Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder

• Published in: Psychiatry research Vol. 178; no. 2; pp. 374 - 380
• Main Authors: Gray, Laura J, Dean, Brian, Kronsbein, Helena C, Robinson, Phillip J, Scarr, Elizabeth
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 30-07-2010; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Bipolar Disorder - metabolism; Bipolar Disorder - pathology; Bipolar disorders; Cerebral Cortex - metabolism; Cohort Studies; Dynamin; Female; Gene Expression Regulation - physiology; Humans; Male; Medical sciences; Membrane Proteins - metabolism; Middle Aged; Mood disorders; NCAM; Nerve Tissue Proteins - metabolism; Neural Cell Adhesion Molecules - metabolism; Psychiatric disorders; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Qa-SNARE Proteins - metabolism; R-SNARE Proteins - metabolism; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; SNAP-25; Statistics, Nonparametric; Synapse; Synaptophysin; Synaptophysin - metabolism; Synaptosomal-Associated Protein 25 - metabolism; Syntaxin; VAMP; α-Synuclein; α-Synuclein; Synaptophysin; Syntaxin; Synapse; NCAM; VAMP; Dynamin; Psychiatric disorders; SNAP-25; Mood disorder; Neural cell adhesion molecule; Schizophrenia; Bipolar disorder; Psychosis; Mental disorder; Diagnosis; α-synuclein
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2008.07.012

Abstract Aberrant regulation of synaptic function is thought to play a role in the aetiology of psychiatric disorders, including schizophrenia and bipolar disorder. Normal neurotransmitter release is dependent on a complex group of presynaptic proteins that regulate synaptic vesicle docking, membrane fusion and fission, including synaptophysin, syntaxin, synaptosomal-associated protein-25 (SNAP-25), vesicle-associated membrane protein (VAMP), α-synuclein and dynamin I. In addition, structural and signalling proteins such as neural cell adhesion molecule (NCAM) maintain the integrity of the synapse. We have assessed the levels of these important synaptic proteins using Western blots, in three cortical regions (BA10, 40 and 46) obtained post-mortem from subjects with bipolar 1 disorder, schizophrenia or no history of a psychiatric disorder. In bipolar 1 disorder cortex (parietal; BA40), we found a significant increase in the expression of SNAP-25, and a significant reduction in α-synuclein compared with controls. These changes in presynaptic protein expression are proposed to inhibit synaptic function in bipolar 1 disorder. In schizophrenia, a significant reduction in the ratio of the two major membrane-bound forms of NCAM (180 and 140) was observed in BA10. The distinct functions of these two NCAM forms suggest that changes in the comparative levels of these proteins could lead to a destabilisation of synaptic signalling. Our data support the notion that there are complex and region-specific alterations in presynaptic proteins that may lead to alterations in synaptic activity in both schizophrenia and bipolar disorder.