Persecutory delusions: Effects of cognitive bias modification for interpretation and the Maudsley Review Training Programme on social anxiety, jumping to conclusions, belief inflexibility and paranoia

Background and objectives: The Threat Anticipation Model (Freeman, 2007) implicates social anxiety, jumping to conclusions (JTC) and belief inflexibility in persecutory delusions. We investigated whether Cognitive Bias Modification for Interpretation (CBM-I; Turner et al., 2011) improves social anxiety by targeting negative interpretation bias of ambiguous social information. We determined whether the Maudsley Review Training Programme (MRTP; Waller et al., 2011) improves JTC, belief inflexibility and paranoia. We also explored effects of CBM-I on JTC/belief inflexibility and paranoia, as well as the MRTP on social anxiety. Methods: Twelve participants from Early Intervention and Recovery Services in East Anglia completed measures of social anxiety, paranoia, JTC and belief inflexibility. A concurrent multiple baseline case series design was used. Results: Three of twelve participants improved in social anxiety following CBM-I, paranoia improved in 6/12 cases. CBM-I had no effect on JTC/belief inflexibility. The MRTP improved JTC and/or belief inflexibility in 9/12 cases, while improving paranoia for 6/12 individuals. The MRTP improved social anxiety in one case. Limitations: The small sample size and large effects necessary for single case series designs limit the generality of findings. These are discussed in more detail. Conclusions: This study suggests that whilst both CBM-I and the MRTP may have a positive impact on paranoia and social anxiety, the effects on JTC/belief inflexibility are largely specific to the MRTP. Relationships between social anxiety, JTC, belief inflexibility and paranoia existed in 10/12 individuals, supporting the Threat Anticipation Model

Biases in probabilistic category learning in relation to social anxiety.

Instrumental learning paradigms are rarely employed to investigate the mechanisms underlying acquired fear responses in social anxiety. Here, we adapted a probabilistic category learning paradigm to assess information processing biases as a function of the degree of social anxiety traits in a sample of healthy individuals without a diagnosis of social phobia. Participants were presented with three pairs of neutral faces with differing probabilistic accuracy contingencies (A/B: 80/20, C/D: 70/30, E/F: 60/40). Upon making their choice, negative and positive feedback was conveyed using angry and happy faces, respectively. The highly socially anxious group showed a strong tendency to be more accurate at learning the probability contingency associated with the most ambiguous stimulus pair (E/F: 60/40). Moreover, when pairing the most positively reinforced stimulus or the most negatively reinforced stimulus with all the other stimuli in a test phase, the highly socially anxious group avoided the most negatively reinforced stimulus significantly more than the control group. The results are discussed with reference to avoidance learning and hypersensitivity to negative socially evaluative information associated with social anxiety

Individual Differences in the Ability to Recognise Facial Identity Are Associated with Social Anxiety

Previous research has been concerned with the relationship between social anxiety and the recognition of face expression but the question of whether there is a relationship between social anxiety and the recognition of face identity has been neglected. Here, we report the first evidence that social anxiety is associated with recognition of face identity, across the population range of individual differences in recognition abilities. Results showed poorer face identity recognition (on the Cambridge Face Memory Test) was correlated with a small but significant increase in social anxiety (Social Interaction Anxiety Scale) but not general anxiety (State-Trait Anxiety Inventory). The correlation was also independent of general visual memory (Cambridge Car Memory Test) and IQ. Theoretically, the correlation could arise because correct identification of people, typically achieved via faces, is important for successful social interactions, extending evidence that individuals with clinical-level deficits in face identity recognition (prosopagnosia) often report social stress due to their inability to recognise others. Equally, the relationship could arise if social anxiety causes reduced exposure or attention to people's faces, and thus to poor development of face recognition mechanisms

Social Anxiety Modulates Subliminal Affective Priming

BACKGROUND: It is well established that there is anxiety-related variation between observers in the very earliest, pre-attentive stage of visual processing of images such as emotionally expressive faces, often leading to enhanced attention to threat in a variety of disorders and traits. Whether there is also variation in early-stage affective (i.e. valenced) responses resulting from such images, however, is not yet known. The present study used the subliminal affective priming paradigm to investigate whether people varying in trait social anxiety also differ in their affective responses to very briefly presented, emotionally expressive face images. METHODOLOGY/PRINCIPAL FINDINGS: Participants (n = 67) completed a subliminal affective priming task, in which briefly presented and smiling, neutral and angry faces were shown for 10 ms durations (below objective and subjective thresholds for visual discrimination), and immediately followed by a randomly selected Chinese character mask (2000 ms). Ratings of participants' liking for each Chinese character indicated the degree of valenced affective response made to the unseen emotive images. Participants' ratings of their liking for the Chinese characters were significantly influenced by the type of face image preceding them, with smiling faces generating more positive ratings than neutral and angry ones (F(2,128) = 3.107, p<0.05). Self-reported social anxiety was positively correlated with ratings of smiling relative to neutral-face primed characters (Pearson's r = .323, p<0.01). Individual variation in self-reported mood awareness was not associated with ratings. CONCLUSIONS: Trait social anxiety is associated with individual variation in affective responding, even in response to the earliest, pre-attentive stage of visual image processing. However, the fact that these priming effects are limited to smiling and not angry (i.e. threatening) images leads us to propose that the pre-attentive processes involved in generating the subliminal affective priming effect may be different from those that generate attentional biases in anxious individuals

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.