CSF SNAP-25 in Schizophrenia and Bipolar Illness A Pilot Study

Abstract

Research efforts to identify and understand the In the past 20 years, scientists have conducted extensive research to identify the pathology and etiology of schizophrenia and bipolar illness. In schizophrenic subjects, neuroimaging and functional analysis has identified abnormalities in various brain structures (Nasrallah 1990). Neuropathological studies of schizophrenics have revealed brain changes ranging from loss of gray matter to disorganization of the normal neuronal architecture (Bloom 1993). More recently, changes in vesicular-and growth-associated proteins have been identified in post-mortem brains of schizophrenics (Barbeau et al. 1995;Browning et al. 1993;Eastwood et al. 1995;Perrone-Bizzozero et al. 1996). Based on the accumulated clinical and laboratory information, investigators have developed two models to explain the pathophysiology of schizophrenia.The neurodegeneration hypothesis proposes that schizophrenia is the result of degeneration or loss of neurons, similar to Alzheimer's disease. This hypothesis dates to 1919, when schizophrenia was referred to as "dementia praecox" (Kraepelin 1919). However, postmortem studies have not consistently identified evidence of abnormal neurodegeneration in schizophrenic brains (Arnold et al. 1991).An alternative hypothesis states that the pathology Received November 24, 1998; revised April 8, 1999; accepted June 7, 1999. 718 P.M. Thompson et al. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 6 of schizophrenia arises during embryonic and fetal developmental (Bloom 1993;Saugstad 1989). In this hypothesis, Weinberger (Weinberger 1987) proposes that a static brain lesion is established early in development and that neurodegeneration is not a major factor in the adult pathology. As the brain matures, it compensates for the lesion until the adaptations are overwhelmed. When the brain adaptions are insufficient to compensate, the final groups of behavioral symptoms are collectively described as schizophrenia. As in the neurodegenerative hypothesis, supporting data are circumstantial (Raedler et al. 1998).In bipolar illness, less is known about brain pathology than with schizophrenia. Consistent findings include mood state-dependent changes in erythrocyte Na-K-ATPase activity (Looney and el-Mallakh 1997) and an increased risk for structural brain abnormalities (Altshuler et al. 1995). Both types of studies may indicate subtle neuronal damage. A question raised by both schizophrenia and bipolar studies is whether there is ongoing neuronal damage or degeneration.The direct approach to test the hypothesis that schizophrenia and bipolar illness are not associated with ongoing neurodegeneration is to study neuronal tissue from living patients. However, moral and ethical restrictions eliminate this type of study. One way to bypass this limitation is to study a protein that has been demonstrated to be involved with the adult post-mortem pathology and can be measured in living subjects. Synaptosomal-associated protein 25kDa (SNAP-25) is a candidate protein for th...

Meta-analyses of 10 polymorphisms associated with the risk of schizophrenia

“…SNAP25 can deliver neurotransmitter-containing vesicles to the inner plasma membrane. Human and animal studies indicate that SNAP25 is a risk factor for mental illness, such as SCZ (38,39). For the SNAP25 rs3746544 polymorphism, there have been two previous studies with positive results (47,48) in Europeans (Czechs and British populations) and one negative result (49) in Asians (Japanese).…”

“…A higher expression of GRIK3 has been found in SCZ cases compared to controls (37). SNAP25 encodes a protein that is implicated in the docking priming and fusion of the vesicles, which has been shown to be associated with SCZ (38,39). Association studies between the genetic polymorphisms of the aforementioned 7 genes and SCZ have been performed in different populations (Table I).…”

Alpha- and Gamma-Synuclein Proteins Are Present in Cerebrospinal Fluid and Are Increased in Aged Subjects with Neurodegenerative and Vascular Changes

“…Ventricular CSF has a somewhat different expression of proteins compared to lumbar CSF [16] . Since it has a substantially lower protein level of both IgG and albumin (up to 9-fold) [17] , the CSF samples were not incubated with protein G as in a previous study [18] .…”

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

“…A study indicated higher SNARE complex formation in the anterior frontal cortex samples obtained from patients who committed suicide . Investigation of CSF samples obtained from living patients indicated higher than expected levels of SNAP-25, and some correlations with symptom severity (Thompson et al, 2003;Thompson et al, 1999). Genetic studies in humans provide indirect evidence for a role for SNARE proteins in brain function, and in psychiatric illness.…”