SU34. A Systematic Review of Behavioral Research and Lesion Evidence for the 2-Factor Theory of Monothematic Delusions

摘要

>Background: Two-factor theory (TFT) posits monothematic delusion formation requires damage producing delusion content (factor 1) and a deficit in belief evaluation (factor 2, posited to be localized in right frontal cortex). The purpose of the current study was 2-fold: (1) to review the behavioral data supporting TFT and (2) to assess whether locations of delusion-inducing lesions were consistent with TFT predictions: ie, common factor 1 damage within a particular monothematic delusion and common factor 2 damage across delusions. Furthermore, factor 2 damage ought to distinguish Capgras syndrome (the delusion that a previously familiar person is an imposter) from nondelusional-affective agnosia (unfamiliarity without delusion). >Methods: We reviewed all papers concerned with TFT and all studies of galvanic skin response (GSR) in monothematic delusions (frequently cited as behavioral evidence for TFT). Next, we reviewed case reports of lesion-induced monothematic delusions including Capgras, Fregoli, Cotard, and somatoparaphrenia, as well as affective agnosia. We report lesion location frequencies in 12 regions of interest. >Results: We found 27 articles on TFT. Only 3 contained empirical evidence (11%, all hypnosis studies): one had no direct hypothesis regarding TFT, one was inconclusive, and another failed to support TFT. We found 7 additional GSR studies of Capgras, 6 of which reported statistically significant abnormal GSR, but no effects were specific to the familiar person accused of being an imposter. One neuroimaging case study of Capgras did find fMRI correlates of perceiving the imposter in the left hemisphere. One study of somatoparaphrenia reported a GSR deficit to noxious stimuli approaching the denied limb. There were no published studies testing TFT predictions about Cotard or Fregoli. We analyzed 46 reports of lesion-induced delusions and 20 cases of affective agnosia. Right hemisphere damage was most common in monothematic delusion cases (χ²(1, N = 46) = 40.09, P < .0001). Within the right hemisphere, frontal and temporal damage were most common (46% of cases had damage in these regions). The patterns of regional codamage were not consistent within delusion contents (as factor 1 would demand). Contrary to TFT, affective agnosia was associated with bilateral frontal damage more frequently than Capgras delusion (P < .005), which calls into question a right frontal locus for factor 2. >Conclusion: Overall, this study found no strong hypothesis-driven support of TFT. GSR findings often failed to account for the specificity of delusional content and no common pattern of brain damage for factor 2 emerged. However, the anatomical analysis was coarse (by dint of the data available in the case reports), and diaschesis effects (wherein damage in one region effects function of a distant region) are also potentially important.