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 #
5P50MH082999-05
Application #
8380305
Study Section
Special Emphasis Panel (ZMH1-ERB-L)
Project Start
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$235,844
Indirect Cost
$83,421
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Lee, Mary R; Wehring, Heidi J; McMahon, Robert P et al. (2016) Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia. Schizophr Res 172:165-8
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Strauss, Gregory P; Keller, William R; Koenig, James I et al. (2015) Plasma oxytocin levels predict olfactory identification and negative symptoms in individuals with schizophrenia. Schizophr Res 162:57-61
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
Wilson, Christina A; Koenig, James I (2014) Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia. Eur Neuropsychopharmacol 24:759-73
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
Taylor, S B; Taylor, A R; Koenig, J I (2013) The interaction of disrupted type II neuregulin 1 and chronic adolescent stress on adult anxiety- and fear-related behaviors. Neuroscience 249:31-42

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