Neural circuitry models of schizophrenia: is it dopamine, GABA, glutamate, or something else?

摘要

In the past 3 decades, the field of schizophrenia research has moved inexorably toward understanding the neurobiology of this disorder. In the 1960s, antipsychotic drugs (APDs) were found to have high affinity for dopamine receptors, and the dopamine hypothesis of schizophrenia began its march toward prominence. This model was a landmark for the field of psychiatry because it marked the first instance in which a non-dementing disorder characterized by disturbances of perception, cognition, and emotion was being conceptualized in terms of brain dysfunction. The earliest iterations of this model were quite broad in their perspective and belied the extraordinary complexity of the human brain. In 1973, Janice Stevens (1) boldly suggested that dopaminergic projections to the limbic system might play a central role in the pathophysiology of schizophrenia. This hypothesis was a landmark for the field of psychiatry because it linked a specific neurotransmitter system with a functional network of connections. Initially, presynaptic components of the dopamine system were represented as specialized areas of axon fibers that contained transmitter-filled vesicles and were equipped with biochemical mechanisms for the synthesis, storage, release, and inactivation of dopamine (2).