Pathophysiologically based treatment interventions in schizophrenia

被引:256
作者
Lewis, David A.
Gonzalez-Burgos, Guillermo
机构
[1] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA
关键词
D O I
10.1038/nm1478
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Identifying the molecular alterations that underlie the pathophysiology of critical clinical features of schizophrenia is an essential step in the rational development of new therapeutic interventions for this devastating illness. Cognitive deficits, such as the impairments in working memory that arise from dysfunction of the dorsolateral prefrontal cortex, are a major determinant of functional outcome in schizophrenia. Here we consider the contributions of disturbances in glutamate, dopamine and GABA neurotransmission to the pathophysiology of working memory impairments in schizophrenia, suggest a cascade of molecular events that might link these disturbances, and argue that the molecular alterations most proximal to the pathophysiology of prefrontal dysfunction offer the most promise as targets for new drug development.
引用
收藏
页码:1016 / 1022
页数:7
相关论文
共 108 条
[1]   Prefrontal dopamine D1 receptors and working memory in schizophrenia [J].
Abi-Dargham, A ;
Mawlawi, O ;
Lombardo, I ;
Gil, R ;
Martinez, D ;
Huang, YY ;
Hwang, DR ;
Keilp, J ;
Kochan, L ;
Van Heertum, R ;
Gorman, JM ;
Laruelle, M .
JOURNAL OF NEUROSCIENCE, 2002, 22 (09) :3708-3719
[2]   Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia [J].
Abi-Dargham, A ;
Moore, H .
NEUROSCIENTIST, 2003, 9 (05) :404-416
[3]   GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss [J].
Addington, AM ;
Gornick, M ;
Duckworth, J ;
Sporn, A ;
Gogtay, N ;
Bobb, A ;
Greenstein, D ;
Lenane, M ;
Gochman, P ;
Baker, N ;
Balkissoon, R ;
Vakkalanka, RK ;
Weinberger, DR ;
Rapoport, JL ;
Straub, RE .
MOLECULAR PSYCHIATRY, 2005, 10 (06) :581-588
[4]   Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia [J].
Adler, CM ;
Malhotra, AK ;
Elman, I ;
Goldberg, T ;
Egan, M ;
Pickar, D ;
Breier, A .
AMERICAN JOURNAL OF PSYCHIATRY, 1999, 156 (10) :1646-1649
[5]  
Akbarian S, 1996, J NEUROSCI, V16, P19
[6]   GENE-EXPRESSION FOR GLUTAMIC-ACID DECARBOXYLASE IS REDUCED WITHOUT LOSS OF NEURONS IN PREFRONTAL CORTEX OF SCHIZOPHRENICS [J].
AKBARIAN, S ;
KIM, JJ ;
POTKIN, SG ;
HAGMAN, JO ;
TAFAZZOLI, A ;
BUNNEY, WE ;
JONES, EG .
ARCHIVES OF GENERAL PSYCHIATRY, 1995, 52 (04) :258-266
[7]   Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders [J].
Akbarian, Schahram ;
Huang, Hsien-Sung .
BRAIN RESEARCH REVIEWS, 2006, 52 (02) :293-304
[8]   Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects [J].
Akil, M ;
Pierri, JN ;
Whitehead, RE ;
Edgar, CL ;
Mohila, C ;
Sampson, AR ;
Lewis, DA .
AMERICAN JOURNAL OF PSYCHIATRY, 1999, 156 (10) :1580-1589
[9]   Working memory [J].
Baddeley, Alan .
CURRENT BIOLOGY, 2010, 20 (04) :R136-R140
[10]   What can research on schizophrenia tell us about the cognitive neuroscience of working memory? [J].
Barch, DM .
NEUROSCIENCE, 2006, 139 (01) :73-84