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White matter alterations in individuals experiencing attenuated positive psychotic symptoms.

ABSTRACT: AIM:Diffusion tensor imaging (DTI) studies suggest that reduced fractional anisotropy (FA) in the inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) occurs among schizophrenia patients and those at risk for psychosis. Nevertheless, there is a dearth of knowledge investigating white matter fibre pathways in non-help-seeking individuals who endorse attenuated positive psychotic symptoms (APPS) across a range of mental disorders. The aim of the current study was to determine if alterations in ILF and SLF microstructures were specific to distressing APPS related to risk for psychosis or to APPS symptoms occurring in multiple mental disorders, which would suggest a shared phenotype among disorders. METHOD:Twenty-six non-help-seeking young adults were administered the Prodromal Questionnaire. DTI was conducted on participants (n?=?13) who endorsed eight or more distressing APPS (D-APPS, a potentially clinically relevant group) and those who endorsed three or fewer distressing APPS (low-APPS; n?=?13). Semistructured interviews were administered to determine diagnoses, as well as clinical risk for psychosis status. RESULTS:Results indicated that the D-APPS group exhibited decreased FA in the left ILF compared with the low-APPS group, even after removing four?D-APPS participants who were considered at risk for psychosis. CONCLUSION:Findings suggest that white matter microstructure is altered in individuals experiencing APPS across a range of disorders, independent of clinical high risk for psychosis status. Reduced FA in the left ILF may not be specific to psychosis risk, but rather for APPS that occur in a number of mental disorders.

SUBMITTER: Cooper S

PROVIDER: S-EPMC4965329 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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White matter alterations in individuals experiencing attenuated positive psychotic symptoms.

Cooper Shanna S Alm Kylie H KH Olson Ingrid R IR Ellman Lauren M LM

Early intervention in psychiatry 20160128 3

<h4>Aim</h4>Diffusion tensor imaging (DTI) studies suggest that reduced fractional anisotropy (FA) in the inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) occurs among schizophrenia patients and those at risk for psychosis. Nevertheless, there is a dearth of knowledge investigating white matter fibre pathways in non-help-seeking individuals who endorse attenuated positive psychotic symptoms (APPS) across a range of mental disorders. The aim of the current study w ...[more]

PMID: 26818412

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Project description:Background: Attenuated positive psychotic symptoms represent the defining features of the clinical high-risk for psychosis (CHR-P) criteria. The effectiveness of each available treatment for reducing attenuated positive psychotic symptoms remains undetermined. This network meta-analysis (NMA) investigates the consistency and magnitude of the effects of treatments on attenuated positive psychotic symptoms in CHR-P individuals, weighting the findings for acceptability. Methods: Web of Science (MEDLINE), PsycInfo, CENTRAL and unpublished/gray literature were searched up to July 18, 2017. Randomized controlled trials in CHR-P individuals, comparing at least two interventions and reporting on attenuated positive psychotic symptoms at follow-up were included, following PRISMA guidelines. The primary outcome (efficacy) was level of attenuated positive psychotic symptoms at 6 and 12 months; effect sizes reported as standardized mean difference (SMD) and 95% CIs in mean follow-up scores between two compared interventions. The secondary outcome was treatment acceptability [reported as odds ratio (OR)]. NMAs were conducted for both primary and secondary outcomes. Treatments were cluster-ranked by surface under the cumulative ranking curve values for efficacy and acceptability. Assessments of biases, assumptions, sensitivity analyses and complementary pairwise meta-analyses for the primary outcome were also conducted. Results: Overall, 1,707 patients from 14 studies (57% male, mean age = 20) were included, representing the largest evidence synthesis of the effect of preventive treatments on attenuated positive psychotic symptoms to date. In the NMA for efficacy, ziprasidone + Needs-Based Intervention (NBI) was found to be superior to NBI (SMD = -1.10, 95% CI -2.04 to -0.15), Cognitive Behavioral Therapy-French and Morrison protocol (CBT-F) + NBI (SMD = -1.03, 95% CI -2.05 to -0.01), and risperidone + CBT-F + NBI (SMD = -1.18, 95% CI -2.29 to -0.07) at 6 months. However, these findings did not survive sensitivity analyses. For acceptability, aripiprazole + NBI was significantly more acceptable than olanzapine + NBI (OR = 3.73; 95% CI 1.01 to 13.81) at 12 months only. No further significant NMA effects were observed at 6 or 12 months. The results were not affected by inconsistency or evident small-study effects, but only two studies had an overall low risk of bias. Conclusion: On the basis of the current literature, there is no robust evidence to favor any specific intervention for improving attenuated positive psychotic symptoms in CHR-P individuals.

Project description:BACKGROUND:Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology. METHODS:Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures. RESULTS:While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = -0.0049, p = .003, CC: B = -0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = -0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density. CONCLUSION:The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.

Project description:22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk.

Project description:Purpose: Psychotic experiences in childhood (such as hearing voices or being suspicious) represent an important phenotype for early intervention. However, these experiences can be defined in several ways: self-reported psychotic experiences (SRPE) rely exclusively on the child's report, clinically validated psychotic experiences (CRPE) are based on clinical assessment, and attenuated psychotic symptoms (APS) represents a categorization to do with clinical relevance in relation to severity. Very few studies have investigated how these distinctions impact clinical and other domains. The present study aims to compare SRPE, CRPE, and APS among children and adolescents. Methods: This study is part of the Brazilian High-Risk Cohort Study for Psychiatric Disorders, in which 2,241 individuals aged 6-14 years provided self-ratings of 20 psychotic experiences using the Community Assessment of Psychic Experiences (CAPE). A trained psychologist conducted an interview to validate or reject reported experiences and to rate the presence of APS and affective flattening. In parallel, parents provided information about child mental health to an independent interviewer. We tested the association of mutually exclusive categories of non-validated SRPE (nSRPE), clinically validated PE below the threshold for APS (nCRPE), and APS (nSRPE = 33%, nCRPE = 11%, APS = 6%), with parents' information about the child's positive attributes and levels of psychopathology and psychologist assessment of blunted affect. Results: Most associations were qualitatively similar, and there was a dose-response in the strength of associations across categories, such that APS > nCRPE > nSRPE. Experiences in all three categories were associated with female sex. nSRPE were associated with overall levels of psychopathology, but to a lesser degree than nCRPE and APS. APS and nCRPE were associated with less positive attributes, with APS more so than nCRPE. Only APS was associated with affective flattening. Conclusions: In children and adolescents, SRPE, CRPE, and APS all index liability for psychopathology, but as clinician rated relevance increases, associations get stronger and become evident across more domains.

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White matter alterations in individuals experiencing attenuated positive psychotic symptoms.

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White matter alterations in individuals experiencing attenuated positive psychotic symptoms.

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