Pitt Psychiatry Reviews: The Association Between Sleep & Substance Use and Sex Differences in Affective Disorders in Adolescents
Recent review articles from the Department of Psychiatry have examined the association between sleep and substance use and sex differences in affective disorders in adolescents.
Molecular Psychiatry: Sleep Regulates Drug Seeking and Relapse – A Perspective
Sleep disturbance is a critical and potentially treatable comorbidity in substance use disorders. Sleep problems are highly prevalent among people with substance use disorders, often persist into abstinence, and may contribute to relapse.
A review by Yanhua Huang, PhD (Pittsburgh Foundation Endowed Professor in Brain and Behavior Research and Associate Professor of Psychiatry), published in Molecular Psychiatry, looks at how sleep-related mechanisms shape reward processing in the brain, surveying the key neurotransmitter and neuromodulator systems through which sleep loss may drive reward-seeking behavior.
Dr. Huang and colleagues from the University of Pittsburgh Department of Psychiatry synthesize current preclinical and clinical literature, summarizing sleep changes in animals and humans following acute and long-term drug exposure and withdrawal. The review details emerging understanding of how sleep regulates glutamatergic, dopaminergic, and peptidergic signaling — all systems centrally implicated in substance use disorder. Their findings suggest that targeting neural circuits governing both sleep and reward may offer therapeutic promise, interrupting a vicious cycle and supporting recovery. The review also raises an important prevention angle: insufficient sleep may increase vulnerability to initial drug use, with particular relevance for adolescent populations.
Yu-zhang Liu, PhD (postdoctoral fellow, Department of Neuroscience); Hannah Rose Martin, BS (graduate student, Center for Neuroscience); Brant Hasler, PhD (Associate Professor of Psychiatry, Clinical and Translational Science, and Psychology); Peter Franzen, PhD (Associate Professor of Psychiatry, Psychology, and Clinical and Translational Science); Marianne Seney, PhD (Associate Professor of Psychiatry and Bioengineering); Mary Torregrossa, PhD (Associate Professor of Psychiatry); and Colleen McClung, PhD (Professor of Psychiatry and Clinical and Translational Science), from the University of Pittsburgh served as co-authors of the paper. The work reflects collaborative research supported by a National Institute on Drug Abuse P50 grant focused on sleep and circadian rhythm-mediated regulation of reward processing in adolescence.
Liu Y, Martin HR, Hasler BP, Franzen PL, Seney ML, Torregrossa MM, McClung CA, Dong Y, Huang YH.
Molecular Psychiatry 31, 2880–2891 (2026). https://doi.org/10.1038/s41380-025-03406-1
Sex Differences in Affective Disorders: A Developmental Neuroscience Framework on the Role of Puberty
Affective disorders such as anxiety and depression increase markedly during adolescence. While rates are similar for boys and girls in childhood, they rise sharply among girls during adolescence, with girls experiencing roughly twice the rate observed in boys. Affective disorders are characterized by disruptions in mesocorticolimbic circuitry but the neurodevelopmental mechanisms underlying sex differences in affective disorder symptoms remain unclear. Early adolescence, with the onset of puberty, represents a sensitive neurodevelopmental period not only for the onset of affective disorders but also for targeted early intervention.
Cecile Ladouceur, PhD (Professor of Psychiatry and Psychology), published a review in the Annual Review of Clinical Psychology describing a heuristic model (the Dynamic Pubertal Tuning model) proposing that the rise in gonadal hormones during puberty triggers sex-specific remodeling of mesocorticolimbic circuits—via changes in GABA, glutamate, and dopamine signaling—that influences threat reactivity, reward processing, and social- and reward-based learning. The model builds upon existing models and reviews on the neural and social bases underlying risk for affective disorders in adolescence, animal studies on the effects of pubertal hormones on neural circuits, and recent research on adolescent neuroplasticity. However, it focuses on how sex differences in hormonal neural sensitivity, combined with earlier pubertal timing and social stress, may dynamically influence the maturation and function of mesocorticolimbic circuitry. Resulting shifts in socio-affective learning could lead to a spiraling trajectory toward anxiety and depression in girls compared to boys.
Cecile D. Ladouceur. 2026. Annual Review of Clinical Psychology 22:215-241. https://doi.org/10.1146/annurev-clinpsy-081423-022321