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Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia.

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  • 1Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, 21228, USA. iwonodi@mprc.umaryland.edu

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
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The dopamine transporter gene (DAT1) 10/10 genotype impacts smooth pursuit eye movement (SPEM), worsening it in schizophrenia patients but improving it in healthy controls. This suggests complex gene regulation in schizophrenia.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Smooth pursuit eye movement (SPEM) deficit is a schizophrenia endophenotype linked to working memory.
  • Dopamine signaling, particularly via the COMT and DAT1 genes, influences neurocognitive functions.
  • The DAT1 gene modulates cortical dopamine levels and associated functions.

Purpose of the Study:

  • To investigate the effect of the DAT1 10/10 genotype on SPEM.
  • To examine DAT1 genotype associations with schizophrenia diagnosis and SPEM performance.
  • To analyze DAT1 gene expression in frontal eye fields (FEF) based on DAT1 genotype and diagnosis.

Main Methods:

  • Genotyping for DAT1 in a cohort of 418 individuals (190 with schizophrenia).
  • Oculomotor assessments of SPEM in 200 participants (87 with schizophrenia).
  • Analysis of DAT1 mRNA expression in postmortem FEF tissue from 32 donors (16 with schizophrenia).

Main Results:

  • DAT1 genotype was not associated with schizophrenia diagnosis.
  • The DAT1 10/10 genotype correlated with better SPEM in controls, intermediate SPEM in relatives, and worse SPEM in schizophrenia patients.
  • DAT1 10/10 genotype showed reduced DAT1 mRNA in healthy controls' FEF but higher expression in schizophrenia patients' FEF.

Conclusions:

  • The DAT1 10/10 genotype differentially affects SPEM across healthy individuals, relatives, and schizophrenia patients.
  • Findings suggest that other genetic or etiological factors in schizophrenia modulate DAT1 gene function.
  • DAT1 genotype influences SPEM and its expression in the frontal eye fields, with disease-specific alterations.