Abstract

EXCEED THE SPACE PROVIDED. Convergent lines of evidence indicate that certain cognitive abnormalities in schizophrenia, such as deficits in working memory, are attributable to dysfunction of the dorsal prefrontal cortex (dPFC). This dysfunction appears to be associated with alterations of the neural circuitry within the dPFC, including disturbances in markers of inhibitory neurotransmission that are restricted to a subset of GABA neurons. During the current period of funding, we conducted studies designed to identify the affected subset of GABA neurons, to define the postsynaptic consequences of the alterations in these neurons, and to characterize the mechanisms that may produce these alterations. We found that 1) the chandelier cell population of GABA neurons exhibits expression deficits in multiple genes; 2) these changes are accompanied by an up-regulation of the

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37MH043784-17
Application #
6979950
Study Section
Special Emphasis Panel (NSS)
Program Officer
Meinecke, Douglas L
Project Start
1988-09-30
Project End
2011-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
17
Fiscal Year
2006
Total Cost
$761,822
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Chung, Daniel W; Chung, Youjin; Bazmi, H Holly et al. (2018) Altered ErbB4 splicing and cortical parvalbumin interneuron dysfunction in schizophrenia and mood disorders. Neuropsychopharmacology 43:2478-2486
Enwright Iii, J F; Huo, Z; Arion, D et al. (2018) Transcriptome alterations of prefrontal cortical parvalbumin neurons in schizophrenia. Mol Psychiatry 23:1606-1613
Glausier, Jill R; Lewis, David A (2017) GABA and schizophrenia: Where we stand and where we need to go. Schizophr Res 181:2-3
Rocco, Brad R; DeDionisio, Adam M; Lewis, David A et al. (2017) Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia. Biol Psychiatry 82:40-48
Chung, Daniel W; Wills, Zachary P; Fish, Kenneth N et al. (2017) Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex. Proc Natl Acad Sci U S A 114:E629-E637
Datta, Dibyadeep; Arion, Dominique; Roman, Kaitlyn M et al. (2017) Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia. Am J Psychiatry 174:163-171
Arion, Dominique; Huo, Zhiguang; Enwright, John F et al. (2017) Transcriptome Alterations in Prefrontal Pyramidal Cells Distinguish Schizophrenia From Bipolar and Major Depressive Disorders. Biol Psychiatry 82:594-600
Hoftman, Gil D; Datta, Dibyadeep; Lewis, David A (2017) Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia. Biol Psychiatry 81:862-873
Kimoto, Sohei; Glausier, Jill R; Fish, Kenneth N et al. (2016) Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in Schizophrenia. Schizophr Bull 42:396-405
Volk, David W; Edelson, Jessica R; Lewis, David A (2016) Altered expression of developmental regulators of parvalbumin and somatostatin neurons in the prefrontal cortex in schizophrenia. Schizophr Res 177:3-9

Showing the most recent 10 out of 137 publications