Predictors of Functional Disability in People Living With Schizophrenia

Video Transcript

Negative symptoms impact real-world functioning. You see, the unemployment status is humongous among people with schizophrenia, but it improves, and people haven't had another relapse. So, positive symptoms obviously get in the way, but still, it's very below the general population.

Generally, negative symptoms are linked to employment status, social functioning, independent living, participation in leisure time activities, and quality of life. Negative symptoms—also because we have little to offer at the moment pharmacologically—are associated with poorer treatment response and may also fuel some of the relapse. So here you see people with more positive symptoms.

They have about half of a good outcome, and about a quarter have either relapse or non-response in this first episode cohort; and, first episode patients generally respond better than chronic patients and that's flipped around. So, we have basically a quarter only that have a good response and half of them are more in the poor response camp. So, we hope as new treatments become available that, this can be flipped to have better outcomes in both domains.

It's important to keep in mind that cognition is associated with functional outcomes, too. In a meta-analysis of 166 studies looking at the connection between neurocognition and functional outcome, you'll see a metacognitive correlation that shares about 10% of the variance between different elements of cognitive impairment and different outcomes. And so community functioning, social behavior in the milieu, social problem-solving, and social skills are all impacted by cognitive impairments.

There are probably some other mediating factors that are also impacted by cognition that were not measured in these older studies. So, in terms of the real-world impact of cognitive impairment, what we're seeing is that cognitive impairment predicts not only getting a job but keeping a job.

In fact, in a couple of studies presenting the average job tenure of people with schizophrenia who are in supported employment programs, the modal job tenure was 1 day, where the person didn't make it to their first day at work even though they were in a rehabilitation program; and what has been discovered since then is if you give people computerized cognitive training, it improves both their ability to get a job and their ability to keep a job. Independent living is also highly impacted by cognitive impairment, and one of the reasons for that is that cognitive impairment impacts your ability to perform critical functional skills. So, people who've got cognitive impairment have more challenges in tasks like going shopping.

They have more tasks than cleaning and cooking. And so, as a result, it becomes very difficult to sustain independent living if you can't perform the component skills that keep you in your residence and out of a supportive living situation. Social functioning is obviously very important, too; social cognition and neurocognition are linked.

Social cognitive abilities are dependent on neurocognitive abilities, and one of the things that happens is that cognitive and social cognitive deficits are associated with interpersonal problems. And one of the things that happens is there's a cascade.

If you misperceive people's emotions a couple of times and you have adverse interactions with them, it's going to undercut your motivation to go out and try to make friends the next time around. Basically, cognitive impairment associated with schizophrenia is linked to the inability to manage medications. That is a link then into maybe exacerbation of positive symptoms.

For many outpatients, medication adherence depends on the ability to sequence events to remember have I taken it or not; and basically, here we have a link to potential exacerbations. Cognitive impairment is more strongly related to medication adherence. There are other demographic factors like age, education, or symptom severity, and there's two elements of medication adherence. One is medication possession.

You've got to refill your prescription so you have it at your house so you can take it. So that's where some of the memory challenges come in. If you neglect to refill, then you don't have any medication to take. Then you have to organize your medication and take them appropriately at the right time, with the right concurrent foods, or whatever, in order to get benefit.

Many anti-psychotic medications have food effects. So, you have to remember to eat and then take your medication. Doing these sorts of highly sequential acts is a challenge, which leads to medication being mis-administered even if you got it in the house.

We need to keep in mind that there's been a lot of confusion about cognitive and negative symptoms and whether they're the same thing or if they're different. Part of this confusion has originated from the definitions of some of the clinical items on the most commonly used clinical rating scale, the PANSS. Because on the PANSS, they define deficits, and abstract thinking, and challenges in concentration as negative symptoms.

If you define negative symptoms in terms of cognitive deficits, of course, there's going to be a correlation between cognitive deficits and negative symptoms because you're measuring the same item and counting it on two different scales at the same time. So, negative symptoms and cognitive impairments also interact. You can be cognitively intact and able to do certain skills, but if you're not motivated to do them, like our case: who hadn't read a book in 3 years? It doesn't matter if you could do the things if you don't make an attempt.

We separate the concept of competence from performance and cognitive abilities. Cognitive competence still requires motivation and opportunities to lead to good performance. So basically, cognitive and negative symptoms predict functioning. There may be separate treatment targets for them.

There is some suggestion that in chronic patients, negative symptoms are more strongly related to social outcomes than everyday functional outcomes, but that's in people with established illness. When you start at the first episode, it looks very different. But what we see here, also, is that there are mediators and defeatist beliefs.

The idea that I couldn't possibly succeed even if I tried are something that contribute to clinical ratings of negative symptoms. Because if you don't believe that you can succeed if you try, you're probably not going to try. And if you're not trying, you get rated clinically as having abolition.

There may be something that underlies this; the connection between neurocognition and functioning is mediated by functional capacity, the ability to perform critical everyday living skills. And certain intervention studies have suggested that if you target functional capacity, you can also improve functional outcomes.

It might very well be that functional capacity is more than a mediator of the effect of cognitive impairment. It may be the pathway to functioning and that improving cognition needs to also consider whether or not people have the ability to do certain skills. For a drug to be approved by the FDA for enhancing cognition, it has to show that that it improves performance on a functionally relevant measure. Well, if the functionally relevant measures are something that you never learned how to do, how would you be expected to improve on it if you've never done it? How can you get a job if you don't know how to write a resume or go on a job interview? The requirement is as unusual as requiring that you should be able to speak French after having cognitive enhancement, too, because that's an important aspect of functioning.

So, I think we need to keep in mind that cognition and skills combined together to lead to outcome, hence, underscoring the need for psychosocial interventions.