Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. To address this issue, we pooled data from four independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) to stimuli that were paired (the CS + ) or not paired (CS−) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS + vs. CS− SCRs) and responses to CS + and CS− separately were assessed. We found that acquisition of differential conditioned fear responses was significantly lower in individuals with schizophrenia than in healthy controls (Cohen’s d = 0.53). This effect was primarily related to a significantly higher response to the CS− stimulus in the schizophrenia compared to the control group. Moreover, the magnitude of this response to the CS− in the schizophrenia group was correlated with the severity of delusional ideation (p = 0.006). Other symptoms or antipsychotic dose were not associated with fear conditioning measures. In conclusion, individuals with schizophrenia who endorse delusional beliefs may be over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of abnormal associative learning in psychosis.
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The collection of the original data was funded by the National Institute of Mental Health (K23 MH076054 (DJH), K24 MH002025 (DCG), R01 MH095904 (DJH)), EU_117 grant from the Translational Medicine Research Collaboration (JH), the National Alliance for Research on Depression and Schizophrenia with the Sidney R. Baer Jr Foundation (DJH). The funding agencies had no role in the design of the studies, in the data collection, analyses, interpretation, writing of the paper, nor in the decision to submit the paper for publication. All views expressed here are those of the authors.
The authors declare no competing interests.
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Tuominen, L., Romaniuk, L., Milad, M.R. et al. Impairment in acquisition of conditioned fear in schizophrenia. Neuropsychopharmacol. 47, 681–686 (2022). https://doi.org/10.1038/s41386-021-01193-1