glucose metabolic rate changes with both drug and behavior therapy for
L. R. Baxter Jr, et. al., Arch Gen Psychiatry.
We used positron emission tomography to investigate local cerebral
metabolic rates for glucose (LCMRG1c) in patients with
obsessive-compulsive disorder before and after treatment with either
fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c
in the head of the right caudate nucleus, divided by that in the
ipsilateral hemisphere (Cd/hem), was decreased significantly compared
with pretreatment values in responders to both drug and behavior
therapy. These decreases in responders were also significantly greater
than right Cd/hem changes in nonresponders and normal controls, in both
of whom values did not change from baseline. Percentage change in
obsessive-compulsive disorder symptom ratings correlated significantly
with the percent of right Cd/hem change with drug therapy and there was
a trend to significance for this same correlation with behavior
therapy. By lumping all responders to either treatment, right orbital
cortex/hem was significantly correlated with ipsilateral Cd/hem and
thalamus/hem before treatment but not after, and the differences before
and after treatment were significant. A similar pattern was noted in
the left hemisphere. A brain circuit involving these brain regions may
mediate obsessive-compulsive disorder symptoms.
For those too impatient to read the abstract, what it shows is that
treatment with either medication or psychotherapy can produce the same
changes in brain chemistry. The changes demonstrated with
psychotherapy were quantitatively smaller than those with medication,
but there were in the same brain regions, and in the same direction.
The changes in the psychotherapy treatment group did not
quite attain statistical significance. However, in 1992, I
was pretty sure that subsequent studies would confirm the original
Because of recent discussions amongst ScienceBloggers, I decided to go
back and see if this has been replicated or expanded upon.
Of course, the findings were simply too tantalizing to be left alone.
Others have indeed followed up on this. It turns
out that the findings are easiest to replicate in OCD and simple
phobias, but much more challenging in other conditions.
A more up-to-date review was published in Nature
Molecular Psychiatry earlier this year:
psychotherapy changes the brain – the contribution of
D E J Linden, Molecular Psychiatry
(2006) 11, 528–538.
A thorough investigation of the neural effects of psychotherapy is
needed in order to provide a neurobiological foundation for widely used
treatment protocols. This paper reviews functional neuroimaging studies
on psychotherapy effects and their methodological background, including
the development of symptom provocation techniques. Studies of cognitive
behavioural therapy (CBT) effects in obsessive-compulsive disorder
(OCD) were consistent in showing decreased metabolism in the right
caudate nucleus. Cognitive behavioural therapy in phobia resulted in
decreased activity in limbic and paralimbic areas. Interestingly,
similar effects were observed after successful intervention with
selective serotonin reuptake inhibitors (SSRI) in both diseases,
indicating commonalities in the biological mechanisms of psycho- and
pharmacotherapy. These findings are discussed in the context of current
neurobiological models of anxiety disorders. Findings in depression,
where both decreases and increases in prefrontal metabolism after
treatment and considerable differences between pharmacological and
psychological interventions were reported, seem still too heterogeneous
to allow for an integrative account, but point to important differences
between the mechanisms through which these interventions attain their
clinical effects. Further studies with larger patient numbers, use of
standardised imaging protocols across studies, and ideally integration
with molecular imaging are needed to clarify the remaining
contradictions. This effort is worthwhile because functional imaging
can then be potentially used to monitor treatment effects and aid in
the choice of the optimal therapy. Finally, recent advances in the
functional imaging of hypnosis and the application of neurofeedback are
evaluated for their potential use in the development of psychotherapy
protocols that use the direct modulation of brain activity as a way of
This shows that so far, no one has been able to find robust, replicable
changes in the brains of persons being treated for depression.
What the author says about it, in the full text of the
article, probably indicates that we have not yet learned to subdivide
depressed patients into neurobiologically distinct groups.
At present, the available evidence suggests that any
model that relies on global frontal hypometabolism to explain symptoms
of depression and its reversal to account for treatment effects would
be oversimplifying the complex nature of cortico-cortical and
subcortical interactions in affective disorders. The
difference between the neural correlates of clinical improvement after
pharmacological and psychological interventions 37,
38 is a case in point. These differences were
particularly pronounced in the study by Goldapple et al.,38
where opposite changes were observed in PFC (decrease after CBT,
increase after paroxetine) and limbic areas (increase after CBT,
decrease after paroxetine).
There is little doubt, that there are many different causes for
depression, as there probably are for OCD. However, OCD seems
to have a common pathway that is more uniform from patient to patient.
That makes it easier to find systematic changes.
I am not quite ready to say that we have a full synthesis between
psychotherapy and neurobiology. However, it is safe to safe
that, as of 2006, we no longer have to worry about the philosophical
mind-body problem. There is no problem.
They are just two different ways of looking at the same thing.