Deep phenotyping of sleep and symptoms in adolescents with psychosis-spectrum conditions

About This Grant

PROJECT SUMMARY Adolescents experiencing psychosis-spectrum (PS) symptoms are at high risk for lifelong mental illness and impairment, including conversion to schizophrenia. Mechanisms influencing the onset or persistence of PS symptoms in adolescence are unclear. Sleep is altered in youth at clinical high risk for psychosis (CHR) compared to controls, and sleep problems may predict the transition to full-threshold psychosis and persist in first episode psychosis (FEP). Studies of sleep and PS symptoms in youth suffer from three main gaps. First, extant studies are overly correlational, with few studies using dense sampling across days to understand temporal fluctuations between PS symptoms and sleep in youth. Second, nonspecific behavioral indices of sleep (from self-report and actigraphy) may reveal the clinical presentation of sleep deficits but not the root mechanistic cause of these difficulties. Finally, studies of sleep in this population have omitted measurement of important co-occurring processes such as stress, which may mediate or moderate the sleep-psychosis relationship in ways important for treatment development. This study seeks to address these three critical gaps by investigating daily fluctuations in PS symptoms, sleep at behavioral and neurobiological levels, and psychological stress in adolescents with PS conditions (n = 40, aged 14-17 years). Across a 3-week sampling period, this study will measure PS symptoms (hallucinations and paranoia), subjective ratings of stress, and objectively measured sleep characteristics, including behavioral (actigraphy-estimated sleep duration, fragmentation, efficiency, timing, rhythmicity, and regularity) and biological (simultaneous PSG/EEG-indexed sleep spindle density, amplitude, duration) markers. Participants will first complete a baseline interview to assess eligibility, PS symptoms, sleep, and stress. For the subsequent 21 days, adolescents will (1) wear a patch-based actigraphy monitor to assess sleep and 24h rest-activity rhythms; (2) complete twice-daily digital diaries probing sleep, stress, as well as PS symptom type (e.g., hallucinations and paranoid thoughts), severity, impairment, and timing; and (3) wear PSG and wearable EEG for 2 consecutive nights to index sleep spindles. This measurement supports 2 specific aims: 1) Examine how subjective ratings of PS symptoms and stress fluctuate with respect to sleep on a daily basis, and 2) Examine the feasibility of collecting at-home EEG data from adolescents with early phase psychosis and establish early links among spindles, PS symptoms, and stress. This study aligns with NIMH objectives to 1) define brain mechanisms underlying complex behavior by characterizing sleep spindles in early psychosis, and 2) examine mental illness trajectories across the lifespan by exploring these mechanisms in an understudied adolescent population. If successful, this will be the first study to employ deep phenotyping of sleep in adolescents with early phase psychosis.