London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. II: Predictors of outcome.
ABSTRACT Despite growing evidence of the effectiveness of cognitive-behavioural therapy (CBT) for psychosis, typically only about 50% of patients show a positive response to treatment. This paper reports the first comprehensive investigation of factors which predict treatment outcome.
In a randomised controlled trial of CBT for medication-resistant psychosis (see Part I) measures were taken at baseline of demographic, clinical and cognitive variables. Changes over time were assessed on the Brief Psychiatric Rating Scale and the relationship between potential predictor variables and outcome was investigated using analysis of variance and covariance.
A number of baseline variables were identified as predictors of good outcome in the CBT group. Key predictors were a response indicating cognitive flexibility concerning delusions (P = 0.005) and the number of recent admissions (P = 0.002). Outcome was less predictable in the control group and was not predicted by any cognitive variable.
Good outcome is strongly predicted in patients with persistent delusions by a cognitive measure, while this was not the case in controls. Thus we argue that positive outcome in CBT is due in part to specific effects on delusional thinking.
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ABSTRACT: Behavioral flexibility is a component of executive functioning that allows individuals to adapt to changing environmental conditions. Independent lines of research indicate that the mu opioid receptor (MOR) is an important mediator of behavioral flexibility and responses to psychosocial stress. The current study bridges these two lines of research and tests the extent to which social defeat and MOR affect behavioral flexibility and whether sex moderates these effects in California mice (Peromyscus californicus). Males and females assigned to social defeat or control conditions were tested in a Barnes maze. In males, defeat impaired behavioral flexibility but not acquisition. Female performance was unaffected by defeat. MOR binding in defeated and control mice in the orbitofrontal cortex (OFC), striatum and hippocampus was examined via autoradiography. Stressed males had reduced MOR binding in the OFC whereas females were unaffected. The MOR antagonist beta-funaltrexamine (1 mg/kg) impaired performance in males naïve to defeat during the reversal phase but had no effect on females. Finally, we examined the effects of the MOR agonist morphine (2.5 and 5 mg/kg) on stressed mice. As expected, morphine improved behavioral flexibility in stressed males. The stress-induced deficits in behavioral flexibility in males are consistent with a proactive coping strategy, including previous observations that stressed male California mice exhibit strong social approach and aggression. Our pharmacological data suggest that a down-regulation of MOR signaling in males may contribute to sex differences in behavioral flexibility following stress. This is discussed in the framework of coping strategies for individuals with mood disorders.European Journal of Neuroscience 01/2015; 41(4). DOI:10.1111/ejn.12824 · 3.67 Impact Factor
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ABSTRACT: Background: Given the evidence that reasoning biases contribute to delusional persistence and change, several research groups have made systematic efforts to modify them. The current experiment tested the hypothesis that targeting reasoning biases would result in change in delusions. Methods: One hundred and one participants with current delusions and schizophrenia spectrum psychosis were randomly allocated to a brief computerized reasoning training intervention or to a control condition involving computer-based activities of similar duration. The primary hypotheses tested were that the reasoning training intervention, would improve (1) data gathering and belief flexibility and (2) delusional thinking, specifically paranoia. We then tested whether the changes in paranoia were mediated by changes in data gathering and flexibility, and whether working memory and negative symptoms moderated any intervention effects. Results: On an intention-to-treat analysis, there were significant improvements in state paranoia and reasoning in the experimental compared with the control condition. There was evidence that changes in reasoning mediated changes in paranoia, although this effect fell just outside the conventional level of significance after adjustment for baseline confounders. Working memory and negative symptoms significantly moderated the effects of the intervention on reasoning. Conclusion: The study demonstrated the effectiveness of a brief reasoning intervention in improving both reasoning processes and paranoia. It thereby provides proof-of-concept evidence that reasoning is a promising intermediary target in interventions to ameliorate delusions, and thus supports the value of developing this approach as a longer therapeutic intervention.Schizophrenia Bulletin 07/2014; DOI:10.1093/schbul/sbu103 · 8.61 Impact Factor
Advances in Psychiatric Treatment 07/1998; 4(4). DOI:10.1192/apt.4.4.235