Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Auditory Stimulation

The purpose of this research is to identify differences in brain activity during sleep between health individuals and individuals with schizophrenia, schizophreniform, or schizoaffective disorder. This study will also investigate whether tones played during deep sleep can enhance specific features of sleep and whether enhancing such features is related to an improvement in cognitive performance.

The overarching goal of the proposed study is to establish sleep spindle and slow wave abnormalities as early pathophysiological biomarkers of schizophrenia (SCZ). The investigators also seek to enhance spindle and slow wave deficits in EC-SCZ by utilizing a closed-loop auditory stimulation during sleep. The investigators will assess improvement of deficits with the use of a memory consolidation task before and after sleeping.

Participants will include early-course schizophrenia (EC-SCZ) subjects and healthy controls (HC). Participants will complete several assessments, including clinical evaluation, an IQ assessment (WASI), and at least 2 nights of sleep EEG recordings in the sleep clinic of UPMC Western Psychiatric Hospital with a polysomnography test (PSG) each night. Study participants will also fill out a Pittsburgh Sleep Quality Index (PSQI) which reports sleep habits. On one of the nights, EC-SCZ participants will receive active closed-loop auditory stimulation, while on another night they will receive sham closed-loop auditory stimulation. On all nights beside the adaptation night (night 1) participants will complete the motor sequence task (MST) and the AX-continuous performance task (AXCPT) before going to sleep. They will also repeat the task the following morning. There will be \~1 week between nights 2 and 3 and \~1 week between nights 3 and 4.

Aim 1. Establish sleep spindle and slow wave deficits in EC-SCZ patients relative to HC using a wireless ambulatory monitor.

H1a. EC-SCZ patients will have reduced sleep spindle duration and density compared to HC.

H1b. Slow wave density will be decreased in EC-SCZ patients relative to HC.

Aim 2. Determine that spindle and slow wave impairments can be acutely improved in EC-SCZ patients using closed-loop auditory stimulation during sleep.

H2a. Sleep spindle duration and density will increase during closed-loop auditory stimulation nights compared to baseline and sham intervention.

H2b. Slow wave density will increase during stimulation nights relative to baseline and sham intervention.

Aim 3. Examine the relationship between spindle and slow wave deficits and memory consolidation before and after their acute improvement in EC-SCZ patients relative to HC.

H3a. At baseline, sleep spindles and slow waves will predict memory consolidation in EC-SCZ patients and HC.

H3b. An increase in sleep spindles and slow waves during stimulating night will be associated with task-assessed memory consolidation improvement in EC-SCZ patients relative to baseline performance.

Eligibility Criteria:
Inclusion Criteria:

Early-course schizophrenia (EC-SCZ):

1. ages 18-40 years
2. current DSM-IV defined diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, not drug-induced, with no previously reported psychotic episode
3. duration of ≤5 years from beginning of psychosis, defined by report of symptoms and/or history of treatment according to clinical guidelines employed in our University of Pittsburgh Medical Center (UPMC) psychoses clinics in Pittsburgh
4. lifetime exposure to antipsychotic medications ≤5 years

Healthy controls (HC):

1. ages 18-40 years
2. no lifetime history of psychiatric disorders
3. no first-degree family history of schizophrenia spectrum disorder or mood disorder with psychotic features.

Exclusion Criteria:

General exclusion criteria:

1. DSM-IV intellectual disability
2. significant head injury
3. medical illness affecting brain function or structure
4. pregnancy or postpartum (\<6 weeks after delivery or miscarriage)
5. significant neurological disorder (e.g. seizure disorder)
6. inability to provide informed consent
7. current or past co-morbidity for alcohol or psychoactive substance dependence
8. substance abuse other than cannabis and/or alcohol within the past one year

For EC-SCZ:

a) a psychotic illness with a temporal relation to substance use or head injury

For healthy controls (HC):

1. difficult falling and/or staying asleep for more than half the nights of a week, on average
2. diagnosis of sleep apnea or restless leg syndrome
3. sleeping less than 5 hours or more than 10 hours daily, on average