# Brain bioenergetics and slow wave activity in first episode psychosis

> **NIH NIH K23** · MCLEAN HOSPITAL · 2020 · $170,490

## Abstract

ABSTRACT
 Schizophrenia (SZ) is a common and severe psychiatric disorder. There is emerging evidence that
multiple structural and functional brain abnormalities develop early in the illness and outcomes can improve
significantly with early intervention as opposed to reversal of morbidity. However, all currently available
antipsychotics are effective on similar pathways; treatment failure is common and patients frequently suffer from
side effects. Therefore, there is a critical need to identify new biological mechanisms that contribute to the
pathology early in the illness and to develop novel treatments targeting these processes.
 Integrity of the high energy phosphate (HEP) metabolism is essential for providing energy required by
myriad neuronal functions, including neurotransmission and plasticity -processes implicated in SZ pathology.
While ATP is the primary energy source, creatine kinase (CK) enzyme reaction plays a central role in maintaining
stable ATP concentrations by creating a HEP pool as PCr, and generating ATP from PCr during increased energy
demand. Recent studies show abnormalities in several bioenergetic mechanisms in psychotic disorders,
including reductions in CK rate at rest. However, CK has not been studied during neuronal activation in psychotic
disorders.
 Identifying mediators of brain energy abnormalities will allow novel treatment approaches. Sleep, and
specifically slow wave sleep (SWS), has a restorative role in brain energy homeostasis, and EEG power density
at the slow wave frequency (slow wave activity, SWA) is the measure associated with the improvements in
energy measures. SZ is characterized by pervasive sleep disturbances, including in the first episode (FE), and
there is evidence for specific SWS deficits. However, the association of sleep characteristics and brain energy
metabolism in this disorder has not been studied.
 Given this background, we propose to study the activity of CK enzyme during neuronal activation in
patients with FE non-affective psychosis, and identify the role of reduced overnight accumulation of SWA in
explaining CK modulation. For this purpose, we will collect overnight polysomnography data and use in vivo
phosphorus magnetization transfer.
 Candidate is a psychiatrist with a background in neuroimaging research in psychotic disorders. Training
objectives for this grant are for the candidate to gain 1. Training in sleep research; 2. Advanced training in
cell biology and biochemical aspects of brain function; 3. Advanced training in statistics; 4. Training in
data presentation and grant writing skills. These goals will be accomplished by mentorship, formal
coursework, and the help of an exceptionally-qualified team of advisors and collaborators. The successful
completion of this career development plan will assist the candidate in making the transition to an independent
investigator with R01 level funding.

## Key facts

- **NIH application ID:** 9892310
- **Project number:** 1K23MH119322-01A1
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Abdullah Cagri Yuksel
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,490
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892310

## Citation

> US National Institutes of Health, RePORTER application 9892310, Brain bioenergetics and slow wave activity in first episode psychosis (1K23MH119322-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892310. Licensed CC0.

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