Tuesday, February 2, 2010

Cognitive Impairment and Schizophrenia

Time to act like a big boy again...

When you hear the word "schizophrenia," what comes to mind? Frequently, people imagine someone who has auditory hallucinations (e.g., a voice keeping a running commentary on the person's behavior) or bizarre delusions, such as having thoughts broadcasted to others.

When mental health professionals discuss the disorder, the most common phrases used are "positive symptoms" (e.g., hallucinations, delusions) and "negative symptoms" (e.g., flat affect, alogia). Current medical treatments almost exclusively focus on treating the positive symptoms. Increasingly, there is more discussion about medications treating the negative symptoms as well; however, most medications do a piss poor job of this (1).

What is also "known" about this disorder, is that individuals who have it often have pervasive cognitive deficits as well. There are some who argue that it is the cognitive symptoms that are a main reason for disability and dysfunction (2).

In this month's American Journal of Psychiatry (3), a group of researchers reported on a 30-year longitudinal study of cognition in individuals who eventually go on to develop schizophrenia.

What they wanted to know, is if cognitive impairment is present from early childhood and if those impairments remain stable throughout a lifetime (the developmental deficit hypothesis); whether future schizophrenia subjects lag behind healthy people in their cognitive development (developmental lag hypothesis); or whether they have a decline in cognitive functioning just prior to illness onset or as a result of psychosis (developmental deterioration hypothesis).
The authors of this study followed a cohort from birth to age 32. The children were initially assessed at age 2, with follow-up assessments occurring at ages 5, 7, 9, 11, and 13.

The children's cognitive abilities were assessed with the Wechsler Intelligence Scale for Children - Revised (WISC-R), which was originally published in 1974 (the WISC is currently in its 4 edition).

Scores are generated from this battery by taking the raw score and converting it to an age-match scaled score (SS). In lay terms, an individual's performance is compared to other individuals who are of a similar age cohort. This way, you can tell how someone's performance compares to other people of the same age. The primary score generated by the WISC is a full-scale IQ. If you read my older post on IQ scores (4), you'll recall that IQ can be a meaningless number as it obscures the variability in an individual's performance. In order to compensate for this, the researchers mainly focused on the composite scores of the WISC: verbal comprehension (information, vocabulary, and similarities; see subtest descriptions below), perceptual organization (block design, picture completion, and object assembly), and freedom from distractibility (arithmetic and digit symbol coding).

(click the below image to enlarge)
  The researchers found support for both the developmental deficit and lag hypotheses but not the developmental deterioration hypothesis. This is consistent with other research, which suggests that cognitive deficits in people diagnosed with schizophrenia remain stable over time (5, 6, 7). As the authors described,
"For all eight cognitive tests, the linear slopes of the growth curves were positive and significant (all p values <0.001), indicating that on average, future case subjects, similar to healthy comparison subjects, showed developmental increases in their cognitive functions between ages 7 and 13 years."
For the developmental deficit hypothesis, the authors noted,
"future schizophrenic case subjects exhibited early and static cognitive deficits on the following four cognitive tests: information, similarities, vocabulary, and picture completion...future schizophrenia subjects had significantly lower [performance] values than healthy comparison subjects.
And for the developmental lag hypothesis,
"on three cognitive tests (block design, arithmetic, and digit symbol)...future schizophrenia case subjects had lower linear slope values than healthy comparison subjects, indicating that their growth on tests measure freedome from distractibility and visual-spatial problem solving skills was developmentally slower."
(click to enlarge)

The researchers concluded,
"The neurodevelopmental model of schizophrenia posits the existence of deviations in cognitive development many years prior to the emergence of overt clinical symptoms of adult schizophrenia. Findings from this study add to what is known about the neurodevelopmental model in three ways. First, our findings point to both cognitive developmental deficits and cognitive developmental lags during childhood in individuals who will go on to develop schizophrenia as an adult. Second, different cognitive functions appear to follow different developmental courses from childhood to early adolescence. The developmental deficit model appears to apply to verbal and visual knowledge acquisition, reasoning, and conceptualization abilities. The developmental lag model appears to apply to freedom from distractibility and visual-spatial problem solving abilities. Third, these patterns of cognitive deviations from childhood to early adolescence in schizophrenia are not shared in recurrent depression."
By this point you may be asking yourself, "what the hell does all this psychobabble mean?"

In short, these results don't mean much for clinical practice. They've reconfirmed that future schizophrenia subjects have baseline cognitive deficits, and their neurodevelopment is slower than healthy people.

Here are the average IQs of the different groups pooled together:

The authors of this study made it sound as if all future schizophrenia subjects had cognitive deficits. They didn't. Future schizophrenia subjects had an average IQ score of 94, while healthy subjects had an IQ of 101. Both of these scores fall in the average range (90-110). 7 points is not a big difference.

Above, are two bell curves I constructed to illustrate my point. IQ is a normally distributed score. The purple curve represents normal subjects (mean IQ 101) and the pink curve represents the future schizophrenia subjects (mean IQ 94).

A standard deviation (i.e., a measure of performance variability) for IQ scores is 15 points. A score of 85 (1 SD below the mean) is considered impaired. As you can see, there is considerable overlap between the schizophrenia bell curve and the normal subject bell curve. Nearly two/thirds of the schizophrenia population will have an IQ in the normal range or better; however, the maximum IQ for most schizophrenia subjects will be caped (i.e., rarely above 115), although there are notable exceptions (e.g., John Nash).

Another important point to note is that while a difference in IQ of 7 points (94 versus 101) is statistically significant, it is not clinically significant. You need a difference between 1 to 1-1/2 standard deviations to achieve clinical significance. Based on the bell curve, only 15% of future schizophrenia subjects will have an IQ that low.

The second problem with this study is that the cognitive assessments were not neurodiagnostic.
"the model posits that there is insult to the brain acquired or inherited in early development" and therefore "the developmental deficit model for the etiology of schizophrenia is supported by our data.
What the data indicate is that some, but not all, future schizophrenia subjects had difficulty on some, but not all, of these tests (remember, performance was lower on average). One of the major criticisms of cognitive tests is that performance is influenced by factors outside of the individual. The only factor that is controlled for by the WISC-R is age. But other factors, such as quality of education, region of habitation, ethnicity, medications, and gender are not controlled. In order to determine if a problem is brain based, one needs to control for those other variables, which is why neuropsychologists should use demographically correct norms when possible.

Here's an example: Future schizophrenia subjects tend to be isolated, are viewed by others as weird, and are stigmatized by their peers. These factors can contribute to poor self esteem, stereotype threat, poor school performance, and most importantly, poor motivation to perform well. Of course a person with this social history will perform poorly on cognitive tests (people with recurrent depression also have lower IQ scores on average, see above).

Here's another problem: let's assume that differences in IQ are brain based. The IQ test results do not pinpoint were the problem actually is. Below is a pyramid that illustrates what brain/neurocognitive functions need to be intact in order for the higher order functions (e.g., IQ) to be accurately assessed.
For example, if a person performs poorly on the WISC-R Vocabulary subtest, you then want to know why that person performed poorly. He or she could of had a poor educational background, the person could have a memory retrieval problem, or an expressive speech problem, or a hearing problem.

For anyone who has undergone neuropsychological testing, you'll recall that we administer a butt-load of tests (between 20-30), which takes between 3-6 hours to complete. We do this so we can accurately pinpoint why a person performed poorly and so we can make useful recommendations. If the problem was educational, a tutor will help, if the problem was memory retrieval, cueing will be helpful, if the problem was hearing, a aid will be helpful.

There are many other problems with this study. However, the take home message is that future schizophrenia subjects, on average, perform poorly on some cognitive tests, but that poor performance difference is not huge. Why some perform poorly while others do not is still unknown. This study and its press release (8) do not help resolve this debate, it only muddies the waters. 


Reichenberg, A., Caspi, A., Harrington, H., Houts, R., Keefe, R., Murray, R., Poulton, R., & Moffitt, T. (2010). Static and Dynamic Cognitive Deficits in Childhood Preceding Adult Schizophrenia: A 30-Year Study American Journal of Psychiatry, 167 (2), 160-169 DOI: 10.1176/appi.ajp.2009.09040574


Anonymous said...

Christ! Go back to the Beyonce-Taylor posts! They are much sexier!

Anonymous said...

So, schizophrenia is correlated with lower childhood IQ. I wonder, though, whether both things might be a manifestation of something else, like poor childhood nutrition, family problems, exposure to pesticides, etc.

If (for example) stress is associated with development of schizophrenia, and stress is associated with poor school performance and low IQ, then it wouldn't seem right to imply that the low IQ scores prove the "neurodevelopmental model" of schizophrenia. The low IQ could be an independent manefestation of the same underlying problem, right?

Also, I think that the fact that the study didn't correct for income or family bacground is HUGE. I've heard that schizophrenia is more common among the disadvantaged. Maybe this study has just shown that lower-income children tend to do more poorly in school. Is this new information?