[Show abstract][Hide abstract] ABSTRACT: Presynaptic dopamine (DA) transmission has been measured in schizophrenia using different paradigms aimed at providing estimates of the integrity or the activity of the presynaptic dopaminergic neuron. RESEARCHERS HAVE MEASURED: (1) DA synthesis capacity with [(18) F]DOPA, a measure of the activity of dopa decarboxylase, (2) DA release with studies measuring the impact of a DA releasing stimulant challenge on the binding of a D(2) receptor radiotracer, (3) D(2) baseline occupancy by DA, a measure of baseline intrasynaptic DA, assessed by the changes in binding of D(2) radiotracer induced by DA depletion, and (4) the DA and the vesicular monoamine transporters, to assess the integrity of presynaptic terminals. The relationship between DA release and D(2) receptor occupancy at baseline by DA has also been assessed in the same patients. Overall, these different imaging modalities have converged to show a dysregulation of presynaptic dopaminergic activity in schizophrenia, leading to excessive DA release in the striatum, particularly in the projection to the associative striatum, an area of integration between cognitive and limbic cortical inputs. Excessive striatal presynaptic DA is linked to the emergence of acute psychotic symptoms and to their response to treatment in schizophrenia. Understanding the etiology of this dysregulation and its consequences on the rest of the circuitry is important for future drug development.
[Show abstract][Hide abstract] ABSTRACT: Cannabis use is reported to increase the risk for psychosis, but no prospective study has longitudinally examined drug use and symptoms concurrently in clinical high risk cases.
We prospectively followed for up to 2 years 32 cases who met research criteria for prodromal psychosis to examine the relationship between substance use and clinical measures.
Cases with a baseline history of cannabis use (41%) were older, but did not differ in clinical measures. Longitudinal assessments showed these cases had significantly more perceptual disturbances and worse functioning during epochs of increased cannabis use that were unexplained by concurrent use of other drugs or medications.
These data demonstrate that cannabis use may be a risk factor for the exacerbation of subthreshold psychotic symptoms, specifically perceptual disturbances, in high risk cases.
Schizophrenia Research 10/2008; 106(2-3):286-93. DOI:10.1016/j.schres.2008.08.008 · 3.92 Impact Factor