2026 ECNP Congress

PS04-4181

Birth weight, cognitive reserve and cognitive performance in schizophrenia

Miguel Bernardo Arroyo — M.F. Forte Rosso, S. Amoretti, G. Anmella, M. Alfonso, C. Hernandez, M.P. García-Portilla, L. González-Blanco, G. Safont, L. Marin Alcaraz, M. Sanchez-Autet, B. Arranz · Emeritus Consultant. Barcelona Clínic Schizophrenia Unit- Hospital Clínic- Institut d’Investigacions Biomèdiques August Pi I Sunyer IDIBAPS- Barcelona- Spain, Schizophrenia Unit, Barcelona, Spain

2026 ECNP Congress

Introduction

Lower birth weight is understood as an indicator of early developmental vulnerability. Within the Developmental Origins of Health and Disease framework, early-life exposures may have long-term consequences for brain and cognition (1). In schizophrenia, cognitive impairment is a core feature and a major contributor to clinical and functional heterogeneity (2). Cognitive reserve, defined as the ability to cope with brain damage in order to delay the onset of clinical, cognitive and functional manifestations of the pathology and minimize their expression, may help explain this variability (3) and act as a protective factor. But its role in the association between birth weight and cognition in schizophrenia remains insufficiently understood.

Aims

We aimed to examine the association between birth weight, cognitive reserve and cognitive performance in individuals with schizophrenia. We further tested whether cognitive reserve moderated the association between birth weight and cognition, considering both global cognitive performance and specific cognitive domains.

Methods

The present sample was derived from an observational, cross-sectional, multicentre study conducted across four centres in Spain. All participants met DSM-5 criteria for schizophrenia. Birth weight was examined as the main predictor in kg. Cognitive reserve was assessed using the Cognitive Reserve Assessment Scale in Health (CRASH). Cognitive performance was measured with the Screen for Cognitive Impairment in Psychiatry (SCIP), including the global score and five subtests: verbal learning-immediate, working memory, verbal fluency, verbal learning-delayed and processing speed. Linear regression models were adjusted for age and sex. Moderation analyses tested the interaction between birth weight and cognitive reserve in relation to global and domain-specific cognitive scores.

Results

The sample included 112 individuals with a diagnosis of schizophrenia. Participants had a mean age of 35.37 years (SD=11.45); 67 were men (59.8%) and 45 were women (40.2%). Mean birth weight was 3.46 kg (SD=0.58), mean CRASH was 32.73 (SD=13.56) and mean global cognitive score (SCIP) was 62.74 (SD=16.57). Birth weight was not directly associated with cognitive reserve after adjustment for age and sex (B=-2.93, p=.185). Birth weight was not directly associated with global cognition (B=-0.77, p=.753) or working memory (B=0.52, p=.537). However, the interaction between birth weight and cognitive reserve significantly predicted working memory performance, explaining additional variance beyond age, sex, birth weight and cognitive reserve (ΔR²=.067, B=0.225, SE=0.076, p=.004, 95% CI 0.075 to 0.375). For global cognition, the interaction showed a trend-level effect (B=0.339, SE=0.198, p=.090, 95% CI -0.054 to 0.732). No significant moderation effects were observed for verbal learning-immediate, verbal fluency, verbal learning-delayed or processing speed.

Conclusions

In this schizophrenia sample, cognitive reserve moderated the association between birth weight and working memory. This domain-specific finding is clinically relevant, as previous evidence links obstetric complications to poorer working memory in schizophrenia (4), and working memory impairment has been associated with poorer functional outcomes psychosis (5). Although preliminary, these findings suggest that cognitive reserve-related factors may help clarify individual differences in the cognitive impact of early developmental vulnerability.

References

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