This study evaluated the effectiveness of 20 sessions of Cognitive Behavioral Therapy for negative symptoms (CBT-n) over 6 months in reducing negative symptoms and dysfunctional beliefs in 21 outpatients with schizophrenia spectrum disorders. Results found a large effect size reduction in negative symptoms, partially mediated by reductions in dysfunctional beliefs about cognitive abilities, performance, emotions, and social exclusion. However, the uncontrolled design and small sample limit conclusions, and larger controlled trials are still needed.
Original Description:
gejala negatif psikotik
Original Title
Cognitive Behavioral Therapy for Negative Symptoms
This study evaluated the effectiveness of 20 sessions of Cognitive Behavioral Therapy for negative symptoms (CBT-n) over 6 months in reducing negative symptoms and dysfunctional beliefs in 21 outpatients with schizophrenia spectrum disorders. Results found a large effect size reduction in negative symptoms, partially mediated by reductions in dysfunctional beliefs about cognitive abilities, performance, emotions, and social exclusion. However, the uncontrolled design and small sample limit conclusions, and larger controlled trials are still needed.
This study evaluated the effectiveness of 20 sessions of Cognitive Behavioral Therapy for negative symptoms (CBT-n) over 6 months in reducing negative symptoms and dysfunctional beliefs in 21 outpatients with schizophrenia spectrum disorders. Results found a large effect size reduction in negative symptoms, partially mediated by reductions in dysfunctional beliefs about cognitive abilities, performance, emotions, and social exclusion. However, the uncontrolled design and small sample limit conclusions, and larger controlled trials are still needed.
Cognitive Behavioral Therapy for negative symptoms (CBT-n) in
psychotic disorders: A pilot study
Anton B.P. Staring a, * , Mary-Ann B. ter Huurne b , Mark van der Gaag c, d a Altrecht Psychiatric Institute, ABC-straat 8, 3512 PX Utrecht, The Netherlands b Mediant Psychiatric Institute, Laan van Driene 101, 7552 EN Hengelo, The Netherlands c Parnassia Psychiatric Institute, Oude Haagweg 357, 2552 ES The Hague, The Netherlands d VU University and EMGO Institute for Health and Care Research, Van Boechorststraat 1, 1081 BT Amsterdam, The Netherlands a r t i c l e i n f o Article history: Received 1 September 2012 Received in revised form 21 January 2013 Accepted 23 January 2013 Keywords: Psychosis Schizophrenia Cognitive therapy CBT Negative symptoms Self-stigma a b s t r a c t Background and objectives: The treatment of negative symptoms in schizophrenia is a major challenge for mental health care. One randomized controlled trial found that cognitive therapy for low-functioning patients reduced avolition and improved functioning, using an average of 50.5 treatment sessions over the course of 18 months. The aim of our current pilot study was to evaluate whether 20 sessions of Cognitive Behavioral Therapy for negative symptoms (CBT-n) would reduce negative symptoms within 6 months. Also, we wanted to test the cognitive model of negative symptoms by analyzing whether a reduction in dysfunctional beliefs mediated the effects on negative symptoms. Method: In an open trial 21 adult outpatients with a schizophrenia spectrum disorder with negative symptoms received an average of 17.5 sessions of CBT-n. At baseline and end-of-treatment, we assessed negative symptoms (PANSS) and dysfunctional beliefs about cognitive abilities, performance, emotional experience, and social exclusion. Bootstrap analysis tested mediation. Results: The dropout rate was 14% (three participants). Intention-to-treat analyses showed a within group effect size of 1.26 on negative symptoms (t 6.16, j Sig 0.000). Bootstrap analysis showed that dysfunctional beliefs partially mediated the change. Limitations: The uncontrolled design induced efcacy biases. Also, the sample was relatively small, and there were no follow-up assessments. Conclusions: CBT-n may be effective in reducing negative symptoms. Also, patients reported fewer dysfunctional beliefs about their cognitive abilities, performance, emotional experience, and social exclusion, and this reduction partially mediated the change in negative symptoms. The reductions were clinically important. However, larger and controlled trials are needed. 2013 Elsevier Ltd. All rights reserved. 1. Introduction 1.1. Negative symptoms Negative symptoms of psychotic disorders include avolition, affective attening, social withdrawal, anhedonia, and poverty of speech. A review demonstrates that these symptoms are strong predictors of poor long-termprognosis (Lang, Ksters, Lang, Becker, & Jger, 2012). They are clearly associated with low levels of functioning (r 0.42), which is not the case for positive symptoms (Ventura, Hellemann, Thames, Koellner, & Nuechterlein, 2009). Even though negative symptoms are often regarded as stable aspects of psychotic disorders such as schizophrenia, not changing much or otherwise worsening over time, there is recent evidence that both at affect and social functioning show important changes during the course of ten years after a rst psychotic episode, slowly deteriorating or improving for different patient subgroups (Evensen et al., 2012). This installs hope for change and targeted interventions. However, the treatment of negative symptoms in schizophrenia is still a major challenge for mental health care. Second generation antipsychotic medications produce only mod- erate effects on negative symptoms (Leucht, Arbter, Engel, Kissling, & Davis, 2009), and an exacerbation of negative symptoms due to antipsychotics has also been reported (Artaloytia et al., 2006). More effective treatments are needed. * Corresponding author. Tel.: 31 (0) 6 815 99 505. E-mail addresses: tonnie@backwash.org, t.staring@altrecht.nl (A.B.P. Staring), mary-ann.huurne@mentrum.nl (M.-A.B. ter Huurne), m.vander.gaag@vu.nl (M. van der Gaag). Contents lists available at SciVerse ScienceDirect Journal of Behavior Therapy and Experimental Psychiatry j ournal homepage: www. el sevi er. com/ l ocat e/ j bt ep 0005-7916/$ e see front matter 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jbtep.2013.01.004 J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 1.2. Cognitive Behavioral Therapy (CBT) for negative symptoms In the US, a randomized controlled trial with 60 patients was conducted to assess the efcacy of a program for low-functioning patients with neurocognitive impairments and negative symp- toms (Grant, Huh, Perivoliotis, Stolar, & Beck, 2012). The program was based on recent evidence that defeatist performance attitudes (e.g. if you cannot do something well, there is little point in doing it at all) correlate with negative symptoms (Beck, Grant, Huh, Perivoliotis, & Chang, 2011; Couture, Blanchard, & Bennett, 2011) and partially mediate the relationship between neurocognitive performance and negative symptoms (Grant & Beck, 2009). This means that patients beliefs about their neurocognitive impair- ments are important in determining the extent to which these impairments lead to withdrawal and inactivity. Also, in three studies, using experience sampling methods, there was no evi- dence for a decit in the experience of pleasure in patients with psychotic disorders e rather, there were strong negative expec- tancies of experiencing pleasure (low anticipatory pleasure: I will not be able to enjoy this) (Gard, Kring, Gard, Horan, & Green, 2007; Oorschot et al., 2011). These beliefs predicted low social activity levels (Oorschot et al., 2011). Another study found that asocial be- liefs (e.g. having close friends is not as important as most people say) were predictive of lowsocial functioning one year later, rather than the other way around (Grant & Beck, 2010). This body of research implicates that low expectations for pleasure and performance may strongly affect negative symptoms. Grant et al. (2012) used cognitive therapy (CT) to correct dysfunc- tional beliefs about pleasure, cognitive abilities, performance and social functioning. Techniques included goal-setting, behavioral experiments, activity scheduling, and more. Several accommoda- tions were used to work around neurocognitive impairments. The CT-group received 18 months of individual treatment. CT was found to be superior in reducing avolition/apathy and improving levels of functioning. However, other negative symptoms did not improve signicantly, such as affective attening, alogia, and anhedonia- asociality. Also, the treatment duration was long: an average of 50.5 sessions. Another recent and large randomized controlled trial compared a shorter version of CBT for negative symptoms (average 16.6 ses- sions) with cognitive remediation in 198 patients (Klingberg et al., 2011). Treatment consisted of case formulation based on a cognitive model, goal setting, discussion of cognitive processes, homework assignments, and role-play. Patients received two out of ve available treatment modules that target negative symptoms. The aim was to reduce generalized expectancy of failure (defeatist be- liefs) and improve social cognitive skills like emotion detection and expression. The CBT treatment, in comparison to the trial of Grant et al. (2012), had a greater focus on training of cognition and behavior, and a somewhat smaller focus on cognitive therapy for dysfunctional beliefs. Results showed moderate improvements in negative symptoms in both groups, but no signicant benet for CBT. Although other studies of psychosocial interventions have been conducted, they rarely targeted negative symptoms as their pri- mary outcome. There have been three small but promising trials on peer support groups (Castelein et al., 2008), music therapy (Gold, Solli, Krger, & Lie, 2009), and body-oriented psychosocial ther- apy (Rhricht & Priebe, 2006). Also, CBT for the positive symptoms of psychotic disorders has been found to decrease negative symp- toms: an average effect size of 0.44 (Wykes, Steel, Everitt, & Tarrier, 2008). Less paranoia and less fear for distressing voices may lead to less withdrawal and more experience of pleasure. This illustrates the well known multifactorial nature of negative symptoms: posi- tive symptoms, anxiety, depression, and other symptom clusters may exacerbate negative symptoms. Interventions that target those factors therefore exert some effect on the negative symptoms as well. For example, antidepressant medications are known to decrease negative symptoms in schizophrenia (Singh, Singh, Kar, & Chan, 2010). However, treatment of the more primary negative symptoms remains a major challenge (Buckley & Stahl, 2007; Kirkpatrick, Fenton, Carpenter, & Marder, 2006). Antipsychotics and family interventions are unsatisfactory in this regard (Mkinen, Miettunen, Isohanni, & Koponen, 2008). The trial of Grant et al. (2012) is one of the most promising. More research is needed to conrm to what extent specic CBT for negative symptoms may reduce these symptoms as well as dysfunctional beliefs, and to evaluate whether it can be achieved in fewer sessions than 50. 1.3. Aims of the study Based on recent literature, we constructed a Dutch treatment manual of Cognitive Behavioral Therapy for negative symptoms (CBT-n) (Staring & Van den Berg, 2010; Staring & Van der Gaag, 2010). The aim of this uncontrolled pilot study was to test: (a) whether the treatment manual is useful for therapists; (b) whether CBT-n may be effective in reducing negative symptoms for patients with a schizophrenia spectrum disorder, using a maximum of 20 treatment sessions in six months; and (c) whether a reduction in dysfunctional beliefs mediates the effect on negative symptoms. Findings within this pilot study will be used as preparation for a large RCT. 2. Materials and methods 2.1. Study design An open pilot trial in which negative symptoms were treated with CBT-n in participants with a schizophrenia spectrum disorder, with a maximum of 20 treatment sessions. 2.2. Setting Participants were outpatients from nine psychiatric institutions in The Netherlands: Altrecht Psychiatric Institute, Mediant Psychi- atric Institute, Parnassia Psychiatric Institute, Mental Health Care Drenthe, Mental Health Care Breburg, Mental Health Care Noord- Holland Noord, Rivierduinen Psychiatric Institute, GGNet, and Reinier van Arkel Group. 2.3. Participants Inclusion criteria were: 1. A chart diagnosis of schizophrenia spectrum disorder; 2. At least some negative symptoms (at least three PANSS neg- ative symptom items scoring a 3 or higher, bringing the total score of the PANSS negative syndrome to at least 13) about which the patient expressed dissatisfaction. Exclusion criteria were: 1. Younger than eighteen years of age; 2. No mastery of the Dutch language; 3. Negative symptoms as a consequence of positive symptoms (e.g. withdrawal due to paranoid delusions). This was assessed within the initial information session by the therapist. He/she asked the patient about the reasons for social withdrawal, low activity levels, low pleasure experience levels, etc., and explic- itly asked whether voices or certain psychotic fears play a role A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 301 or not. Positive symptoms as such were not an exclusion cri- terion; only whenthey were considered to be the primarycause of the negative symptoms, in which case CBT-p or another type of intervention for positive symptoms was called for. 2.4. Procedure After referral to this study, information was given verbally as well as in writing, and written informed consent was obtained. After that, baseline measurements were administered (T0). Par- ticipants were then treated with weekly sessions of 45 min ac- cording to the CBT-n manual, with a maximum of 20 sessions. Treatment as usual (e.g. case management) was also continued. Therapists worked in the same team as the case managers and kept in touch about progress. Measurements were administered again at the end-of-treatment (T1). In total, thirteen therapists participated in the study. All therapists were health and clinical psychologists with experience in CBT for psychosis. Ten had at least a two-year post-doctoral clinical specialization. The therapists received a one-day training in the CBT-n manual. Treatment integrity mea- surements were not collected. The rst author did keep in touch with all therapists about progress and gave consultation for the various phases of the treatment for each participant. The Medical Ethics Committee of the University Medical Center of Utrecht approved the study protocol (METC-protocol number: 11-228/C, date 10-06-2011). 2.5. Cognitive Behavioral Therapy for negative symptoms (CBT-n) The treatment manual was based on the work of Grant and col- leagues (Grant et al., 2012; Perivoliotis & Cather, 2009), but adapted here and there, e.g. in order to make distinctions between various dysfunctional beliefs andto further t the model withinsights about self-stigma, perceived discrimination and social exclusion, mourn- ing over experienced losses, and states of demoralization. This is based onsome recent literature. For example, ina recent study using time budget to concisely measure activity levels, perceived dis- crimination, within a measure of stigma appraisals, was found to be associatedwithreducedactivity(Moriarty, Jolley, Callanan, &Garety, 2012). Patients withpsychosis epossiblyas a consequence of insight into neurocognitive impairments and of the experienced losses due to psychotic episodes and hospital admissions e may be vulnerable for internalizing some highly stigmatizing beliefs about their illness and for sliding into a state of demoralization. Indeed, assessing 145 outpatients, it was found that high insight combined with high self- stigma predicted levels of demoralization in patients with psychotic disorders (Cavelti, Kvrgic, Beck, Rsch, & Vauth, 2011). This is in line with other studies that have found that a combination of good insight together with stigmatizing illness appraisals renders a pa- tient at risk for highlevels of hopelessness as well as lowself-esteem and low quality of life (Lysaker, Roe, & Yanos, 2007; Staring, Van der Gaag, Van den Berge, Duivenvoorden, & Mulder, 2009). Based on this, as well as onthe work of Grant et al., we constructed a cognitive model of negative symptoms (Fig. 1). The treatment manual started with a structured interview in order to make an individual case formulation based on the model in Fig. 1. A patients individual goals were assessed, and psycho- education about neurocognitive impairments and dysfunctional attitudes was provided. General activity scheduling and registra- tions were applied, and signicant others were informed about the treatment rationale. When the rst treatment goal had been cho- sen, the case formulation provided insight into possible obstacles. Dysfunctional beliefs and avoidance behaviors that stood in the way of the goal constituted the targets of CBT-techniques, e.g. cognitive restructuring and roleplay. Behavioral experiments and other cognitive methods took place within the treatment sessions as much as possible. Typical dysfunctional beliefs that were tar- geted included: I got damaged by my psychotic episode and I cannot enjoy things anymore, I have no energy at all and when I start working again, even for a few hours, I will get a psychotic breakdown, Negative self-image, self-stigmatization, expectation of social exclusion Reduced emotional competencies Reduced Reduced behavioral competencies cognitive competencies Setbacks, internal and external loss- experiences (e.g. identity, capacities, education, work, relationships) Negative expectations about cognitive capacities, e.g. memory, concentration, energy levels Negative expectations about agency, performance and social skills Negative expectations about the ability to enjoy and experience positive emotions Primary interpretation: Impairment: Secondary interpretation: Avoidance: Withdrawal, less expression, inactivity, defeatist attitude, thought and emotion suppression Psychoses Fig. 1. Cognitive model of negative symptoms (Staring & Van der Gaag, 2010). On the left side, impairments are included that may be present in a psychotic disorder and that are considered unchangeable using CBT. The psychotic episodes, setbacks, and experienced losses are summarized in the upper mid section of the gure; they have taken place in the past and constitute no target for change. The current problems are summarized in the right and lower sides of the model. These are dysfunctional beliefs that are often characterized by all-or-nothing polarization as well as by a connection with avoidance behavior. A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 302 or I am unable to concentrate and memorize anything new, and therefore unable to study again. Visual aids, text-messages, imagery, and the help of signicant others were used to work around neu- rocognitive impairments. In order to promote a sense of personal efcacy as much as possible, each failure of the patient to execute a new behavior was interpreted to be the therapists fault by insufcient preparation or setting the goals too high. They responded with sentences like: This is my fault, I did not prepare you enough for this step. Therapists were instructed to repeatedly get this message across, as authentically as they were able to. The idea is that small successes are highly needed for the patient to expe- rience a sense of hope and personal efcacy. Little failures are threats that patients may interpret as evidence for negative beliefs about performance. Patients do not learn from failure and perform better after errorless learning (Pope & Kern, 2006). However, therapists were always careful to not install unrealistic beliefs or goals. Finally, several techniques were used to keep the patient attending the sessions, e.g. watching entertaining youtube-movies during the rst part of the session. 2.6. Measurements 2.6.1. Primary outcome The negative syndrome of the Positive And Negative Syndrome Scale (PANSS) (Kay, Fiszbein, & Opler, 1987) was used to assess negative symptoms. It consists of 7 items and produces a total score ranging from 7 (minimum) to 49 (maximum). 2.6.2. Mediator: dysfunctional beliefs We intended to measure typical dysfunctional beliefs that con- stitute the targets of CBT-n, in order to assess whether these would mediate an effect on negative symptoms. However, no existing scale ts these beliefs accurately. Although the Dysfunctional Attitudes Scale e Defeatist Performance Attitude (DAS-DPA) (Weissman, 1978) correlated with negative symptoms in the aforementioned studies, many of its items reect other attitudes than the perfor- mance expectancies that constitute the beliefs in the model of Fig. 1, and some of the beliefs we wanted to measure (e.g. low expec- tancies about pleasure, energy or concentration) are not included in this scale. We therefore selected specic items from a range of existing scales that seemed useful: the Beck Depression Inventory second edition (BDI-2) (Beck, Steer, Ball, &Ranieri, 1996; Beck, Steer, & Brown, 1996; Beck, Steer, & Garbin, 1988), the Beck Hopelessness Scale (BHS) (Beck, Weissman, Lester, & Trexler, 1974), the Dysfunc- tional Attitudes Scale e Defeatist Performance Attitude (DAS-DPA) (Weissman, 1978), and the Internalized Stigma of Mental Illness (ISMI) scale (Ritsher, Otilingam, & Grajales, 2003). Reasoning from the model in Fig. 1, the selected items should reect dysfunctional beliefs about cognitive abilities, (social) per- formance, and the ability to experience positive emotions. Also, we planned to measure beliefs about social exclusion and internalized stigma. (1) Dysfunctional beliefs about cognitive abilities: BDI-13 (indici- siveness), BDI-15 (subjective loss of energy), BDI-19 (subjective concentration difculty), and BDI-20 (experienced tiredness or fatigue). (2) Dysfunctional beliefs about (social) performance: BHS-2 (I might as well give up because theres nothing I can do to make things better for myself), BHS-6 inverted (In the future I expect to succeed in what concerns me most), DAS-DPA-6 (If I fail at my work, then I am a failure as a person), DAS- DPA-14 (If I ask a question, it makes me look inferior), DAS-DPA-15 (I cannot trust other people because they might be cruel to me). (3) Dysfunctional beliefs about experiencing pleasure and positive emotions: BDI-4 (subjective loss of pleasure), BDI-10 (crying too much or cannot cry), BDI-12 (loss of interest), BDI-21 (loss of interest in sex), BHS-17 (It is very unlikely that I will get any real satisfaction in the future). Based on standardized item-scores (to equal their weights), these 14 items were summed to constitute a score that reects the primary beliefs in the model of Fig. 1. Cronbachs alpha of this measure was 0.719, indicating an acceptable internal consistency. (4) Beliefs about social exclusion and internalized stigma: ISMI total score. The ISMI contains 29 items rated on a four-point Likert-type scale, ranging from 1 (strongly agree) to 4 (strongly disagree). It contains ve subscales: alienation, stereotype endorsement, perceived discrimination, social withdrawal, and stigma resist- ance. For this study, ISMI total scores were used, in which higher scores indicate more internalized stigma as well as more expe- rienced or expected social exclusion. The measure has high internal consistency and testeretest reliability. Construct and concurrent validity were supported by comparisons with other measures. The ISMI total score as well as the sum of the selected 14 items were both standardized (transformed into z-scores). These two scales were then added up to constitute a total measure of the dysfunctional beliefs that were the main target of CBT-n. Higher scores indicated more dysfunctional beliefs, with an average score of zero at baseline. 2.7. Statistical analyses Descriptive statistics were produced to describe the de- mographic characteristics and baseline variables of the total sample. Paired samples t-tests for means were performed to determine the statistical signicance of the changes in scores on the primary outcome as well as the mediating measure. Effect sizes were used as indicators of clinical relevance of the observed changes (Cohen, 1992). We also performed a regression-analysis, in which it was checked whether a change in negative symptoms would still be signicant when depression scores were controlled for. Deeper understanding is gained when we comprehend the process that causes the effect. A variable is a mediating variable if it (to a certain extent) accounts for the association between the therapy and symptom reduction. Perfect or complete mediation refers to an absence of treatment effect when the mediator has been controlled for. When the treatment effect is reduced by a non-trivial amount, but not to zero, partial mediation has occurred (Baron & Kenny, 1986). To demonstrate mediation, the causal steps strategy should be applied (Fig. 2). This means that several results must be ascertained: (1) an effect of treatment on B A M C' Y C Y X X Fig. 2. Path models of the total effect of treatment on symptoms (upper gure) and mediated effects of treatment on symptoms (lower gure). C is the total effect of treatment X on symptoms Y. C 0 is the direct effect of treatment X on symptoms Y with the effects of mediator M partialled out. A is the effect of treatment X on mediator M and B is the effect of mediator M on symptoms Y. A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 303 symptoms (C path); (2) an effect of treatment on the mediator (A path); (3) an effect of the mediator on symptoms (B path); and (4) the effect of treatment on symptoms without the indirect effect of the moderator must be non-trivially reduced or absent (C 0 path). In order to analyze whether dysfunctional beliefs mediated the treatment effects on negative symptoms, we used the bootstrap method that can handle non-parametric data and relatively small sample sizes (Preacher & Hayes, 2008). The algorithm and syntax for SPSS 18 are available on the Internet (Hayes, 2011). In our uncontrolled design, however, all changes and mediations must be interpreted with caution, as time effects are not necessarily due to the treatment. 3. Results 3.1. Participants A total of 34 patients, who met the criteria of the study, were asked to participate. Eight refused. The remaining 26 patients wanted to participate, but two did not enroll because of a physical illness that required hospital treatment, two missed out on the participation deadline, and one patient started another exper- imental treatment. Twenty-one patients enrolled in the study, and they constitute the participants sample for the intention-to-treat analyses. Three patients prematurely stopped treatment. Two of them stopped halfway due to low motivation. Another patient got too depressedtocontinue. All threewere available for T1-measurements and so we had no missing data for the intention-to-treat analyses. Eighteen patients completed the treatment (Table 1). 3.2. Treatment execution On average 17.5 sessions of CBT-n were provided to each participant. Although most patients seemed to benet from the therapy, the pace of progress varied considerably. Some therapists noted that, when they continued the treatment program after the end-of-treatment measurement (T1) and beyond the maximum of 20 sessions, patients would continue to benet in terms of improved functioning and fewer negative symptoms. It thus seems that some patients may accomplish more treatment gains if CBT-n would be extended. Therapists also described that change in beliefs and attitudes would come rst, followed by successful behavioral activation. In two cases, delusions turned out to be an obstacle for the patient to engage in desired activities. Their positive symptoms stood in the way of escaping withdrawal. One patient reported the fear e after working with this goal for various sessions e that if he would start socializing, his mother would read his thoughts and disapprove. And one patient was afraid to return to horse riding, because they might still be out to get him. Despite the exclusion criterion of positive symptoms causing withdrawal, we had been unable to see this beforehand. These patients were kept in treat- ment and CBT-techniques were used to work on the positive symptoms. After doing so, at least one of them was able to engage in more constructive activity. Therapists generally found that the treatment manual was clear and concise. However, some therapists were struggling with the distinction between actual neurocognitive impairments and the patients beliefs about these impairments. Behavioral experiments for testing beliefs in goal-specic situations (e.g. I want to study this book for college, but my memory does not work), rather than using neurocognitive test-batteries, often proved satisfactory in solving this issue. 3.3. Outcome The pre- to posttreatment results are shown in Table 2. The improvement on the primary outcome measure was highly signif- icant and clinically relevant. The effect size and PANSS-scores indicate an important reduction of negative symptoms during the course of treatment. In order to control for depression, we performed a stepwise regression-analysis to predict negative symptom levels, in which we rst entered depression (BDI-2) as the independent variable, and time point (either baseline or end of treatment) in the second block. This analysis showed that the change in negative symptoms was not explained by a change in depression scores, as the effects of depression in the regression analysis were non-signicant (t 1.07 j p 0.291) and the changes achieved during the treatment period remained signicant (t 2.96 j p 0.005). 3.4. Mediation of dysfunctional beliefs Specic results of the mediation analysis are presented in Table 3. The total mediator model was signicant F(2, 39) 11.838, p 0.0001. The total explained variance (R 2 ) was 38%. The adjusted R 2 was 35%. Dysfunctional beliefs fullled the criteria for partial mediation: therapy signicantly affected the mediator (path A), the mediator signicantly affected negative symptoms (B), the direct effect of therapy on negative symptoms reduced when corrected for dysfunctional beliefs (path C 0 is less strong than path C), and the bootstrap indirect effects were signicant. In short, the reduction of dysfunctional beliefs partially mediated the reduction in negative symptoms, although not completely. 4. Discussion 4.1. Outcome The dropout rate was 14% (three out of twenty-one patients), indicating that CBT for negative symptoms was an acceptable treatment for these patients. This dropout rate is similar to other psychosocial interventions for psychotic disorders (Villeneuve, Table 1 Demographic characteristics of participants. Frequency (n 21) Mean age 40.6 years (range 22e58) Sex Male 14 Female 7 Living status Alone, independently 19 In sheltered living 1 With parents 1 Ethnicity Dutch (western) 17 Non-western Immigrant 4 Psychotic disorder Schizophrenia 17 Schizoaffective disorder 1 Schizophreniform disorder 1 Psychotic disorder NOS 2 Mean duration of psychotic disorder 13.0 years (range 1e26) Substance abuse Alcohol abuse 4 Medication First generation antipsychotic 7 Second generation antipsychotic 14 A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 304 Potvin, Lesage, & Nicole, 2010). This is positive in our view, given the likelihood that patients with negative symptoms may be dif- cult to motivate to fully complete their treatments. A large within-group effect size was found on the PANSS negative syndrome, changing from an average of 20.2 to 14.1, indicating that CBT-n ts its purpose: to decrease negative symptoms. The changes were clinically important and may surpass the effects of other treatment methods for negative symptoms. The Klinberg et al. (2011) study, for example, found the PANSS negative syndrome score only changing from an average of 18.9 to 16.1 (in their article they mention the average item-scores of 2.7 and 2.3). And the controlled trial on body-oriented psychosocial therapy (Rhricht & Priebe, 2006) found the PANSS negative syn- drome changing from an average of 23.4 to 18.2. To conrm the effectiveness of CBT-n, however, larger and controlled trials are needed. Also, we found a large effect size on our measure of dysfunc- tional beliefs, which indicates that CBT-n may effectively target the beliefs of our cognitive model. Furthermore, a reduction in these beliefs partially mediated the change in negative symptoms. This nding is evidence for their clinical importance and it supports our cognitive model of negative symptoms. The mechanism of change in negative symptoms is in part explained by the reduction of dysfunctional beliefs. Also, however, a signicant part of the change in negative symptoms was unexplained by dysfunctional beliefs. This part of the effect may for example be more associated with the goal-setting and behavioral activation components of the treatment. Patients appraised their illnesses in a less stigmatizing way and became more hopeful for the future. Besides relevant as a mecha- nism for reducing negative symptoms, this improvement is also important in itself. Other studies on psychosocial interventions that target self-stigma, for example, have mostly produced small to medium effects (Mittal, Sullivan, Chekuri, Allee, & Corrigan, 2012). 4.2. CBT-n manual Based on the ndings we learned that although 20 treatment sessions may accomplish important improvements for most pa- tients, the therapy should probably be allowed to extend its dura- tion when needed. It was difcult to exclude patients that experience negative symptoms as a consequence of delusions. We may sometimes fail to detect positive symptoms up until the time that a patient is actively engaged to achieve goals. It is desirable that CBT-techniques for positive symptoms are available when needed. 4.3. Limitations This was an uncontrolled study. Therefore the efcacy ndings are biased. Patients may have improved over the course of the study by self-initiated change or because other treatments were helpful. The lack of a control group means that this effect was not controlled for. Second, also as a consequence of the uncontrolled design, measurements were not blind. We mostly used self-report mea- surements, and patients were fully aware that they had received an active treatment for their negative symptoms. This may have caused efcacy to be overestimated. Third, about 25% of the patients that we initially asked to par- ticipate refused. Some of them did not want to participate in a sci- entic project, whereas others seemed unwilling to work on their negative symptoms. This is a problem, as the negative symptoms themselves may in part be the cause of these patients refusing participation. Although we used various strategies to facilitate participation, we were unable to engage 25% of the patients at the start. Fourth, we did not formally measure treatment integrity. The therapists did ll in a form every therapy session, and the rst author monitored the therapists adherence to the manual. Finally, there was no follow-up assessment, making it impos- sible to determine whether treatment gain was maintained over time. Randomized controlled trials with sufcient statistical power will need to be performed in order to conrm or refute our results. 4.4. Conclusions CBT-n seemed effective in reducing negative symptoms. The changes were partially explained by a reduction in dysfunctional beliefs about cognitive abilities, performance, emotional experi- ence, self-stigma, and social exclusion. The changes were clinically important. Limitations of this study include the uncontrolled design. Ef- cacy was probably overestimated. Also, the patient sample was relatively small, and we performed no follow-up measurements. Larger and better designed trials are needed. Declaration of interest None. No special funding was used and no conicts of interest exist with regard to this study. Table 3 Results of mediation analysis on negative symptoms (PANSS) with bootstrapping. Direct and total effects p-values Bootstrap indirect effects 95% condence interval (A*B path) A B C( 0 ) Lower limit Upper limit Total treatment effect (without mediation) 0.000 (C) Dysfunctional beliefs as mediator 0.004 0.028 0.007 (C 0 ) 0.285 3.669 C, total effect of treatment (time) on negative symptoms; A, effect of treatment on the mediator dysfunctional beliefs; B, effect of dysfunctional beliefs on negative symptoms; C 0 effect of treatment on negative symptoms without the indirect effect of the mediator dysfunctional beliefs; A*B path, bootstrap results for the indirect effect; lower and upper limits of condence interval for test of mediation with 5.000 bootstrap re-samples and bias correction. Table 2 Paired samples t-test statistics for the mean changes between baseline and end-of-treatment. Intention-to-treat analysis (n 21). Baseline mean (sd) End-of-treatment mean (sd) t (2-tailed) p Effect size Cohens d PANSS negative syndrome 20.2 (4.3) 14.1 (5.3) 6.16 0.000 1.26 Dysfunctional beliefs 0.00 (1.68) 1.51 (1.50) 3.84 0.001 0.95 PANSS: positive and negative syndrome scales. A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 305 Acknowledgments We would like to acknowledge the contributions by the thera- pists of this study: Rob van Grunsven, Chris van Oeveren, Kwok Wong (Altrecht Psychiatric Institute), Anouk Nienhuis, Mary-Ann ter Huurne, Peter van Veen (Mediant Psychiatric Institute), Clau- dia Berwers (Parnassia Psychiatric Institute), Roxanne Valk (Mental Health Care Drenthe), Marije Quadackers (Mental Health Care Breburg), Heleen Begheijn (Mental Health Care NoordHolland Noord), Matty Geurink (Rivierduinen Psychiatric Institute), Fabian Shug (GGNet), and Bas van Oosterhout (Reinier van Arkel Group). References Artaloytia, J. F., Arango, C., Lathi, A., Sanz, J., Pascual, A., Cubero, P., et al. (2006). Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers. American Journal of Psychiatry, 163, 488e493. Baron, R. M., & Kenny, D. A. (1986). The moderatoremediator variable distinction in social psychological research: conceptual, strategic, and statistical consider- ations. Journal of Personality and Social Psychology, 6, 1173e1182. Beck, A. T., Grant, P. M., Huh, G. A., Perivoliotis, D., & Chang, N. A. (2011). Dysfunctional attitudes and expectancies in decit syndrome schizophrenia. Schizophrenia Bulletin, http://dx.doi.org/10.1093/schbul/sbr040. Beck, A. T., Steer, R. A., Ball, R., & Ranieri, W. F. (1996). Comparison of beck depression inventories-IA and -II in psychiatric outpatients. Journal of Person- ality Assessment, 67, 588e597. Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the beck depression inventory-II. San Antonio: Psychological Corporation. Beck, A. T., Steer, R. A., & Garbin, M. G. (1988). Psychometric properties of the beck depression inventory: twenty-ve years of evaluation. Clinical Psychology Review, 8, 77e100. Beck, A. T., Weissman, A., Lester, D., & Trexler, L. (1974). The measurement of pessimism: the hopelessness scale. Journal of Consulting and Clinical Psychology, 42(6), 861. Buckley, P. F., & Stahl, S. M. (2007). Pharmacological treatment of negative symptoms of schizophrenia: therapeutic opportunity or cul-de-sac? Acta Psychiatrica Scandinavica, 115(2), 93e100. http://dx.doi.org/10.1111/j.1600- 0447.2007.00992.x. Castelein, S., Bruggeman, R., van Busschbach, T., van der Gaag, M., Stant, D., Knegtering, H., et al. (2008). The effectiveness of peer support groups in psychosis: a randomized controlled trial. Acta Psychiatrica Scandinavica, 118(1), 64e72. http://dx.doi.org/10.1111/j.1600-0447.2008.01216.x. Cavelti, M., Kvrgic, S., Beck, E. M., Rsch, N., & Vauth, R. (2011). Self-stigma and its relationship with insight, demoralization, and clinical outcome among people with schizophrenia spectrum disorders. Comprehensive Psychiatry, http:// dx.doi.org/10.1016/j.comppsych.2011.08.001. Cohen, J. (1992). A power primer. Psychological Bulletin, 112, 155e159. Couture, S. M., Blanchard, J. J., & Bennett, M. E. (2011). Negative expectancy appraisals and defeatist performance beliefs and negative symptoms of schizophrenia. Psychiatry Research, 189(1), 43e48. http://dx.doi.org/10.1016/ j.psychres.2011.05.032. Evensen, J., Rssberg, J. I., Barder, H., Haahr, U., Hegelstad, W. T., Joa, I., et al. (2012). Flat affect and social functioning: a 10 year follow-up study of rst episode psychosis patients. Schizophrenia Research, http://dx.doi.org/10.1016/ j.schres.2012.04.019. Gard, D. E., Kring, A. M., Gard, M. G., Horan, W. P., & Green, M. F. (2007). Anhedonia in schizophrenia: distinctions between anticipatory and consummatory plea- sure. Schizophrenia Research, 93(1e3), 253e260. http://dx.doi.org/10.1016/ j.schres.2007.03.008. Gold, C., Solli, H. P., Krger, V., & Lie, S. A. (2009). Doseeresponse relationship in music therapy for people with serious mental disorders: systematic review and meta-analysis. Clinical Psychology Review, 29(3), 193e207. http://dx.doi.org/ 10.1016/j.cpr.2009.01.001. Grant, P. M., & Beck, A. T. (2009). Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizo- phrenia Bulletin, 35(4), 798e806. http://dx.doi.org/10.1093/schbul/sbn008. Grant, P. M., & Beck, A. T. (2010). Asocial beliefs as predictors of asocial behavior in schizophrenia. Psychiatry Research, 177(1e2), 65e70. http://dx.doi.org/10.1016/ j.psychres.2010.01.005. Grant, P. M., Huh, G. A., Perivoliotis, D., Stolar, N. M., & Beck, A. T. (2012). Randomized trial to evaluate the efcacy of cognitive therapy for low- functioning patients with schizophrenia. Archives of General Psychiatry, 69(2), 121e127. http://dx.doi.org/10.1001/archgenpsychiatry.2011.129. Hayes, A. F. (2011). SPSS-Macro. School of Communication, The Ohio State Univer- sity. hayes.338@osu.edu. http://afhayes.com/spss-sas-and-mplus-macros-and- code.html */* version 4.1, January 21, 2011. Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scales (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261e276. Kirkpatrick, B., Fenton, W. S., Carpenter, W. T., & Marder, S. R. (2006). The NIMH- MATRICS consensus statement on negative symptoms. Schizophrenia Bulletin, 32(2), 214e219. http://dx.doi.org/10.1093/schbul/sbj053. Klingberg, S., Wlwer, W., Engel, C., Wittorf, A., Herrlich, J., Meisner, C., et al. (2011). Negative symptoms of schizophrenia as primary target of cognitive behavioral therapy: results of the randomized clinical TONES study. Schizophrenia Bulletin, 37(Suppl. 2), S98eS110. http://dx.doi.org/10.1093/schbul/sbr073. Lang, F. U., Ksters, M., Lang, S., Becker, T., & Jger, M. (2012). Psychopathological long-term outcome of schizophrenia e a review. Acta Psychiatrica Scandinavica, http://dx.doi.org/10.1111/acps.12030. Leucht, S., Arbter, D., Engel, R. R., Kissling, W., & Davis, J. M. (2009). How effective are second-generation antipsychotic drugs? A meta-analysis of placebo- controlled trials. Molecular Psychiatry, 14(4), 429e447. http://dx.doi.org/ 10.1038/sj.mp.4002136. Lysaker, P. H., Roe, D., & Yanos, P. T. (2007). Toward understanding the insight paradox: internalized stigma moderates the association between insight and social functioning, hope, and self-esteem among people with schizophrenia spectrum disorders. Schizophrenia Bulletin, 33(1), 192e199. http://dx.doi.org/ 10.1093/schbul/sbl016. Mkinen, J., Miettunen, J., Isohanni, M., & Koponen, H. (2008). Negative symptoms in schizophrenia: a review. Nordic Journal of Psychiatry, 62(5), 334e341. http:// dx.doi.org/10.1080/08039480801959307. Mittal, D., Sullivan, G., Chekuri, L., Allee, E., & Corrigan, P. W. (2012). Empirical studies of self-stigma reduction strategies: a critical review of the literature. Psychiatric Services (Washington, D.C.), http://dx.doi.org/10.1176/appi.ps.201100459. Moriarty, A., Jolley, S., Callanan, M. M., & Garety, P. (2012). Understanding reduced activity in psychosis: the roles of stigma and illness appraisals. Social Psychiatry and Psychiatric Epidemiology, http://dx.doi.org/10.1007/s00127-012-0475-z. Oorschot, M., Lataster, T., Thewissen, V., Lardinois, M., Wichers, M., van Os, J., et al. (2011). Emotional experience in negative symptoms of schizophrenia e no evidence for a generalized hedonic decit. Schizophrenia Bulletin, http:// dx.doi.org/10.1093/schbul/sbr137. Perivoliotis, D., & Cather, C. (2009). Cognitive behavioral therapy of negative symptoms. Journal of Clinical Psychology, 65(8), 815e830. http://dx.doi.org/ 10.1002/jclp.20614. Pope, J. W., & Kern, R. S. (2006). An errorful learning decit in schizophrenia? Journal of Clinical and Experimental Neuropsychology, 28(1), 101e110. Preacher, K. J., & Hayes, A. F. (2008). Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behavior Research Methods, 40(3), 879e891. http://dx.doi.org/10.3758/BRM.40.3.879. Ritsher, J., Otilingam, P. G., & Grajales, M. (2003). Internalized stigma of mental illness: psychometric properties of a new measure. Psychiatry Research, 121(1), 31e49. http://dx.doi.org/10.1016/j.psychres.2003.08.008. Rhricht, F., &Priebe, S. (2006). Effect of body-orientedpsychological therapyonnegative symptoms in schizophrenia: a randomized controlled trial. Psychological Medicine, 36(5), 669e678. http://dx.doi.org/10.1017/S0033291706007161. Singh, S. P., Singh, V., Kar, N., & Chan, K. (2010). Efcacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. The British Journal of Psychiatry: The Journal of Mental Science, 197(3), 174e179. http://dx.doi.org/10.1192/bjp.bp.109.067710. Staring, A. B., Van der Gaag, M., Van den Berge, M., Duivenvoorden, H. J., & Mulder, C. L. (2009). Stigma moderates the associations of insight with depressed mood, low self-esteem, and low quality of life in patients with schizophrenia spectrum disorders. Schizophrenia Research, 115(2e3), 363e369. http://dx.doi.org/10.1016/j.schres.2009.06.015. Staring, A. B. P., & Van den Berg, N. (2010). Cognitieve gedragstherapie voor patinten met postpsychotische demoralisatie. Directieve Therapie, 30(4), 280e302. Staring, A. B. P., & Van der Gaag, M. (2010). Cognitieve gedragstherapie voor demoralisatie bij schizofrenie. Gedragstherapie, 43, 205e224. Ventura, J., Hellemann, G. S., Thames, A. D., Koellner, V., & Nuechterlein, K. H. (2009). Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophrenia Research, 113(2e3), 189e199. http://dx.doi.org/10.1016/j.schres.2009.03.035. Villeneuve, K., Potvin, S., Lesage, A., & Nicole, L. (2010). Meta-analysis of rates of drop-out from psychosocial treatment among persons with schizophrenia spectrum disorder. Schizophrenia Research, 121(1e3), 266e270. http:// dx.doi.org/10.1016/j.schres.2010.04.003. Weissman, A. (1978). Dysfunctional attitudes scale: A validation study. Philadelphia: University of Pennsylvania. Wykes, T., Steel, C., Everitt, B., & Tarrier, N. (2008). Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizo- phrenia Bulletin, 34(3), 523e537. http://dx.doi.org/10.1093/schbul/sbm114. A.B.P. Staring et al. / J. Behav. Ther. & Exp. Psychiat. 44 (2013) 300e306 306