Neurocircuitries and neurotransmitter interactions in schizophrenia

This review describes an attempt to widen the perspective on schizophrenia and to go beyond the dopamine hypothesis. In recent animal experiments corticofugal glutamatergic pathways have emerged as powerful regulators of a variety of subcortical mechanisms, where the dorsal and ventral striatum appear to play a major role in feedback loops controlling a thalamic filter function. These loops appear to be important regulators of wakefulness and psychomotor activity. A deficient filter function will lead to an overload of sensory input to the cerebral cortex and hyperarousal and may ultimately cause breakdown of the integrative capacity of the cerebral cortex and psychosis. Both negative and positive feedback loops appear to be driven by corticofugal glutamatergic pathways, and deficient functions of these loops may cause or contribute to the positive and negative symptomatology of schizophrenia, respectively. In addition to dopamine and glutamate, several other neurotransmitters, including gamma-aminobutyric acid, noradrenaline, serotonin and acetylcholine, appear to play an important role in psychomotor activity and psychotogenesis. Behavioural and biochemical animal models illustrate the interplay between the various neurotransmitters in these respects.