# Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $471,199

## Abstract

Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally
Project summary: Schizophrenia and related disorders are one of leading causes of disability worldwide, thus
making the early identification of neurobiological vulnerabilities, which may serve as treatment targets, a critical
research priority. In recent work, we found that individuals with chronic schizophrenia had a striking deficit in
sleep spindles. A hallmark of Stage 2 Non-Rapid Eye Movement (N2) Sleep, spindles are short (0.5-2 s),
waxing/waning oscillations within the 12-16 Hz range. Spindle abnormalities are also present in early course and
early onset schizophrenia, and spindle-related measures, including amplitude, duration, and density, are
associated with cognitive ability, social functioning, and tendency for magical thinking in healthy individuals,
including adolescents and young adults. By investigating individual spindle parameters, we established that
reduced spindle density and amplitude are associated with severity of symptoms and cognitive impairments
respectively, in chronic schizophrenia patients. We also found that Integrated Spindle Activity (ISA), which
combines individual spindle parameters in a single value, was the most discriminating measure, yielding ~90%
separation between schizophrenia and control groups. Youth at Clinical High Risk (CHR) are a unique population
enriched for precursors of major psychiatric disorders, such as schizophrenia, who also experience emergent
cognitive impairments, social dysfunction, and sub-syndromal clinical symptoms. What we do not know is when
spindle impairments occur, and how they may affect the development of psychopathology in this population.
Thus, the first broad aim of this project is to characterize the role of sleep spindle parameters in moderating
cognitive, social, and clinical functioning trajectories, including transition to psychosis, among youth at CHR.
Sleep spindles are initiated by the interplay of the Thalamic Reticular Nucleus (TRN) with the dorsal thalamus.
Thalamic activity is then relayed to the cortex, where spindle oscillations are synchronized. Specific features of
spindles—density, amplitude and duration—reflect neural function in the thalamus, cortex, and thalamo-cortical
connections, respectively. Moreover, GABA neurotransmission and thalamo-cortical connectivity play a critical
role in generating and sustaining spindle oscillations. In recent work, we found that spindle deficits were most
prominent in frontal and prefrontal scalp regions, and that reduced medio-dorsal (MD) thalamic volumes were
associated with decreased sleep spindles in source localized prefrontal cortex (PFC) in schizophrenia. Building
on these findings, we will integrate data across multiple levels of analysis, from electrophysiology to neural to
molecules, to characterize this spindle-related thalamo-cortical circuitry. Specifically, the second broad aim of
this project is to ide...

## Key facts

- **NIH application ID:** 9952419
- **Project number:** 5R01MH113827-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fabio Ferrarelli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,199
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952419

## Citation

> US National Institutes of Health, RePORTER application 9952419, Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally. (5R01MH113827-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9952419. Licensed CC0.

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