Sex-specific neurocognitive patterns in schizophrenia spectrum psychoses: psychometric quantification and neurobiological implications

Introduction

Cognitive impairment represents a central and clinically relevant dimension of schizophrenia spectrum psychoses and is among the strongest predictors of long-term functional outcome, occupational capacity, and quality of life. Contemporary neurobiological models of schizophrenia emphasize disturbances in large-scale brain network connectivity, particularly within frontotemporal and frontoparietal pathways. In addition, dysregulation of mesocortical dopaminergic pathways and glutamatergic NMDA receptor hypofunction are considered key pathophysiological mechanisms. These alterations contribute to deficits in working memory, executive functions, and processing speed. A particularly important conceptual distinction is that between fluid intelligence, which reflects real-time neurocognitive efficiency, cortical network integrity, and intelligence, which represents accumulated knowledge and tends to be more resilient to acute neurobiological disruption.

Objectives

The aim of this study was to quantify both global and domain-specific cognitive deterioration in patients with schizophrenia spectrum psychoses and to examine sex-specific differences in patterns of neurocognitive impairment, with a focus on potential underlying neurobiological mechanisms.

Methods

The study included a total of 52 participants: 32 patients diagnosed with schizophrenia (F20.0–F20.9 according to ICD-10 criteria) who were hospitalized at the Psychiatric Clinic of the Clinical Center University of Sarajevo, and 32 healthy control subjects matched for age, sex, and socioeconomic status. The mean age of patients was 39.7 years, with an average duration of illness of approximately 9 years. All participants underwent a standardized psychometric evaluation of general intellectual functioning (IQ), with specific differentiation between fluid and crystallized components. Statistical analysis included both descriptive measures and inferential testing to assess group differences and correlations.

Results

Patients with schizophrenia demonstrated significantly lower total IQ scores compared to healthy controls. The most pronounced impairments were observed in the domain of fluid intelligence, supporting the hypothesis of frontocortical dysfunction and disrupted functional connectivity, particularly involving the dorsolateral prefrontal cortex. Sex-stratified analyses revealed notable differences: male patients exhibited a generalized pattern of cognitive deficits across all domains when compared to healthy male controls. In contrast, female patients showed relative preservation of intelligence, while fluid intelligence remained significantly reduced. Furthermore, a significant negative correlation between illness duration and total IQ was identified, suggesting a progressive course of neurocognitive decline. This deterioration may be linked to chronic glutamatergic dysregulation, oxidative stress mechanisms, and long-term structural brain changes, particularly within cortical and hippocampal regions.

Conclusions

The findings confirm the predominant involvement of fluid cognitive functions in schizophrenia spectrum psychoses and provide further support for neurobiological models emphasizing mesocortical dopaminergic hypofunction and NMDA receptor-mediated dysfunction. The relative preservation of crystallized intelligence in female patients may indicate the presence of sex-specific neuroprotective factors, potentially related to the modulatory effects of estrogen on dopaminergic and glutamatergic neurotransmission. These results have important clinical implications, highlighting the need for targeted cognitive remediation strategies and pharmacological interventions focused on these neurobiological systems. Moreover, they underscore the importance of early neurocognitive assessment as part of personalized and precision-based treatment approaches in schizophrenia.

References

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