Dopamine regulation in schizotypal personality disorder and psychosis

Abstract

It has recently been proposed that reduced stimulation of prefrontal cortex DI receptors secondary to hypoactivity of mesocortical dopamine (DA) projections may explain the cognitive impairments experienced by patients with schizophrenia and the schizophrenia spectrum. Findings from studies done during the past two decades suggest that schizotypal personality disorder (SPD), the prototypic disorder of the schizophrenia spectrum, is associated with cognitive deficits and social deterioration that are qualitatively similar, although less severe, to those observed in schizophrenia. It generally is acknowledged that the psychotic symptoms of schizophrenia are associated with hyperactivity of mesolimbic DA projections resulting in excessive stimulation of striatal D2 receptors. In contrast with schizophrenia, dopaminergic interventions improved cognitive function in SPD without worsening psychotic-like symptoms, raising the possibility that patients with SPD are protected against increases in subcortical dopaminergic activity associated with psychosis. However, mounting evidence suggests that alterations in other neurotransmitter systems (eg, glutamate, γ-aminobutyric acid, opioid, serotonergic) may be involved in the pathophysiology of schizophrenia. This over view focuses on common DA-related neurobiological vulnerabilities shared by schizophrenia and the schizophrenia spectrum, in addition to factors that protect SPD from the overt psychotic symptoms and more severe social and cognitive deficits experienced by patients with chronic schizophrenia.