Genetic Liability Accounts for Some Schizophrenia Symptoms

Sophia Legge, PhD

New research sheds light on the genetic liability interplay that results in cognitive impairment and different symptom scores for patients with schizophrenia.

It is not currently known how variability in schizophrenia symptom dimensions and cognitive ability is linked with genetic liability for the disease.

A team based in the UK, led by Sophie E. Legge, PhD, MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, determined whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and overall intelligence.

“A better understanding of the different factors underlying these symptom dimensions could contribute to the development of novel treatments for schizophrenia; currently available treatments predominantly affect only positive symptoms,” the authors wrote.

The Study

The genetic association study included 3 cross-sectional samples involving 1220 patients with schizophrenia. The patients were recruited from community, inpatient, and voluntary sector mental health services in the UK. The mean age of the patient population was 43.10 years and 67% (n = 817) of the patients were male.

The investigators created 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 by using confirmatory factor analysis.

The team also assessed whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were linked to phenotypic dimensions using an analyses of polygenic risk scores (PRSs).

The data was collected between 1993-2016.

Main Outcomes

The investigators sought main outcomes of phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability.

They also looked at various exposure measures, including PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence.

Results

A key finding was schizophrenia PRS was linked to increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4).

On the other hand, current cognitive ability was linked to genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3), as well as intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10).

The investigators then controlled for estimated premorbid IQ and found current cognitive performance was linked to schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3). However, there was no link in intelligence PRS.

“The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions,” the authors wrote. “Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia.”

The study, “Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia,” was published online in JAMA Psychiatry.