21 June 2011. At the Thirteenth International Congress on Schizophrenia Research, a session called “What really improves people’s lives? Surprising findings on functional outcome in schizophrenia” drew a roomful of people on 3 April. Session chair Sophia Vinogradov, University of California at San Francisco, told those who had braved the bracing Colorado Springs wind that, although another session had discussed biomarkers to gauge patients’ responses to treatment, what really matters is whether treatment helps people live better. Accordingly, the 10 talks that followed focused on predictors of how well people live and interventions to help them live better. Vinogradov kept the speakers on a strict timetable as they sailed through plenty of new and at times preliminary data, along with some fresh thinking about old problems.
Living well with others
To help patients develop life-enriching social ties, several of the speakers addressed social deficits in subjects with psychosis or a high risk for it. In the first talk, Raimo Salokangas, University of Turku, Finland, examined whether subjects at current risk for psychosis are more likely to develop a psychotic disorder if they think that other people harbor negative attitudes toward them. As part of the European Prediction of Psychosis Study, Salokangas and colleagues assessed the perceptions of 55 young psychiatric outpatients and then determined whether they developed psychosis in the follow-up period of up to 60 months. During that time, psychosis emerged in over half of subjects who reported at baseline that other people held poor attitudes toward them, compared to 9 percent of those who had described others’ attitudes toward them as moderate or good (Salokangas et al., 2011). The results suggest that asking people how others perceive them might flag those at risk for psychosis, said Salokangas.
The next talk continued the interpersonal theme. Maria Jalbrzikowski, University of California at Los Angeles, presented a study inspired by autism research. It focused on reciprocal social behavior, which she defined as the ability to process social information and to respond appropriately. To measure this ability in 50 teens at clinical high risk for psychosis and 26 healthy teens, she and her colleagues asked parents to complete the Social Responsiveness Scale. This revealed autism-like deficits in reciprocal social behavior in the high-risk group. These deficits not only encompassed expressive, motivational, receptive, and cognitive aspects of social behavior, but also autistic mannerisms such as rocking.
In preliminary analyses, the deficits stayed moderately stable over six to 12 months, but failed to predict conversion to psychosis. Even so, these findings point to a need to screen clinical high-risk youth for autism-like phenotypes, Jalbrzikowski said. To address such deficits, she proposed borrowing social skills interventions from the autism literature.
Interventions might also target patients’ negative attitudes, suggested Paul Grant, University of Pennsylvania, Philadelphia. He discussed whether defeatist beliefs, asocial beliefs, and low expectations that social activities will be pleasurable play a role in deficit syndrome schizophrenia, which involves persistent, primary negative symptoms. His recently published study (Beck et al., 2011) compared the beliefs and expectations of 22 patients with deficit schizophrenia and 72 with non-deficit schizophrenia, while controlling for depression. The results showed that deficit patients endorsed more defeatist beliefs such as “If I fail partly, it is as bad as being a complete failure.” Such patients were also more likely to endorse asocial beliefs, such as “People sometimes think I am shy, when I really just want to be left alone.” On the other hand, the two patient groups did not differ in their expectations of enjoyment from future social activities.
Putting these findings into context, Grant noted that deficit patients typically benefit little from available treatments. Perhaps goal-directed cognitive therapy could address their dysfunctional beliefs and increase their involvement in constructive activity, he said.
The next few speakers addressed predictors of functional outcomes. For example, Stephen Austin, Aarhus University Hospital, Risskov, Denmark, examined the effects of ramping up treatment for early psychosis. He presented findings from the OPUS study, which he described as the largest randomized controlled trial to evaluate the effects of early assertive treatment versus standard treatment in first-episode psychosis. The study randomized 547 subjects with schizophrenia spectrum disorder to either intensive treatment or care as usual. The intensive approach, which included community treatment, psycho-educational family groups, and social skills training, produced greater improvement than standard care on measures of positive symptoms, negative symptoms, and global functioning two years later. However, by the 10-year mark, the advantage of intensive treatment had disappeared, prompting Austin to suggest that achieving lasting improvement might require over two years of treatment.
Even so, Alexander Wunderink, University Medical Centre Groningen, Leeuwarden, The Netherlands, suggested that many patients with first-episode psychosis go into remission; some may not need to stay on antipsychotic medication. To study this issue, he and his colleagues used data from the MESIFOS study, in which 128 patients with first-episode psychosis were randomly assigned to either an antipsychotic discontinuation challenge or standard maintenance treatment. All of the subjects had previously experienced symptom remission within the first year of treatment. At 18 months, 43 percent of those in the discontinuation group had relapsed, compared to 21 percent of those still on medication, but the two groups had similar functional outcomes.
At the eight-year follow-up, 70 percent of patients were in symptomatic remission and a third in functional remission. A sizable fraction, 29 percent, had reached recovery, which required both symptomatic and functional remission. According to Wunderink, logistic regression found that discontinuation challenge actually predicted long-term functional remission and recovery, without causing adverse effects.
Many studies look at schizophrenia outcomes thought to be objective, but the next speaker examined the quality of life as perceived by individuals with schizophrenia. Matthew Kurtz, Wesleyan University, Middletown, Connecticut, said that researchers are showing increasing interest in using well-designed, reliable measures of subjective quality of life or life satisfaction in schizophrenia. In a recent meta-analysis (Tolman and Kurtz, 2010), Kurtz and Arielle Tolman, Wesleyan University, Middletown, Connecticut, found that measures of crystallized verbal ability and processing speed were inversely related to subjective quality of life in schizophrenia. This led them to think that better cognition might give subjects greater insight into their illness and the toll it takes on their lives.
To determine whether insight mediates or moderates the link between neurocognition and subjective quality of life, Kurtz presented recently published findings (Kurtz and Tolman, 2011) from a study of 71 “mid-career folks with schizophrenia.” It found that insight, three measures of cognitive function, and the severity of depression correlated negatively with subjects’ perceived life quality. Regression analyses suggested that insight neither mediates nor moderates the link between cognition and subjective life quality, leading Kurtz to think that neurocognition might affect life satisfaction directly. He raised the possibility that efforts to improve insight and neurocognitive functioning in schizophrenia might actually worsen patients’ subjective quality of life.
Without motivation, patients’ capacity for better living may be limited, an issue examined in a prospective study by George Foussias, University of Toronto, Canada. He and his colleagues hypothesized that motivational deficits would prove a key predictor of functional outcomes in 23 adults with schizophrenia. In stepwise hierarchical regressions, baseline motivational deficits emerged as the strongest predictor of functioning at baseline and a year later, overshadowing negative symptoms, positive symptoms, depression, cognition, and other factors. In fact, baseline motivation explained 70 percent of the variance in functioning at the one-year follow-up. Although Foussias said that positive symptoms, cognitive functioning, and diminished expression each added some predictive value, he sees motivational deficits as crucial to understanding long-term functional outcomes in schizophrenia, at least in subjects who were motivated enough to participate in a study.
Help for patients?
Functional outcomes remained front and center in the presentation by Kelly Allott, University of Melbourne, Parkville, Australia. Noting that cognitive behavioral therapy (CBT) does not help everyone, she said that research has yet to clarify the predictors of functional outcomes after CBT, which would help clinicians identify patients who would be likely to benefit from it. As a result, she and her colleagues reanalyzed data from a study (Jackson et al., 2008) that randomly assigned 62 subjects with first-episode psychosis to 14 weeks of treatment with either CBT or befriending. The latter, in which patient and therapist engage in small talk, controlled for nonspecific aspects of therapy, such as the therapist’s attention.
The study measured a range of possible predictors, including patient sociodemographic characteristics, cognition, and symptoms, but only the patient’s vocational status predicted functional outcomes after CBT. Specifically, whether the patient was working or studying at baseline predicted 35 percent of the variance in post-CBT function, suggesting that first-episode patients may gain more from CBT if they already have relatively high vocational function. For the others, Allott suggested alternative approaches, such as supported employment or education.
Switching the subject to a different kind of intervention, Katy Harper, University of North Carolina-Chapel Hill, Durham, discussed training patients in dating skills. This idea arose from focus groups in which young men with psychosis expressed keen interest in learning how to ask someone out and how to behave on a date. Consequently, Harper conducted a pilot study of a dating skills group for young men who were in the first five years of schizophrenia or schizoaffective disorder. For 12 weeks, the nine subjects were to attend an hour-long group session, where they received training in general social skills, such as how to read body language and build rapport. They also learned dating-specific skills, such as when to ask for someone’s phone number. They practiced their skills in role-playing with female volunteers.
According to Harper, most subjects reported finding the training helpful, fun, and at least somewhat easy to follow; only one dropped out of treatment. Yet, analyses showed only a trend for improved social skills, as rated by independent raters, at the three-month follow-up. More encouragingly, Harper said that during treatment, the appropriateness of the conversational topics raised by subjects with the female volunteers improved. Her study did not look at whether subjects actually dated.
The last speaker, Stynke Castelein, University of Groningen, The Netherlands, said that negative symptoms of schizophrenia predict poor social outcomes, but respond only somewhat to medication or to physical treatments such as transcranial magnetic stimulation. Therefore, she described a study that evaluated the effectiveness of psychosocial interventions for negative symptoms and the quality of evidence behind each approach. The systematic literature search examined papers published from 1990 to 2010.
As it turned out, CBT received the highest level of empirical support, with evidence from at least two independent randomized controlled trials. It produced a small improvement in negative symptoms, an effect that lasted at least two years. In contrast, social skills training, music therapy, psychomotor therapy, and peer support groups received less impressive support, with backing from either one single-blind or at least two poorer quality randomized controlled trials. Evidence supporting arts therapy as treatment for negative symptoms stood on shakier ground, and neither psychoeducation, consumer-run programs, family interventions, cognitive remediation, nor ergo therapy lightened patients’ load of negative symptoms. Closing out the talks, Castelein said that individual pharmacological, physical, and psychosocial interventions may lessen negative symptoms, but with only small to medium effect sizes.—Victoria L. Wilcox.