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Longitudinal Impact of Birthweight and its Polygenic Risk Score on Glucose and Antipsychotic-Induced Weight Gain in

Nora Guasch-Capella1,2,3, Patricia Gassó2,3,4, Miquel Bioque1,2,4,5

  • 1Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Villarroel, 170 08036 Barcelona, Spain.

Schizophrenia Bulletin
|June 8, 2026
PubMed

Insights

Early life factors like birth weight (BW) and its genetic proxy (PRSBW) influence antipsychotic-induced weight gain (AIWG) in first-episode psychosis (FEP) patients. Higher BW and PRSBW are linked to steeper AIWG progression over 24 months.

Area of Science:

  • Psychiatry and Metabolic Health
  • Genetics and Developmental Origins of Health

Background:

  • First-episode psychosis (FEP) patients often experience metabolic disturbances, including antipsychotic-induced weight gain (AIWG) and glucose dysregulation.
  • Birth weight (BW) and its genetic proxy, polygenic risk score for BW (PRSBW), may impact these metabolic trajectories.
  • Understanding these early-life influences is crucial for managing metabolic risks in FEP.

Purpose of the Study:

  • To investigate the association between BW, PRSBW, and the progression of AIWG and fasting glucose levels over 24 months in FEP patients.
  • To determine if early-life factors predict metabolic alterations during early psychosis treatment.
  • To explore the interplay between genetic and environmental factors in metabolic dysregulation.

Main Methods:

  • A cohort of 277 FEP patients with genetic, BW, and longitudinal metabolic data was analyzed.
  • Linear mixed-effects models were employed to assess associations between BW, PRSBW, and metabolic outcomes (AIWG, glucose).
  • Interactions with time were examined to understand the progression of metabolic changes over 24 months.

Main Results:

  • Higher BW was significantly associated with greater mean AIWG over 24 months (p=.009).
  • Neither BW nor PRSBW showed association with mean fasting glucose levels.
  • Significant time×BW and time×PRSBW interactions indicated steeper AIWG trajectories for individuals with higher BW or PRSBW.

Conclusions:

  • Both BW and PRSBW significantly influence the progression of AIWG in the early stages of psychosis.
  • These findings underscore the role of early-life environmental and genetic factors in metabolic vulnerability.
  • BW-related markers may aid in early risk stratification and targeted prevention of adverse metabolic outcomes in FEP.
Abstract

Keywords:
early psychosisgenetic liabilitymetabolic trajectoriesmetabolic vulnerabilityrisk stratification

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