Dataset Information

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum.

ABSTRACT: Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.

SUBMITTER: Kirschner M

PROVIDER: S-EPMC8084448 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Autism spectrum disorder (ASD) and schizophrenia (SZ) are heterogenous neurodevelopmental disorders that overlap in symptom presentation. The purpose of this study was to specify overlapping symptom domains and to identify symptoms that can reliably differentiate adults with ASD (n = 53), SZ (n = 39), and typical development (TD; n = 40). All participants regardless of diagnosis were administered gold-standard diagnostic assessments of ASD and SZ characteristics including the Autism Diagnostic Observation Schedule (ADOS-2) and the Positive and Negative Syndrome Scale (PANSS). Sensitivity and specificity of the ADOS were assessed using diagnostic cut-off scores. The degree of symptom overlap on these measures between participant groups was analyzed using Analyses of Variance (ANOVAs), Receiver Operating Characteristic (ROC) Curves, and Analyses of Covariance (ANCOVAs) to control for group differences in IQ and sex distributions. The ADOS reliably discriminated ASD and TD adults, but there was a high rate of "false positives" in SZ patients who did not meet the DSM-5 criteria for ASD. To identify the reasons for low specificity in the SZ sample, we categorized ASD and SZ symptoms into 'positive' (presence of atypical behaviors) and 'negative' (absence of typical behaviors) symptoms. ASD and SZ groups overlapped on negative symptoms largely related to the absence of typical social and communicative behaviors, whereas disorder-specific positive symptoms differentiated ASD and SZ. For example, those with ASD scored higher on restricted and repetitive behaviors and stereotyped language, whereas those with SZ scored higher on psychotic symptoms such as delusions and hallucinations. These results suggest that, when making a differential diagnosis between ASD and SZ, clinicians may benefit from focusing on the presence or absence of positive ASD and SZ symptoms. Standardized measures to classify ASD symptoms into positive and negative symptoms have not yet been developed but represent a potentially viable clinical tool.

Project description:ImportanceNegative symptoms are associated with a range of poor clinical outcomes, and currently available treatments generally do not produce a clinically meaningful response. Limited treatment progress may be owing in part to poor clarity regarding latent structure. Prior studies have inferred latent structure using exploratory factor analysis, which has led to the conclusion that there are 2 dimensions reflecting motivation and pleasure (MAP) and diminished expressivity (EXP) factors. However, whether these conclusions are statistically justified remains unclear because exploratory factor analysis does not test latent structure. Confirmatory factor analysis (CFA) is needed to test competing models regarding the latent structure of a construct.ObjectiveTo evaluate the fit of 4 models of the latent structure of negative symptoms in schizophrenia using CFA.Design, setting, and participantsThree cross-sectional studies were conducted on outpatients with schizophrenia who were rated on the 3 most conceptually contemporary measures: Scale for the Assessment of Negative Symptoms (SANS), Brief Negative Symptom Scale (BNSS), and Clinical Assessment Interview for Negative Symptoms (CAINS). Confirmatory factor analysis evaluated the following 4 models: (1) a 1-factor model; (2) a 2-factor model with EXP and MAP factors; (3) a 5-factor model with separate factors for the 5 domains of the National Institute of Mental Health consensus development conference (blunted affect, alogia, anhedonia, avolition, and asociality); and (4) a hierarchical model with 2 second-order factors reflecting EXP and MAP and 5 first-order factors reflecting the 5 consensus domains.Main outcomes and measuresOutcomes included CFA model fit statistics derived from symptom severity scores on the SANS, BNSS, and CAINS.ResultsThe study population included 860 outpatients with schizophrenia (68.0% male; mean [SD] age, 43.0 [11.4] years). Confirmatory factor analysis was conducted on each scale, including 268 patients for the SANS, 192 for the BNSS, and 400 for the CAINS. The 1- and 2-factor models provided poor fit for the SANS, BNSS, and CAINS as indicated by comparative fit indexes (CFIs) and Tucker Lewis indexes (TLIs) less than 0.950, RMSEAs that exceeded the 0.080 threshold, and WRMRs greater than 1.00. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model being more parsimonious. The CFIs and TLIs met the 0.95 threshold and the 1.00 threshold for both factor models with all 3 measures. Interestingly, the RMSEAs for the 5-factor model and the hierarchical model fell under the 0.08 threshold for the BNSS and the CAINS but not the SANS.Conclusions and relevanceThese findings suggest that the recent trend toward conceptualizing the latent structure of negative symptoms as 2 distinct dimensions does not adequately capture the complexity of the construct. The latent structure of negative symptoms is best conceptualized in relation to the 5 consensus domains. Implications for identifying pathophysiological mechanisms and targeted treatments are discussed.

Dataset Information

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets