GAD67: the link between the GABA-deficit hypothesis and the dopaminergic- and glutamatergic theories of psychosis

@article{Kalkman2003GAD67TL,
  title={GAD67: the link between the GABA-deficit hypothesis and the dopaminergic- and glutamatergic theories of psychosis},
  author={Hans Otto Kalkman and Erika Loetscher},
  journal={Journal of Neural Transmission},
  year={2003},
  volume={110},
  pages={803-812}
}
Summary. Decreases in the 67 kDa isoenzyme of brain glutamic acid decarboxylase (GAD67) expression have been consistently found in patients with bipolar disorder and schizophrenia. In animals GAD67 expression is diminished by chronic, but not acute stimulation of dopamine D2 receptors and by short-term blockade of NMDA receptors. In contrast, chronic treatment with D2 receptor antagonists enhances GAD67 expression. Thus, antipsychotic treatment cannot explain the reduction in GAD67 levels in… 
View on Springer
ncbi.nlm.nih.gov
53 Citations
Background Citations
20
Results Citations
1

53 Citations

Citation Type

Citation Type

Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders
Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression
TLDR
Quantitative transmission disequilibrium test analyses revealed that variation in GAD1 influenced multiple domains of cognition, including declarative memory, attention and working memory, and suggest that the mechanism involves altered cortical GABA inhibitory activity, perhaps modulated by dopaminergic function.
Altered Excitatory-Inhibitory Balance in the NMDA-Hypofunction Model of Schizophrenia
TLDR
Recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia are discussed, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro.
The role of anti-glutamic acid decarboxylase autoantibodies in mood disorders
TLDR
A very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies (GADA) in determining a decreased enzymatic function of GAD, and it is possible to improve diagnosis and treatment of mood disorders.
Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications
TLDR
The results indicate that GAD67 mRNA level was reduced by 40% in the autistic group, suggesting that reduced Purkinje cell GABA input to the cerebellar nuclei potentially disrupts Cerebellar output to higher association cortices affecting motor and/or cognitive function.
Reelin down-regulation in mice and psychosis endophenotypes
Molecular mechanisms underlying synergistic effects of SSRI–antipsychotic augmentation in treatment of negative symptoms in schizophrenia
TLDR
While as yet limited in scope, the evidence suggests definable molecular targets which may be implicated in drug development based on SSRI–antipsychotic synergistic actions.
Methamphetamine induces long-term changes in GABAA receptor alpha2 subunit and GAD67 expression.
Neurotransmitter receptor binding in the posterior cingulate cortex in schizophrenia and in the phencyclidine mouse model: an exploration of the NMDA hypofunction hypothesis of schizophrenia
TLDR
Results have shown for the first time that there are specific neurotransmitter imbalances in this region of the posterior cingulate cortex in schizophrenia, and it is possible that these changes stem from NMDA hypofunction.
Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems
TLDR
The results indicate that GAD67 haplodeficiency impairs sociability and increases vulnerability to social stress, provokes depressive-like behavior and alters the catecholaminergic innervation in brain areas associated with schizophrenia.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 55 REFERENCES
Dopaminergic and glutamatergic blocking drugs differentially regulate glutamic acid decarboxylase mRNA in mouse brain.
Dopamine in schizophrenia: a review and reconceptualization.
TLDR
The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms) and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.
Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.
TLDR
The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss, bringing about an activity-dependent down-regulation associated with the functional hypoactivity of the DLPFC and implying that overall cortical neuronal migration had not been compromised in development.
Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia.
TLDR
The hypothesis that the expression of the 2 isoforms of GAD, 65 kd and 67 kd, is differentially affected in the hippocampus in schizophrenia and bipolar disorder is tested and a region-specific deficit of G AD(65) and GAD(67) mRNA expression is found in bipolar disorder.
A decrease of reelin expression as a putative vulnerability factor in schizophrenia.
TLDR
In all of the brain areas studied, RELN and its mRNA were significantly reduced in patients with schizophrenia; this decrease was similar in patients affected by undifferentiated or paranoid schizophrenia and is interpreted within a neurodevelopmental/vulnerability "two-hit" model for the etiology of schizophrenia.
Brain SPECT imaging of amphetamine-induced dopamine release in euthymic bipolar disorder patients.
TLDR
D dopamine receptor imaging combined with a pharmacological challenge of amphetamine was used to assess both pre- and postsynaptic aspects of dopamine neurotransmission in euthymic bipolar disorder patients, and data are consistent with enhanced post Synaptic dopamine responsivity in patients with bipolar disorder.
The GABAergic system in schizophrenia.
  • B. Blum, J. Mann
  • Psychology
    The international journal of neuropsychopharmacology
  • 2002
TLDR
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.
The Relationship between Dorsolateral Prefrontal Neuronal N-Acetylaspartate and Evoked Release of Striatal Dopamine in Schizophrenia
Dopaminergic regulation of glutamic acid decarboxylase mRNA expression and GABA release in the striatum: A review
  • N. Lindefors
  • Biology
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 1993
Traditional and new antipsychotic drugs differentially alter neurotransmission markers in basal ganglia‐thalamocortical neural pathways
TLDR
Results are consistent with the idea that the two new antipsychotics tested have mild and regionally restricted actions within the basal ganglia nuclei and a common action on increasing GAD expression in the reticular nucleus of the thalamus (RtN).
...
1
2
3
4
5
...