Where is depression “located” in the brain? Researchers and clinicians both are showing increasing interest in an area called the prefrontal cortex.
This afternoon, I’m scheduled to participate in the National Public Radio program, Talk of the Nation: Science Friday, hosted by Ira Flatow. I’ll be on with James Gordon, a psychiatrist and expert on alternative medicine, who believes that depression is not a disease. One of Gordon’s arguments follows the Thomas Szasz line, that diseases show specific pathology in the relevant organ — here, the brain.
In particular, in his new book, Unstuck, Gordon is critical of research I have cited in Against Depression that associates the mood disorder with cellular disruption in the part of the brain behind and above the eyes, the prefrontal cortex, or PFC. The PFC performs many functions, but the regions implicated in depression seem to be involved with reasoning, memory, and overall "executive" functioning that allows people to get things done.
The PFC is interesting because, until the emergence of studies by Grazyna Rajkowska and others in the 1990s, the main focus for anatomical research on depression was the limbic circuit, or the “emotional brain.” Looking at autopsy material, Rajkowska found distinctive changes in cells, especially supporter cells called glia, in the PFCs of depressives. She saw her findings as a contribution to the argument that depression might be understood as “a brain disease with distinct histopathological features,” that is, structural changes visible under the microscope.
Gordon criticizes the Rajkowska report because many of the subjects studied had committed suicide — they came from the severe end of the mood disorder spectrum — and many had been on psychotherapeutic medications that can affect brain cells.
As readers of Against Depression know, I do not agree that to be a disease, a mental illness needs to demonstrate consistent, local pathology. (Think of schizophrenia and autism, are they diseases?) But in preparation for the discussion, I thought I would see how researchers had responded to findings like Rajkowska’s.
I went to the database PubMed and entered the words depression and prefrontal. The site lists 1460 articles, almost all published during and after the mid-1990s, when modern research on mood disorder and the PFC began. Well over 100 have appeared this year. Scientists are betting their careers on the likelihood that the connection between depression and the PFC is of interest.
To show where research is heading, I thought I might mention three very recent contributions, all published online in advance of print versions.
Mounira Banasr and Ronald Duman, in work prepared for Biological Psychiatry, have found a method for diminishing the presence of glia in the prefrontal cortex of rats. The rats with impaired glial function show a depression-like syndrome, struggling on tests that rats struggle on when they’ve been subjected to early life trauma and not then protected by antidepressants. The authors conclude that their results “support the hypothesis that loss of glia [in the PFC] contributes to the core symptoms of depression.”
In a monograph for the Journal of Affective Disorders, Yvette Sheline’s group at Washington University in St. Louis reports that antidepressants (according to their own preference, subjects took Lexapro, Zoloft, or Paxil) restore activity to a relevant part of the PFC that in depressed subjects is otherwise under-active in the face of emotional challenges.
Probably the most impressive indication of the acceptance of the link between PFC pathology and depression comes from a different arena. In an e-article for the American Journal of Psychiatry, Aaron T. Beck, the pioneering psychotherapist, reviews “neurobiological correlates” of the theory of cognitive therapy. Beck discusses a handful of studies that find PFC abnormalities, anatomical and functional, in depressed subjects. A core aspect of Beck’s theory is a link between diminished activity in the PFC and impaired cognition in depression, an association that might explain aspects of the maladaptive thinking that cognitive therapy targets.
Brain differences in depression appear to be widely distributed. Beyond the PFC, abnormalites have been found in the hippocampus as well as in the amygdala and other limbic regions. But judging from the research agenda across a broad range of topics — from neurons to psychotherapy — a decade after Rajkowska’s historic report, interest in PFC impairment in depression remains robust.
