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Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State-A Systematic Review.

ABSTRACT: Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-high risk of psychosis (UHR) with the use of diffusion tensor imaging (DTI) available from the National Center for Biotechnology Information PubMed (Medline) and Health Source: Nursing/Academic Edition databases. Of 358 relevant articles identified, 25 papers published in the years 2008-2020 were ultimately included in the review. Most of them supported the presence of subtle aberrations in WM in UHR individuals, especially in the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). These alterations may therefore be considered a promising neurobiological marker for the risk of psychosis. However, due to methodological discrepancies and the relative scarcity of evidence, further investigation is called for, especially into connectome analysis in UHR patients.

SUBMITTER: Waszczuk K

PROVIDER: S-EPMC8201371 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State-A Systematic Review.

Waszczuk Katarzyna K Rek-Owodziń Katarzyna K Tyburski Ernest E Mak Monika M Misiak Błażej B Samochowiec Jerzy J

Journal of clinical medicine 20210606 11

Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-hig ...[more]

PMID: 34204171

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Project description: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.

Project description:Background:Individuals at ultra-high risk for psychosis (UHR) present with subtle alterations in cerebral white matter (WM), which appear to be associated with clinical and functional outcome. The effect of cognitive remediation on WM organization in UHR individuals has not been investigated previously. Methods:In a randomized, clinical trial, UHR individuals aged 18 to 40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation for 20 weeks. Cognitive remediation comprised 20 x 2-h sessions of neurocognitive and social-cognitive training. Primary outcome was whole brain fractional anisotropy derived from diffusion weighted imaging, statistically tested as an interaction between timepoint and treatment group. Secondary outcomes were restricted to five predefined region of interest (ROI) analyses on fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity. For significant timepoint and treatment group interactions within these five ROIs, we explored associations between longitudinal changes in WM and cognitive functions/clinical symptoms. Finally, we explored dose-response effects of cognitive remediation on WM. Results:A total of 111 UHR individuals were included. Attrition-rate was 26%. The cognitive remediation group completed on average 12 h of neurocognitive training, which was considerably lower than per protocol. We found no effect of cognitive remediation on whole-brain FA when compared to treatment as usual. Secondary ROI analyses revealed a nominal significant interaction between timepoint*treatment of AD in left medial lemniscus (P=0.016) which did not survive control for multiple comparisons. The exploratory test showed that this change in AD correlated to improvements of mental flexibility in the cognitive remediation group (p=0.001). We found no dose-response effect of neurocognitive training on WM. Conclusions:Cognitive remediation comprising 12 h of neurocognitive training on average did not improve global or regional WM organization in UHR individuals. Further investigations of duration and intensity of cognitive training as necessary prerequisites of neuroplasticity-based changes are warranted. Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02098408.

Project description:Diffusion kurtosis imaging (DKI) is a diffusion MRI approach that enables the measurement of brain microstructural properties, reflecting molecular restrictions and tissue heterogeneity. DKI parameters such as mean kurtosis (MK) provide additional subtle information to that provided by popular diffusion tensor imaging (DTI) parameters, and thus have been considered useful to detect white matter abnormalities, especially in populations that are not expected to show severe brain pathologies. However, DKI parameters often yield artifactual output values that are outside of the biologically plausible range, which diminish sensitivity to identify true microstructural changes. Recently we have proposed the mean-kurtosis-curve (MK-Curve) method to correct voxels with implausible DKI parameters, and demonstrated its improved performance against other approaches that correct artifacts in DKI. In this work, we aimed to evaluate the utility of the MK-Curve method to improve the identification of white matter abnormalities in group comparisons. To do so, we compared group differences, with and without the MK-Curve correction, between 115 individuals at clinical high risk for psychosis (CHR) and 93 healthy controls (HCs). We also compared the correlation of the corrected and uncorrected DKI parameters with clinical characteristics. Following the MK-curve correction, the group differences had larger effect sizes and higher statistical significance (i.e., lower p-values), demonstrating increased sensitivity to detect group differences, in particular in MK. Furthermore, the MK-curve-corrected DKI parameters displayed stronger correlations with clinical variables in CHR individuals, demonstrating the clinical relevance of the corrected parameters. Overall, following the MK-curve correction our analyses found widespread lower MK in CHR that overlapped with lower fractional anisotropy (FA), and both measures were significantly correlated with a decline in functioning and with more severe symptoms. These observations further characterize white matter alterations in the CHR stage, demonstrating that MK and FA abnormalities are widespread, and mostly overlap. The improvement in group differences and stronger correlation with clinical variables suggest that applying MK-curve would be beneficial for the detection and characterization of subtle group differences in other experiments as well.

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Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State-A Systematic Review.

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Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State-A Systematic Review.

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