乌鸦传媒

CAMBRIDGE, England, May 8 -- The lack of motivation characteristic of schizophrenia and other psychoses may not be a result of long-term treatment or institutionalization, researchers here suggested.

In fact, it appears that the deficits in motivation are present the first time patients are seen with a first episode of psychosis, Graham Murray, M.D., Ph.D., of the University of Cambridge, and colleagues, reported in a small study online in BMC Psychiatry.

On a test of reaction time designed to measure motivation, only four of 18 patients with a first episode of psychosis improved their time in response to a greater likelihood of reward -- called reinforcement-related speeding -- compared with 17 of 19 healthy controls from the general population (P=0.00004).

Use of atypical antipsychotic medications and differences in attentional or executive function had no effect on the results, the researchers said.

"Patients with psychosis already have motivational deficits the first time they present to health services," Dr. Murray said in a statement. "Understanding the brain basis of these problems will ultimately help in developing new treatments."

It has been proposed that there are abnormalities in the brain's reward system and in the processing of incentive motivation in psychosis, and that dopamine dysfunction may be responsible, but this has not been well evaluated clinically, the researchers said.

So the investigators recruited 18 patients (mean age 23, nine males) who had symptoms of psychosis for the first time and 19 healthy controls (mean age 25, nine males) to complete the Cued Reinforcement Reaction Time Task, which measures motivationally driven behavior.

Eleven of the 18 psychosis patients were taking atypical antipsychotics, including olanzapine (Zyprexa) (three), risperidone (Risperdal) (two), quetiapine (Seroquel) (two), clozapine (Clozaril) (one), aripiprazole (Abilify) (two), and amisulpride (one).

A year after the evaluation, nine patients were diagnosed by a psychiatrist with schizophrenia, two with schizoaffective disorder, five with bipolar disorder, one with delusional disorder, and one with a psychosis not otherwise specified.

On the task, all participants were asked to choose which of a simple set of three shapes did not belong in 96 trials, with varying likelihood of reward indicated by three different colors as the test progressed. Previous studies in healthy participants have shown increased reaction times associated with a higher likelihood of reward, the researchers said.

Although psychosis patients did not respond to the task as well as the controls, both groups were equally likely to correctly identify the color associated with the greatest likelihood of reward (P=0.89).

"As such, there was a disconnection between their awareness of the environment, and their ability to modulate their behavior in accordance with that knowledge," the researchers said. "This supports the theory that patients with early psychosis show deficits in incentive motivation."

Additionally, the researchers assessed attentional and executive function in the participants using the Cambridge Neuropsychological Test Automated Battery.

Psychosis patients were impaired only in spatial working memory.

"However," the researchers said, "patients' spatial working memory deficits did not relate to their performance on the [Cued Reinforcement Reaction Time Task], indicating that the incentive motivation abnormalities we observed were not confounded by the patients' cognitive deficits."

They acknowledged that the study was limited by the small size and the fact that some of the patients were taking antipsychotic medication, which my have affected the results.

Nevertheless, on the basis of these results and those of past studies, they suggested that the impaired ability to change behavior in response to incentive "may be secondary to dopamine dysfunction, though we acknowledge that, as yet, no direct evidence has proved that performance on the [Cued Reinforcement Reaction Time Task] is dopamine dependent."

They concluded, "Future studies should examine whether incentive motivation deficits in psychosis are sensitive to pharmacological, especially dopaminergic, modulation."

One of Dr. Murray's co-authors is an employee of and two others have been consultants for Cambridge Cognition, which supplies the Cambridge Neuropsychological Test Automated Battery.

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