γ‐Aminobutyric Acid Concentration in Cerebrospinal Fluid in Schizophrenia

Mccarthy, Brian W.; Gomes, Úrsula R; Neethling, A. C.; Shanley, B. C.; Taljaard, J. J. F.; Potgieter, L.; Roux, JN

doi:10.1111/j.1471-4159.1981.tb00579.x

Cited by 39 publications

(13 citation statements)

References 19 publications

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“…Our glutamate finding is consistent with the theory that chronic NMDAR hypofunction in schizophrenia results in a compensatory hyperglutamatergic state (16; 17). In addition, we observed elevations in frontal cortex GABA levels in SR−/− mice that correspond with GABA elevations reported in unmedicated (18; 21; 22) humans with schizophrenia. It is important to note that studies of humans with schizophrenia currently being treated with antipsychotic medications have yielded conflicting findings for both glutamate (18; 44; 45) and GABA (44; 46; 47; 48; 49).…”

Section: Discussionsupporting

confidence: 84%

“…Evidence suggests that one of the consequences of NMDAR hypofunction is down-regulation of the fast-firing, parvalbumin-positive γ-aminobutyric acid (GABA) interneurons, resulting in disinhibition of pyramidal neurons (14; 15) and a hyperglutamatergic state (16; 17). Indeed, unmedicated (i.e., antipsychotic naïve or off antipsychotic medications for at least 2 weeks) humans with schizophrenia exhibit increases in glutamate levels (18; 19; 20), as well as increases in GABA levels (18; 21; 22). Furthermore, schizophrenia is characterized by neuroanatomical abnormalities, including cortical atrophy accompanied by ventricular enlargement (23; 24; 25).…”

Section: Introductionmentioning

confidence: 99%

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In vivo magnetic resonance studies reveal neuroanatomical and neurochemical abnormalities in the serine racemase knockout mouse model of schizophrenia

Puhl

Mintzopoulos

Jensen

et al. 2015

Neurobiology of Disease

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BACKGROUND Decreased availability of the N-methyl-D-aspartate receptor (NMDAR) co-agonist D-serine is thought to promote NMDAR hypofunction and contribute to the pathophysiology of schizophrenia, including neuroanatomical abnormalities, such as cortical atrophy and ventricular enlargement, and neurochemical abnormalities, such as aberrant glutamate and γ-aminobutyric acid (GABA) signaling. It is thought that these abnormalities directly relate to the negative symptoms and cognitive impairments that are hallmarks of the disorder. Because of the genetic complexity of schizophrenia, animal models of the disorder are extremely valuable for the study of genetically predisposing factors. Our laboratory developed a transgenic mouse model lacking serine racemase (SR), the synthetic enzyme of D-serine, polymorphisms of which are associated with schizophrenia. Null mutants (SR−/−) exhibit NMDAR hypofunction and cognitive impairments. We used 9.4 Tesla magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to compare in vivo brain structure and neurochemistry in wildtype (WT) and SR−/− mice. METHODS Mice were anesthetized with isoflurane for MRI and MRS scans. RESULTS Compared to WT controls, SR−/− mice exhibited 23% larger ventricular volumes (p<0.05). Additionally, in a medial frontal cortex voxel (15 μl), SR−/− mice exhibited significantly higher glutamate/water (12%, t=1.83, p<0.05) and GABA/water (72%, t=4.10, p<0.001) ratios. CONCLUSIONS Collectively, these data demonstrate in vivo neuroanatomical and neurochemical abnormalities in the SR−/− mouse comparable to those previously reported in humans with schizophrenia.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

In vivo magnetic resonance studies reveal neuroanatomical and neurochemical abnormalities in the serine racemase knockout mouse model of schizophrenia

Puhl

Mintzopoulos

Jensen

et al. 2015

Neurobiology of Disease

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“…Platelet GABA transaminase level n l 14 schizophrenics White et al (1980) (1982) noted a significant decrease in the female schizophrenic sub-population compared to female controls while also reporting a tendency towards increased GABA levels with increased length of illness. That elevation of CSF GABA levels may be correlated with length of schizophrenic illness finds support in a study by McCarthy et al (1981) in which a sub-population of chronic schizophrenics had higher GABA levels compared to controls. However, Gerner et al (1984) did not corroborate this suggestion.…”

Section: Csf Studiesmentioning

confidence: 88%

The GABAergic system in schizophrenia

Blum

Mann

2002

Int. J. Neuropsychopharm.

121

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A defect in neurotransmission involving γ-amino butyric acid (GABA) in schizophrenia was first proposed in the early 1970s. Since that time, a considerable effort has been made to find such a defect in components of the GABAergic system. After a brief introduction focusing on historical perspectives, this paper reviews postmortem and other biological studies examining the following components of the GABAergic system in schizophrenic subjects : the GABA biosynthetic enzyme, glutamate decarboxylase ; free GABA ; the GABA transporter ; the GABA A , GABA B and benzodiazepine receptors ; and the catabolic enzyme GABA transaminase. Additionally, post-mortem studies using morphology or calcium-binding protein to identify GABAergic neurons are also reviewed. Substantial evidence argues for a defect in the GABAergic system of the frontal cortex in schizophrenia which is limited to the parvalbumin-class of GABAergic interneurons.

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“…For the study of physiology and pathophysiology of the central nervous system (CNS), cerebrospinal fluid (CSF) is often used because its composition reflects the global metabolism of this system. There is a wide spectrum of pathological conditions where changes in amino acid concentrations in the CSF can be detected, including multiple sclerosis, intracraneal hypertension, hepatic coma, phenylketonuria, Parkinson's disease, epilepsy, Alzheimer's disease, Alzheimer-type dementia, major depressive disorder and schizophrenia [1][2][3][4][5][6]. The analysis of CSF is useful to determine the biochemical mechanisms underlying such pathologies.…”

Section: Introductionmentioning

confidence: 99%