Overview of Negative Symptoms and Cognitive Impairment in Schizophrenia

Video Transcript

What are the negative symptoms? It's basically the Five As. Affective blunting, that’s diminished facial, vocal expression, minimal use of gestures, and poor eye contact. So, that's something you just observe. You don't need to spend any time asking a question.

So, make it part of your assessment. Alogia, the same thing. Do people have very short answers? Do they actually speak longer sentences or only when you prompt them? And then the anhedonia, asociality, and avolition. Here, you need to ask a question.

And what are these questions? Well, what have you done socially since we last met? Do you actually want to be with people? And do you enjoy things that you used to enjoy? So here, things we should ask anyway. That's in order to understand where the patients are, but also maybe to have an alliance with them and that they feel you would try to understand them. And beyond that, if you want to prescribe something for patients, they need to have not just compliance, adherence; they need medication interest.

What's in there for me? Why should I take this? And linking the medication to their goals that are individualized is something that you can only do when you've asked about these things. What do you like to do? Do you still like to do it? Who do you meet with? And is it only when they prompt you to do so? Basically, if you really look for it, there is not only an overproduction of dopamine that gives you the positive symptoms. There are areas in the brain where there's too little juice, too little fuel, and many patients have that.

Now, it can be difficult to sometimes differentiate depression from negative symptoms. That's true, and that might be in the mix. And a meta-analysis has given very nice guidance on that.

So, how do you actually differentiate depression and negative symptoms? What do you need to do? I'll go to the ultimate: ask the patient. Do you feel depressed? Well, as they say, no. High likelihood is it's not depression.

And there are two other symptoms that were much more prevalent in the depression group, and that is pessimistic thoughts and suicidality. On the other hand, nothing is pathognomonic, but what was much more prevalent in people with negative symptoms than depression was alogia: the active social withdrawal and affective blunting. Can someone with melancholia be affectively blunt; blunted and not talk much? But they would want to.

They may be withdrawing because they feel a burden and are also feeling too weak to go out, but they would want to be with people. So, these are some things which you can use in order to tease out those two things. But one question really gets to it: Do you feel depressed? 73 % of patients experience negative symptoms before the onset of the positive symptoms. So, if that's now more of the negative symptoms, not just one. And up to 60% of stable outpatients have, again, one or more negative symptoms. It's a clear treatment target that we need to go after.

But how do you ask about them? You know, one of the things that we see is that if you're not bothered by your situation, you're not depressed by it. I think that's one of the clear differentiations. If you've got significant treatment-resistant depression, you are bothered by the fact that you can't get things done. If you're just not getting things done and not bothered by it, that helps to understand. So, let's switch to cognitive impairments.

I mean, cognitive impairments in schizophrenia, commonly, as you know, cognition, in general, commonly can be presented as something that's very complicated. But in actuality, all of these cognitive domains that we're talking about here were defined by Kraepelin before they had computers. So, Kraeplin defined every element of cognitive impairment in schizophrenia in the early parts of the 20th century.

So, his observational powers were able to detect all these things. There's attention and vigilance, which basically sums up to the very simple idea of being able to pay continuous attention to what's going on. Like being able to read a book or watch a movie and keep track of what's going; or on a more simpler than molecular basis, like being able to listen to a lecture long enough to get the information.

It's just sustaining your attention. And there's working memory, which is holding information in your mind until you use it. Like remembering directions long enough to drive or remembering a phone number long enough to dial. And there's a fun fact that underlies the idea: why do telephone numbers have seven digits? Because seven digits is the average capacity of a normal person's working memory. The magic number seven plus or minus two. So, it's remembering something long enough to operate on it. And the telephone company back in the 1940s captured the idea that people can remember seven digit numbers and longer ones are harder.

Verbal learning and memory, like learning verbal information and being able to retain it after a delay. Remember, it's like remembering something people told you to buy at the store. So like, keep having a mental shopping list is what episodic memory is.

Remembering what you did, remembering what you're supposed to do. Visual learning and memory, same sort of things spatially. If you're parking your car a couple blocks away from where you're going to be going to dinner, being able to remember the spatial trajectory that's involved to find it. Reasoning and problem-solving, it's just applying logic; and it's commonly called executive functioning, but it's really the ability to solve problems and coordinate component cognitive skills. What do you need to pay attention to? What can you temporarily ignore? And so, our example is, for example, arriving on time for work even though your bus schedule changed.

A lot of our patients who don't look particularly cognitively impaired can't adapt to the idea that they go to their bus stop and there's no bus there. And so, they've figured out how to get to your office. Because you think they remember the way, but no, they remember the bus. And so, they can't problem solve their way to your office if they can't get there the regular way. Speed of processing, again, probably the core impairment in schizophrenia because if you are slow, everything else is fast.

And so, even tests that aren't targeting speed become speed tasks if you can't keep up. Typically, we measure that on a performance-based basis by having people do some coding or some trail-making or stuff like that.

And social cognition, which is cognitively demanding socially relevant tasks. Being able to perceive and process emotions, being able to generate a hypothesis about what someone else is thinking about you. And many of our patients with schizophrenia get in trouble because they make social approaches to people that they think are interested in them, and the person is really not, and then that causes a sort of interpersonal challenge for them. So, there are a number of different domains of social cognition. It's the intersection between social abilities and cognitive demands.

And so, here's the impairment profile. View zero, at the top, is how the patient's pre-morbid functioning would have been. So, this is indexed relative to where you would have been if schizophrenia had not intervened. And 1.5 standard deviations is the equivalent of basically dropping down to an IQ score of like 76 when you started at 100. So, this is a really big drop in performance. It's a very big discrepancy relative to previous abilities. And as you work your way across, you see that fluency, which is the ability to use words in an efficient and rapid way. The continuous performance test, which is a vigilance test. Trail-making part B, which is an executive function test.

All those things are impaired at levels that are close to a standard deviation below the mean, which means that people are performing essentially 25 percentile points worse, at best, compared to how they were functioning beforehand. So, it's not hard to see why this level of cognitive impairment can lead to significant challenges, particularly since we're indexing against where you should be, not against other standards.