Schizophrenia neurotransmitter systems

The neurochemistry of schizophrenia has been considered in a variety of ways by numerous investigators and most have, as here, focussed on the role of abnormalities and/or dysfunction of brain neurotransmitter systems in the disease. Implicit in a book on the neurochemistry of consciousness is the assumption that this chapter will address the neurochemical basis of the disturbance (s) of consciousness that occurs in schizophrenia. Consciousness in its particular and generally-understood meaning is not obviously distorted in schizophrenia, although schizophrenic patients clearly have a different, or abnormal experience of the external world—their conscious awareness is disturbed. 

Stahl s Essential Psychopharmacology has established itself as the preeminent source of education and information in its field. This much expanded second edition enlists advances in neurobiology and recent clinical developments to explain with renewed clarity the concepts underlying drug treatment of psychiatric disorders. New neurotransmitter systems, new theories of schizophrenia, clinical advances in antipsychotic and antidepressant therapy, new coverage of attention deficit disorder, sleep disorders, and drug abuse, and a new chapter on sex-specific and sexual function-related psychopharmacology—these are all features of this edition. 

In this section, we will review first the literature dealing with how alterations in NRGl/ErbB signaling affect neurotransmitter systems and synapses that are hypothesized to underlie aspects of schizophrenia. Then we will discuss the results of behavioral analyses of NRG1 and ErbB mutant mice, focusing on behavioral tests designed to probe circuits associated with endophenotypes of the disease. 

Q8 Dopamine is thought to be the main neurotransmitter associated with schizophrenia. But there is evidence of the involvement of other neurotransmitter systems, particularly glutamate, and also serotonin (5-HT) and GABA. 

Although the nature of the brain abnormalities seen in schizophrenia is not clearly known at present, certain pieces of the puzzle are being identified. Overall, schizophrenic patients appear to have some degree of cerebral atrophy (about 5% loss of cerebral mass), enlarged cerebral ventricles, and decreased size of certain other brain structures. From a functional perspective, the prefrontal and medial temporal brain appear to be particularly affected. Several neurochemical abnormalities are also associated with the disorder, and several neurotransmitter systems have been implicated (Table 5.5). 

TABLE 5.5. Neurotransmitter Systems Postulated to Be Involved in Schizophrenia... 

As described in the previous sections, neuropathological studies demonstrated alterations in the levels of several synaptic proteins in the PFC, hippocampus, and cerebellum of patients with schizophrenia (13, 15, 53). These observations have lead to the hypothesis that the clinical symptoms of schizophrenia are manifestations of abnormal neural circuitry and dysfunctional communication between different brain regions (22, 51). These abnormalities affect multiple neurotransmitter systems. Although dopamine dysfunction in schizophrenia is widely accepted, a growing body of evidence suggests the involvement of glutamate, GABA, and other neurotransmitters in schizophrenia. 

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