Faculty Bibliography

Cocaine intoxication and acute abstinence alter brain dopaminergic functioning, resulting in behavioral changes closely mimicking the positive and negative symptoms of schizophrenia. In emergency room settings, recent cocaine abuse can be mistaken for schizophrenia and may cause inappropriate diagnosis and in some instances medical mismanagement. Schizophrenia patients presenting with recent cocaine abuse may also present with significant diagnostic and treatment dilemmas. This study attempts to distinguish between cocaine and schizophrenic psychosis by examining patients who present with both recent cocaine abuse and acute schizophrenia (CA+SZ), cocaine intoxication without schizophrenic illness (CA), and acute schizophrenia with no comorbid substance abuse (SZ) within the first 24 hours after arrival at the Bellevue psychiatric emergency service. Clinical assessment included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Positive Symptoms, and the Schedule for the Assessment of Negative Symptoms. Both cocaine abusing groups were required to have positive urine toxicology screens for inclusion in the study. Multivariate analysis of variance showed the CA+SZ patients present with a clinical profile that overlaps with CA patients on mood and negative symptom dimensions and overlaps with SZ patients on most positive symptoms. CA+SZ patients differed from both groups, however, by presenting with significantly more hallucinatory experiences than cocaine abusing or schizophrenia patient counterparts. Despite considerable overlap, each group of patients presented with a discernible cross-sectional symptom pattern

OBJECTIVE: The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. METHOD: Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. RESULTS: The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. CONCLUSIONS: The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques

Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, i.v. infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function

A 33-year-old man presented with a 10-year history of psychosis and an imaginary companion; he carried a past diagnosis of chronic schizophrenia. He responded quickly to neuroleptic and was noted to be an easily engageable person. It is argued that despite his first-rank Schneiderian symptoms, the patient may not best be conceptualized as having schizophrenia. Specific treatment recommendations are made, predicated on this man's developmental history, his attachment and separation behavior, and his response to a structured social milieu.

Positron emission tomography and the fluorodeoxyglucose method were used to measure regional brain metabolism before and 2 h after haloperidol (5 mg, i.m.) in 11 young normal men. These data were compared with measures obtained from nine previously studied normal men who had received no drug intervention. Although a previously published study had demonstrated significantly decreased metabolism in whole brain, neocortex, limbic cortex, thalamus, and caudate nucleus 12 h after a 5-mg dose of haloperidol, the present 2-h study did not show significant metabolic changes despite the fact that significant extrapyramidal effects occurred. Taken together, these studies demonstrate differences in the temporal organization of behavioral and metabolic responses to haloperidol challenge