Proof-of-concept studies are planned in Project #2 that will examine the effects of novel drug probes on the biomarkers associated with schizophrenia cognitive phenotype and negative symptom phenotype. Participants will be relatives of schizophrenia probands who show evidence of schizophrenia liability as suggested by the presence of schizophrenia spectrum personality traits and poor visuo-spatial working memory. These studies provide a means of ascertaining an early human signal of potential efficacy of a compound for schizophrenia cognition and/or negative symptoms. There are several advantages to the proposed study design that recruits participants who are positive for biomarkers without having the full-blown schizophrenia. These studies will allow evaluation of the effects of the novel pharmacological agents on the physiological deficit in isolation, absent the effects of current or past antipsychotic drugs, overt psychosis, and generalized cognitive deficits that may cloud or modulate the treatment related cognitive """"""""signal"""""""". Two studies are proposed that will examine the effects of oxytocin and a nicotinic agonist, DMXB-A, on a battery of biomarkers. We will test the hypothesis that oxytocin will benefit negative symptom phenotype confirmed by significant improvements in measures of social drive, olfaction, facial affect recognition, smooth pursuit eye movement initiation and latency of internally-driven saccades. DMXB-A will benefit cognition as confirmed by significant improvements in visuo-spatial working memory, processing speed, verbal episodic memory, P50 sensory gating, and predictive pursuit eye movement gain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH082999-03
Application #
8080312
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2010-06-01
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$242,675
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Carpenter Jr, William T; Buchanan, Robert W (2017) Negative Symptom Therapeutics. Schizophr Bull 43:681-682
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Strauss, Gregory P; Keller, William R; Koenig, James I et al. (2015) Plasma oxytocin levels predict social cue recognition in individuals with schizophrenia. Schizophr Res 162:47-51
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Schulz, Kalynn M; Andrud, Kristin M; Burke, Maria B et al. (2013) The effects of prenatal stress on alpha4 beta2 and alpha7 hippocampal nicotinic acetylcholine receptor levels in adult offspring. Dev Neurobiol 73:806-14
Braff, David L; Ryan, James; Rissling, Anthony J et al. (2013) Lack of use in the literature from the last 20 years supports dropping traditional schizophrenia subtypes from DSM-5 and ICD-11. Schizophr Bull 39:751-3

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