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MRI Indices of Cortical Development in Young People With Psychotic Experiences: Influence of Genetic Risk and Persistence of Symptoms.

ABSTRACT: Background:Psychotic experiences (PEs) are considered part of an extended psychosis phenotype and are associated with an elevated risk of developing a psychotic disorder. Risk of transition increases with persistence of PEs, and this is thought to be modulated by genetic and environmental factors. However, it is unclear if persistence is associated with progressive schizophrenia-like changes in neuroanatomy. Methods:We examined cortical morphometry using MRI in 247 young adults, from a population-based cohort, assessed for the presence of PEs at ages 18 and 20. We then incorporated a polygenic risk score for schizophrenia (PRS) to elucidate the effects of high genetic risk. Finally, we used atlas-based tractography data to examine the underlying white matter. Results:Individuals with persisting PEs showed reductions in gyrification (local gyrification index: lGI) in the left temporal gyrus as well as atypical associations with brain volume (TBV) in the left occipital and right prefrontal gyri. No main effect was found for the PRS, but interaction effects with PEs were identified in the orbitofrontal, parietal, and temporal regions. Examination of underlying white matter did not provide strong evidence of further disturbances. Conclusions:Disturbances in lGI were similar to schizophrenia but findings were mostly limited to those with persistent PEs. These could reflect subtle changes that worsen with impending psychosis or reflect an early vulnerability associated with the persistence of PEs. The lack of clear differences in underlying white matter suggests our findings reflect early disturbances in cortical expansion rather than progressive changes in brain structure.

SUBMITTER: Fonville L

PROVIDER: S-EPMC6293214 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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MRI Indices of Cortical Development in Young People With Psychotic Experiences: Influence of Genetic Risk and Persistence of Symptoms.

Fonville Leon L Drakesmith Mark M Zammit Stanley S Lewis Glyn G Jones Derek K DK David Anthony S AS

Schizophrenia bulletin 20190101 1

<h4>Background</h4>Psychotic experiences (PEs) are considered part of an extended psychosis phenotype and are associated with an elevated risk of developing a psychotic disorder. Risk of transition increases with persistence of PEs, and this is thought to be modulated by genetic and environmental factors. However, it is unclear if persistence is associated with progressive schizophrenia-like changes in neuroanatomy.<h4>Methods</h4>We examined cortical morphometry using MRI in 247 young adults, f ...[more]

PMID: 29385604

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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.

Project description:BackgroundDespite experiencing high rates of trauma and trauma-related conditions, people with psychosis are seldomly asked about possible traumatic events. While there are some barriers to discussing trauma in clinical services, research has shown that disclosure is not only possible but also beneficial to both psychotic and traumatic symptoms. The current study is the first to evaluate service users' perception of the influence of trauma on the development and maintenance of their psychotic symptoms, as well as their views on how their life and mental health have been affected by traumatic events and their disclosure (or lack of).MethodsEleven participants with experiences of psychosis and trauma took part in semi-structured interviews.ResultsConsistently with previous literature, our participants reported high rates of interpersonal trauma, but had rarely had the opportunity to discuss any of these events. Using thematic analysis, we identified three major themes that have important implications for healthcare: factors that facilitate or hinder talking about trauma; consequences of talking or not; and relationship between trauma and psychosis. Participants generally benefited from talking about trauma and concerningly often associated the prolonged lack of opportunities to discuss traumatic events with negative feelings towards the self and with a deterioration of their mental health. Participants also recognised direct links between past traumas and the content and characteristics of their psychotic experiences.ConclusionsOur findings highlight the importance, as perceived by service users, of discussing trauma and looking at psychosis through a "trauma lens". These results stress the need to systematically assess trauma history and traumatic symptoms in psychosis and might potentially help to overcome clinicians' worries about discussing trauma with service users. Our findings underscore the need to change current practice and implement trauma-informed approaches to understand clients' difficulties and provide support.

Project description:Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.

Project description:BackgroundYoung Australians (16-25 years) have the highest rates of past-month cannabis use in the world. Cannabis use increases the risk of alcohol and other drug disorders and depressive disorders, and has a robust dose-response association with psychotic experiences (PEs) and disorders. PEs are subthreshold positive psychotic symptoms, including delusions and hallucinations, which increase the risk of substance use, depressive or anxiety disorders, and psychotic disorders. Access to effective web-based early interventions targeting both cannabis use and PEs could reduce such risk in young people.ObjectiveThe objective of this study is to determine the efficacy and cost-effectiveness of the Keep it Real web-based program compared to an information-only control website among young cannabis users (16-25 years) with PEs.MethodsParticipants are recruited online, and consenting individuals meeting inclusion criteria (aged 16-25 years, who have used cannabis in the past month and experienced PEs in the past 3 months) are automatically randomized to either the Keep it Real web-based program (n=249) or an information-only control website (n=249). Both websites are self-guided (fully automated). The baseline and follow-up assessments at 3, 6, 9, and 12 months are self-completed online. Primary outcome measures are weekly cannabis use, PEs, and the relative cost-effectiveness for quality-adjusted life years. Secondary outcomes include other substance use and related problems, PE-related distress, cannabis intoxication experiences, severity of cannabis dependence, depression/anxiety symptoms, suicidality, and mental well-being and functioning.ResultsRecruitment commenced in February 2019, and the results are expected to be submitted for publication in mid-2021.ConclusionsThis study protocol describes a large randomized controlled trial of a new web-based program for young cannabis users experiencing PEs. If effective, the accessibility and scalability of Keep it Real could help reduce growing public health concerns about the significant social, economic, and health impacts of cannabis use.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618001107213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374800.International registered report identifier (irrid)DERR1-10.2196/15803.

Dataset Information

MRI Indices of Cortical Development in Young People With Psychotic Experiences: Influence of Genetic Risk and Persistence of Symptoms.

Publications

MRI Indices of Cortical Development in Young People With Psychotic Experiences: Influence of Genetic Risk and Persistence of Symptoms.

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