When I was in training, the chairperson (John Greden)
of the department never spoke about schizophrenia. Instead, he
always used the phrase, "the schizophrenias." He believed that
there were different disease states that all produced similar clinical
presentations. But because of the rudimentary state of our
knowledge, we were unable to make clear, meaningful distictions between
these different illnesses. As a result, we were improperly
lumping them together. He thought that soon, we would be able to
make meaningful distinctions between these different illnesses.
Perhaps the advances would come from genetics, or neuroimaging, or
something yet to be developed. Now, we see that progress is being made:
Neuropsychological Near Normality and Brain Structure Abnormality in Schizophrenia *
Bruce E. Wexler, M.D., Hongtu Zhu, Ph.D., Morris D. Bell, Ph.D., Sarah S. Nicholls, Ph.D., Robert K. Fulbright, M.D., John C. Gore, Ph.D., Tiziano Colibazzi, M.D., Jose Amat, M.D., Ravi Bansal, Ph.D., and Bradley S. Peterson, M.D.
Objective: Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness.
Method: Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates.
Results: Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects.
Conclusions: Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.
What the authors did was this: they divided patients with schizophrenia into two groups: those with minimal cognitive impairment, and those with significant cognitive impairment. Then they looked to see if their brains were different in some way that distinguished the two groups. What they found was that both groups had problems with the gray matter, but only the cognitivly impaired group had problems also with the white matter.
The sample size seems kind of small, only 75 patients and 30 controls. However, for this kind of study, that is a respectable number of patients. These studies are expensive to do, and they take a lot of time for each subject. Naturally, it is only a starting point.
The importance of this study is not entirely clear, because it is only a starting point. First, it will have to be replicated, then expanded upon. Assuming it holds up, it will provide clues that will help us understand more about the pathophysiology (the study of what goes wrong) of schizophrenia. This could lead to a meaningful way of defining "the schizphrenias."
Presumably, such enhanced understanding would lead to opportunities for improved diagnosis, better estimation of prognosis, and -- we can hope -- better treatment.
*Citation:
B. E. Wexler, H. Zhu, M. D. Bell, S. S. Nicholls, R. K. Fulbright, J. C. Gore, T. Colibazzi, J. Amat, R. Bansal, B. S. Peterson (2008). Neuropsychological Near Normality and Brain Structure Abnormality in Schizophrenia American Journal of Psychiatry DOI: 10.1176/appi.ajp.2008.08020258
Brain & Behavior
Comments
Just curious--was he similarly conservative about "the depressions"? (for lack of a better term, and to keep it consistent with your usage)
Posted by: Anon | January 6, 2009 11:10 AM
As far as I can see the best dissection of the schizophrenias remains Crow's Type I vs Type II schizophrenia theory. It's old school (and I'm not keen on Crow's recent work) but pretty convincing.
Posted by: Neuroskeptic | January 6, 2009 2:06 PM
What about if schizophrenia is a clinically meaningless term and cannot be split at all because it's not valid? Crow's distinction isn't perfect, and if that's the best we have, maybe we should abandon the label and diagnose symptom-by-symptom.
Posted by: AnonUK | January 9, 2009 11:08 AM
One of the things that i love about science is that no one is above reproach.
Posted by: chat | January 11, 2009 10:33 AM
Yes, I agree with the idea of establishing more homogenous groups within the category of schizophrenia that was initially distilled from Kraepelin's grouping of disparate conditions based on clinical course - ie downward. More specific to this study, it would be nice to link these cognitive deficits to more meaningful behaviours, or even clinical symptoms. For example, do those schizophrenic patients with near-normal attentional functioning look better in social interaction? This study represents a good first step, but since one could literally describe hundreds of such deficits in schizophrenic patients, we should focus on efforts or those that either reflect the basic genotype or mirror real-world behaviour.
Posted by: Ian Bradley | April 10, 2009 7:38 PM