Discriminatory experiences predict neuroanatomical changes and anxiety among healthy individuals and those at clinical high risk for psychosis.
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ABSTRACT:
SUBMITTER: Collins MA
PROVIDER: S-EPMC8283423 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMT(Met) compared to COMT(Val), and greater reduction in those with greater decline in verbal IQ over time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.
| S-EPMC3000448 | biostudies-literature
Project description:Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
| S-EPMC9325730 | biostudies-literature
Project description:Sex differences have been widely observed in clinical presentation, functional outcome and neuroanatomy in individuals with a first-episode of psychosis, and chronic patients suffering from schizophrenia. However, little is known about sex differences in the high-risk stages for psychosis. The present study investigated sex differences in cortical and subcortical neuroanatomy in individuals at clinical high risk (CHR) for psychosis and healthy controls (CTL), and the relationship between anatomy and clinical symptoms in males at CHR. Magnetic resonance images were collected in 26 individuals at CHR (13 men) and 29 CTLs (15 men) to determine total and regional brain volumes and morphology, cortical thickness, and surface area (SA). Clinical symptoms were assessed with the brief psychiatric rating scale. Significant sex-by-diagnosis interactions were observed with opposite directions of effect in male and female CHR subjects relative to their same-sex controls in multiple cortical and subcortical areas. The right postcentral, left superior parietal, inferior parietal supramarginal, and angular gyri [<5% false discovery rate (FDR)] were thicker in male and thinner in female CHR subjects compared with their same-sex CTLs. The same pattern was observed in the right superior parietal gyrus SA at the regional and vertex level. Using a recently developed surface-based morphology pipeline, we observed sex-specific shape differences in the left hippocampus (<5% FDR) and amygdala (<10% FDR). Negative symptom burden was significantly higher in male compared with female CHR subjects (p?=?0.04) and was positively associated with areal expansion of the left amygdala in males (<5% FDR). Some limitations of the study include the sample size, and data acquisition at 1.5?T. This study demonstrates neuroanatomical sex differences in CHR subjects, which may be associated with variations in symptomatology in men and women with psychotic symptoms.
| S-EPMC5744013 | biostudies-literature
Project description:Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions.
| S-EPMC5605267 | biostudies-literature
Project description:Many neuropsychiatric illnesses are associated with psychosis, i.e., hallucinations (perceptions in the absence of causative stimuli) and delusions (irrational, often bizarre beliefs). Current models of brain function view perception as a combination of two distinct sources of information: bottom-up sensory input and top-down influences from prior knowledge. This framework may explain hallucinations and delusions. Here, we characterized the balance between visual bottom-up and top-down processing in people with early psychosis (study 1) and in psychosis-prone, healthy individuals (study 2) to elucidate the mechanisms that might contribute to the emergence of psychotic experiences. Through a specialized mental-health service, we identified unmedicated individuals who experience early psychotic symptoms but fall below the threshold for a categorical diagnosis. We observed that, in early psychosis, there was a shift in information processing favoring prior knowledge over incoming sensory evidence. In the complementary study, we capitalized on subtle variations in perception and belief in the general population that exhibit graded similarity with psychotic experiences (schizotypy). We observed that the degree of psychosis proneness in healthy individuals, and, specifically, the presence of subtle perceptual alterations, is also associated with stronger reliance on prior knowledge. Although, in the current experimental studies, this shift conferred a performance benefit, under most natural viewing situations, it may provoke anomalous perceptual experiences. Overall, we show that early psychosis and psychosis proneness both entail a basic shift in visual information processing, favoring prior knowledge over incoming sensory evidence. The studies provide complementary insights to a mechanism by which psychotic symptoms may emerge.
| S-EPMC4629373 | biostudies-other
Project description:There is increasing evidence pointing toward a continuous distribution of psychotic symptoms and accompanying factors between subclinical and clinical populations. However, for the construction of continuum models, a more detailed knowledge of different types of psychotic-like experiences (PLE) and their associations with distress, functional impairment, and demographic variables is needed. We investigated PLE in a sample of healthy adults (N = 206) incorporating the recently developed revised Exceptional Experiences Questionnaire (PAGE-R). For the first time, the PAGE-R was cross validated with PLE, disorganized-, and negative-like symptoms [Schizotypal Personality Questionnaire (SPQ), Physical Anhedonia Scale (PAS)]. We subjected the PAGE-R to exploratory factor analyses and examined the resulting subtypes of EE for specific associations with contextual factors, valence ratings, socio-demographic variables, and general psychological burden (Revised Symptom-Checklist-90). Correlational cross-validation suggested that the PAGE-R measures facets of PLE. Importantly, we (1) identified three types of exceptional experiences (EE): Odd beliefs, dissociative anomalous perceptions, and hallucinatory anomalous perceptions. Further, the results suggested that even in healthy individuals (2) PLE and EE are indicative of reduced functioning, as reflected by increased psychological burden and lower educational achievement. Moreover, (3) similar sex-differences might exist as in psychotic patients with women reporting more positive-like symptoms and EE but less disorganized-like symptoms than men. Importantly, (4) EE might be differentially implicated in psychological functioning. We suggest that the PAGE-R holds the potential to complement the current assessment of sub-clinical psychosis. However, whereas our results might point toward a continuity of psychotic symptoms with EE and normal experiences, they require replication in larger samples as well as equivalence testing across the psychosis continuum. Future analyses incorporating the PAGE-R might shed more light onto mechanisms that are implicated in the progress or resilience toward clinical illness.
| S-EPMC5431212 | biostudies-literature
Project description:ObjectivesThe State-Trait Anxiety Inventory (STAI) and the Hamilton scale for anxiety (HARS) are two of the most important scales employed in clinical and psychological realms for the evaluation of anxiety. Although the reliability and sensibility of these scales are widely demonstrated there is an open debate on what exactly their scores reflect. Neuroimaging provides the potential to validate the quality and reliability of clinical scales through the identification of specific biomarkers. For this reason, we evaluated the neural correlates of these two scales in a large cohort of healthy individuals using structural neuroimaging methods.Case reportNeuroimaging analysis included thickness/volume estimation of cortical and subcortical limbic structures, which were regressed on anxiety inventory scores with age and gender used for assessing discriminant validity. A total of 121 healthy subjects were evaluated. Despite the two anxiety scales, at a behavioral level, displaying significant correlations among them (HARS with STAI-state (r = 0.24; P = 0.006) and HARS with STAI-trait (r = 0.42; P < 0.001)), multivariate neuroimaging analyses demonstrated that anatomical variability in the anterior cingulate cortex was the best predictor of the HARS scores (all ?'s ? 0.31 and P's ? 0.01), whereas STAI-related measures did not show any significant relationship with regions of limbic circuits, but their scores were predicted by gender (all ?'s ? 0.23 and P's ? 0.02).ConclusionAlthough the purpose of HARS and STAI is to quantify the degree and characteristics of anxiety-like behaviors, our neuroimaging data indicated that these scales are neurobiologically different, confirming that their scores might reflect different aspects of anxiety: the HARS is more related to subclinical expression of anxiety disorders, whereas the STAI captures sub-dimensions of personality linked to anxiety.
| S-EPMC4128032 | biostudies-literature
Project description:ObjectiveTo investigate the association between facial affect recognition (FAR) and type of adverse childhood experiences (ACEs) in a sample of clinical high risk (CHR) individuals and a matched sample of healthy controls (HCs).MethodsIn total, 309 CHR individuals and 51 HC were recruited as part of an European Union-funded multicenter study (EU-GEI) and included in this work. During a 2-year follow-up period, 65 CHR participants made a transition to psychosis (CHR-T) and 279 did not (CHR-NT). FAR ability was measured using a computerized version of the Degraded Facial Affect Recognition (DFAR) task. ACEs were measured using the Childhood Experience of Care and Abuse Questionnaire, the Childhood Trauma Questionnaire, and the Bullying Questionnaire. Generalized regression models were used to investigate the relationship between ACE and FAR. Logistic regressions were used to investigate the relationship between FAR and psychotic transition.ResultsIn CHR individuals, having experienced emotional abuse was associated with decreased total and neutral DFAR scores. CHR individuals who had experienced bullying performed better in the total DFAR and in the frightened condition. In HC and CHR, having experienced the death of a parent during childhood was associated with lower DFAR total score and lower neutral DFAR score, respectively. Analyses revealed a modest increase of transition risk with increasing mistakes from happy to angry faces.ConclusionsAdverse experiences in childhood seem to have a significant impact on emotional processing in adult life. This information could be helpful in a therapeutic setting where both difficulties in social interactions and adverse experiences are often addressed.
| S-EPMC7345818 | biostudies-literature
Project description:Psychosis-like experiences are present in the general population and may indicate risk for more severe forms of psychosis. They are associated with cognitive impairments, potentially impacting ability to accurately complete certain self-report measures. This study investigated whether the presence of psychosis-like experiences was associated with impairments in retrospective reports of physical activity, a measure salient to this population, by comparing post-study questionnaire data on activity level with reports of activity contemporaneously collected through ecological momentary assessment (EMA). Participants (n = 39) were 18-25 years of age and recruited via stratified sampling to maximize representation of a full psychosis-like experience spectrum. Mobile questionnaires were sent six times a day for one week, and included questions probing amount and intensity of activity. Upon completion of the EMA week, participants completed a retrospective recall of the past week's activity. High levels of psychosis-like experiences were associated with poorer recall for past sedentary behavior as evidenced by the moderating effect of psychosis-like experiences on the relation between retrospective and in vivo measured sedentary activity (interaction effect: b = -0.26, t(1) = -2.04, p = 0.05, f2 = 0.08). Findings call into question the validity of retrospective self-reporting of activity level for those experiencing psychosis-like experiences.
| S-EPMC7535082 | biostudies-literature
Project description:ImportanceCognitive deficits are a key feature of risk for psychosis. Longitudinal changes in cognitive architecture may be associated with the social and occupational functioning in young people.ObjectivesTo examine longitudinal profiles of cognition in individuals at ultrahigh risk (UHR) for psychosis, compared with healthy controls, and to investigate the association of cognition with functioning.Design, setting, and participantsThis study has a multiple-group prospective design completed in 24 months and was conducted from January 1, 2009, to November 11, 2012, as part of the Longitudinal Youth at-Risk Study conducted in Singapore. Participants either were recruited from psychiatric outpatient clinics, educational institutions, and community mental health agencies or self-referred. Follow-up assessments were performed every 6 months for 2 years or until conversion to psychosis. Individuals with medical causes for psychosis, current illicit substance use, or color blindness were excluded. Data analysis was conducted from June 2014 to May 2018.Main outcomes and measuresNeuropsychological, perceptual, and social cognitive tasks; semi-structured interviews, and the Structured Clinical Interview for DSM-IV Axis I disorders were administered every 6 months. The UHR status of nonconverters, converters, remitters, and nonremitters was monitored. Cognitive domain scores and functioning were investigated longitudinally.ResultsIn total, 384 healthy controls and 173 UHR individuals between ages 14 and 29 years were evaluated prospectively. Of the 384 healthy controls, 153 (39.8%) were female and 231 (60.2%) were male with a mean (SD) age of 21.69 (3.26) years. Of the 173 individuals at UHR for psychosis, 56 (32.4%) were female and 117 (67.6%) were male with a mean (SD) age of 21.27 (3.52) years). After 24 months of follow-up, 383 healthy controls (99.7%) and 122 individuals at UHR for psychosis (70.5%) remained. Baseline cognitive deficits were associated with psychosis conversion later (mean odds ratio [OR], 1.66; combined 95% CI, 1.08-2.83; P = .04) and nonremission of UHR status (mean OR, 1.67; combined 95% CI, 1.09-2.95; P = .04). Five cognitive components-social cognition, attention, verbal fluency, general cognitive function, and perception-were obtained from principal components analysis. Longitudinal component structure change was observed in general cognitive function (maximum vertical deviation = 0.59; χ2 = 8.03; P = .01). Group-by-time interaction on general cognitive function (F = 12.23; η2 = 0.047; P < .001) and perception (F = 8.33; η2 = 0.032; P < .001) was present. Changes in attention (F = 5.65; η2 = 0.013; P = .02) and general cognitive function (F = 7.18; η2 = 0.014; P = .01) accounted for longitudinal changes in social and occupational functioning.Conclusions and relevanceIndividuals in this study who met the UHR criteria appeared to demonstrate cognitive deficits, and those whose UHR status remitted were seen to recover cognitively. Cognition appeared as poor in nonremitters and appeared to be associated with poor functional outcome. This study suggests that cognitive dimensions are sensitive to the identification of young individuals at risk for psychosis and to the longitudinal course of those at highest risk.
| S-EPMC6142925 | biostudies-literature