Gender differences in neurocognitive impairment among first-episode, drug-naïve schizophrenia patients: a cross-sectional study

Abstract

Introduction: Cognitive impairment is a core feature of first-episode schizophrenia (FES), yet the influence of biological sex on its manifestation remains under characterized. Existing evidence suggests sex differences in cognitive profiles among chronic schizophrenia patients, but whether these patterns emerge in drug-naïve FES patients-and how they relate to clinical symptoms-requires clarification.

Methods: We recruited 382 drug-naïve FES patients and 522 healthy controls (HCs) matched for age and education. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Clinical symptoms were evaluated via the Positive and Negative Syndrome Scale (PANSS).

Results: FES patients demonstrated global cognitive deficits compared to HCs. When stratified by diagnostic group (FES and HC), males outperformed females in planning and problem-solving, as measured by the Neuropsychological Assessment Battery Mazes subtest (p < 0.001), whereas females showed superior performance in visuospatial memory, as assessed by the Brief Visuospatial Memory Test-Revised (p < 0.001) in both groups. When stratified by gender, FES patients exhibited similar patterns of impairment severity relative to their gender-matched HCs: both male and female FES patients showed the most pronounced deficits in processing speed (BACS) and sustained attention (CPT), with effect sizes of 1.64 and 1.52 for males, and 1.36 and 1.48 for females, respectively. Correlational analyses revealed that male FES patients' cognitive impairments were specifically associated with negative symptoms, while female impairments correlated broadly with all PANSS domains. Correlational analyses revealed that in FEP patients, male cognitive impairments were specifically associated with negative symptoms, while female impairments showed broad associations with all domains of the PANSS.

Conclusion: FES manifests as sex-divergent cognitive profiles, with males showing executive/processing speed deficits tied to negative symptoms and females exhibiting memory impairments with broader symptom associations. These findings underscore the need for sex-sensitive approaches in characterizing cognitive dysfunction in early psychosis.

Keywords: cognition; first-episode; gender; psychosis; schizophrenia.

Figure 1

Radar plots and bar charts of effect sizes illustrating gender-based cognitive differences in healthy controls (HC) and first - episode schizophrenia (FES) patients. The radar plots display male and female performance across various cognitive tests, while the bar charts quantify the magnitude of gender differences with corresponding statistical significance levels. TMT refers to Trail Making Test, assessing visual attention and task-switching; BACS symbol coding from the Brief Assessment of Cognition in Schizophrenia, evaluating processing speed; HVLT is the Revised Hopkins Verbal Learning Test, evaluating verbal learning and memory; WMS represents the Wechsler Memory Scale; NAB mazes from the Neuropsychological Assessment Battery, testing planning and problem-solving; BVMT is the Revised Brief Visuospatial Memory Test, focusing on visuospatial memory; CF is the Category Fluency test, evaluating verbal fluency; MSCEIT is the Mayer-Salovey-Caruso Emotional Intelligence Test, measuring emotional intelligence; CPT is the Continuous Performance Test-Identical Pairs, assessing sustained attention. For the purpose of enhancing comparability, all samples underwent Z-score transformation. Since for TMT, a lower score indicates better performance, after the Z-score transformation, a negative sign was added to make it consistent with other tests. The calculation method for Effect Size is calculated by subtracting the mean of the second group from the mean of the first group. The resulting difference is then divided by the square root of the average of the squared standard deviations of the two groups.

Figure 2

Radar plots and bar charts of effect sizes showing cognitive differences between healthy controls (HC) and first - episode schizophrenia (FES) patients, stratified by gender. The radar plots display the cognitive performance of HC and FES in different tests for males and females respectively, while the bar charts quantify the magnitude of differences between HC and FES with corresponding effect sizes. TMT refers to Trail Making Test, assessing visual attention and task-switching; BACS symbol coding from the Brief Assessment of Cognition in Schizophrenia, evaluating processing speed; HVLT is the Revised Hopkins Verbal Learning Test, evaluating verbal learning and memory; WMS represents the Wechsler Memory Scale; NAB mazes from the Neuropsychological Assessment Battery, testing planning and problem-solving; BVMT is the Revised Brief Visuospatial Memory Test, focusing on visuospatial memory; CF is the Category Fluency test, evaluating verbal fluency; MSCEIT is the Mayer-Salovey-Caruso Emotional Intelligence Test, measuring emotional intelligence; CPT is the Continuous Performance Test-Identical Pairs, assessing sustained attention. For the purpose of enhancing comparability, all samples underwent Z-score transformation. Since for TMT, a lower score indicates better performance, after the Z-score transformation, a negative sign was added to make it consistent with other tests. The calculation method for Effect Size is calculated by subtracting the mean of the second group from the mean of the first group. The resulting difference is then divided by the square root of the average of the squared standard deviations of the two groups.

Figure 3

Plots illustrating the correlations between cognitive test scores and PANSS clinical symptoms, stratified by gender, in FES patients. TMT refers to Trail Making Test, assessing visual attention and task-switching; BACS symbol coding from the Brief Assessment of Cognition in Schizophrenia, evaluating processing speed; HVLT is the Revised Hopkins Verbal Learning Test, evaluating verbal learning and memory; WMS represents the Wechsler Memory Scale; NAB mazes from the Neuropsychological Assessment Battery, testing planning and problem-solving; BVMT is the Revised Brief Visuospatial Memory Test, focusing on visuospatial memory; CF is the Category Fluency test, evaluating verbal fluency; MSCEIT is the Mayer-Salovey-Caruso Emotional Intelligence Test, measuring emotional intelligence; CPT is the Continuous Performance Test-Identical Pairs, assessing sustained attention. For the purpose of enhancing comparability, FES samples underwent Z-score transformation. Since for TMT, a lower score indicates better performance, after the Z-score transformation, a negative sign was added to make it consistent with other tests. The F-value is used to determine whether the slope is significant, and a p-value less than 0.05 indicates significance.