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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Sep 22, 2015; 5(3): 260-272
Published online Sep 22, 2015. doi: 10.5498/wjp.v5.i3.260
Role of presynaptic phosphoprotein synapsin II in schizophrenia
Luke Molinaro, Patricia Hui, Mattea Tan, Ram K Mishra
Luke Molinaro, Patricia Hui, Mattea Tan, Ram K Mishra, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Author contributions: All authors contributed to this manuscript.
Supported by The Canadian Institute of Health Research (CIHR).
Conflict-of-interest statement: All authors declare no conflict of interest regarding the content discussed in this review.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ram K Mishra, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. mishrar@mcmaster.ca
Telephone: +1-905-5259140-22396 Fax: +1-905-5228804
Received: February 5, 2015
Peer-review started: February 7, 2015
First decision: April 10, 2015
Revised: May 26, 2015
Accepted: June 9, 2015
Article in press: June 11, 2015
Published online: September 22, 2015
Abstract

Synapsin II is a member of the neuronal phosphoprotein family. These phosphoproteins are evolutionarily conserved across many organisms and are important in a variety of synaptic functions, including synaptogenesis and the regulation of neurotransmitter release. A number of genome-wide scans, meta-analyses, and genetic susceptibility studies have implicated the synapsin II gene (3p25) in the etiology of schizophrenia (SZ) and other psychiatric disorders. Further studies have found a reduction of synapsin II mRNA and protein in the prefrontal cortex in post-mortem samples from schizophrenic patients. Disruptions in the expression of this gene may cause synaptic dysfunction, which can result in neurotransmitter imbalances, likely contributing to the pathogenesis of SZ. SZ is a costly, debilitating psychiatric illness affecting approximately 1.1% of the world’s population, amounting to 51 million people today. The disorder is characterized by positive (hallucinations, paranoia), negative (social withdrawal, lack of motivation), and cognitive (memory impairments, attention deficits) symptoms. This review provides a comprehensive summary of the structure, function, and involvement of the synapsin family, specifically synapsin II, in the pathophysiology of SZ and possible target for therapeutic intervention/implications.

Keywords: Synapsin II, Schizophrenia, Dopamine, Glutamate, Neuropsychiatry, Antipsychotic drugs

Core tip: The pre-synaptic phosphoprotein, synapsin II, is important in a variety of synaptic functions, including synaptogenesis and regulation of neurotransmitter release. Reduced levels of synapsin II in the prefrontal cortex of humans and animals have been found to confer susceptibility to schizophrenia (SZ). Disruptions in synapsin II gene expression, during development and/or adulthood, may cause synaptic dysfunction, resulting in neurotransmitter imbalances that likely contribute to the pathogenesis of SZ. Understanding synapsin II and its role in disease development will help unravel the pathogenic mechanisms of SZ, and may form the basis for use of novel therapeutics in the treatment of SZ.