White matter microstructure and sleep-wake disturbances in individuals at ultra-high risk of psychosis

Abstract

AimWhite matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology.MethodsSixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations.ResultsUltra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = −0.34, p = 0.011) and increased sleep fragmentation index (r = −0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses.ConclusionCompromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target.

Sleep disruptions and the pathway to psychosis: An in‐depth case and literature review

“…Psychotic disorders can also influence the sleep quality of affected individuals. A case‐control study by Rasmussen 8 found that aberrations in the callosal microstructure within the white matter of ultra‐high‐risk individuals were linked to observed disruptions in sleep‐wake functioning. An ultra‐high risk (UHR) individual for psychosis refers to someone who is considered clinically at very high risk of developing a full‐blown psychotic disorder, such as schizophrenia, within the next year 9 …”

Poor Self-Reported Sleep is Associated with Prolonged White Matter T2 Relaxation in Psychotic Disorders

“…To the best of our knowledge, there are no studies in schizophrenia that examined this relationship. In a recent study in individuals at ultra-high risk for psychosis, poor sleep was associated with lower FA in corpus callosum and both increased and decreased FA in the ventral brain regions (29). In BD, lower objective and self-reported sleep duration correlated with reduced FA and increased radial diffusivity (RD) in multiple white matter tracts (Benedetti et al, 2017).…”