0065 Sleep and Wake Biomarkers of Psychotic Disorders and Their Relations with Thalamocortical Connectivity. (12th April 2019)

• Record Type: Journal Article
• Authors: Baran, Bengi; Karahanoglu, F Isik; Mylonas, Dimitrios; Denis, Dan; Keshavan, Matcheri; Stickgold, Robert; Manoach, Dara S
• Is Part Of: Sleep. Volume 42(2019)Supplement 1
• Page Start: A27
• Page End: A27
• Publication Date: 2019-04-12
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsz067.064
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Recent data implicate abnormalities of the thalamic reticular nucleus (TRN) and thalamocortical circuitry in schizophrenia (SZ) risk. Sleep spindles are initiated by the TRN and propagated to the cortex via thalamocortical feedback loops.During wakefulness, TRN modulates sensory processing by gating thalamocortical communication. Patients with SZ and their first-degree relatives (familial-high-risk, FHR) exhibit sleep spindle and sensory gating deficits. In two studies, we investigated the two SZ biomarkers in relation to thalamocortical connectivity in chronic and early-course psychotic disorders and FHR. Methods: Twenty-six SZ and 29 healthy controls (HC) participated in Study1; 10 early-course patients with psychotic disorders (PSY), 14 FHR and 16 HC participated in Study2. All participants completed a resting-state fMRI session and thalamocortical seed-to-voxel connectivity was computed. In a separate session, nocturnal sleep was monitored with PSG for Study1. Sleep spindles were identified using an automated wavelet detector. Study2 included a sensory gating event-related-potentials (ERP) experiment. Gating was calculated as the suppression of the auditory P50 for the second of a pair of identical clicks. Whole brain regression analyses were used to examine relations of thalamocortical connectivity with spindles and sensory gating (we report p FDR ≤.05). Results: SZ showed widespread reductions in spindle density (38 electrodes, p corrected =.009). Reduced spindle density was associated with significantly greater thalamic connectivity with left sensory-motor cortex (MNI:x=-24, y=-16, z=64; BA4; no slope difference) in regions that overlap with those SZ patients show abnormal thalamocortical hyperconnectivity. Relative to HC, PSY exhibited marginally-reduced sensory gating (t(19)=-1.9, p =.07; FHR vs HC non-significant). Reduced sensory gating correlated with weaker thalamocortical connectivity in the right dorsolateral-prefrontal-cortex (DLPFC;[44, 44, -2]; BA46; no slope difference) connectivity in this cluster was significantly reduced in PSY vs. HC (t(19)= 2.2, p =.04; FHR vs HC non-significant). Conclusion: In two experiments, we show that two SZ biomarkers, sleep spindle and sensory gating deficits are associated with abnormal thalamocortical connectivity, suggesting that they arise from a common mechanism. Data collection for Study2 is ongoing and increased sample sizes will allow for analysis of the specificity of these abnormalities to SZ and SZ risk. Support (If Any): K01MH114012