Over 20 years have now passed since the first positron emission
tomography (PET) studies were published. At the time, it seemed
that the mysteries of psychiatric illnesses would be revealed in
only a few years. How naïve we were: the brain has proved to
be unbelievably complex. After 2 decades of expensive and difficult
research, we do not have a single brain-imaging test that can be
used to diagnose a common psychiatric condition, and the mysteries
of schizophrenia, autism, mood, and anxiety disorders appear to
be safely concealed. However, this issue of the Journal contains
2 articles that review developments in brain imaging not foreseen
20 years ago.
Dr Jeffrey Stanley (1) describes findings with magnetic resonance
spectroscopy (MRS), a technique for studying brain chemistry in
living patients. With MRS, it is possible to study aspects of brain
function not possible with PET. Membrane phospholipids measured
with phosphorus (31P) MRS provide important clues to the nature
and location of neurodevelopmental abnormalities in schizophrenia.
Proton (1H) MRS allows the quantification of glutamate and its metabolites,
as well as N-acetyl aspartate (NAA), a marker of neuronal integrity.
Longitudinal studies of these metabolites in schizophrenia could
tell us something about the nature of neurodegeneration in this
disorder and point to new pharmacologic approaches to it. As with
PET, findings using MRS in mood disorders are more difficult to
replicate, but preliminary studies seem to suggest a pattern different
from that in schizophrenia, with higher membrane precursors in patients
suffering from bipolar depression. Work in areas such as autism
is just beginning, but it is likely to bring results, because MRS
can be used safely in children, and repeated measures can be done
to understand the course of illness.
Dr Cheryl Grady and Michele Keightley (2) take a different approach
to functional brain imaging studies using functional magnetic resonance
imaging (fMRI) and PET, reflecting recent thinking about the network
of brain regions involved in social cognition. Although we like
to think of psychiatric conditions as being unitary entities, they
clearly are not. Regions that mediate working memory, perception,
emotion, and other cognitive processes have to be involved. Grady
and Keightley argue that, while there may be some specificity in
brain regions involved in autism, depression, schizophrenia, and
posttraumatic stress disorders, all are associated with dysfunction
in the dorsal cingulate gyrus and amygdala. This type of neural
network approach has greatly helped our understanding of how antidepressants
work (3). It might also explain some of the discrepancies in the
literature that examines a single brain region, rather than thinking
about the functional networks involved.
To some extent the findings in the 2 papers are complementary.
For example, patients with schizophrenia typically show membrane
abnormalities in prefrontal regions (4). These same regions seem
to be implicated in task-performance deficits seen in these patients
on fMRI (5). Not surprisingly, both membrane and functional abnormalities
are found in the regions that mediate emotion. However, each technique
offers a different view of the disorders. MRS studies provide some
clues to the nature of the abnormality at a neurochemical level,
while fMRI and PET highlight neural networks involved. Both help
us understand how the available treatments work and point to possible
While our expectations of brain imaging are more realistic than
they were 20 years ago, it is also clear that we have learned much
about these disorders. In the past, we looked for the
part of the brain that could explain a particular disorder. There
is now a general consensus that no single brain region can explain
a particular condition any more than a single gene can.
We treat complex disorders affecting multiple common pathways caused
not just by genetic, but by many environmental, factors. Although
we may not be able to understand all these factors, there is hope
that we may be able to understand something about the final common
pathways and thereby more effectively minimize the impact of these
1. Stanley JA. In vivo magnetic resonance
spectroscopy and its application to neuropsychiatric disorders.
Can J Psychiatry 2002;47:315326.
2. Grady CL, Keightley ML. Studies of altered
social cognition in neuropsychiatric disorders using functional
neuroimaging. Can J Psychiatry 2002;47:327336.
3. Mayberg HS, Liotti M, Brannan SK, McGinnis
S, Mahurin RK, Jerabek PA, and others. Reciprocal limbic-cortical
function and negative mood: converging PET findings in depression
and normal sadness. Am J Psychiatry1999;156:67582.
4. Stanley JA, Williamson PC, Drost DJ, Carr
T, Rylett J, Malla A, Thompson RT. An in vivo study of the prefrontal
cortex of schizophrenic patients at different stages of illness
via phosphorus magnetic resonance spectroscopy. Arch Gen Psychiatry
5. Barch DM, Carter CS, Braver TS, Sabb FW,
MacDonald 3rd A, Noll DC, and others. Selective deficits in prefrontal
cortex function in medication-naive patients with schizophrenia.
Arch Gen Psychiatry 2001;58:2808.
Peter C Williamson, MD, FRCPC