This proposal for a Mentored Research Scientist Development Award is designed to provide the candidate with training in the neurobiological sciences. The long-term goal is to establish the candidate as an independent investigator in the area of substance abuse and schizophrenia. The extremely high rate of co-morbidity of substance abuse and schizophrenia presents a serious problem in delivery of public mental health care to the chronically mentally ill. The candidate's preliminary studies on outpatients attending a community mental health clinic indicate that concurrent substance abuse is not only a common occurrence in schizophrenia patients (55 percent) but is also a major contributor to acute exacerbations as manifested by re-hospitalization. The candidate hypothesizes that these disorders share a common neurobiologic substrate involving the hypothalamic-pituitary-adrenal (HPA) axis and mesolimbic dopamine (DA) pathways. Specifically, it is the candidate's belief that in schizophrenia patients who become substance abusers, increases in stress hormones (corticosteroids) lead to increased mesolimbic DA activity, accompanied by an increase in psychotic symptoms, drug craving and sensitivity to drugs of abuse, enhancing the potential for addiction. To test this hypothesis, the following specific aims are proposed Aim 1: To characterize clinical features (including stress, depression and social support) of subjects with co-morbid substance abuse and schizophrenia as distinguished from subjects with schizophrenia or substance abuse alone, and healthy age-, sex- and race-matched controls.
Aim 2 : To characterize baseline neuroendocrine function (plasma ACTH, cortisol, and homovanillic acid (HVA)) in the four matched groups of subjects.
Aim 3 : To test the hypothesis that substance abusers will exhibit an increased dopaminergic response to cortisol administration with subsequently increased DA activity in mesolimbic pathways as assessed by plasma HVA, the Positive and Negative Symptom Scale, and Craving Indices. This research project, taken together with the training component of the proposal and the resources of Emory University, will help develop the candidate's skills as a researcher and will allow the candidate to make significant contributions to our understanding and treatment of co-morbid substance abuse and schizophrenia.
|Fisher, Robin Scott (2007) Co-localization of glutamic acid decarboxylase and phosphate-activated glutaminase in neurons of lateral reticular nucleus in feline thalamus. Neurochem Res 32:177-86|
|Scheller-Gilkey, Geraldine; Moynes, Kelly; Cooper, Ilene et al. (2004) Early life stress and PTSD symptoms in patients with comorbid schizophrenia and substance abuse. Schizophr Res 69:167-74|
|Scheller-Gilkey, Geraldine; Woolwine, Bobbi J; Cooper, Ilene et al. (2003) Relationship of clinical symptoms and substance use in schizophrenia patients on conventional versus atypical antipsychotics. Am J Drug Alcohol Abuse 29:553-66|
|Scheller-Gilkey, Geraldine; Thomas, Shannon M; Woolwine, Bobbi J et al. (2002) Increased early life stress and depressive symptoms in patients with comorbid substance abuse and schizophrenia. Schizophr Bull 28:223-31|
|Fisher, R S; Buchwald, N A; Hull, C D et al. (1988) GABAergic basal forebrain neurons project to the neocortex: the localization of glutamic acid decarboxylase and choline acetyltransferase in feline corticopetal neurons. J Comp Neurol 272:489-502|
|Fisher, R S; Levine, M S; Adinolfi, A M et al. (1987) The morphogenesis of glutamic acid decarboxylase in the neostriatum of the cat: neuronal and ultrastructural localization. Brain Res 430:215-34|