Cognitive Impairment in Treatment-Naive Patients With First Episode Psychosis

Individuals with first episode psychosis (FEP) experience cognitive impairment in all cognitive domains before receiving antipsychotic treatment, according to results from a systematic review and meta-analysis published in JAMA Psychiatry. These findings highlight the importance of identifying patients with severe cognitive challenges who may gain from cognitive remediation.

Cognitive impairment is closely associated with functional and clinical outcomes in schizophrenia and other psychotic disorders, frequently manifesting before the onset of illness. Previous meta-analyses have highlighted notable cognitive deficits in patients with FEP who have not been treated with antipsychotic drugs. However, it remains unclear as to which cognitive domains may be differentially impacted in psychosis. To bridge this gap, investigators conducted a systematic review and meta-analysis to measure cognitive decline across domains in patients at the start of psychosis before undergoing antipsychotic treatment.

The investigators searched the PubMed database for original studies that compared cognitive function among individuals with schizophrenia and other psychotic disorders who were having FEP and healthy controls. Cognitive outcomes were evaluated across 7 domains: processing speed, attention, working memory, verbal learning, visual learning, reasoning and problem-solving, and executive function. In addition to the data gathered through the literature search, the investigators also included cognitive data from the Karolinska Schizophrenia Project, which matched antipsychotic drug-naive patients with FEP with age- and sex-matched controls.

The investigators included a total of 50 studies for a pooled sample size of 2625 individuals with FEP. On average, participants with FEP were 25.2 (SD, 3.6) years of age and 60% were men. The study quality ratings varied between 3 and 8, and the meta-regression analysis revealed no significant impacts of potential moderators in terms of age, sex, education, publication year, and study quality.

The findings suggest that individuals experiencing their FEP who had not yet begun treatment displayed significant cognitive deficits across all cognitive domains, compared with controls. Individuals with FEP had the largest impairments in speed of processing (Hedges g, -1.16; 95% CI, -1.35 to -0.98), followed by verbal learning (Hedges g, -1.08; 95% CI, -1.28 to -0.88), visual learning (Hedges g, -1.05; 95% CI, -1.27 to -0.82), working memory (Hedges g, -1.04; 95% CI, -1.35 to -0.73), attention (Hedges g, -1.03; 95% CI, -1.24 to -0.82), reasoning and problem-solving (Hedges g, -0.90; 95% CI, -1.12 to -0.68), and executive function (Hedges g, -0.88; 95% CI, -1.07 to -0.69).

Antipsychotic drug-naive patients with FEP also demonstrated significantly higher variability in cognitive performance relative to controls, with coefficient of variation ratios [CVRs] ranging from 1.34 to 1.92 – indicating that the variability for individuals with FEP was 30% to almost twice the variability of controls. The highest CVR was observed for attention (CVR=1.92), followed by visual learning (CVR=1.87), working memory (CVR=1.61), verbal learning (CVR=1.55), reasoning and problem-solving (CVR=1.46), speed of processing (CVR=1.43), and executive function (CVR=1.34).

Study authors concluded, “The results highlight the importance of cognitive assessments in clinical practice, in order to identify individuals at risk for poor functional outcome, and to select individuals for cognitive remediation, as part of a precision medicine approach.”

The main study limitation was the potential confounders associated with cognitive testing of unmedicated individuals with psychosis (eg, sleep deprivation, disruptive symptoms, lack of motivation).

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Psychiatry Advisor