Ryan P. Balzan

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

Over-adjustment or miscomprehension? A re-examination of the jumping to conclusions bias.

Objective: Previous research has consistently shown that individuals with delusions typically exhibit a jumping to conclusions (JTC) bias when administered the probabilistic reasoning ‘beads task’ (i.e. decisions made with limited evidence or ‘premature decisions’ and decisions over-adjusted in light of disconfirming evidence or ‘over-adjustment’). More recent work, however, also suggests that these effects may also be influenced by miscomprehension of the task. The current paper is an investigation into the contributing effects of miscomprehension on the JTC bias. Method: A total of 75 participants (25 diagnosed with schizophrenia with a history of delusions; 25 non-clinical delusion-prone; 25 non-delusion-prone controls) completed two identical versions of the beads task, distinct only by the inclusion of an extra instructional set designed to increase comprehension. Results: Qualitative data confirmed that miscomprehension is a valid construct, and the results showed that the addition of an instructional set to the second version of the task led to greater comprehension and a statistically significant drop in ‘over-adjustment’. Nevertheless, both tasks showed that ‘premature decisions’ were significantly more prevalent in the schizophrenia group and were unaffected by the intervention. Conclusions: It was concluded that the ‘premature decisions’ component of the JTC bias remains a feature of decision-making in schizophrenia, but that previously reported ‘over-adjustment’ effects are likely to be influenced by miscomprehension of the beads task instructional set. These findings are discussed in light of the recently proposed ‘hypersalience of evidence-hypothesis matches’ account of the JTC bias.

Metacognitive training for patients with schizophrenia: Preliminary evidence for a targeted, single-module programme

Objective: Metacognitive training is an eight-module, group-based treatment programme for people with schizophrenia that targets the cognitive biases (i.e. problematic thinking styles) thought to contribute to the genesis and maintenance of delusions. The present article is an investigation into the efficacy of a shorter, more targeted, single-module metacognitive training programme, administered individually, which focuses specifically on improving cognitive biases that are thought to be driven by a ‘hypersalience of evidence-hypothesis matches’ mechanism (e.g. jumping to conclusions, belief inflexibility, reasoning heuristics, illusions of control). It was hypothesised that a more targeted metacognitive training module could still improve performance on these bias tasks and reduce delusional ideation, while improving insight and quality of life. Method: A sample of 28 patients diagnosed with schizophrenia and mild delusions either participated in the hour-long, single-session, targeted metacognitive training programme (n = 14), or continued treatment as usual (n = 14). All patients were assessed using clinical measures gauging overall positive symptomology, delusional ideation, quality of life and insight, and completed two cognitive bias tasks designed to elucidate the representativeness and illusion of control biases. Results: After a 2-week, post-treatment interval, targeted metacognitive training patients exhibited significant decreases in delusional severity and conviction, significantly improved clinical insight, and significant improvements on the cognitive bias tasks, relative to the treatment-as-usual controls. Performance improvements on the cognitive bias tasks significantly correlated with the observed reductions in overall positive symptomology. Patients also evaluated the training positively. Conclusions: Although interpretations of these results are limited due to the lack of an optimally designed, randomised controlled trial and a small sample size, the results are promising and warrant further investigation into targeted versions of the metacognitive training programme.

Confirmation biases across the psychosis continuum: The contribution of hypersalient evidence-hypothesis matches

OBJECTIVES Hypersalience of evidence-hypothesis matches has recently been proposed as the cognitive mechanism responsible for the cognitive biases, which, in turn, may contribute to the formation and maintenance of delusions. However, supporting evidence for this construct is still required. Using two tasks designed to elicit three core facets of the confirmation bias (i.e., biased search of confirming evidence; biased interpretation of confirming evidence; and biased recall of confirming evidence), this article investigated the possibility that individuals with delusions and those identified as delusion-prone are hypersalient to evidence-hypothesis matches. METHODS A total of 75 participants (25 diagnosed with schizophrenia with a history of delusions; 25 non-clinical delusion-prone; 25 non-delusion-prone controls) completed both tasks. RESULTS The results across both tasks showed that participants with schizophrenia and delusion-prone participants prefer: non-diagnostic or non-specific positive tests over diagnostic negative tests (biased search); rate confirming evidence as more important than disconfirming evidence (biased interpretation); and remember confirming evidence with greater ease than disconfirming evidence (biased recall). Participants with higher delusional ideation also failed to integrate disconfirmatory evidence to modify prior hypotheses. CONCLUSIONS These results suggest that delusional ideation is linked to a hypersalience of evidence-hypothesis matches. The theoretical implications of this cognitive mechanism on the formation and maintenance of delusions are discussed.

Metacognitive training (MCT) for schizophrenia improves cognitive insight: A randomized controlled trial in a Chinese sample with schizophrenia spectrum disorders

Metacognitive training (MCT) is a group-based treatment program for people with schizophrenia that targets the cognitive biases thought to contribute to the pathogenesis and maintenance of delusions. Although effective in reducing the severity of delusions, the influence of MCT on cognitive insight, and its feasibility in Chinese culture, has yet to be investigated. The present randomized-controlled trial attempted to address these inconsistencies. A Chinese sample of 80 participants with schizophrenia spectrum disorders was randomized to the eight-module MCT program or continued treatment as usual (TAU). All participants were assessed using the Beck Cognitive Insight Scale, which assesses two components of cognitive insight (self-reflectiveness and self-certainty). Participants in the MCT condition subjectively rated their satisfaction with the training. Retention rates were high after four-weeks of MCT (n = 38) or TAU (n = 39). Clients randomized into the MCT condition rated the program favourably and showed significant improvements in cognitive insight (i.e., increased self-reflectiveness), relative to TAU controls, who exhibited decreases in cognitive insight at follow-up. These findings suggest that the MCT program is not only subjectively efficacious in Chinese samples, but also improves metacognitive awareness of the processes underlying delusional symptoms.

Illusory correlations and control across the psychosis continuum: the contribution of hypersalient evidence-hypothesis matches

Abstract It has recently been proposed that individuals with delusions may be hypersalient to evidence-hypothesis matches, which may contribute to the formation and the maintenance of delusions. However, empirical support for the construct is limited. Using cognitive tasks designed to elicit the illusory correlation bias (i.e., perception of a correlation in which none actually exists) and the illusion of control bias (i.e., overestimation of one’s personal influence over an outcome), the current article investigates the possibility that individuals with delusions are hypersalient to evidence-hypothesis matches. It was hypothesized that this hypersalience may increase a person’s propensity to rely on such illusory correlations and estimates of control. A total of 75 participants (25 participants diagnosed with schizophrenia with a history of delusions, 25 nonclinical participants with delusion proneness, and 25 controls without delusion proneness) completed computerized versions of the “fertilizer” illusory correlation task developed by Kao and Wasserman (J Exp Psychol Learn Mem Cogn 19:1363–1386; 1993) and the “light-onset” illusion of control task created by Alloy and Abramson (J Exp Psychol Gen 108:441–485; 1979). The results across both tasks showed that the participants with schizophrenia were more susceptible than the nonclinical groups to illusory correlations (i.e., higher estimates of covariation between unrelated events) and illusions of control (i.e., higher estimates of control and perceived connection between the responses and the outcome). These results suggest that delusional ideation is linked to a hypersalience of evidence-hypothesis matches. The theoretical implications of this cognitive mechanism on the formation and the maintenance of delusions are discussed.

Cognitive subtypes of schizophrenia characterized by differential brain volumetric reductions and cognitive decline

Importance Cognitively distinct subgroups of schizophrenia have been defined based on premorbid and current IQ, but little is known about the neuroanatomical differences among these cognitive subgroups. Objectives To confirm previous findings related to IQ-based subgroups of patients with schizophrenia in an independent sample and extend those findings to determine the extent to which brain volumetric differences correspond to the IQ-based subgroups. Design, Setting, and Participants A total of 183 participants were assessed at the outpatient settings of Neuroscience Research Australia and Lyell McEwin Hospital from September 22, 2009, to August 1, 2012. Patients were classified using cluster analysis on the basis of current and premorbid IQ differences. Regional magnetic resonance imaging (MRI) brain volumes were compared among the IQ-based subgroups using analysis of covariance with intracranial volume and age as covariates. Main Outcomes and Measures Wechsler Adult Intelligence Scale, third edition, scores; Wechsler Test of Adult Reading scores; Positive and Negative Syndrome Scale scores; and MRI brain volumes. Results Ninety-six outpatients (mean [SD] age, 35.7 [8.4] years; age range, 18-51 years; 59 men) with schizophrenia or schizoaffective disorder and 87 healthy controls (mean [SD] age, 31.9 [8.4] years; age range, 20-50 years; 46 men) were studied. Sixty-two patients and 67 healthy controls underwent structural MRI of the brain. Cluster analyses revealed 25 putatively preserved patients (26%), 33 moderately deteriorated patients (34%), 27 severely deteriorated patients (28%), and 11 compromised patients (12%). Negative symptom scores were significantly worse in the severely deteriorated group relative to the putatively preserved group (F2,82 = 13.8, P < .001, effect size [ES] = 1.40). Patient subgroups analyzed revealed significantly reduced inferior parietal volume relative to controls (F3,113 = 9.7, P < .001, ES = 0.85-1.24). The severely deteriorated group had significantly reduced total hippocampal (mean [SEM], 8309.6 [175.0] vs 9024.0 [145.5]; P = .01), lingual gyrus (mean [SEM], 11 996.0 [531.5] vs 13 838.1 [441.9]; P = .05), and superior temporal sulcus (mean [SEM], 4697.8 [192.0] vs 5446.0 [159.6]; P = .05) gray matter volumes relative to the putatively preserved group (ES = 0.91-1.10). Conclusions and Relevance Using an independent sample, we obtained proportions in each IQ-based subgroup that were similar to our previous work. Inferior parietal volume reduction was characteristic of schizophrenia relative to controls, and the severely deteriorated IQ group had widespread volumetric reductions. Classifying cognitive heterogeneity in schizophrenia provides a platform to better characterize the neurobiological underpinnings of the illness and its treatment.

Overconfidence in psychosis: The foundation of delusional conviction?

Abstract A number of recent studies have identified an “overconfidence effect” in psychosis, whereby people with schizophrenia are overconfident in errors while simultaneously slightly underconfident when accurate. This effect may have implications for why delusions, which are based on inaccurate inferences, perceptions and judgements, are typically held with high conviction. Given the importance the overconfidence effect may have in accounting for delusional conviction, the current narrative review aims to summarise and critique the recent evidence for the effect within schizophrenia. People with schizophrenia were consistently found to be overconfident in errors and slightly underconfident in correct appraisals, and this effect appears not to be an artefact of poor task performance. While the overconfidence effect has been linked to delusion-proneness in the general population, there was less direct evidence linking overconfidence to delusional symptoms in clinical populations. Future studies need to adopt longitudinal designs and include additional measures of overconfidence to investigate this association more appropriately, and to also investigate possible mediators of this postulated relationship, such as dopaminergic activity.

The Benefits of Doubt: Cognitive Bias Correction Reduces Hasty Decision-Making in Schizophrenia

Many patients with schizophrenia display neuropsychological deficits in concert with cognitive biases, particularly the tendency to jump to conclusions (JTC). The present study examined the effects of a generic psychoeducational cognitive bias correction (CBC) program. We hypothesized that demonstrating the fallibility of human cognition to patients would diminish their susceptibility to the JTC bias. A total of 70 participants with schizophrenia were recruited online. At baseline, patients were asked to fill out a JTC task (primary outcome) and the Paranoia Checklist before being randomized to either the CBC or a waitlist control condition. The CBC group received six successive pdf-converted PowerPoint presentations teaching them about cognitive biases; we neither placed any emphasis on psychosis-related cognitive distortions nor addressed psychosis. Six weeks after inclusion, subjects were re-administered the JTC task and the Paranoia Checklist. At a medium-to-large effect size the JTC bias was significantly improved under the CBC condition in comparison to controls for both the per protocol and the intention to treat analysis. The Paranoia Checklist remained essentially unchanged over time. No effects were observed for depression. Psychoeducational and cognitive programs are urgently needed as many patients are still deprived of any psychological treatment despite recommendations of most guidelines. Self-help may bridge the large treatment gap in schizophrenia and motivate patients to seek help. The study asserts both the feasibility and effectiveness of self-help programs in schizophrenia.

Metacognitive therapy (MCT+) in patients with psychosis not receiving antipsychotic medication: A case study

Background: Psychotherapies for psychosis typically aim to develop an awareness of the implausible content of a delusion or target the underlying cognitive biases (i.e., problematic thinking styles, such as hasty decisions and illusory control) that foster and maintain delusional beliefs. A recently designed individual-based treatment entitled metacognitive therapy (MCT+) combines these two approaches. Emerging evidence suggests individualized MCT+, when used concurrently with antipsychotic medication, may be an effective psychological treatment for reducing delusional symptoms. However, it remains to be tested whether MCT+ can be effective in patients with active delusions who are not currently receiving psychotropic drugs. Method: We present two cases (one patient with schizophrenia and the other with delusional disorder) experiencing active delusions who underwent 4-weeks of intensive MCT+, without concurrent antipsychotic medication (minimum 6-months unmedicated). Baseline and 6-week follow-up data are presented on a variety of measures assessing delusion symptom severity (i.e., PANSS, PSYRATS, SAPS), clinical insight, and cognitive bias propensity. Results: After 4-weeks of MCT+, both patients showed substantial reduction in delusional symptoms, reported improved clinical insight, and were less prone to making illusory correlations. Conclusions: The presented case studies provide preliminary evidence for the feasibility of MCT+ in treating patients not taking, or resistant to, antipsychotic medication.