Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque

Biol Psychiatry. 2005 Jan 1;57(1):83-90. doi: 10.1016/j.biopsych.2004.10.014.

Abstract

Background: Schizophrenia is associated with reductions in thalamic neuronal number and cortical gray matter volume. Exposure of nonhuman primates to x-irradiation in early gestation has previously been shown to decrease thalamic volume and neuronal number. Here we examine whether early gestational irradiation also results in cortical volume reduction.

Methods: High-resolution, T1-weighted magnetic resonance scans were collected in adult monkeys 1) exposed to irradiation during the early gestational period (E33-E42) corresponding to thalamic neurogenesis, 2) irradiated in midgestation (E70-81) during neocortical neurogenesis, and 3) not exposed to irradiation. Cortical gray matter and white matter volumes were derived via manual segmentation; frontal and nonfrontal volumes were distinguished via sulcal landmarks.

Results: Monkeys irradiated in early gestation exhibited a trend reduction in nonfrontal gray matter volume (17%) and significant reductions in white matter volume in frontal (26%) and nonfrontal (36%) lobes. Monkeys irradiated in midgestation had smaller gray (frontal: 28%; nonfrontal: 22%) and white matter (frontal: 29%; nonfrontal: 38%) volumes.

Conclusions: The cortical deficits observed in midgestationally irradiated monkeys are consistent with a reduction in cortical neuronal number. Cortical volume reductions following early gestational irradiation may be secondary to reduced thalamic neuronal number and therefore model the thalamocortical pathology of schizophrenia.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Brain Mapping
  • Cerebral Cortex / pathology
  • Cerebral Cortex / radiation effects*
  • Female
  • Macaca
  • Magnetic Resonance Imaging, Cine / methods
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Radiation Injuries / pathology*
  • Thalamus / pathology
  • Thalamus / radiation effects