Neural Changes Following Cognitive Behaviour Therapy for Psychosis

A Longitudinal Study

Veena Kumari; Dominic Fannon; Emmanuelle R. Peters; Dominic H. ffytche; Alexander L. Sumich; Preethi Premkumar; Anantha P. Anilkumar; Christopher Andrew; Mary L. Phillips; Steven C. R. Williams; Elizabeth Kuipers


Brain. 2011;134(8):2396-2407. 

In This Article

Abstract and Introduction


A growing body of evidence demonstrates that persistent positive symptoms, particularly delusions, can be improved by cognitive behaviour therapy for psychosis. Heightened perception and processing of threat are believed to constitute the genesis of delusions. The present study aimed to examine functional brain changes following cognitive behaviour therapy for psychosis. The study involved 56 outpatients with one or more persistent positive distressing symptoms of schizophrenia. Twenty-eight patients receiving cognitive behaviour therapy for psychosis for 6–8 months in addition to their usual treatment were matched with 28 patients receiving treatment as usual. Patients' symptoms were assessed by a rater blind to treatment group, and they underwent functional magnetic resonance imaging during an affect processing task at baseline and end of treatment follow-up. The two groups were comparable at baseline in terms of clinical and demographic parameters and neural and behavioural responses to facial and control stimuli. The cognitive behaviour therapy for psychosis with treatment-as-usual group (22 subjects) showed significant clinical improvement compared with the treatment-as-usual group (16 subjects), which showed no change at follow-up. The cognitive behaviour therapy for psychosis with treatment-as-usual group, but not the treatment-as-usual group, showed decreased activation of the inferior frontal, insula, thalamus, putamen and occipital areas to fearful and angry expressions at treatment follow-up compared with baseline. Reduction of functional magnetic resonance imaging response during angry expressions correlated directly with symptom improvement. This study provides the first evidence that cognitive behaviour therapy for psychosis attenuates brain responses to threatening stimuli and suggests that cognitive behaviour therapy for psychosis may mediate symptom reduction by promoting processing of threats in a less distressing way.


According to Beck's cognitive model of psychopathology (Beck, 1963), biased processing of external and/or internal events or stimuli distorts an individual's construction of experiences and leads to problematic behavioural and emotional responses. This model served as the basis for development of cognitive behaviour therapy (CBT) for depression >40 years ago (Beck, 2005). Numerous studies since then have established the effectiveness of CBT, applied in varied forms depending upon the cognitive formulation of a particular disorder, in reducing symptoms across a range of psychiatric disorders, including obsessive compulsive disorder, social phobia, panic disorder and psychosis (Butler et al., 2006). The most common application of CBT for psychosis has been as an additional treatment to drug therapy for medication-resistant patients with schizophrenia, with its beneficial effects evident as a reduction in persistent positive symptoms, particularly delusions, and secondary disturbances such as depression (Pfammatter et al., 2006; Wykes et al., 2008; NICE, 2009).

The neuroscience of CBT is a novel area with important implications for our understanding of the mechanisms of maintenance of symptoms and of therapeutic change (Brenner et al., 2006; van der Gaag, 2006). A number of studies have already documented significant neural changes following psychological therapies for depression (Martin et al., 2001; Goldapple et al., 2004; Fu et al., 2008), obsessive compulsive disorder (Schwartz et al., 1996), panic disorder (Prasko et al., 2004) and social (Furmark et al., 2002) and animal phobias (Paquette et al., 2003; Straube et al., 2006; Schienle et al., 2009).

The aim of the present study was to examine, for the first time to our knowledge, what kind of functional brain changes, if any, might emerge following CBT for psychosis in patients with persistent and distressing positive symptom(s) of schizophrenia. To achieve this, we applied functional MRI during implicit processing of facial expressions denoting direct as well as indirect threat (Frijda, 1986; Fridlund, 1994). Angry expressions signal a direct and immediate threat, while fearful expressions indicate the presence of a significant, but uncertain, source of threat in the environment (Fridlund, 1994). Paranoia, a main symptom of psychosis, is fundamentally a threat response (Freeman et al., 2002). Heightened perception and processing of social threat has been suggested to constitute the genesis of persecutory delusions (Green and Phillips, 2004), explained at least in part by inappropriate engagement of the brain's fear system (Corlett et al., 2010). Both a pre-attentive bias for detection of threat-related information as well as difficulty disengaging threat-related emotional material from conscious awareness are considered to be involved in delusional beliefs (Green and Phillips, 2004).

Given consistent evidence for improvement in persistent positive symptoms, especially delusions, after CBT for psychosis (Pfammatter et al., 2006; Wykes et al., 2008; Rathod et al., 2010), and the association between paranoia and aberrant processing of social threat (Green and Phillips, 2004), the present investigation tested the hypothesis that psychotic individuals with persistent positive symptoms of schizophrenia following a course of CBT for psychosis would display attenuated neural processing within the network of brain regions processing facial expressions, particularly those related to threat (i.e. fearful and angry expressions). The network of regions processing emotional facial expressions includes visual (fusiform gyrus, inferior and middle occipital gyrus, lingual gyrus), limbic (amygdala, parahippocampal gyrus), temporoparietal (middle–superior temporal gyrus, parietal lobule), prefrontal and subcortical areas (putamen), insula and the cerebellum (Fusar-Poli et al., 2009). Of these regions, activation of the amygdala, which signifies fear processing (LeDoux, 2000), and of the insula, which is associated with anticipation and evaluation of potentially distressing cognitive and sensory information (Reiman et al., 1997; Kumari et al., 2009a), was hypothesized in particular to show reduced activation following a course of CBT for psychosis. No specific hypothesis was formulated with regard to neural response to happy expressions since enhancement of positive emotions is not a primary target of CBT for psychosis.