The Corpus Callosum

Splitting the Schizophrenias

ResearchBlogging.orgWhen 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. 


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


  1. #1 Anon
    January 6, 2009

    Just curious–was he similarly conservative about “the depressions”? (for lack of a better term, and to keep it consistent with your usage)

  2. #2 Neuroskeptic
    January 6, 2009

    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.

  3. #3 AnonUK
    January 9, 2009

    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.

  4. #4 chat
    January 11, 2009

    One of the things that i love about science is that no one is above reproach.

  5. #5 Ian Bradley
    April 10, 2009

    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.