title: Modulation of limbic circuitry predicts treatment response to antipsychotic medication: a functional imaging study in schizophrenia.
abstract: The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive of or are correlated with treatment response. Using PET with 15O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug in patients with schizophrenia during a 6-week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (2 weeks), and then blindly randomized to treatment with haloperidol (n=12) or olanzapine (n=17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both the drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some patterns seen at weeks 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated (anterior cingulate/medial frontal cortex) stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observed differential patterns of rCBF activation between good and poor responders. After 1 week of treatment, greater rCBF increase in the ventral striatum and greater decrease in the hippocampus were associated with good response.
authors.affiliation: Department of Psychiatry, University of Alabama at Birmingham, Birmingham, AL 35294, USA. alahti@uab.edu
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Lahti
authors.forename: Martin A
authors.initials: MA
authors.lastname: Weiler
authors.forename: Henry H
authors.initials: HH
authors.lastname: Holcomb
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.forename: Karen L
authors.initials: KL
authors.lastname: Cropsey
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008032:Limbic System / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011877:Radionuclide Imaging; D012039:Regional Blood Flow / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine
references.citation: Neuropsychopharmacology. 1999 May;20(5):403-12
references.pmid: 10192821
references.citation: Nat Rev Neurosci. 2006 Apr;7(4):268-77
references.pmid: 16552413
references.citation: Neuropsychopharmacology. 1997 Oct;17(4):230-40
references.pmid: 9326747
references.citation: Am J Psychiatry. 2006 Apr;163(4):600-10
references.pmid: 16585434
references.citation: Prog Neurobiol. 1994 Oct;44(2):163-96
references.pmid: 7831476
references.citation: Trends Cogn Sci. 2000 Jun;4(6):215-222
references.pmid: 10827444
references.citation: J Neurosci. 1983 Aug;3(8):1607-19
references.pmid: 6135762
references.citation: Neuroscience. 1992;46(2):315-28
references.pmid: 1347406
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40
references.pmid: 8799184
references.citation: Neuropsychopharmacology. 2004 Jan;29(1):133-45
references.pmid: 14583740
references.citation: Synapse. 1996 Sep;24(1):12-8
references.pmid: 9046072
references.citation: Br J Psychiatry. 2005 Oct;187:366-71
references.pmid: 16199797
references.citation: Schizophr Bull. 1997;23(2):287-303
references.pmid: 9165638
references.citation: Psychiatry Res. 1997 Nov 28;76(1):51-61
references.pmid: 9498309
references.citation: Hippocampus. 2001;11(5):543-50
references.pmid: 11732707
references.citation: Eur J Pharmacol. 1997 Nov 5;338(2):R3-5
references.pmid: 9456005
references.citation: Schizophr Res. 2009 Jan;107(1):13-21
references.pmid: 18930379
references.citation: J Nucl Med. 1983 Sep;24(9):790-8
references.pmid: 6604140
references.citation: Neuropsychopharmacology. 2005 Dec;30(12):2283-9
references.pmid: 16123775
references.citation: Am J Psychiatry. 2004 Jun;161(6):985-95
references.pmid: 15169686
references.citation: Psychopharmacology (Berl). 1995 Nov;122(2):198-201
references.pmid: 8848537
references.citation: Neuroimage. 1996 Dec;4(3 Pt 1):223-35
references.pmid: 9345513
references.citation: Science. 1983 Sep 9;221(4615):1054-7
references.pmid: 6136093
references.citation: Arch Gen Psychiatry. 1992 Aug;49(8):624-9
references.pmid: 1637252
references.citation: Psychiatry Res. 2005 May 30;139(1):19-30
references.pmid: 15950442
references.citation: Schizophr Res. 2007 Aug;94(1-3):293-305
references.pmid: 17574821
references.citation: Synapse. 1995 Apr;19(4):264-93
references.pmid: 7792721
references.citation: Biol Psychiatry. 2003 Apr 1;53(7):601-8
references.pmid: 12679238
references.citation: Neuropsychopharmacology. 1996 Feb;14(2):105-110
references.pmid: 8822533
references.citation: Am J Psychiatry. 1996 Jan;153(1):41-9
references.pmid: 8540590
references.citation: Arch Gen Psychiatry. 2005 Apr;62(4):361-70
references.pmid: 15809403
references.citation: Br J Psychiatry. 2000 Nov;177:402-7
references.pmid: 11059992
references.citation: J Neurochem. 1990 May;54(5):1755-60
references.pmid: 1969939
references.citation: J Neurol Neurosurg Psychiatry. 2002 Jan;72(1):106-10
references.pmid: 11784835
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8104-9
references.pmid: 10884434
references.citation: Neuropsychopharmacology. 2008 May;33(6):1276-86
references.pmid: 17687264
references.citation: J Clin Psychiatry. 2001 Oct;62(10):757-71
references.pmid: 11816864
references.citation: Neurochem Int. 1998 Nov;33(5):383-97
references.pmid: 9874089
references.citation: Neuropsychopharmacology. 2004 Jan;29(1):171-8
references.pmid: 14520337
references.citation: Neuropsychopharmacology. 1998 Jul;19(1):36-47
references.pmid: 9608575
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8
references.pmid: 12506194
references.citation: Neuropsychopharmacology. 2006 Jan;31(1):221-30
references.pmid: 16123774
references.citation: Prog Brain Res. 1990;85:119-46
references.pmid: 2094891
references.citation: Arch Gen Psychiatry. 1992 Dec;49(12):966-74
references.pmid: 1449383
references.citation: Arch Gen Psychiatry. 2003 Dec;60(12):1228-35
references.pmid: 14662555
references.citation: Neuroimage. 1997 May;5(4 Pt 1):261-70
references.pmid: 9345555