Cerebrospinal fluid schizophrenia

Although the role of neurotransmitter dysfunction in schizophrenia remains an exciting and important avenue of exploration, we are only aware of one study of neurotransmitters in COS. Jacobsen and colleagues (1997a) measured cerebrospinal fluid (CSF) levels of HVA and 5-HIAA, metabolites of dopamine and serotonin, respectively. While the concentrations of these monoamine metabolites were similar to that seen in adults with schizophrenia, they did not change significantly with treatment. 

There is no evidence for an elevated dopamine content or hypersensitivity of dopamine receptors in the brain of schizophrenic patients. Breakdown products of dopamine and noradrenaline are elevated neither in the urine nor in the blood or cerebrospinal fluid of schizophrenic patients. In some patients with chronic schizophrenia there is even evidence of dopamine hypofunction IKaroum et al.. 1987). 

It has not been possible to show abnormalities in overall dopamine content of brains of people with schizophrenia. Total dopamine content can, incidentally, only be measured at post-mortem (Scott 2006), and overall such studies have not shown any differences between people with schizophrenia and those without (Reynolds Czudek 1988). As one of the main researchers in the field put it, the dopamine content is found to be normal in the schizophrenic brain (Seeman 1995). Research into levels of dopamine metabolites in the cerebrospinal fluid,3 which initially claimed to find increased levels in people with schizophrenia, also proved to be inconclusive when people who had not been treated with drugs were investigated (Reynolds 1989 Tuckwell Koziol 1993). 

Clinical studies have suggested a relationship between low cerebrospinal fluid homovanillic acid, a measure reflecting DA activity in the PFC, and poor performance at tasks involving WM in schizophrenia (Kahn et al., 1994 Weinberger et al., 1998). DA agonists have beneficial effects on the pattern of prefrontal activation measured with PET during these tasks (Daniel et al., 1991 Dolan et al., 1995). 

Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, et al. 2000. Schizophrenia Glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 12 3721-3728. 

Erhardt S, Blennow K, Nordin C, Skogh E, Lindstrom LH, et al. 2001. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 313 96-98. 

Several studies have consistently implicated SNAP-25 in schizophrenia. Postmortem SNAP-25 protein was found to be decreased in the hippocampus (Young et al., 1998 Fatemi et al., 2001 Thompson et al., 2003a), prefrontal cortex (Thompson et al., 1998 Karson et al., 1999), temporal cortex (Thompson et al., 1998), anterior frontal cortex (Honer et al., 2002), and cerebellum (Mukaetova-Ladinska et al., 2002) of individuals with schizophrenia. Conversely, elevated SNAP-25 in cerebrospinal fluid of patients with schizophrenia was observed (Thompson et al., 1999 Thompson et al., 2003b). One study failed to find a change in SNAP-25 in the prefrontal cortex (Brodman s area 9) of individuals with schizophrenia, but did find an increase in individuals with bipolar disorder (Scarr et al., 2006). 

Thompson PM, Kelley M, Yao J, Tsai G, van Kammen DP. 2003b. Elevated cerebrospinal fluid SNAP-25 in schizophrenia. Biol Psychol 53 1132-1137. 

Glutathione synthesis is impaired in patients at the level of the GCL enzyme, as measured in fibroblasts. In addition, genetic analysis showed an association between schizophrenia and the two GCL subunits. These findings are consistent with low brain and cerebrospinal fluid (CSF) glutathione levels. 

The observations reported below, made in five different cohorts with various methodologies, converge to suggest that anomalies of GSH metabolism represent a vulnerability factor in at least a subgroup of schizophrenia patients. They concern cerebrospinal fluid (CSF) and brain GSH levels, enzymatic activity, protein and gene expression in fibroblasts and allelic variants of the GCL genes ( Figure 2.5-2). 

Kim JS, Komhuber HH, Schmid-Burgk W, Holzmuller B. 1980. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis of schizophrenia. Neurosci Lett 20 379-382. 

Prell GD, Green JP, Kaufmann CA, Khandelwal JK, Morrishow AM, et al. 1995. Histamine metabolites in cerebrospinal fluid of patients with chronic schizophrenia Their relationships to levels of other aminergic transmitters and ratings of symptoms. Schizophr Res 14 93-104. 

Gu, N. F., Langen, H., He, L., Fountoulakis, M. (2003). Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. Amino Acids 25, 49-57. 

Koponen, H., Riekkinen, P.J. (1991). Cerebrospinal fluid acetylcholinesterase in patients with dementia associated with schizophrenia or chronic alcoholism. Acta Psychiatr. Scand. 83 441-3. 

Patients with schizophrenia have increased concentrations of pro-inflammatory cytokines both in the systemic circulation and cerebrospinal fluid and showed decreased EPA and DHA in the plasma phospholipid. Clinical trials showed that supplementation of ethyl EPA is of significant benefit to these patients (228). 

Several reports described increased serum IL-6 levels in schizophrenia. IL-6 serum levels might be especially high in patients with an unfavourable course of the disease (Muller et al., 2000). IL-6 is a product of activated monocytes and of the activation of the type-2 immune response. Moreover, several other signs of activation of the type-2 immune response are described in schizophrenia, including the increased production ofIgE and an increase ofIL-10 serum levels (Cazzullo et al., 1998 Schwarz et al., 2001). In the cerebrospinal fluid (CSE), IL-10 levels were found to be related to the severity of the psychosis (van Kamnmnen et al., 1997). 

Cerebrospinal Fluid cCorticotropin Releasing Factor-like Immunoreactivity in depression and Schizophrenia. Am J Psychiatry 1987 144 873-877. Barrowcliff, M., Carr, F., H., Organic Medicinal Chemicals (Synthetic and Natural) pub. by D. Van Nostrand Co. 1920... 

Perry T. L. (1982b) Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutaminergic neuronal dysfunction Neurosci Lett 28, 81-85... 

Bogoch, S., 1958, Cerebrospinal fluid neuraminic acid deficiency in schizophrenia. Arch. Neurol. Psychiat. 80 221. 

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