S77. ANHEDONIA IN NON-PSYCHOTIC INDIVIDUALS IS ASSOCIATED WITH DIMINISHED FEAR GENERALIZATION

Generalization from previous experiences allows us to evaluate the affective value of novel events. In a previous study, we found that negative symptoms disrupt this ability in schizophrenia. A core negative symptom is an inability to anticipate pleasure (anticipatory anhedonia). Here, in a functional MRI experiment, we examined whether the generalization of conditioned fear responses is affected by the ability to anticipate pleasure in non-psychotic individuals. 72 non-psychotic young adults with a range of subthreshold symptoms of psychopathology underwent a functional MRI scan while participating in a Pavlovian fear conditioning and generalization paradigm. Skin conductance responses were measured throughout the experiment. During the conditioning phase, one face was used as a conditioned stimulus and paired with an electrical shock (the CS+), whereas a different face was used as a neutral stimulus that was never paired with a shock (the CS-). For the generalization phase, eight stimuli that gradually morphed from the CS+ to the CS- were selected based on each individual’s ability to discriminate the two faces. Immediately after the experiment, subjects were asked to rate how likely each stimulus was followed by the shock (explicit shock likelihood ratings). The Temporal Experience of Pleasure Scale was used to measure the ability to experience and anticipate pleasure. We hypothesized that subjects with a diminished ability to anticipate pleasure would show lower levels of fear generalization. Across the full cohort, we observed typical (CS+ and CS+-like morphs > CS-) generalization gradients in the explicit ratings, skin conductance responses, and the BOLD responses of the anterior insula and dorsal anterior cingulate cortex. The reversed pattern of responses (CS- > CS+ and CS+ like morphs) was observed in the posterior cingulate cortex and angular gyrus. The caudate nucleus showed highest responses to the most ambiguous morphs. Individuals with a diminished ability to anticipate pleasure showed lower generalization (as reflected by their explicit ratings) and the ability to anticipate pleasure correlated negatively with responses of the caudate nucleus to ambiguous morphs. Non-psychotic individuals with a reduced ability to experience anticipatory pleasure show impairments in the generalization of conditioned fear. This finding parallels a similar, prior finding in schizophrenia patients with prominent negative symptoms. These results suggest that impairment in fear generalization may be linked to the pathophysiology of negative symptoms, even prior to the onset of psychotic illness. The study was supported by the grant 4R01MH095904.

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