Abstract

Major findings to date involve progress in elucidating the neuropathology of schizophrenia. In particular, abnormalities involve a neuronal circuit of the striatum/nucleus accumbens, the hippocampus/entorhinal cortex (ERC) and the dorsolateral prefrontal cortex (DLPFC). In the striatum/nucleus accumbens, we demonstrated increased dopamine type IV (D4) receptors in the brains of schizophrenics. The major findings in the DLPFC remained reductions in serotonin type II (5HT-2) receptors and reuptake sites. The primary structural abnormality appears to involve a reduction in the cytoarchitecture of the ERC which is associated with reductions in neurotensin receptors in layer 2 of the ERC and mRNA for cholecystokinin (CCK) in subiculum and layers 3-6 of the ERC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002399-10
Application #
5203720
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Kaalund, S S; Newburn, E N; Ye, T et al. (2014) Contrasting changes in DRD1 and DRD2 splice variant expression in schizophrenia and affective disorders, and associations with SNPs in postmortem brain. Mol Psychiatry 19:1258-66
Hyde, Thomas M; Lipska, Barbara K; Ali, Towhid et al. (2011) Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci 31:11088-95
Bigos, Kristin L; Mattay, Venkata S; Callicott, Joseph H et al. (2010) Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67:939-45
Montague, D; Weickert, C S; Tomaskovic-Crook, E et al. (2008) Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species. J Neuroendocrinol 20:893-903
Weickert, Cynthia Shannon; Rothmond, Debora A; Hyde, Thomas M et al. (2008) Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients. Schizophr Res 98:105-10
Weickert, C S; Webster, M J; Gondipalli, P et al. (2007) Postnatal alterations in dopaminergic markers in the human prefrontal cortex. Neuroscience 144:1109-19
Meyer-Lindenberg, Andreas; Straub, Richard E; Lipska, Barbara K et al. (2007) Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. J Clin Invest 117:672-82
Straub, R E; Lipska, B K; Egan, M F et al. (2007) Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry 12:854-69
Mathew, Shiny V; Law, Amanda J; Lipska, Barbara K et al. (2007) Alpha7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1. Hum Mol Genet 16:2921-32
Tseng, Kuei-Yuan; Lewis, Barbara L; Lipska, Barbara K et al. (2007) Post-pubertal disruption of medial prefrontal cortical dopamine-glutamate interactions in a developmental animal model of schizophrenia. Biol Psychiatry 62:730-8

Showing the most recent 10 out of 73 publications