A deregulation of the stress response is a potential etiological factor in the development and relapse of dopamine (DA)-related human disorders, including addiction, drug-induced psychosis, and schizophrenia. Schizophrenia is characterized by a chronic relapsing nature and vulnerability to exacerbation following stress or dopaminergic drugs. Indeed, the most replicated finding so far in schizophrenia positron emission tomography (PET) research has been an increased DA release after the administration of amphetamine, and this DA increase has been associated with positive psychotic symptoms and active stages of the illness. As increased stimulant-induced DA release is a hallmark of sensitization, several pieces of evidence support the view that schizophrenia is associated with a process of dopamine sensitization (Laruelle and Abi-Dargham, 1999).

Psychosis sufferers themselves often cite a link between the experience of stress and psychotic symptoms. The stress-vulnerability model suggests that an endogenous, organic diathesis or vulnerability interacts with internal or external stressors in the development of psychotic disorders. However, the underlying neurobiological condition/event that results in an exaggerated response to stressors is unknown. One proposed mechanism is neurochemical sensitization of the DA system—dopamine sensitization—, whereby repeated exposure to sensitizing life stressors (or DA drugs) progresses into increased stress-associated DA release. Hence, during active periods of the illness (that is, prodromal phase, initial episode, and subsequent relapses), dopaminergic neurons may be hyperresponsive to environmental stimuli, and exposure to even moderate levels of stress (or DA drugs) produces excessive DA release, precipitating illness in vulnerable individuals and relapse in those with schizophrenia.

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