Search

Group comparisons of individuals with psychotic disorder and controls have shown alterations in white matter microstructure. Whether white matter microstructure and network connectivity is altered in adolescents with subclinical psychotic experiences (PE) at the lowest end of the psychosis severity spectrum is less clear. DWI scan were acquired in 48 individuals with PE and 43 healthy controls (HC). Traditional tensor-derived indices: Fractional Anisotropy, Axial Diffusivity, Mean Diffusivity and Radial Diffusivity, as well as network connectivity measures (global/local efficiency and clustering coefficient) were compared between the groups. Subclinical psychopathology was assessed with the Community Assessment of Psychic Experiences (CAPE) and Montgomery–Åsberg Depression Rating Scale (MADRS) questionnaires and, in order to capture momentary subclinical expression of psychosis, the Experience Sampling Method (ESM) questionnaires. Within the PE-group, interactions between subclinical (momentary) symptoms and brain regions in the model of tensor-derived indices and network connectivity measures were investigated in a hypothesis-generating fashion. Whole brain analyses showed no group differences in tensor-derived indices and network connectivity measures. In the PE-group, a higher positive symptom distress score was associated with both higher local efficiency and clustering coefficient in the right middle temporal pole. The findings indicate absence of microstructural white matter differences between emerging adults with subclinical PE and controls. In the PE-group, attenuated symptoms were positively associated with network efficiency/cohesion, which requires replication and may indicate network alterations in emerging mild psychopathology. Electronic supplementary material The online version of this article (10.1007/s11682-019-00129-0) contains supplementary material, which is available to authorized users.

Background Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods The participants (N = 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes (SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility. The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from the Brainmap database). Results At the global level, participants with psychotic-like symptoms had higher CVBOLD in cerebrospinal fluid (CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analyses revealed that CVBOLD was increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlapped Background: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods: The participants (N= 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes(SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility.The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from theBrainmap database). Results: At the global level, participants with psychotic-like symptoms had higher CVBOLDin cerebrospinal fluid(CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analy-ses revealed that CVBOLDwas increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlappedb6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. Conclusions: Psychotic-like symptoms were associated with elevated CVBOLDin a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.

Previously, schizophrenia is found to be related to the variability of the functional magnetic resonance imaging (fMRI) signal in the white matter. However, evidence about the relationship between genetic vulnerabilities and physiological fluctuation in the brain is lacking. We investigated whether familial risk for psychosis (FR) and polygenic risk score for schizophrenia (PRS) are linked with physiological fluctuation in fMRI data. We used data from the Oulu Brain and Mind study (n. = 140-149, aged 20-24 years) that is a substudy of the Northern Finland Birth Cohort 1986. The participants underwent a resting-state fMRI scan. Coefficient of variation (CV) of blood oxygen level dependent (BOLD) signal (CVBOLD) was used as a proxy of physiological fluctuation in the brain. Familial risk was defined to be present if at least one parent had been diagnosed with psychosis previously. PRS was computed based on the results of the prior GWAS by the Schizophrenia Working Group. FR or PRS were not associated with CVBOLD in cerebrospinal fluid, white matter, or grey matter. The findings did not provide evidence for the previous suggestions that genetic vulnerabilities for schizophrenia become apparent in alterations of the variation of the BOLD signal in the brain.

BackgroundThere is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.MethodsWe measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.ResultsPrincipal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).ConclusionThe effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.