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Int. J. Mol. Sci. 2017, 18(8), 1689; doi:10.3390/ijms18081689

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

1,2,3
and
1,2,*
1
Department of Psychiatry, Taipei Veterans General Hospital, Taipei 112, Taiwan
2
Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
3
Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Received: 14 July 2017 / Revised: 30 July 2017 / Accepted: 1 August 2017 / Published: 3 August 2017
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Abstract

Schizophrenia has been primarily associated with dopamine dysfunction, and treatments have been developed that target the dopamine pathway in the central nervous system. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid (GABA) signaling, which may lead to aberrant functioning of interneurons that manifest as cognitive, behavioral, and social dysfunction through altered functioning of a broad range of macro- and microcircuits. The interactions between neurotransmitters can be modeled as nodes and edges by using graph theory, and oxidative balance, immune, and glutamatergic systems may represent multiple nodes interlocking at a central hub; imbalance within any of these nodes might affect the entire system. Therefore, this review attempts to address novel treatment targets beyond the dopamine hypothesis, including glutamate, serotonin, acetylcholine, GABA, and inflammatory cytokines. Furthermore, we outline that these treatment targets can be possibly integrated with novel treatment strategies aimed at different symptoms or phases of the illness. We anticipate that reversing anomalous activity in these novel treatment targets or combinations between these strategies might be beneficial in the treatment of schizophrenia. View Full-Text
Keywords: schizophrenia; dopamine hypothesis; novel treatment target schizophrenia; dopamine hypothesis; novel treatment target
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Yang, A.C.; Tsai, S.-J. New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis. Int. J. Mol. Sci. 2017, 18, 1689.

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