Dreaming of New Treatments

Paul Gleason, PhD

Sleep problems are understudied, underdiagnosed, and undertreated.


“Sleep problems are understudied,” Ellen Lee, MD, told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “They’re underdiagnosed and undertreated in people with mental illness.” Thus, Lee encouraged clinicians to screen for sleep problems, because sleep “is a modifiable and important target for intervention.” Lee, along with other colleagues, shared insights and preliminary research results on how sleep may impact mental health and psychiatric disorders.

Sleep problems affect between 30 and 80% of individuals with schizophrenia and are associated with lower quality of life and poorer cognitive and frontal lobe functioning, explained Lee, assistant professor in residence in the Department of Psychiatry at the University of California at San Diego.1-3 In as-yet unpublished research, Lee found that sleep apnea is associated with increased inflammation, while higher subjective reports of sleep quality are associated with lower levels of inflammation. Since inflammation is also associated with psychosis,4 treating sleep problems could also improve the symptoms of mental illnesses.

Beyond schizophrenia, sleep issues also appear in mood disorders like depression. Stephen Smagula, PhD, presented research on possible links between morning activation deficits and depression among family members caring for patients with dementia.

Older individuals with depression often report difficulty getting up and active in the morning.5 Morning activation deficits are sometimes thought to be immutable (some individuals are just not morning people), but in functional magnetic resonance imaging readings, dementia caregivers with depression showed higher resting-state amygdala-PCC connectivity, which is associated with stress, fear, and escape responses.6 “Although this is speculative,” Smagula cautioned, “it seems plausible that the non-morning type caregivers are doing behaviorally disengaged, emotion-focused coping. So put another way, some caregivers might wake up, feel overwhelmed, say ‘Expletive! I’m going back to bed.’”

This raises the possibility, according to Smagula, who is assistant professor of psychiatry and epidemiology at the University of Pittsburg, that “instead of treating the depression and hoping the morning activation deficit goes away, we could be targeting the morning activation deficit to treat the depression.” Clinicians could consider treatments such as activity scheduling, which would get the caregivers up and moving, increase their light exposure, decrease fragmented sleep, and limit the time they spend ruminating—all of which could improve their depressive symptoms.

Sleep also affects cognition, especially in older adults. Ruth O’Hara, PhD, presented initial data on the impacts of delta activity at sleep onset (DASO). Study participants with DASO demonstrated better affective function overall and over time, which led O’Hara to conclude that testing DASO or other variables may help clinicians predict patients’ cognitive futures. “We think that characterizing sleep dysregulation in older adults may in fact identify valuable biomarkers,” explained O’Hara, who is the Josephine Q. Berry Professor of Psychiatry and Behavioral Sciences at Stanford University. They could “help us predict cognitive decline and onset of dementia, as well as predicting affective dysfunction.”


1. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. CNS Drugs. 2008;22(11):939-962.

2. Keshavan MS, Montrose DM, Miewald JM, Jindal RD. Sleep correlates of cognition in early course psychotic disorders. Schizophr Res. 2011;131(1-3):231-234.

3. Bromundt V, Köster M, Georgiev-Kill A, et al. Sleep-wake cycles and cognitive functioning in schizophrenia. Br J Psychiatry. 2011;198(4):269-276.

4. Lee EE, Ancoli-Israel S, Eyler LT, et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. Am J Geriatr Psychiatry. 2019;27(1):21-31.

5. Smagula SF, Capps CS, Krafty RT. Evaluating the timing of differences in activity related to depression symptoms across adulthood in the United States. J Affect Disord. 2021;284:64-68.

6. Smagula SF, Karim HT, Ibrahim TS, et al. Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity. J Gerontol B Psychol Sci Soc Sci. 2020:gbaa115.