Deficits in striatal dopamine release in cannabis dependence.

Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbid conditions, including nicotine use. Eleven CD and 12 healthy controls (HC) completed two positron emission tomography scans with [11C]-(+)-PHNO, before and after oral administration of d-amphetamine. CD stayed inpatient for 5-7 days prior to the scans to standardize abstinence. Magnetic resonance spectroscopy (MRS) measures of glutamate in the striatum and hippocampus were obtained in the same subjects. Percent change in [11C]-(+)-PHNO-binding potential (ΔBPND) was compared between groups and correlations with MRS glutamate, subclinical psychopathological and neurocognitive parameters were examined. CD had significantly lower ΔBPND in the striatum (P=0.002, effect size (ES)=1.48), including the associative striatum (P=0.003, ES=1.39), sensorimotor striatum (P=0.003, ES=1.41) and the pallidus (P=0.012, ES=1.16). Lower dopamine release in the associative striatum correlated with inattention and negative symptoms in CD, and with poorer working memory and probabilistic category learning performance in both CD and HC. No relationships to MRS glutamate and amphetamine-induced subclinical positive symptoms were detected. In conclusion, this study provides evidence that severe cannabis dependence-without the confounds of any comorbidity-is associated with a deficit in striatal dopamine release. This deficit extends to other extrastriatal areas and predicts subclinical psychopathology.

Convergent validity and neuropsychological correlates of the schedule for the assessment of negative symptoms (SANS) attention subscale.

Cognitive deficits have come to be viewed as a hallmark feature of schizophrenic illness. Although laboratory based assessment of patients' cognitive deficits has been well investigated, few studies to date have examined the utility of clinical ratings of cognitive symptoms using the Schedule for the Assessment of Negative Symptoms (SANS) attention subscale. In this report, we examined the convergence between clinical ratings of cognitive impairment using the SANS attention subscale and performance on a variety of neurocognitive tests designed to measure attentional impairment, as well as other cognitive constructs such as working memory and executive functioning. A total of 56 acute schizophrenic inpatients were clinically rated with the SANS and completed the Continuous Performance Test, Digit Span Distraction Test, Wisconsin Card Sorting Task, and the Trailmaking Test. A series of correlational and regression analyses were conducted to test the concurrent and discriminant validity of the SANS attention subscale. Performance measures of attention, but not working memory or executive functioning, were significantly correlated with and moderately predicted the severity of SANS rated inattention. Additionally, the attention subscale was discriminated from the other SANS negative symptom subscales in predicting a laboratory measure of attentional functioning. The SANS attention subscale demonstrated both concurrent and discriminant validity. These data indicate that attentional dysfunction in schizophrenia can be meaningfully rated and interpreted using the SANS.