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Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness.

ABSTRACT: Recent diffusion imaging studies using free-water (FW) elimination have shown increased FW in gray matter (GM) and white matter (WM) in first-episode psychosis (FEP) and lower corrected fractional anisotropy (FAt) in WM in chronic schizophrenia. However, little is known about the longitudinal stability and clinical significance of these findings. To determine tissue-specific FW and FAt abnormalities in FEP, as part of a multicenter Spanish study, 132 FEP and 108 healthy controls (HC) were clinically characterized and underwent structural and diffusion-weighted MRI scanning. FEP subjects were classified as schizophrenia spectrum disorder (SSD) or non-SSD. Of these subjects, 45 FEP and 41 HC were longitudinally assessed and rescanned after 2 years. FA and FW tissue-specific measurements were cross-sectional and longitudinally compared between groups using voxel-wise analyses in the skeletonized WM and vertex-wise analyses in the GM surface. SSD and non-SSD subjects showed (a) higher baseline FW in temporal regions and in whole GM average (P.adj(SSD vs HC) = .003, P.adj(Non-SSD vs HC) = .040) and (b) lower baseline FAt in several WM tracts. SSD, but not non-SSD, showed (a) higher FW in several WM tracts and in whole WM (P.adj(SSD vs HC)= .049) and (b) a significant FW decrease over time in temporal cortical regions and in whole GM average (P.adj = .011). Increased extracellular FW in the brain is a reliable finding in FEP, and in SSD appears to decrease over the early course of the illness. FAt abnormalities are stable during the first years of psychosis.

SUBMITTER: Berge D

PROVIDER: S-EPMC7342177 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThough olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions.MethodFEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined.ResultsIndividuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles.ConclusionsThese findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Project description:Background: Cognitive impairment may be a risk factor for, as well as a consequence of, psychosis. Non-remitting symptoms, premorbid functioning, level of education, and socioeconomic background are known correlates. A possible confounder of these associations is substance use, which is common among patients with psychosis and linked to worse clinical outcomes. Studies however show mixed results for the effect of substance use on cognitive outcomes. In this study, the long-term associations of substance use with cognition in a representative sample of first-episode psychosis patients were examined. Methods: The sample consisted of 195 patients. They were assessed for symptom levels, function, and neurocognition at 1, 2, 5, and 10 years after first treatment. Test scores were grouped into factor analysis-based indices: motor speed, verbal learning, visuomotor processing, verbal fluency, and executive functioning. A standardized composite score of all tests was also used. Patients were divided into four groups based on substance-use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users, and nonusers. Data were analyzed using linear mixed effects modeling. Results: Gender, premorbid academic functioning, and previous education were the strongest predictors of cognitive trajectories. However, on motor speed and verbal learning indices, patients who stopped using substances within the first 2 years of follow-up improved over time, whereas the other groups did not. For verbal fluency, the longitudinal course was parallel for all four groups, while patients who stopped using substances demonstrated superior performances compared with nonusers. Persistent users demonstrated impaired visuomotor processing speed compared with nonusers. Within the stop- and episodic use groups, patients with narrow schizophrenia diagnoses performed worse compared with patients with other diagnoses on verbal learning and on the overall composite neurocognitive index. Discussion: This study is one of very few long-term studies on cognitive impairments in first-episode psychosis focusing explicitly on substance use. Early cessation of substance use was associated with less cognitive impairment and some improvement over time on some cognitive measures, indicating a milder illness course and superior cognitive reserves to draw from in recovering from psychosis.

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Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness.

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