Disorganized, cognitive symptoms ‘core characteristics’ of schizophrenia

Schizophrenia genetic liability correlated with higher disorganized dimension scores but not other symptom dimensions, according to results of a genetic association study published in JAMA Psychiatry.

“We know that schizophrenia is a clinically heterogeneous disorder, which means that there is a lot of variability from one person to another in terms of the symptoms they experience, how much it impairs their ability to work and socialize, how they respond to treatment and how long they will experience symptoms,” Sophie E. Legge, PhD, of the MRC Centre for Neuropsychiatric Genetics and Genomics in the division of psychological medicine and clinical neurosciences at Cardiff University School of Medicine in the U.K., told Healio Psychiatry. “Schizophrenia is currently characterized by the presence of positive, negative and/or disorganized symptoms, while cognitive impairment and mood symptoms are also common. The aim of this study was to investigate whether the heterogeneity in schizophrenia symptoms and cognitive ability could be partly explained by each individual’s genetic liability to schizophrenia, other psychiatric disorders or poorer cognition.”

Legge and colleagues analyzed data from three cross-sectional samples of 1,220 individuals (men = 67%; mean age at interview, 43.1 years) diagnosed with schizophrenia who were recruited from community, inpatient and voluntary mental health services in the U.K. They used confirmatory factor analysis to estimate phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms and the MATRICS Consensus Cognitive Battery. They used analyses of polygenic risk scores to assess whether associations existed between these phenotypic dimensions and genetic liability to schizophrenia, other neuropsychiatric disorders and intelligence. Phenotypic dimensions defined via confirmatory factor analysis related to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms and current cognitive ability served as main outcomes and measures. Polygenic risk scores for schizophrenia, bipolar disorder, major depression, ADHD, autism spectrum disorder and intelligence served as exposure measures.

Results showed an association between schizophrenia polygenic risk score and increased disorganized symptoms dimension scores in both a five-factor model (beta = 0.14; 95% CI, 0.07-0.22) and a three-factor model across all samples (beta = 0.1; 95% CI, 0.05-0.15). Moreover, they noted an association between current cognitive ability and genetic liability to schizophrenia (beta = 0.11; 95% CI, 0.19 to 0.04) and intelligence (beta = 0.23; 95% CI, 0.16-0.3). They also observed an association between current cognitive performance and schizophrenia polygenic risk score (beta = 0.08; 95% CI, 0.14 to 0.02) but not intelligence polygenic risk score after controlling for estimated premorbid IQ.

“This study reinforces the importance of disorganized and cognitive symptoms as core characteristics of schizophrenia and that further investigation of these phenotypes and their underlying mechanisms may provide a means of better targeting new treatments,” Legge said.