sleep-related items on the clinician-rated Inventory of Depressive Symptomatology (sleep onset insomnia, mid-nocturnal insomnia, early morning insomnia and hypersomnia) assessed self-reported sleep quality. Inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6) and brain-derived neurotrophic factor (BDNF) were assessed in blood samples collected before and following the 12-week intervention. Reduction in hypersomnia was correlated with reductions in BDNF (ρ = 0.26, P = 0.029) and IL-1β (ρ = 0.37, P = 0.002). Changes in these biomarkers were not associated with changes in insomnia; however, lower baseline levels of IL-1β were predictive of greater improvements in insomnia (F = 3.87, P = 0.050). In conclusion, improvement in hypersomnia is related to reductions in inflammatory markers and BDNF in persons with non-remitted MDD. Distinct biological mechanisms may explain reductions in insomnia.
authors.affiliation: Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Rethorst
authors.affiliation: Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Greer
authors.affiliation: Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: M S P
authors.initials: MS
authors.lastname: Toups
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: I
authors.initials: I
authors.lastname: Bernstein
authors.affiliation: 1] Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA [2] Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Carmody
authors.affiliation: Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Trivedi
mesh_terms: D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000502:physiology*; D003865:Major Depressive Disorder / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D006970:Disorders of Excessive Somnolence / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology; D008297:Male; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000502:physiology
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha