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Patients With First-Episode Psychosis Found to Have Cognitive Impairment Before Medication Use

Evi Arthur

Patients with first-episode psychosis (FEP) were found to have cognitive impairment prior to their first use of antipsychotic medications, particularly with large effect sizes, according to recent meta-analysis results published in JAMA Psychiatry. 

“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,” noted lead author Maria Lee, MScPsych, Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden, and co-authors. 

Related: Young Adults Who Self-Harm May Be More at Risk of Psychosis Diagnosis

Authors searched PubMed for original studies reporting data on cognitive function in antipsychotic drug-naive patients with FEP up to September 15, 2022. Cognitive tasks were organized according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. 

“Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias,” authors noted.

The analysis included 50 studies involving 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). Results showed significant impairment across all cognitive domains in the FEP group compared to controls, with large effect sizes observed for speed of processing (Hedges g = −1.16), verbal learning (Hedges g = −1.08), visual learning (Hedges g = −1.05), working memory (Hedges g = −1.04), attention (Hedges g = −1.03), reasoning/problem solving (Hedges g = −0.90), and executive function (Hedges g = −0.88). Additionally, individuals with FEP exhibited greater variability across all cognitive domains, as indicated by a range of CVR values (1.34 to 1.92).

The limitations of this study include concerns regarding cognitive testing of unmedicated individuals with psychosis, which may be affected by factors like sleep deprivation and disruptive psychotic symptoms. Additionally, the analysis of cerebrovascular reactivity (CVR) depends on both patient and control group characteristics, with potential biases in control group selection and variability. The recruitment procedures for controls were mostly from the community, aiming to mitigate these issues, but factors like medication status and task reliability could still influence results. Additionally, while the study aimed to include early psychosis cases, some studies did not report duration of untreated psychosis (DUP), which could be a potential limitation.


Reference
Lee M, Cernvall M, Borg J, et al. Cognitive function and variability in antipsychotic drug–naive patients with first-episode psychosis: A systematic review and meta-analysis. JAMA Psychiatry. Published online February 28, 2024. doi:10.1001/jamapsychiatry.

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