Objective: This study sought to determine whether thought disorder induced in healthy volunteers by the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine resembles the thought disorder found in patients with schizophrenia. Method: The Scale for the Assessment of Thought, Language, and Communication was used to assess thought disorder in healthy volunteers (N=10) who received subanesthetic doses of ketamine and in a group of clinically stable inpatients with schizophrenia (N=15) who did not receive ketamine. Results: Mean scores on the Scale for the Assessment of Thought, Language, and Communication for patients with schizophrenia and healthy volunteers receiving ketamine did not differ significantly. Moreover, three of the four highest rated test items in both groups were the same. Conclusions: These data suggest that ketamine-induced thought disorder in healthy volunteers is not dissimilar to the thought disorder in patients with schizophrenia and provide support for the involvement of the NMDA receptor in a cardinal symptom of schizophrenia. (Am J Psychiatry 1999; 156:1646-1649) Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartic acid (NMDA) receptor is involved in the pathophysiology of schizophrenia. Postmortem studies have revealed a lower density of glutamatergic receptors in patients with schizophrenia, and one study of CSF reported lower levels of glutamate in patients with schizophrenia than in healthy comparison subjects (1-3). The most compelling evidence is provided by the psychotomimetic effects of the NMDA antagonists phencyclidine (PCP) and ketamine. In patients with schizophrenia, the administration of PCP and ketamine exacerbates existing psychotic symptoms and may reactivate symptoms in remittance (4-6). The administration of PCP or ketamine to healthy volunteers reproduces many of the symptoms of schizophrenia, including aspects of formal thought disorder (4, 7, 8). Because the effects of ketamine resemble many of the clinical features of schizophrenia, this ketamine-induced behavioral syndrome has been proposed as a model for schizophrenia. Nonetheless, few direct comparisons between the thought disorder of schizophrenia and the thought disorder induced by NMDA antagonists have been conducted. Ketamine-induced thought disorder has been primarily assessed with the Brief Psychiatric Rating Scale (BPRS) (9). We have found that the BPRS conceptual disorganization item is significantly affected by the administration of ketamine (7). Krystal et al. (8) also reported a marked ketamine effect on the thought disturbance factor of the BPRS, which contains the conceptual disorganization item. Many elements of formal thought disorder, however, are poorly measured by the BPRS. Recently, we found that the administration of ketamine to healthy volunteers significantly increases scores on the Scale for the Assessment of Thought, Language, and Communication (10). The Scale for the Assessment of Thought, Language, and Communication is a clinical, interview-based assessment of thought disorder (11) that has been used to assess thought disorder in studies of several psychiatric diagnoses and conditions (12-17). The Scale for the Assessment of Thought, Language, and Communication provides a more comprehensive evaluation of thought disorder than does the BPRS and permits an examination of subfactors (18) that address aspects of thought disorder. In this study, we used the Scale for the Assessment of Thought, Language, and Communication to compare
However, common clinical symptom assessment instruments or scales, such as Brief Psychiatric Rating Scale (BPRS) poorly capture many elements of FTD REF .
Comparison of Ketamine-Induced Thought Disorder in Healthy Volunteers and Thought Disorder in Schizophrenia
The American journal of psychiatry
The American journal of psychiatry
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