The Stanford Mental Health Clinical Research Center (MHCRC) proposes to continue its productive operation in fostering multidisciplinary collaboration in the search for biological correlates of psychiatric illness. We will test pharmacological agents whose actions relate to specific biochemical hypothesis of psychopathology. In schizophrenia we examine cerebrospinal fluid (CSF) catecholamine, phenylethylamine, tyramine, and serotonin metabolites, and endorphin concentrations. We also measure platelet monoamine oxidase activity. We evaluate schizophrenic patients using neuropsychological testing asnd computerized axial tomographic scanning. Experimental treatments for schizophrenic patients include naloxone, Beta-endorphin, des-tyrosine-Gamma-endorphin and metkephamid (a methionine-enkephalin analogue). In depression we are measuring the same CSF neurotransmitter metabolites mentioned above, urinary MHPG, the pituitary thyrotropin response to thyrotropin-releasing hormone and the cortisol response to dexamethasone. We also assess schizophrenic and depressed patients and controls using a battery of event-related brain electrical potentials which reflect cortical excitability, stimulus intensity modulation and attention. We are investigating the utility of sleep variables such as sleep onset latency, REM latency, middle ear muscle activity, and burst eye movement activity among others, in distinguishing schizophrenic patients from depressed patients and from normal controls. In patients with manic psychosis, tardive dyskinesia, Huntington's chorea, Tourette syndrome, and dystonias, we are investigating neurotransmitter imbalance hypotheses by administering choinomimetics (physostigmine and choline chloride). Finally, we hope that the correlation of biochemical, psychological, physiological, and clinical variables will help classify patients with psychiatric disorders, predict their response to specific pharmacological treatments, and improve our understanding of the biological basis of psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH030854-11
Application #
3106965
Study Section
(TDAC)
Project Start
1977-09-29
Project End
1989-01-31
Budget Start
1987-12-01
Budget End
1989-01-31
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Deshmukh, Anjali; Rosenbloom, Margaret J; De Rosa, Eve et al. (2005) Regional striatal volume abnormalities in schizophrenia: effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type. Schizophr Res 79:189-200
Sullivan, Edith V; Rosenbloom, Margaret J; Pfefferbaum, Adolf (2004) Balance and gait deficits in schizophrenia compounded by the comorbidity of alcoholism. Am J Psychiatry 161:751-5
Mathalon, Daniel H; Pfefferbaum, Adolf; Lim, Kelvin O et al. (2003) Compounded brain volume deficits in schizophrenia-alcoholism comorbidity. Arch Gen Psychiatry 60:245-52
Mathalon, Daniel H; Bennett, Amy; Askari, Nusha et al. (2003) Response-monitoring dysfunction in aging and Alzheimer's disease: an event-related potential study. Neurobiol Aging 24:675-85
Sullivan, Edith V; Rosenbloom, Margaret J; Serventi, Kathleen L et al. (2003) Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia. Am J Psychiatry 160:1110-6
Panizzon, Matthew S; Hoff, Anne L; Nordahl, Thomas E et al. (2003) Sex differences in the corpus callosum of patients with schizophrenia. Schizophr Res 62:115-22
Deshmukh, Anjali; Rosenbloom, Margaret J; Pfefferbaum, Adolf et al. (2002) Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their comorbidity. Schizophr Res 57:281-91
Pfefferbaum, Adolf; Rosenbloom, Margaret; Serventi, Kathleen L et al. (2002) Corpus callosum, pons, and cortical white matter in alcoholic women. Alcohol Clin Exp Res 26:400-6
Alpert, Murray; Shaw, Richard J; Pouget, Enrique R et al. (2002) A comparison of clinical ratings with vocal acoustic measures of flat affect and alogia. J Psychiatr Res 36:347-53
Mathalon, Daniel H; Fedor, Mark; Faustman, William O et al. (2002) Response-monitoring dysfunction in schizophrenia: an event-related brain potential study. J Abnorm Psychol 111:22-41

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