Schizophrenia Research Forum - A Catalyst for Creative Thinking

Added Value: Combined Therapy Benefits People With Schizophrenia

27 September 2010. Combining psychosocial treatments with antipsychotic medication can lead to greater gains in early-stage schizophrenia patients compared to taking medication alone, according to a study published in the September issue of Archives of General Psychiatry.

Led by Jingping Zhao at Central South University in Changsha, China, the study addresses whether treatment with current antipsychotic medications—the mainstay for people with schizophrenia—can be improved upon. Though these medications effectively quell some symptoms, they often fail to address others and have adverse effects that compel many to stop taking them. The end result is that many patients are unable to live independent lives with regular employment, responsibilities, and relationships. With no new drugs on the horizon, the researchers asked whether adding an intensive psychosocial component to treatment could help.

While other studies have taken this combination therapy approach before (e.g., Tarrier et al., 2004 and Bertelsen et al., 2008), this study is notable for its wide scope in both treatment components and measured outcomes. Study participants assigned to the medication plus psychosocial treatment group attended group therapy sessions that discussed various aspects of schizophrenia, provided skills training, and employed cognitive behavioral therapy, which helps people adapt their emotions and cognitive habits appropriately. For outcomes, the researchers looked at rates of treatment discontinuation and relapse, as well as other real-world factors like social functioning, quality of life, and employment. Almost across the board, the combined treatment resulted in greater improvements than those observed in the group taking medication alone.

One year, 48 hours later
Conducted in China, the one year-long study enrolled 1,268 people (average age 26 years) who had been diagnosed with schizophrenia within the past five years. The study participants were randomly assigned to either the medication alone group or the combined treatment group, who received both medication and psychosocial therapy. These groups did not differ in their demographic or clinical characteristics, including the dosage and kind of antipsychotic drugs taken.

Once a month, study participants visited their clinic so that clinicians could assess their responses to medication. Those in the combined treatment group also received four hours of group psychosocial therapy there that same day. Over the year, this amounted to 48 hours of psychosocial therapy. Their accompanying family members also received psychosocial education in a group setting during these visits.

Of those in the combined treatment group, 67.2 percent made it to the end of the study—significantly more than the 53.2 percent of those in the medication alone group (HR, 0.62; 95 percent CI, 0.52-0.74; P <.001). People left the study for a number of reasons, including clinical relapse, refusal to participate, or changing medications. The researchers noted a significantly lower rate of clinical relapse in the combined treatment group (14.6 percent) compared to the medication alone group (22.5 percent) (HR, 0.57; 95 percent CI, 0.44-0.74; P <.001). Preventing relapse bodes well for long-term improvements for people with schizophrenia.

Though both groups had similar decreases in symptom severity, as measured by the Positive and Negative Symptom Scale (PANSS), the combined treatment group seemed to have greater insight into their disorder, obtaining higher scores on the Insight and Treatment Attitudes Questionnaire (ITAQ) than did the medication alone group.

The researchers also found that the combined treatment favorably influenced how the study participants live and integrate into society. Compared to the medication alone group, the combined treatment group had greater gains in measures of social functioning, daily living skills, and four areas of quality of life, including general and emotional health. A greater proportion of people in the combined group got a job or pursued education during the year than those in the medication alone group (30.1 percent vs. 22.2 percent χ2 = 10.09; P = .001).

Though it is hard to draw conclusions about which component of the psychosocial intervention influenced which outcomes, the study demonstrates the feasibility of delivering psychosocial intervention in conjunction with medication. The researchers suggest that this model—which requires a family commitment to get the patient to the clinic and to participate in family sessions themselves—may work best in countries like China, where people with schizophrenia tend to live with their families.

The study also emphasizes the importance of early-stage treatment in schizophrenia, and the importance of finding ways to manage the disease—both with and without drugs—before it becomes chronic and disabling.—Michele Solis.

Reference:
Guo X, Zhai J, Liu Z, Fang M, Wang B, Wang C, Hu B, Sun X, Lv L, Lu Z, Ma C, He X, Guo T, Xie S, Wu R, Xue Z, Chen J, Twamley EW, Jin H, Zhao J. Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study. Arch Gen Psychiatry. 2010 Sep; 67: 895-904. Abstract

Comments on News and Primary Papers
Comment by:  Wendy Camp
Submitted 18 October 2010
Posted 18 October 2010

In Connecticut we have a wonderful Medicaid/T19/Behavioral Health program that allows home health nurses to monitor and/or administer medications for noncompliant mental health patients and home health aides to be in the home up to 14 hours a week to assist with medication reminders, ADLs, and IADLs.

I would be interested to know what impact our behavioral health nurses might have on an early-stage schizophrenia population versus our chronic noncompliant population. If we had our nurses in the home sooner, could we correct potentially problematic behavior before it became chronic?

View all comments by Wendy CampComment by:  Douglas Turkington (Disclosure)
Submitted 16 November 2010
Posted 17 November 2010

This paper is important because of its power and because this most basic question has never been satisfactorily answered. My concern is the very high dropout rate in both groups. Dropout across CBT of schizophrenia trials normally averages about 15 percent. CBT also usually attempts to work from a mini-formulation or macro-formulation which extends beyond the A-B-C. The CBT given here, however, does parallel the pragmatic technique-orientated CBT given in the Insight trial (Turkington et al., 2002). The problem here would appear to be the delivery of all four interventions in group format on the same day once per month. This is a massive burden on patients with cognitive deficits, negative symptoms, and treatment-resistant hallucinations and delusions. We must therefore be guarded about the conclusions. There is a signal, however, of the need for a psychosocial component in the management of every patient with schizophrenia. We are grateful to the authors for this publication.

References:

Turkington D, Kingdon D and Turner T. (2002) Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia. British Journal of Psychiatry 180, 523-527. Abstract

View all comments by Douglas Turkington

Comments on Related News


Related News: Cognitive Therapy May Power a Cycle of Recovery in Chronic Schizophrenia

Comment by:  Robert Paul Liberman
Submitted 14 October 2011
Posted 14 October 2011

This study of a well-established, psychosocial treatment, which has been documented to be effective for depression, anxiety disorders, and positive symptoms of schizophrenia (Salkovskis, 1996; Kingdon and Turkington, 2004), presents credible evidence of efficacy for some, but not all, negative symptoms and possibly for social functioning in schizophrenia. The study has a number of strong methodological features; for example, protecting the “blind” for assessors, appropriate frequency and duration of treatment sessions necessary to achieve therapeutic outcomes in this population, controls for differences in types and doses of antipsychotic medication, a “standard treatment” comparison group which is consistent with the vast majority of community mental health, a sample that includes different racial and ethnic groups consistent with an inner-city population, and appropriate statistical analyses for measuring outcome. My comments address a number of concerns that may attenuate the clinical significance of the authors’ findings and interpretations.

Selection Criteria for Subjects
There is no indication whether the subjects had primary negative symptoms (i.e., the deficit state defined by enduring negative symptoms not related to positive symptoms including anxiety and depression, under-stimulating environments, side effects of medication (e.g., sedation, akathisia, akinesia, weight gain) or negative symptoms secondary to the above listed remediable interferences. In fact, it is likely that they had secondary negative symptoms because, as noted by the authors, the subjects showed significant reductions in positive symptoms and social anxiety, which often are associated with reductions of negative symptoms.

While the subjects were described as “low functioning” and “highly regressed,” the eligibility criteria for entry into the study did not use a well-established and psychometrically sound assessment instrument for measuring social functioning. For some inexplicable reason, the Global Assessment Scale was chosen as the measure of “social functioning,” despite the authors appropriately pointing out how the GAS confounds symptoms with functioning and has woefully inadequate anchor points for rating psychosocial adjustment and poor inter-rater reliability. The finding that, at baseline, their subjects were rated by the GAS in the mid- to high 40s suggests functioning that reflects “serious symptoms” and “serious impairment in social occupational or school functioning,” with the latter exemplified by “no friends” and “unable to keep a job.” This range in the GAS is hardly consistent with schizophrenia patients who are “repressed” and “severely socially impaired.” Individuals with schizophrenia who are low functioning would ordinarily fall into the 25-40 range on the GAS (e.g., “unable to work,” “socially isolated with little contact with other persons outside the family”). Many persons with schizophrenia who would not be considered “low functioning,” even those in remission of their positive and negative symptoms, have no friends and are unable to keep a job.

While the authors point out in their discussion that the GAS is a poor indicator of social functioning, it is not clear why they chose this instrument for their design, since it is well known that the GAS has poor inter-rater reliability, poor anchor points, and confounds symptoms with functioning (Dickerson, 1997).

The authors fail to describe specific improvements in social functioning that would convince readers that the cognitive therapy resulted in clinically significant improvements in work, school, friendships, family life, self-care skills, medication and money self-management, independent living, and other convincing examples of successes in community living.

The therapeutic methods as described by the authors clearly confound cognitive therapy procedures with those developed and validated for social skills training (Liberman et al. Social Skills Training for Psychiatric Patients, 1989; Bellack et al. Social Skills Training for Schizophrenia, 2006; Liberman. Recovery from Disability: Manual of Psychiatric Rehabilitation, 2008). For example, as described in the description of cognitive therapy, the following techniques were used that are key elements of social skills training in particular, and other evidence-based practices for the treatment of schizophrenia as well (e.g., supported employment, behavioral family therapy and its variants, assertive community treatment, cognitive adaptive therapy):

Specificity of Cognitive Therapy for Negative Symptoms
It is possible that the many elements in the experimental treatment condition that were similar to those used in social skills training, rather than the specific cognitive interventions, could have brought about the improvements reported in negative symptoms and social functioning.

Contrary to the assertion of the authors that “studies of other psychosocial, behavioral, or cognitive remediation interventions…[have failed]…to find that treatment effects generalized adequately to psychosocial functioning,” there are a number of evidence-based, psychosocial treatments that have been shown to significantly improve psychosocial functioning and negative symptoms. These include social skills training, behavioral family management, supported employment, and assertive community treatment (Bellack, 2004; Liberman et al., 1998; Glynn et al., 2002; Bellack and Mueser, 1993; Heinssen et al., 2000; Kurtz and Mueser, 2008; Kopelowicz et al., 1997; Falloon et al., 1987; Falloon et al., 1999; Drake et al., 1999; Drake et al., 1996; Stein and Test, 1980).

The authors give examples of how subjects’ symptoms interfered with social functioning, such as social anxiety and positive symptoms of schizophrenia. Since anxiety disorders are very common comorbidities in schizophrenia and have been shown to be responsive to cognitive therapy (Rector and Beck, 2001), it is possible that the cognitive therapy improved social interaction and adjustment by reducing anxiety. It is also possible, as noted by the authors, that the cognitive therapy brought about reductions in three of the four domains of negative symptoms secondarily as a function of rather marked decrease in positive symptoms. The reductions in positive symptoms were much greater than the rather small reductions in negative symptoms. This reverse direction of causality is acknowledged as a possible explanation of their results on negative symptoms by the authors in their Comment section.

One finding of the authors strongly suggests that the cognitive therapy did not produce improvements in psychosocial functioning by reducing negative symptoms. In Figure 3, it is clearly seen that the cognitive therapy had nil therapeutic impact on alogia, which is the critical negative symptom that would be expected to mediate improved social functioning. If subjects’ speech and conversational skills showed little improvement, it is questionable to attribute improvements in social interaction and relationships to the other three negative symptoms. The non-specific effects of 18 months and 50 sessions of community-based activities and homework assignments to attain incremental goals, instigated by competent, upbeat, and engaging therapists, would be expected to reduce apathy, anhedonia, and flat affect temporarily—which might rapidly erode once the spirited and therapeutically active sessions ended.

Also acknowledged by the authors in their Comment section is the possibility that improvements in three of four negative symptoms and marginal changes in social functioning (difficult to conceptualize without more behaviorally specific examples and typologies of goals attained in the arenas of social functioning) might be attributed to non-specific factors in the therapeutic relationships and instigative array of interventions used in the active therapy condition. As they point out, it may be appropriate to withhold an evidence-based attribution of the therapeutic benefits found in this study until a study is conducted with a comparison treatment equated for therapist enthusiasm, duration, time involvement, and other elements not specifically related to cognitive therapy.

Finally, one further cautionary note stems from the failure of the investigators to assess adherence to medication in the two treatment conditions. While the prescribed types and doses of medication did not differ between the conditions, it is well known that adherence to medication regimens is rather poor among persons with schizophrenia. Improved adherence to pharmacotherapy may have contributed to the superior therapeutic outcomes, given the fact that the therapists in the cognitive therapy program offered “personalized treatment” that included “laminated cards” and “colorful signs that patients posted at home to remind them of daily activities and other therapy assignments” which may have included concrete or implicit reminders to take their medication.

References:

Salkovskis PM: Frontiers of Cognitive Therapy. New York: Guilford Press, 1996. Kingdon D and Turkington D: Cognitive Therapy of Schizophrenia. New York: Guilford Press, 2004.

Dickerson FB. Assessing clinical outcomes: the community functioning of persons with serious mental illness. Psychiatr Serv . 1997 Jul 1 ; 48(7):897-902. Abstract

Liberman RP, DeRisi WJ, Mueser KT: Social Skills Training for Psychiatric Patients. Norwood MA: Allyn and Bacon, 1989.

Bellack AS, Mueser KT, Gingerich S and Agresta J: Social Skills Training for Schizophrenia. New York: Guilford Press, 2006.

Liberman RP: Recovery from Disability: Manual of Psychiatric Rehabilitation. Arlington VA: American Psychiatric Publishing Inc., 2008.

Bellack AS. Skills training for people with severe mental illness. Psychiatr Rehabil J . 2004 Jan 1 ; 27(4):375-91. Abstract

Liberman RP, Wallace CJ, Blackwell G, Kopelowicz A, Vaccaro JV, Mintz J. Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia. Am J Psychiatry . 1998 Aug 1 ; 155(8):1087-91. Abstract

Glynn SM, Marder SR, Liberman RP, Blair K, Wirshing WC, Wirshing DA, Ross D, Mintz J. Supplementing clinic-based skills training with manual-based community support sessions: effects on social adjustment of patients with schizophrenia. Am J Psychiatry . 2002 May 1 ; 159(5):829-37. Abstract

Bellack AS, Mueser KT. Psychosocial treatment for schizophrenia. Schizophr Bull . 1993 Jan 1 ; 19(2):317-36. Abstract

Heinssen RK, Liberman RP, Kopelowicz A. Psychosocial skills training for schizophrenia: lessons from the laboratory. Schizophr Bull . 2000 Jan 1 ; 26(1):21-46. Abstract

Kurtz MM, Mueser KT. A meta-analysis of controlled research on social skills training for schizophrenia. J Consult Clin Psychol . 2008 Jun 1 ; 76(3):491-504. Abstract

Kopelowicz A, Liberman RP, Mintz J, Zarate R. Comparison of efficacy of social skills training for deficit and nondeficit negative symptoms in schizophrenia. Am J Psychiatry . 1997 Mar 1 ; 154(3):424-5. Abstract

Falloon IR, McGill CW, Boyd JL, Pederson J. Family management in the prevention of morbidity of schizophrenia: social outcome of a two-year longitudinal study. Psychol Med . 1987 Feb 1 ; 17(1):59-66. Abstract

Falloon IRH, Held T, Coverdale J, ARoncone and Laidlaw T. Family interventions for schizophrenia: A review of long-term benefits of international studies. Psychiatric Rehabilitation Skills. 3:268-290, 1999.

Drake RE, McHugo GJ, Bebout RR, Becker DR, Harris M, Bond GR, Quimby E. A randomized clinical trial of supported employment for inner-city patients with severe mental disorders. Arch Gen Psychiatry . 1999 Jul 1 ; 56(7):627-33. Abstract

Drake RE, McHugo GJ, Becker DR, Anthony WA, Clark RE. The New Hampshire study of supported employment for people with severe mental illness. J Consult Clin Psychol . 1996 Apr 1 ; 64(2):391-9. Abstract

Stein LI, Test MA. Alternative to mental hospital treatment. I. Conceptual model, treatment program, and clinical evaluation. Arch Gen Psychiatry . 1980 Apr 1 ; 37(4):392-7. Abstract

Rector NA, Beck AT. Cognitive behavioral therapy for schizophrenia: an empirical review. J Nerv Ment Dis . 2001 May 1 ; 189(5):278-87. Abstract

View all comments by Robert Paul Liberman

Related News: Cognitive Therapy May Power a Cycle of Recovery in Chronic Schizophrenia

Comment by:  Alan S Bellack
Submitted 10 November 2011
Posted 10 November 2011

Grant and colleagues are to be congratulated on their noteworthy trial. Anyone who has conducted clinical trials with seriously ill schizophrenia patients must be impressed by the ability of the research team to recruit a large cohort in an intensive treatment and keep them engaged over such a long period of time. The team also deserves credit for demonstrating that a psychosocial intervention can have a meaningful impact with this population. Added to the increasing literature on cognitive therapies with schizophrenia patients, and on recovery-based interventions, this report reinforces the argument that people with schizophrenia can and should be engaged as partners in the treatment process.

In a previous post, Bob Liberman identified a number of crucial limitations of this trial that raise questions about the findings and limit enthusiasm for the intervention. I concur with almost all of Bob's observations and analysis. The primary outcome variable (the GAS) has marked limitations and does not provide objective or detailed information about any changes in social or occupational functioning in the community. Thus, the authors' conclusion that "cognitive therapy can be successful in promoting clinically meaningful improvements in functioning" is not supported by the data. We simply do not know much about community functioning beyond what the patients report, and the reports are especially suspect given that subjects receiving the cognitive therapy attended weekly sessions with a study therapist in which a primary focus of discussions was enhancing community activities and role functioning. A related concern pertains to the course of change noted on both the GAS and SANS ratings. The graphic representation of the data indicates that most, if not all, of the change manifested across measures occurred before the first (six-month) assessment. This raises questions about the operating mechanism of the CT intervention, as well as the value of the succeeding 12 months of treatment. As stated in the article, "Early sessions focused on engaging the patient and strengthening the therapeutic relationship." This implies that any changes induced during that early period may have resulted from non-specific effects rather than any specific cognitive therapy activities. Given that (almost) no community program could afford to administer a weekly individual treatment for 18 months, it should be underscored that at best, the data do not support anything beyond six months of treatment.

Another important issue noted by Liberman was the multifaceted composition of the CT intervention. It included elements of cognitive therapy, skills training, behavior therapy, motivational enhancement, and cognitive remediation, among others. In fact, it is difficult to justify calling the intervention "cognitive therapy" when so little of it entails cognitive therapy per se. While most of the elements have face validity and independent empirical support, the resulting combination has two significant limitations. First, it is impossible to determine the active components of the treatment. Second, it would be virtually impossible to replicate or disseminate the intervention. This latter point is of particular concern, as the trial has been reported in the media (e.g., The New York Times) as demonstrating that cognitive therapy is effective for schizophrenia patients with negative symptoms. To the contrary, this trial does not demonstrate that CT is effective for reducing negative symptoms, or that CT is a cognitive therapy.

In sum, this is an important trial that should and will have an important heuristic role for the field. It is a trial that should have been done and probably could not have been done by any other research group. While acknowledging and applauding its strengths and value for the field, it is important to consider its limitations and be cautious about what conclusions can be drawn from the results.

View all comments by Alan S Bellack

Related News: Cognitive Therapy May Power a Cycle of Recovery in Chronic Schizophrenia

Comment by:  Paul Grant
Submitted 31 January 2012
Posted 2 February 2012

We thank Professors Liberman and Bellack for their thoughtful critiques of our work and welcome the opportunity to answer their questions and concerns, and thereby clarify our study beyond the space limitations of the original paper.

Liberman and Bellack express several concerns regarding the number and types of techniques employed in therapy, as well as the length of therapy. Liberman states that our therapy is “confounded” with other treatment approaches because the intervention contains many treatment techniques (e.g., skills training, cognitive remediation, motivational enhancement) that overlap with other psychosocial treatments for schizophrenia; Bellack indicates that he does not believe our treatment should properly be called “cognitive therapy” because “so little of it entails cognitive therapy per se.” We appreciate that they have raised this issue because it affords us an opportunity to explain in greater detail why we use the term cognitive therapy and what we mean by it.

Our formulation of cognitive therapy is based on the cognitive model of schizophrenia (Beck et al., 2009) rather than specific techniques. Basically, we view the low-functioning problems in these patients as due to the interaction of neurocognitive deficits and negative attitudes about performance and social relations. Our basic research has shown both in cross-sectional (Grant and Beck, 2009; Grant and Beck, 2009) and longitudinal (Grant and Beck, 2010) studies that these low-functioning patients have very powerful negative attitudes about the possibility of achieving any goals (e.g., “there is no point in trying because I will only fail”), as well as negative attitudes about the desirability of social contact. In non-technical terms, these patients have given up and have walled themselves off from usual activities of everyday life because of their expectations that they are only going to fail if they try something. While there evidently is an upper limit on how much they can achieve due to their neurocognitive deficits, they do have considerable latent capacity that they are not utilizing. Since the negative attitudes seem to account for their loss of motivation, we use a variety of methods to ameliorate them. Since we frame the problems in cognitive terms, and our understanding of each case is based on a cognitive model, we utilize the term cognitive therapy. We would, therefore, expect that any change would be mediated by cognitive variables. To produce this change, we formulate each case in terms of the individual’s goals and identify the various obstacles to reaching these goals. We select specific techniques ranging from skills training, problem solving, explicit cognitive restructuring, etc., to overcome these obstacles. If the patient is blocked by social inhibition, we use assertiveness training; if the problem is fear of failing, we use cognitive restructuring. According to our thesis, each specific successful experience tends to undercut the negative attitudes that sap the patient’s motivation. Support for our formulation is based on an experimental study which showed that success experiences not only modify negative attitudes, but increase motivation and performance (Perivoliotis et al., 2011). Once the patients start to modify their attitudes, they become more engaged in real life and begin to take advantage of various rehabilitative services that are offered. The question of when and how to apply these strategies is described in the volume by Perivoliotis, Grant, and Beck (Perivoliotis et al., in press).

The multifaceted nature of our CT intervention prompts both Bellack and Liberman to wonder about the mechanism of change. In response to Bellack’s concern that it would be impossible to determine the “active ingredients” of the treatment, we propose that the beliefs targeted by the formulation-driven interventions are producing change. Mediation analysis (beliefs as mediators) would allow us to test this hypothesis. Liberman, in a similar vein, proposes several alternative explanations for our results: behavioral methods, social anxiety, positive symptoms, and medication adherence. He also proposes that, since we did not observe changes in alogia, we did not really affect social functioning. In regard of this last point, we think it is notable that the mean alogia ratings were in the questionable to mild range at baseline and remained in this range throughout the course of the trial. This finding suggests that if improvements were made, it is unlikely that they would be clinically meaningful due to a floor effect.

Additionally, it does not seem likely that the global improvement in the patients’ functioning was due to compliance with medication, since previous research has shown minimal impact from medication (Swartz et al., 2007). However, if medication compliance was improved, this would indicate a positive result from our multifaceted intervention. A similar argument extends to positive symptoms and social anxiety. Finally, while it is possible that behavioral methods could be the mechanisms of change in our study, it is also possible that cognitive change is produced by social skills training and cognitive remediation. We think that exploring beliefs in psychosocial treatments for schizophrenia is a rich area to pursue.

Bellack makes three final points regarding the CT treatment: he questions whether it would be possible to “replicate or disseminate the intervention”; he proposes that our data do not support providing more than six months of CT; and he suggests that “all of the changes induced during that early period may have resulted from non-specific effects rather than any specific cognitive therapy activities.” In regard to dissemination, we have already successfully trained masters-level community therapists in the manualized intervention, and have applied for funding to conduct a systematic study. As to the length of treatment, 50 sessions was the average for the entire group in the study: some participants completed therapy in fewer sessions and some required more. Thus, consistent with an individualized recovery orientation, we argue that some patients can benefit from shorter course of therapy whilst others will require more sessions. This is a matter for future study. And, in regard to non-specific factors, the best way to test this alternative hypothesis is to conduct a new study that compares CT to a supportive therapy control group.

Turning to the methods of the study, both authors are concerned about the measurement of functioning in our study. Liberman states that we did not use a well-established and psychometrically sound assessment instrument measuring social functioning for inclusion, while Bellack and Liberman both criticize our outcome measure as inadequate. We did not specifically describe social functioning as a key outcome, but rather global functioning. The Global Assessment Scale (GAS) was a conventional measure of global functioning at the time we initiated our study. Since that time, new measures have been developed, such as the Schizophrenia Objective Functioning Instrument (SOFI; Kleinman et al., 2009), and research by Phil Harvey’s group (Harvey et al., 2011; Leifker et al., 2011) has indicated that the preferred measure of functioning is the Specific Levels of Functioning scale (SLOF; Schneider and Struenging, 1983). In our next study, we plan to use the SLOF as the primary outcome measure.

Liberman proposes that our sample may not have been composed of patients with primary negative symptoms. In other words, the patients in the study had negative symptoms that were secondary to positive symptoms, with the observed improvement in negative symptoms being produced by improvement in positive symptoms. We did not formally assess primary versus secondary negative symptoms in the clinical trial. However, clinically, we observed that defeatist beliefs occurred independently of the presence of positive symptoms. And, as the beliefs were modified by the CT treatment, patients improved.

Finally, Bellack suggests our data do not support the conclusion that “cognitive therapy can be successful in promoting clinically meaningful improvements in functioning.” We disagree with his inference. We believe the intervention, by whatever name, produced successful results, as was evident in the collateral reports factored into the ratings of functioning.

The authors wish to acknowledge the contributions of Drs. Jessica Murakmi-Brundage and Yael Perry in developing this response.

References:

1. Beck AT, Rector NA, Stolar NM, Grant PM. Schizophrenia: Cognitive Theory, Research and Therapy. NY: Guilford Press; 2009.

2. Grant PM, Beck AT. Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizophr Bull. Jul 2009;35(4):798-806. Abstract

3. Grant PM, Beck AT. Evaluation sensitivity as a moderator of communication disorder in schizophrenia. Psychol Med. Jul 2009;39(7):1211-1219. Abstract

4. Grant PM, Beck AT. Asocial beliefs as predictors of asocial behavior in schizophrenia. Psychiatry Res. 2010;177(1-2):65-70. Abstract

5. Perivoliotis D, Grant PM, Beck AT. The impact of success in low-functioning schizophrenia: an analogue study. International Conference on Schizophrenia Research. Colorado Springs, CO. April 02, 2011.

6. Perivoliotis D, Grant PM, Beck AT. Cognitive behavior therapy for schizophrenia: a comprehensive treatment manual. New York: Guilford; in press.

7. Swartz MS, Perkins DO, Stroup TS, Davis SM, Capuano G, Rosenheck RA, Reimherr F, McGee MF, Keefe RSE, McEvoy JP, Hsiao JK, Lieberman JA, Investigators ftC. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry. 2007;164(3):428-436. Abstract

8. Kleinman L, Lieberman J, Dube S, Mohs R, Zhao Y, Kinon B, Carpenter W, Harvey PD, Green MF, Keefe RSE, Frank L, Bowman L, Revicki DA. Development and psychometric performance of the schizophrenia objective functioning instrument: an interviewer administered measure of function. Schizophr Res. 2009;107(2-3):275-285. Abstract

9. Harvey PD, Raykov T, Twamley EW, Vella L, Heaton PK, Patterson TL. Validating the measurement of real-world functional outcomes: phase I results of the VALERO study. Am J Psychiatry. 2011;168:1195-1201. Abstract

10. Leifker FR, Patterson TL, Heaton PK, Harvey PD. Validating measures of real-world outcome: the results of the VALERO expert survey and RAND panel. Schizophr Bull. 2011;37:334-343. Abstract

11. Schneider LC, Struenging EL. SLOF: a behavioral rating scale for assessing the mentally ill. Soc Work Res Abstr. 1983;19:9-21.

View all comments by Paul Grant

Related News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Til Wykes
Submitted 24 August 2012
Posted 24 August 2012

The notion that cognitive remediation is effective in producing cognitive and functional gains in established schizophrenia (Wykes et al., 2011), and produces other gains such as changes identified in brain imaging (e.g., Wykes et al., 2002) is unsurprising. But the paper on remediation in adolescent rats by Lee and colleagues provides results that the authors do consider surprising, and could lead to further extensions of cognitive remediation to those who are "at risk" for disorders such as schizophrenia. This is because of the procognitive effects of providing training in youthful rats.

Procognitive effects of experience-based training are not, however, surprising. The authors quote research showing that there are functional changes with training—the one that springs to my mind is London taxi drivers whose hippocampi are larger following their "training" for The Knowledge—an all-roads-in-London test. So why are the authors surprised? Perhaps it is because the results may have further implications for treatment and prevention, but only if followed up in those who are “at risk,” a notion that has produced much heat and not much light in the annals of SRF. We have been optimistic about the possibility of change in prodromal patients using cognitive behavioral therapy, but that hope has not yet been justified in the current research. It may be that this form of experience-based learning is of greater help in the prodromal group than the traditional cognitive behavioral therapies. It may also be that we need to begin our interventions in school by identifying those who are cognitively at risk for many different future problems, not just schizophrenia.

The results also suggest that even when there is a known lesion, it is possible to normalize behavior as well as produce some correlated neuronal change. This is exciting, as it opens up the possibility of finding cures, if not for the whole disorder at least for some of the problems or symptoms of schizophrenia. All this can be produced by a non-pharmacological intervention. This is something that will surely excite the providers of healthcare, as the cost-benefit would be very high if the future health costs for these patients were reduced through such means.

References:

Wykes T, Brammer M, Mellers J, Bray P, Reeder C, Williams C, Corner J. Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia. Br J Psychiatry. 2002 Aug;181:144-52. Abstract

Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry . 2011 May ; 168(5):472-85. Abstract

View all comments by Til Wykes

Related News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Angus MacDonald, SRF Advisor
Submitted 24 August 2012
Posted 24 August 2012

In their new Neuron article, Lee and colleagues from Andre Fenton’s group at NYU report that spatial cognitive control deficits in a rat model of schizophrenia can be prevented through a ratish analogue of cognitive remediation therapy during adolescence. The importance of early intervention has been one of the hottest debates in applied schizophrenia research; the current findings suggest a basic mechanism in support of such efforts.

What is remarkable about the Fenton study is how small a training “dosage” was required to lead to markedly different adult performance. Two days of training about five weeks after birth led to marked changes in the rats’ capacity to use spatial cognitive control eight to nine weeks after birth.

Rats were sacrificed at the end of the experiment, allowing the researchers to examine the extent to which the initial lesion had affected brain development. The initial lesions dramatically altered hippocampal development. Despite this, lesioned rats who received training did not show any observable difference in brain morphology in adulthood compared to lesioned rats who did not receive training. That is to say, the integrity of the hippocampus measured grossly did not predetermine that rats would perform poorly on the spatial cognitive control task—if they received training. However, subsequent analysis demonstrated that phase synchronization between the hippocampus and prefrontal cortex (which rats possess, albeit not in extremis) was compromised in the lesioned rats who did not receive training, but was recovered in those that did receive training.

Thus, the data suggest that fundamentally important circuitry can be guided through training that is relevant for later cognitive functioning.

What is absent is evidence for the specialness of adolescent intervention. This seems to be assumed from previous work rather than the result of comparisons of implementing the intervention at different ages.

It’s also interesting to note that hippocampal lesion models are generally evaluated using memory-related tasks. Fenton’s task presents something of a hybrid. The spatial cognitive control paradigm used is appropriately adapted to the species in question, but in the abstract it has features similar to that of the Stroop task. In Fenton’s active place avoidance task, there is a dominant channel for responding on which the rat is over-trained, like the Stroop task's word reading component on which most people reading this text have been over-training. There is also a subordinate channel for responding, with which the rat is familiarized, something like color naming on the Stroop task. However, a key aspect of the manipulation is the inability to learn a new zone to avoid, which may be more akin to perseveration than to Stroop performance. Rotation of shock zone to a new location is described as task transference, but since the original learning was a source of interference (and needed to be inhibited) in the subsequent task, I’m not sure I agree with this description.

This work will be warmly received by a large number of advocates who are pushing for interventions earlier in the risk period. One advantage the authors had compared to those in the clinical schizophrenia field is that they knew which of their rats were strongly exposed and were therefore at the highest risk. While our screening tools have been honed over the past decade, they still have a high false-positive rate. One can take some solace, though, that cognitive remediation is unlikely to have extensive negative side effects. Except, perhaps, boredom.

View all comments by Angus MacDonald

Related News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Patrick McGorry, SRF Advisor
Submitted 27 August 2012
Posted 27 August 2012

I am always a little skeptical of animal models of psychosis or schizophrenia, which are pretty high-order disturbances and seem very specific to humans. If this model has some validity, the preventive therapy in humans would be more akin to cognitive remediation therapy rather than cognitive therapy per se, which has more CBT links or connotations.

View all comments by Patrick McGorry

Related News: Is Early Cognitive Training Key to Minimizing Schizophrenia Impact?

Comment by:  Barbara K. Lipska
Submitted 27 August 2012
Posted 27 August 2012

Lee et al. report exciting new data in support of the neurodevelopmental hypothesis of schizophrenia and the plausibility of the early intervention that might prevent the emergence of schizophrenia symptoms. Lee and colleagues used a neonatal ventral hippocampal lesion in rats as a model of schizophrenia.

First, using the active place avoidance task with carefully designed control tasks, they showed that the animals with neonatal lesions are cognitively impaired as adults, consistent with the results of the previous studies (see Tseng et al., 2009, for review). Next, they examined whether training of the lesioned animals in adolescence would prevent the emergence of these abnormalities. They exposed the animals to a series of cognitive tests and found that, indeed, the neonatally lesioned rats that acquired additional training as adolescents showed improved cognition in adulthood. Moreover, specific measures of neural function were also improved. The authors recorded local field potentials in the hippocampi and found that the neonatally lesioned animals showed deficits in interhippocampal synchrony, the findings similar to the changes reported in patients with schizophrenia. Adolescent cognitive training normalized interhippocampal synchrony and improved performance on the cognitive tasks in the neonatally hippocampally lesioned rats. Finally, to gain more insight into the mechanisms of these changes, the authors measured cortical thickness and parvalbumin protein content, but these parameters were not informative about the benefits of cognitive training in this animal model of schizophrenia.

The results of this study support the notion that schizophrenia is a neurodevelopmental disorder characterized by discoordinated neural networks, and provide critical evidence for the benefits of early behavioral intervention. Although we still do not fully understand the pathophysiological mechanisms underlying schizophrenia, or the mechanisms responsible for the improvements due to cognitive training, this work certainly offers a potential new therapeutic tool in the form of preemptive cognitive therapy.

References:

Tseng KY, Chambers RA, Lipska BK. The neonatal ventral hippocampal lesion as a heuristic neurodevelopmental model of schizophrenia. Behav Brain Res . 2009 Dec 7 ; 204(2):295-305. Abstract

View all comments by Barbara K. Lipska