Background:
Ketamine is used acutely as a model of schizophrenia. It has been suggested that chronic ketamine use may also mimic aspects of this disorder, in particular cognitive function. Semantic processing deficits are considered to be central to cognitive impairments in schizophrenia and are related to thought disorder. This study aimed to characterize semantic impairments following both acute and chronic ketamine.
Methods:
We examined the acute effects of ketamine using a double-blind, placebo-controlled, independent groups design with 48 volunteers examining the effects of two doses of ketamine (100 ng/ml and 200 ng/ml). The chronic effects of ketamine were explored with 32 volunteers, 16 regular ketamine users and 16 matched polydrug controls. Semantic processing was examined using a lexical-decision semantic priming task with a frequency (high and low) and stimulus onset asynchrony (SOA; short – 200 ms, long – 750 ms) manipulation. Schizophrenic and dissociative symptoms were also examined.
Results:
Acute ketamine produced a dose-dependent reduction in priming (hypopriming) and increased schizophrenic thought disorder. Ketamine users showed impaired priming for low-frequency words at the long SOA compared with polydrug controls, and there was some evidence of increased priming for high-frequency words. Ketamine users did not differ from controls in schizophrenic-like or dissociative symptoms.
Discussion:
The dose-dependent hypopriming effect at the long SOA induced by acute ketamine was indicative of controlled processing impairments. In ket-amine users, there was also an indication of controlled processing impairments and a suggestion that longterm ketamine abuse results in damage to the semantic store.
