More Ado About Area 25

Some may recall Brodmann
(a part of the brain also known as the subgenual area or area
.  It was mentioned by Orli Van Mourik ( id="a028464"
Ado About Area 25) in 2006, and by me in 2008 ( href="">Update
on Deep Brain Stimulation).  David Dobbs profiled one of the
key researchers, Helen Mayberg, ( href="">Neurologist
Helen Mayberg in SciAm Mind) in 2007, and wrote about the topic
again last month ( href="">Refining
Depression's Wiring Diagram).

The key thing about Area 25 is that it is the spot that is affected
when href="">deep
brain stimulation (DBS) is used to treat Major Depression. 
post last month detailed some of the more recent research on the
tractography (the study of the white matter connections in the brain)
of Area 25.  See his post (as linked above, and href="">here
for convenience) for diagrams.

In that post, Dobbs mentioned that Mayberg was conducting more research
on Area 25,
hoping to find a way to identify which patients would be most likely to
benefit from deep brain stimulation.  While that remains a work in
progress, there are some interim findings:

of nonresponse to cognitive behavioural therapy or venlafaxine using
glucose metabolism in major depressive disorder

Jakub Z. Konarski, MSc; Sidney H. Kennedy, MD; Zindel V. Segal, PhD;
Mark A. Lau, PhD; Peter J. Bieling, PhD; Roger S. McIntyre, MD; Helen
S. Mayberg, MD

J Psychiatry Neurosci 2009;34(3):175-80.

neuroimaging investigations of antidepressant treatment offer the
opportunity to identify potential baseline biomarkers associated with
poor outcome. Methods: To
the neural correlates of nonresponse to cognitive behavioural therapy
(CBT) or venlafaxine (VEN), we compared pretreatment
(18)F-fluoro-2-deoxy-D-glucose positron emission tomography scans of
participants with major depressive disorder responding to either 16
weeks of CBT (n = 7) or VEN
treatment (n = 9) with treatment
nonresponders (n = 8). class="articletextbold">Results:
Nonresponders to CBT or VEN, in contrast to responders, exhibited
pretreatment hypermetabolism at the interface of the pregenual and
subgenual cingulate cortices. Limitations: class="articletextbold"> Limitations of our study include
the small sample sizes and the absence
of both arterial sampling to determine absolute glucose metabolism and
high-resolution structural magnetic resonance imaging coregistration
for region-of-interest analyses. class="articletextbold">Conclusion: Our current findings
are consistent with those reported in
studies of relative hyperactivity in the ventral anterior cingulate
cortex in treatment-resistant populations.  class="articletextbold">

The full text of the study is freely available in a href="">PDF.

This particular study does not specifically address the question of
which patients would be most likely to benefit from DBS, but it does
strengthen the hypothesis that Area 25 is important in the
pathophysiology of (at least some) patients with Major
Depression.  It also shows that there may be a systematic
physiological difference between those who respond to antidepressant
medication, and those who do not.  Furthermore, it shows that the
same difference may distinguish those who respond to psychotherapy, and
those who do not.

Granted, those speculations are overly broad: venlafaxine is not all
antidepressants, and CBT is not all psychotherapies.  Furthermore,
it is only one study, and it included only a small number of

What I find interesting, though, is the possibility that we may be able
to expand on this line of research to find a valid way to delineate
subtypes of depression in a way that guides treatment efficiently.
Mayberg et. al. are hopeful that they may be able to determine
who is most likely to benefit from DBS.  That would be a good
start.  But the ultimate goal is to be able to predict who will
respond to which treatment, regardless of the specific type of
treatment under consideration.

Neuroscience research is like this:  it is a body of knowledge,
built up very slowly, from studies that indicate what might be
true.  The more studies we have that seem to point in the same
direction, the more tempting it is to think we know what the truth is.

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Depression is a common neuropsychiatric disorder which affects at least 1 in 7 adults. The condition can have a major effect on patients' quality of life, and is a major cause of both disability and suicide. Many patients with depression can be treated effectively with antidepressant medications,…
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I've got a story about Helen Mayberg's work on depression circuits in the new Scientific American Mind. I first wrote about Mayberg in the Times Magazine three years ago, in an article about her experimental use of deep brain stimulation to treat depression, and I later profiled her for SciAm Mind…

I thought Area 25 was where they keep the UFOs that landed in my brain? :)