Cerebrospinal fluid amino acid concentrations in chronic schizophrenia

Korpi, Esa R.; Kaufmann, Charles A.; Marnela, Kirsi-Marja; Weinberger, Daniel R.

doi:10.1016/0165-1781(87)90095-3

Cited by 74 publications

(32 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alfredsson and colleagues reported that during sulpiride treatment, serum glutamate levels increased in responders while they were decreased in non-responders (Alfredsson and Wiesel, 1990). Korpi and colleagues reported no difference in glutamate concentrations between untreated and haloperidol treated schizophrenic patients (Korpi et al, 1987). In this study, the one patient whose glutamate and aspartate concentrations were decreased on clozapine was on haloperidol 15 mg/d and lorazepam ling/d, and the other patient whose aspartare concentration was decreased on clozapine was on thioridazine 800mg/d.…”

Section: Discussionmentioning

confidence: 87%

Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics

Evins

Amico

Shih

et al. 1997

J. Neural Transmission

View full text Add to dashboard Cite

To examine whether serum excitatory amino acid concentrations change with clozapine treatment and whether these changes correlate with improvement in negative symptoms, serum excitatory amino acids were measured and clinical scales administered in seven subjects with schizophrenia before and after switching from conventional neuroleptics to clozapine. Clozapine treatment was associated with increased serum glutamate and aspartate concentrations. Clinical improvement was negatively correlated with baseline glycine concentrations. These results support the hypothesis that clozapine acts at least in part by increasing glutamatergic activity.

show abstract

Section: Discussionmentioning

confidence: 87%

Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics

Evins

Amico

Shih

et al. 1997

J. Neural Transmission

View full text Add to dashboard Cite

show abstract

“…156 Although, this report was not consistently replicated, [157][158][159] (because the fraction of CSF glutamate considered to come from the transmitter pool is so small (o5%), the method was not considered sensitive enough to reliably find changes. However, Kornhuber's idea 156 of reduced glutamatergic transmission in schizophrenia has continued to capture the interest of the field.…”

Section: Characteristics Of Postmortem Tissuementioning

confidence: 80%

Phenotype of schizophrenia: a review and formulation

2004

View full text Add to dashboard Cite

The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.

show abstract

“…Recent data regarding a glutamate hypothesis has been limited and conflicting. Several studies failed to find decreased CSF levels of glutamate in schizophrenic patients (Gattaz et al, 1985;Korpi et al, 1987), although others found an inverse correlation between CSF glutamate levels and positive symptoms in schizophrenic patients (Faustman et al, 1999). A post-mortem study of glutamate levels did not find significant changes in the frontal cortex, caudate nucleus, putamen, thalamus, nucleus accumbens, or olfactory tubercle (Perry, 1982).…”

Section: Introductionmentioning

confidence: 95%

Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats

Spurney

Baca

Murray

et al. 1999

Synapse

View full text Add to dashboard Cite

Despite multiple lines of investigation the effect of neuroleptics on glutamate-mediated neurotransmission remains controversial. To study the effects of typical and atypical neuroleptics on selected parameters of glutamate-mediated neurotransmission, male Sprague-Dawley rats were randomly assigned to a 21-day oral treatment course with vehicle, haloperidol (HDL), or clozapine (CLZ). Coronal slices of rat brain were then incubated with tritiated ligands to measure NMDA, AMPA, and kainate receptor, and glutamate reuptake site density. Regions of interest included the frontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, and the nucleus accumbens. CLZ increased the density of AMPA receptors significantly in the frontal and anterior cingulate cortices compared with normal controls. In the dorsal and ventral striatum, and nucleus accumbens as a whole, CLZ-treated rats had a higher AMPA receptor density compared with both the HDL- and vehicle-treated controls. Additionally, within the nucleus accumbens, CLZ-treated rats had a higher density of AMPA receptors compared with the HDL group in the core, and at trend level in the shell. There was a group by region interaction for NMDA receptor density, primarily reflecting the tendency of HDL treated rats to have high receptor densities in the frontal and anterior cingulate cortices. Kainate receptors and glutamate reuptake site densities did not differ significantly across groups. These results suggest a critical role for glutamate in the mediation of atypical antipsychotic drug action in anatomically-specific regions, and further encourage the investigation of glutamate neurotransmitter systems in schizophrenia.

show abstract

Cerebrospinal fluid amino acid concentrations in chronic schizophrenia

Cited by 74 publications

References 22 publications

Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics

Clozapine treatment increases serum glutamate and aspartate compared to conventional neuroleptics

Phenotype of schizophrenia: a review and formulation

Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats

Contact Info

Product

Resources

About