Psychopharmacology Research Group (PRG)

The PRG at Dartmouth Medical School designs, leads and coordinates both NIH (NIMH, NIDA and NIAAA) and industry sponsored (investigator-initiated) studies at Dartmouth Hitchcock Medical Center (DHMC) and through a network of clinical sites in New Hampshire, Vermont and across the country. The mission of the PRG is to increase our understanding of the basis of severe mental illness and to improve overall treatment options. The areas of focus of the on-going studies of the group are schizophrenia, schizophrenia and co-occurring substance use disorder, and alcoholism.

Animal Studies
On-going animal research within the PRG is closely linked to the work of the Neuroscience Center at Dartmouth. These translational research studies involve investigation of animal models of schizophrenia and alcoholism to further probe the basis of these disorders, and to test out potential new therapeutic agents and techniques. Among these new therapies are novel pharmacological approaches and neurosurgical methods to modulate activity of the mesolimbic reward system.

Neuroimaging Studies
On-going neuroimaging studies (in partnership with the Department of Psychiatry's Brain Imaging Lab) use functional magnetic resonance imaging (fMRI) techniques to elucidate structural and functional deficits in patients with serious psychiatric disorders. One area of focus at present involves the use of fMRI to elucidate brain reward circuitry as a target for therapeutic intervention. A recent study is seeking to assess the effect of cannabis on brain function in people with schizophrenia and co-occurring cannabis abuse.

Clinical Trials
The PRG has a number of on-going clinical trials, most of which are hypothesis testing proof of concept studies. In these studies, therapeutic agents (some of which are also studied within our animal research and neuroimaging programs) can be evaluated in human populations. These trials are undertaken at sites in the region of DHMC, in sites throughout New Hampshire and Vermont, and in affiliated sites across the country.

Membership
Alan I. Green, M.D. Director
Mary F. Brunette, M.D. Medical Director
Christopher O'Keefe, M.A. Administrative Director
Ree Dawson, Ph.D., Senior Statistician
Kari A. Barton, M.S.
Daniel R. Bateman, M.D.
David T. Chau, Ph.D.
Katherine A. Epstein, A.B.
Jeffrey C. Fetter, M.D
Laura A. Flashman, Ph.D.
Matthew A. Garlinghouse, Ph.D.
Pamela T. Geiger, B.S.
Danielle Gulick, Ph.D.
Hisham M. Hafez, M.D.
Sandra Harger, B.A.
Michael B. Henderson, B.A., JD
Audrey M. Kern, M.D.
James C. Leiter, M.D.
Suzanne M. Miller, B.S.
Douglas L. Noordsy, M.D.
Joseph F. Rancourt, B.A
David W. Roberts, M.D.
Shannon E. Rondeau, R.N.
Robert M. Roth, Ph.D.
Rachel L. Schoolcraft, M.D.
Amy E. Wallace, M.D., M.P.H.
Marjorie H. W. Weeks, M.P.A.
Rosemarie S. Wolfe, M.S

Collaborating Sites/groups
Dartmouth Hitchcock Medical Center
West Central Behavioral Health
New Hampshire Hospital
Mental Health Center of Greater Manchester
White River Junction VA Medical Center
Center for Psychiatric Advancement
Community Council of Nashua
Riverbend Community Mental Health Center
Dartmouth Psychiatric Research Center

Affiliated Academic Institutions
University of California at Los Angeles
University of Miami
University of Missouri at Kansas City
University of South Carolina
Washington University

Current Funding
NIDA: Cannabis and Schizophrenia: Self-Medication and Agonist Treatment? (2009-2011)
NIMH: Toward a Rat Model of Alcohol Abuse in Schizophrenia. (2007-2010)
NIAAA/Fast Track Drugs & Biologics: A Phase Two, Double-Blind, Placebo-Controlled Trial of Levetiracetam XR in Very Heavy Drinkers. (2009-2011)
NIAAA/CSP: A Phase Two, Double-Blind Placebo-Controlled Trial to Assess the Efficacy of Quetiapine Fumarate Sustained Release for the Treatment of Alcohol Dependence in Very Heavy Drinkers. (2007-2009)
NIAAA: Integrating Etiologic Models and optimizing Treatment for Alcohol Disorders in Schizophrenia Patients. (2009-2010)
NARSAD: Functional MRI of Brain Reward Circuitry in Schizotypal Personality Disorder. (2007-2009)
Investigator-Initiated Janssen Pharmaceuticals: Risperidone Long-Acting in the Treatment of Comorbid Alcohol Use Disorder and Schizophrenia. (2004-2010)
Investigator-Initiated Ortho-McNeil Janssen Scientific Affairs: Paliperidone and Alcohol Drinking in the Syrian Golden Hamster and in the Alcohol-Preferring "P" Rat. (2008-2010)
West Foundation: Interventions for Persons with Severe Mental Illness and Co-Occurring Substance Use Disorders. (2006-2011)
Eli Lilly and Co.: A Phase 2 Study of LY2196044 Compared with Naltrexone and Placebo in the Treatment of Alcohol Dependence. (2008-2010)

Recent Publications (2004-2009)

  1. Green AI, Tohen MF, Hamer RM, Strakowski SM, Lieberman JA, Glick I, Clark WS, HGDH Research Group. First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol. Schizophrenia Research, 2004; 66(2-3): 125-135.
  2. Le Fauve CE, Litten RZ, Randall CL, Moak DH, Salloum IM, Green AI. Pharmacological treatment of alcohol abuse/dependence with psychiatric comorbidity, Alcoholism: Clinical and Experimental Research 2004; 28(2): 302-312.
  3. Perkins DO, Lieberman JA, Gu H, Tohen M, McEvoy J, Green AI, Zipursky RB, Strakowski SM, Sharma T, Kahn RS, Gur R, Tollefson G, HDGH Research Group. Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective, and schizophreniform disorders. Brit J Psychiatry, 2004; 185: 18-24.
  4. Elman I, Rott D, Green AI, Langleben DD, Lukas SE, Goldstein DS, Breier A. Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia. Psychopharmacology (Berl), 2004; 176(3-4): 369-375.
  5. Alphs LD, Anand R, Islam MZ, Meltzer HY, Kane J, Krishnan R, Green AI, Potkin S, Chouinard G, Lindenmayer J-P, Kerwin R. The international suicide prevention trial (InterSePT): Rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients. Schizophrenia Bulletin, 2004; 30: 577-586.
  6. Green AI, Chau DT, Keung WM, Dawson R, Mesholam RI, Schildkraut JJ. Clozapine reduces alcohol drinking in Syrian golden hamsters. Psychiatry Research, 2004; 128(1): 9-20.
  7. Chau DT, Roth RM, Green AI. The neural circuitry of reward and its relevance to psychiatric disorders. Current Psychiatry Reports, 2004; 6(5): 391-399.
  8. Brunette MF, Mueser KT, Drake RE.A review of research on residential programs for people with severe mental illness and co-occurring substance use disorders. Drug Alcohol Rev. 2004; 23(4): 471-481.
  9. Brunette MF, Richardson F, White L, Bemis G, Eelkema RE. Integrated family treatment for parents with severe psychiatric disabilities. Psychiatr Rehabil J. 2004; 28(2): 177-180.
  10. Drake RE, Mueser KT, Brunette MF, McHugo GJ.A review of treatments for people with severe mental illnesses and co-occurring substance use disorders. Psychiatr Rehabil J. 2004; 27(4): 360-374.
  11. Clark RE, Xie H, Brunette MF. Benzodiazepine prescription practices and substance abuse in persons with severe mental illness. J Clin Psychiatry. 2004; 65(2): 151-155.
  12. Milovan DL, Baribeau J, Roth RM, Stip E.ERP study of pre-attentive auditory processing in treatment-refractory schizophrenia. Brain Cogn. 2004; 55(2): 355-357.
  13. Roth RM, Flashman LA, Saykin AJ, McAllister TW, Vidaver R. Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits. Am J Psychiatry. 2004; 161(1): 157-159.
  14. Flashman LA, Green MF. Review of cognition and brain structure in schizophrenia: profiles, longitudinal course, and effects of treatment. Psychiatr Clin North Am. 2004; 27(1): 1-18, vii.
  15. Wallace AE, Weeks WB. Substance abuse intensive outpatient treatment: does program graduation matter? J Subst Abuse Treat. 2004; 27(1): 27-30.
  16. Mellman, TA, Knorr B, Pigeon WR, Leiter JC, Akay M. Heart rate variability during sleep and the early development of PTSD. Biol Psychiatry. 2004; 55: 953-956.
  17. Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, Keefe RSE, Green AI, Gur RE, McEvoy J, Perkins D, Hamer RM, Gu H, Tohen M for the HGDH Study Group. Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry, 2005; 62(4): 361-370.
  18. Cimpean D, Torrey WC, Green AI. Schizophrenia and co-occurring general medical illness. Psychiatric Annals, 2005; 35(1): 70-81
  19. Strakowski SM, Johnson JL, DelBello MP, Hamer RM, Green AI, Tohen M, Lieberman JA, Glick I, Patel JK and HGDH Research Group. Quality of life during treatment with haloperidol or olanzapine in the year following a first psychotic episode. Schizophrenia Research, 2005; 78(2-3): 161-169.
  20. Drake RE, Brunette MF, Mueser KT, Green AI. Management of patients with severe mental illness and co-occurring substance use disorder. Minerva Psichiatrica, 2005; 46: 119-132
  21. Zipursky R, Gu H, Green AI, Perkins DO, Tohen M, McEvoy J, Strakowski SM, Sharma T, Kahn R, Gur R, Tollefson G, Lieberman JA, HGDH Research Group. Course and predictors of weight gain in first episode patients with psychosis treated with olanzapine or haloperidol. British Journal of Psychiatry, 2005; 187: 537-543.
  22. Niznikiewicz MA, Patel JK, McCarley R, Sutton J, Chau DT, Wojcik J, Green AI. Clozapine action on auditory P3 response in schizophrenia. Schizophrenia Research, 2005; 76(1): 119-121.
  23. Brunette MF, Noordsy DL, Green AI. A challenging mix: co-occurring schizophrenia and substance use disorders. Psychiatric Times, 2005; 22(3): 29-33.
  24. Brunette MF, Noordsy DL, Green AI, Buckley PF. Pharmacologic treatments for co-occurring substance use disorders in patients with schizophrenia: A Research Review, Journal of Dual Diagnosis, 2005; 1(2): 41-55.
  25. Roth RM, Brunette MF, Green AI. Treatment of substance use disorders in schizophrenia: A unifying neurobiological mechanism? Current Psychiatry Reports, 2005; 7(4): 283-291.
  26. Green AI. Editorial. Journal of Dual Diagnosis, 2005; 1(2): 7-9.
  27. Green AI. Schizophrenia and comorbid substance use disorder: effects of antipsychotics. Journal of Clinical Psychiatry, 2005; 66(suppl 6): 21-26.
  28. Ziedonis DM, Smelson D, Rosenthal RN, Batki SL, Green AI, Henry RJ, Montoya I, Parks J, Weiss RD. Improving the care of individuals with schizophrenia and substance use disorders: Consensus recommendations. Journal of Psychiatric Practice, 2005; 11(5): 315-339.
  29. Rosenberg SD, Drake RE, Brunette MF, Wolford GL, Marsh BJ. Hepatitis C virus and HIV co-infection in people with severe mental illness and substance use disorders. AIDS. 2005; 19 Suppl 3: S26-33.
  30. Lee KH, Hitti F, Shalinsky MH, Kim U, Leiter JC, Roberts DW. Abolition of spindle oscillations and 3 Hz absence-like seizure activity in the thalamus by high frequency stimulation: Potential mechanism of action. J. Neurosurg. 2005; 10: 538-545.
  31. Perkins DO, Johnson JL, Hamer RM, Zipursky RB, Keefe RS, Centorrhino F, Green AI, Glick IB, Kahn RS, Sharma T, Tohen M, McEvoy JP, Weiden PJ, Lieberman JA. Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophrenia Research, 2006; 83: 53-63.
  32. Brunette MF, Drake RE, Xie H, McHugo GJ, Green AI. Clozapine use and relapse of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophrenia Bulletin, 2006; 32(4): 637-643.
  33. Green AI, Lieberman JA, Hamer RM, Glick ID, Gur RE, Kahn RS, McEvoy JP, Perkins DO, Rothschild AJ, Sharma T, Tohen MF, Woolson S, Zipursky RB, HGDH Study Group. Olanzapine and haloperidol in first-episode psychosis: Two year data. Schizophrenia Research, 2006; 86(1-3): 234-243.
  34. McHugo GJ, Drake RE, Brunette MF, Xie H, Essock SM, Green AI. Enhancing validity in co-occurring disorders treatment research. Schizophrenia Bulletin, 2006; 32(4): 655-665.
  35. Drake RE, Green AI. Introduction: Current research on co-occurring substance use disorder in schizophrenia. Schizophrenia Bulletin, 2006; 32 (4): 616-617.
  36. Green, AI. Treatment of schizophrenia and comorbid substance abuse: Pharmacologic approaches. Journal of Clinical Psychiatry, 2006; 67(suppl 7): 31-35.
  37. Mistler LA, Brunette MF, Rosenberg SD, Vidaver RM, Luckoor R, Iber M. Case report of 3 patients with severe mental illness and chronic hepatitis C virus infection treated with interferon-alpha. Int J Psychiatry Med. 2006; 36(4): 449-455.
  38. Brunette MF, Mueser KT. Psychosocial interventions for the long-term management of patients with severe mental illness and co-occurring substance use disorder. J Clin Psychiatry. 2006; 67 Suppl 7: 10-17.
  39. Mistler LA, Brunette MF, Marsh BJ, Vidaver RM, Luckoor R, Rosenberg SD. Hepatitis C treatment for people with severe mental illness. Psychosomatics. 2006; 47(2): 93-107.
  40. Kinon BJ, Noordsy DL, Liu-Seifert H, Gulliver AH, Ascher-Svanum H, Kollack-Walker S. Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning. J Clin Psychopharmacol. 2006; 26(5): 453-461.
  41. Marshall RC, McGurk SR, Karow CM, Kairy TJ, Flashman LA. Performance of subjects with and without severe mental illness on a clinical test of problem solving. Schizophr Res. 2006; 84(2-3): 331-344.
  42. Wallace AE, Weeks WB, Wang S, Lee AF, Kazis LE. Rural and urban disparities in health-related quality of life among veterans with psychiatric disorders. Psychiatr Serv. 2006;57(6):851-856.
  43. Lee KH, Blaha C, Cooper S, Hitti FL, Leiter JC, Roberts DW, Kim U. Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease. Eur. J. Neurophysiol. 2006; 23: 1005-1014.
  44. Altamura AC, Mundo E, Bassetti R, Green A, Lindenmayer JP, Alphs L, Meltzer HY. Transcultural Differences in Suicide Attempters: Analysis on a High-Risk Population of Patients with Schizophrenia or Schizoaffective Disorder. Schizophrenia Research, 2007; 89(3): 140-146.
  45. Green AI. Pharmacotherapy for schizophrenia and co-occurring substance use disorders. Neurotoxicity Research, 2007; 11(1): 33-40.
  46. Green AI, Drake RE, Brunette MF, Noordsy DL. Schizophrenia and Co-Occurring Substance Use Disorder. American Journal of Psychiatry, 2007; 164(3): 402-408.
  47. Green AI. Substance Abuse and Schizophrenia: Pharmacological Approaches. Journal of Dual Diagnosis, 2007; 3(2): 63-72.
  48. Dunayevich E, Ascher-Svanum H, Zhao F, Jacobson JG, Phillips G, Dellva MA, Green AI. Longer Time to Antipsychotic Treatment Discontinuation for Any Cause Is Associated with Better Functional Outcomes for Patients with Schizophrenia. Journal of Clinical Psychiatry, 2007; 68(8):1163-1171.
  49. Drake RE, Mueser KT, Brunette MF. Management of persons with co-occurring severe mental illness and substance use disorder: program implications. World Psychiatry. 2007; 6(3): 131-136.
  50. Salyers MP, Rollins AL, Bond GR, Tsai J, Moser L, Brunette MF. Development of a scale to assess practitioner knowledge in providing integrated dual disorders treatment.Adm Policy Ment Health. 2007; 34(6): 570-581.
  51. Roth RM, Koven NS, Pendergrass JC, Flashman LA, McAllister TW, Saykin AJ. Apathy and the processing of novelty in schizophrenia. Schizophr Res. 2008; 98(1-3): 232-238.
  52. Flashman LA, Roth RM, Pixley HS, Cleavinger HB, McAllister TW, Vidaver R, Saykin AJ. Cavum septum pellucidum in schizophrenia: clinical and neuropsychological correlates. Psychiatry Res. 2007; 154(2): 147-155.
  53. Lee KH, Kristic K, van Hoff R, Hitti FL, Blaha C, Harris B, Roberts DW, Leiter JC. High frequency stimulation of the subthalamic nucleus increases glutamate in the subthalamic nucleus of rats as demonstrated by in vivo enzyme-linked glutamate sensor. Brain Res. 2007; 1162: 121-129.
  54. Green AI, Noordsy DL, Brunette MF, O'Keefe CO. Substance abuse and schizophrenia: Pharmacotherapeutic intervention. Journal of Substance Abuse Treatment, 2008; 34(1): 61-71.
  55. Flashman LA. Neuroanatomy with a behavioral twist. J Clin Exp Neuropsychol. 2008: 1-3.
  56. Wang JF, Min JY, Hampton TG, Amende I, Yan X, Malek S, Abelmann WH, Green AI, Zeind J, Morgan JP. Clozapine-induced myocarditis: Role of catecholamines in a murine model. Eur J Pharmacol, 2008; 592(1-3):123-7.
  57. Riggs PD, Levin FR, Green AI, and Vocci FJ. Co-Morbid Psychiatric and Substance Abuse Disorders: Recent Treatment Research. Substance Abuse, 2008; 29 (3): 51-63.
  58. Brunette MF, O'Keefe C, Zimmet SV, Wojcik JD, Dawson R, Green AI. Clozapine, Olanzapine, or Typical Antipsychotics for Alcohol Use Disorder in Patients with Schizophrenia. Journal of Dual Diagnosis, 2008; 4 (4): 344-354.
  59. Dawson R, Green AI, Drake RE, McGlashan TH, Schanzer B, Lavori PW. Developing and Testing Adaptive Treatment Strategies Using Substance-Induced Psychosis as an Example. Psychopharmacology Bulletin, 2008; 41(3): 51-67.
  60. Riggs PD, Levin FR, Green AI, and Vocci FJ. Comorbid Psychiatric and Substance Abuse Disorders: Recent Treatment Research. Substance Abuse, 2008; 29 (3): 51-63.
  61. Lindenmayer JP, McGurk SR, Mueser KT, Khan A, Wance D, Hoffman L, Wolfe R, Xie H. A randomized controlled trial of cognitive remediation among inpatients with persistent mental illness. Psychiatr Serv. 2008; 59(3):241-247.
  62. Woltmann EM, Whitley R, McHugo GJ, Brunette M, Torrey WC, Coots L, Lynde D, Drake RE. The role of staff turnover in the implementation of evidence-based practices in mental health care. Psychiatr Serv. 2008; 59(7):732-737.
  63. Brunette MF, Asher D, Whitley R, Lutz WJ, Wieder BL, Jones AM, McHugo GJ. Implementation of integrated dual disorders treatment: a qualitative analysis of facilitators and barriers. Psychiatr Serv. 2008; 59(9):989-995.
  64. McGurk SR, Mueser KT, DeRosa TJ, Wolfe R. Work, recovery, and comorbidity in schizophrenia: a randomized controlled trial of cognitive remediation. Schizophr Bull. 2009; 35(2):319-335.
  65. Cummings TS, Noordsy DL. Treatment of catatonic schizophrenia with lorazepam and aripiprazole. Schizophr Res. 2009; 112(1-3):194-195.
  66. Kruck CL, Flashman LA, Roth RM, Koven NS, McAllister TW, Saykin AJ. Lack of relationship between psychological denial and unawareness of illness in schizophrenia-spectrum disorders. Psychiatry Res. 2009 30; 169(1):33-38.
  67. Mueser KT, Glynn SM, Cather C, Zarate R, Fox L, Feldman J, Wolfe R, Clark RE. Family intervention for co-occurring substance use and severe psychiatric disorders: participant characteristics and correlates of initial engagement and more extended exposure in a randomized controlled trial. Addict Behav. 2009; 34(10):867-877.
  68. Whitfield-Gabrieli S, Thermenos HW, Milanovic S, Tsuang MT, Faraone SV, McCarley RW, Shenton ME, Green AI, Nieto-Castanon A, LaViolette P, Wojcik J, Gabrieli JDE, Seidman LJ. Hyperactivity and Hyperconnectivity of the Default Network in Schizophrenia and in First Degree Relatives of Persons with Schizophrenia. Proceedings of the National Academy of Science (PNAS), 2009; 106(4): 1279-1284.
  69. Green AI. Statement 10: Managing Substance Abuse is A Key Target of Treatment. Proceedings and Data from the Schizophrenia Summit: A Critical Appraisal to Improve the Management of Schizophrenia. Journal of Clinical Psychiatry, 2009: 70 (Suppl 1): 37-40.
  70. Brunette MF, O'Keefe C, Dawson R, Buckley P, Green AI. An open label study of quetiapine in patients with schizophrenia and alcohol disorders. Mental Health and Substance Use: Dual Diagnosis, In Press.
  71. Chau DT, Gulick D, Xie H, Dawson R, Green AI. Clozapine chronically suppresses alcohol drinking in Syrian golden hamsters. Neuropharmachology, In Press.