When to hold that thought: an experimental study showing reduced inhibition of pre-trained associations in schizophrenia.

Schizophrenia encompasses a wide variety of cognitive dysfunctions, a number of which can be understood as deficits of inhibition. To date, no research has examined 'conditioned inhibition' in schizophrenia--the ability of a stimulus that signals the absence of an expected outcome to counteract the conditioned response produced by a signal for that outcome (a conditioned excitor). A computer-based task was used to measure conditioned excitation and inhibition in the same discrimination procedure, in 25 patients with a confirmed diagnosis of schizophrenia and a community-based comparison sample. Conditioned inhibition was measured by a ratio score, which compared the degree to which the inhibitory stimulus and a neutral control stimulus reduced conditioned responding to the excitatory cue: the lower the ratio, the greater the inhibitory learning. At test the ratios were 0.45 and 0.39 for patient and control groups respectively, and the relevant interaction term of the ANOVA confirmed that the degree of inhibition was reduced in the patient group, with an effect size of r = 0.28.These results demonstrate for the first time that inhibitory learning is impaired in schizophrenia. Such an impairment provides an attractive framework for the interpretation of the positive symptoms of schizophrenia. However, we were unable to demonstrate any relationship between the level of conditioned inhibition and medication. Similarly, in the present study it must be emphasised that the available data did not demonstrate any relationship between individual variation in inhibitory learning and the level of positive symptoms as measured by the PANSS. In fact inhibitory learning impairment was relatively greater in participants with a predominantly negative symptom profile and their excitatory learning was also reduced. Accordingly the next step will be to investigate such relationships in a larger sample with a priori defined sub-groups displaying predominantly positive versus predominantly negative symptoms