Review ArticlesGABA-ergic neurons and the neurobiology of schizophrenia and other psychoses
Section snippets
Cortical GABA-ergic neurons, dopamine receptors, and schizophrenia
Chandelier cells are gamma-aminobutyric acid (GABA)-ergic interneurons with a unique synaptic specificity enabling them to exert a strong inhibitory influence on pyramidal cells [14]. They are located in all regions of the hippocampal formation, temporal neocortex, and prefrontal cortex. The chandelier GABA-ergic neurons are a distinct type of inhibitory interneuron the axon terminals of which form arrays or “cartridges,” which provide inhibitory input exclusively to the axon initial segment of
Epilepsy
It is commonly accepted that people with epilepsy have more psychiatric problems than those without epilepsy. In particular, non-affective psychosis is increased in men and women with epilepsy, and this pathogenic association has been found both in selected patient populations and from more extensive epidemiological studies [9]. Several investigations have found an excess of temporal lobe epilepsy [5] among people with psychosis and epilepsy, while others have registered psychosis due to
Psychosis—a disorder of neurodevelopment
The view that schizophrenia is a disorder of brain development has received considerable attention in recent years [27]. A number of these reports have pointed to structural changes in the cortex including neurons being misplaced, and asymmetry of the cortex being reduced in schizophrenics. Moreover, children at risk of developing schizophrenia show delayed neurological development, while there is an increased incidence of cerebral anomalies such as agenesis of the corpus collosum in
GABA-ergic neurons and cortical development
The cells of the cerebral cortex, both neurons and glia originate from the ventricular zone and sub-ventricular zone in the developing telencephalon [38]. The predominant mode of cell migration into the cerebral cortex is both radially and clonally based [47], but recent studies have revealed a sub-population of neocortical interneurons that express GABA and migrate from the developing striatum [49]. This cell migration occurs between the primordia of the basal ganglia and cerebral cortex,
Psychosis: functional imaging of the brain
Brain imaging in schizophrenia has provided important evidence that the disorder is associated with disturbances in cerebral structure. Computerised tomography (CT) provided the early evidence for enlarged ventricular size. Magnetic resonance imaging (MRI) with its greater resolution has tended to confirm these early findings [54] and extend them to specific cerebral structures [20]. Decreases in size of the pre-frontal lobe, temporal lobe and amygdala have also been reported. However, it
GABA-ergic interneurons—importance for “binding” and synchronisation of neural networks
In the early 1980s it was proposed on theoretical grounds that assemblies of synchronously firing neurons may provide the basic building blocks of neuronal representations. Several important studies have gone some way to support this viewpoint 23, 48. Neuronal activity in the frontal cortex of monkeys can show a systematic relationship to behavioural events, and synchronisation of neuronal activity rather than the level of activity itself seems to be the important correlate [61]. For the visual
Conclusions
This review has provided compelling evidence for a pivotal role of cortical GABA-ergic interneurons in psychoses of the kind seen in schizophrenia, at menopause and post-partum, as a result of drug abuse, and secondary to other medical conditions such as epilepsy and Prader-Willi syndrome. This does not provide an alternative to the dopamine hypothesis or rule out the involvement of other transmitters such as serotonin and glutamate, but integrates these transmitters with GABA-ergic
Acknowledgements
This work was supported by MRC Brain, Behaviour and Neuropsychiatry co-operative. I would like to thank James Leckman for his stimulating discussion that generated much of the thinking behind this review.
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