Title

White matter neuron alterations in schizophrenia and related disorders

Student Author(s)

Caroline Connor

GSBS Program

Neuroscience

UMMS Affiliation

Brudnick Neuropsychiatric Research Institute, Department of Psychiatry

Date

5-10-2011

Document Type

Article

Medical Subject Headings

Schizophrenia; Neurons; Leukoencephalopathies

Disciplines

Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology

Abstract

Increased density and altered spatial distribution of subcortical white matter neurons (WMNs) represents one of the more well replicated cellular alterations found in schizophrenia and related disease. In many of the affected cases, the underlying genetic risk architecture for these WMN abnormalities remains unknown. Increased density of neurons immunoreactive for Microtubule-Associated Protein 2 (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent studies, though there are negative reports as well; additionally, group differences in some of the studies appear to be driven by a small subset of cases. Alterations in markers for inhibitory (GABAergic) neurons have also been described. For example, downregulation of neuropeptide Y (NPY) and nitric oxide synthase (NOS1) in inhibitory WMN positioned at the gray/white matter border, as well as altered spatial distribution, have been reported. While increased density of WMN has been suggested to reflect disturbance of neurodevelopmental processes, including neuronal migration, neurogenesis, and cell death, alternative hypotheses-such as an adaptive response to microglial activation in mature CNS, as has been described in multiple sclerosis -should also be considered. We argue that larger scale studies involving hundreds of postmortem specimens will be necessary in order to clearly establish the subset of subjects affected. Additionally, these larger cohorts could make it feasible to connect the cellular pathology to environmental and genetic factors implicated in schizophrenia, bipolar disorder, and autism. These could include the 22q11 deletion (Velocardiofacial/DiGeorge) syndrome, which in some cases is associated with neuronal ectopias in white matter.

Rights and Permissions

Citation: Int J Dev Neurosci. 2011 May;29(3):325-34. Epub 2010 Aug 4. Link to article on publisher's site

Related Resources

Link to Article in PubMed