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.

The convergence of neuropsychological testing and clinical ratings of cognitive impairment in patients with schizophrenia.

This study examined the relationship between clinical rating of cognitive symptoms and performance on neuropsychological tests in acute and chronic samples of patients with schizophrenia. Two separate studies examined patients who varied widely in their lifetime functional outcome, including 263 elderly poor-outcome inpatients and 20 acutely admitted patients. In the first study, six cognitive performance measures were collected, and in the second study, five different measures were collected. Correlations with different symptom models of cognitive and negative symptoms were examined. In both samples, cognitive symptoms were never more highly correlated with cognitive test performance than with negative symptoms. When cognitive and negative symptom ratings were combined, they never accounted for as much as half of the variance in performance on the cognitive tests in both samples. These data suggest that clinical assessment of symptoms is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia. These results may also be specific to the clinical rating scale used, the Positive and Negative Syndrome Scale (PANSS).

Neurocognitive functioning in recently abstinent, cocaine-abusing schizophrenic patients.

PURPOSE: This report examined a broad range of cognitive functioning in a group of recently abstinent, cocaine-abusing schizophrenic patients (CA + SZ). METHODS: Measures of selective and sustained attention, learning and memory, and executive functioning were administered to CA + SZ patients within 72 h of last cocaine use. A comparison group of non-substance-abusing schizophrenic patients (SZ) presenting for inpatient psychiatric treatment were also examined in an identical time frame. We hypothesized that the neurobiological impact of cocaine abuse and acute abstinence would cause CA + SZ to manifest deficits in all domains of cognitive functioning relative to non-abusing SZ patients. RESULTS: Results revealed that CA + SZ displayed significant memory impairment relative to their non-abuser SZ counterparts. No group differences, however, were detected on any other neurocognitive measure. CA + SZ were able to selectively process digit strings during the presence and absence of distracting stimuli, sustain attention, and perform executive functions at performance levels equal to their non-abuser SZ counterparts. IMPLICATIONS: These results are consistent with many past studies that have found CA + SZ patients to manifest memory impairment but have relatively well preserved functioning in other cognitive domains. The results are discussed in terms of the biological concomitants of cocaine abuse and acute abstinence in schizophrenia.