The Effects of Atypical Antipsychotics on Implicit Reward Learning in Schizophrenia

Abstract

Implicit (or non-conscious) reward learning, which is necessary for healthy cognitive, emotional, and social functioning, is often impaired in schizophrenia. However, few studies have examined this type of learning in first-episode patients, and almost none have used unmedicated samples. Therefore, it remains unclear if implicit reward learning is spared or impaired in schizophrenia, and whether the first-line medications used to treat the disorder (i.e., atypical antipsychotics) enhance, depress, or have no appreciable effect on this ability. Implicit reward learning performance was measured in three groups (controls [N = 19]; unmedicated [N = 26] and medicated [N = 21] first-episode schizophrenia patients) using the Weather Prediction Task (WPT) and Iowa Gambling Task (IGT). These tasks were administered at two different testing sessions (i.e., time 1 and time 2), at least one month apart. All medicated patients who entered the study were being treated with the following atypicals: olanzapine (N = 11), quetiapine (N = 3), risperidone (N = 3), or a combination (N = 4). After the initial assessment, unmedicated patients were randomly prescribed one of these three medications and re-tested after therapeutic doses had been established. At time 1, unmedicated patients performed as well as controls on the WPT and IGT, whereas the atypicals medication group showed impairment. Controls demonstrated improvement on both tasks from time 1 to time 2. In contrast, unmedicated patients failed to improve on either test after being treated with atypicals (olanzapine [N = 9]; quetiapine [N = 2], risperidone [N = 1]). In addition, a significant inverse correlation was found between WPT performance and severity of negative symptoms among medicated patients. Results suggest that implicit reward learning is preserved in schizophrenia and impaired by treatment with olanzapine and other atypicals. These findings have important clinical implications. The benefits of atypical antipsychotic treatment, such as possible relief from delusions and hallucinations and improvement in mood and select cognitive abilities, must be balanced against potentially adverse effects, such as life-threatening cardiometabolic syndromes and reward learning deficits. The latter are associated with the negative and cognitive symptoms of schizophrenia, which cause greater functional impairment than positive symptoms. Therefore, it is important to carefully consider the effects of various antipsychotics on implicit reward learning when designing a treatment plan for schizophrenia.