PSYCHOSIS: NOVEL PHARMACOTHERAPY AND BIOLOGICAL MECHANISMS
Psychosis Research Group, Commonwealth Research Center, Massachusetts Mental Health Center
Alan I. Green, M.D., Joseph J. Schildkraut, M.D., Carla M. Canuso, M.D., Suzanna Zimmet, M.D., Wilson Woo, M.D., Ph.D., Brina Caplan, Ph.D., Joanne Wojcik, R.N., Ree Dawson, Ph.D., Mark Brenner, Ph.D., Melinda Salomon, Ph.D., Kimberly Rawlins, M.D, Larry J. Seidman, Ph.D., Jill Goldstein, Ph.D., Ellen S. Burgess, Ph.D., Elizabeth Macaulay, MS, David Chau, M.D., Wing Ming Keung, Ph.D., William Stone, Ph.D., Bruce Jenkins, Ph.D., Rahim Shafa, M.D., James Feldman, M.D., Martha Schinagle, M.D., Kathleen Pappalardo, B.S., M.T., Nancy McHale, B.S., Mary Anne Badaracco, M.D.
The Psychosis Research Group is engaged in a series of studies of the clinical and biological effects of typical and atypical antipsychotic drugs in patients with schizophrenia. One focus of the work involves the longitudinal evaluation of biologic probes (e.g., measures of biogenic amines, hormones, evoked potentials, cognition and neuroimaging) before and during treatment with antipsychotic drugs with the aim of developing biologic predictors and correlates of clinical response. On-going work focuses on early intervention in first episode patients, in an attempt to improve long-term outcome, and on treatment of patients with comorbid substance use disorder, in an attempt to decrease the substance use. Studies attempt to elucidate the mechanisms of action of antipsychotic drugs and the underlying pathophysiologic basis of schizophrenia. Ongoing major projects include: 1) first episode schizophrenia - studies of clozapine vs. haloperidol, olanzapine vs. haloperidol, and clozapine vs. risperidone; 2) comorbid alcohol/substance use disorder and schizophrenia - studies of clozapine vs. typical antipsychotics, clozapine vs. risperidone, and clozapine vs. risperidone in first episode comorbid patients; 3) chronic schizophrenia - study of the clinical and biological effects of clozapine; 4) women with schizophrenia - studies of the effects of antipsychotics on ovarian function and of hormone replacement therapy; 5) "real world effectiveness study" - a comparative study of the effectiveness of clozapine and olanzapine; 6) experimental antipsychotics - the safety and efficacy of novel experimental agents are tested in patients with schizophrenia. Pilot projects include: 1) studies of brain reward networks in patients with schizophrenia and the effect of antipsychotic treatment on such networks; and 2) studies of the effects of antipsychotic medications on alcohol drinking in alcohol-preferring animals. Additional patient populations under study include those with: 1) schizophrenia and suicidality; and 2) first degree relatives of patients with schizophrenia.
Key words: schizophrenia, neuropsychopharmacology, neuroendocrinology, antipsychotics, first episode, substance abuse, ovarian function, neuroimaging, brain reward circuits.
Grant Support: NIMH: Clozapine response and biogenic amines in schizophrenia (R01 MH49891 [AG]); Clozapine or haloperidol in first episode schizophrenia (R01 MH52376 [AG]); Clozapine, cannabis and first episode schizophrenia (MH62157 [AG]). NIAAA: Alcoholism and schizophrenia: effects of clozapine (AA11904 [AG]); Cannabis and schizophrenia: effects of clozapine (DA13196 [AG]). NARSAD Independent Investigator Award (AG); Junior Investigator Award (CC). Stanley Foundation Award (WW). Also: Eli Lilly and Company (AG); Novartis Pharmaceuticals (AG, WMK); Astra Zeneca (AG); Otsuka America Pharmaceutical, Inc. (AG); Bristol Myers (AG); and the Commonwealth Research Center.
Project Sites: Commonwealth Research Center, MMHC; Erich Lindemann Mental Health Center; Neuropsychopharmacology Laboratory, MMHC; Beth Israel Deaconess Medical Center; Brain Imaging Center, Massachusetts General Hospital; Brigham and Women's Hospital. Project Director: Alan I. Green, M.D., Commonwealth Research Center, Massachusetts Mental Health Center, 74 Fenwood Road Boston, MA 02115. Contact Person, Joanne Wojcik, R.N., Research Nurse. (617) 232-5274. FAX: (617) 734-6206
Training Opportunities: A range of pre-doctoral and post-doctoral opportunities are available. Currently, there is 1 post-doctoral fellow and 1 minority investigator. This is a program site for the Clinical Research Training Program (HMS/MMHC). Other sources for support of fellows are also available.
Representative Publications:
Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among schizophrenic patients.
Schiz. Bull. 2000; 26(2):441-449.
Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI. Effects of clozapine on substance use in patients with
schizophrenia_and schizoaffective disorder: a retrospective survey. Journ. Clin. Psychopharm. 2000, 20:94-98.
Green AI, Tohen M, Patel JK, Banov M, DuRand C, Berman I, Chang H, Zarate C, Posener J, Lee H, Richards C, Cole JO,
Schatzberg AF. Clozapine in the treatment of refractory psychotic mania. Amer. J. Psych. 2000;157:6,982-986.
Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid substance use disorder and schizophrenia: do patients with
schizophrenia have a reward deficiency syndrome that can be ameliorated by clozapine? Harv. Rev. Psychiatry 1999;6:287-296.
Canuso CM, Goldstein JM, Green AI. The evaluation of women with schizophrenia. Psychopharm. Bull. 1998;34(3):271-277