Depression: talk or pills?

Which works best for getting rid of depression: hope for the best from a pill, or talking to a shrink?

The answer to this, according to recent research [1] won't surprise you (the answer is to do both), but the reason for it may surprise you. It has to do with a battle of sorts between two very different parts of the brain: the amygdala and the PreFrontalCortex .

Both are involved in the severe hopelessness, helplessness, sadness and sometimes suicidal impulses that plague people with depression. The lifetime prevalence of depression in the US is 16% of the population, which means that 32-35 million Americans will likely battle this disease at sometime in their lifetimes.

Fortunately, there is a recent clue from research on the disease which brings a spark of beauty to the understanding of it

It's rare that a scientific concept can be so clear and simple as the results in this journal article, but this article seems to have accomplished that. The brain is a very complex organism and there are many many parts of it involved in depression, but the faulty interaction between these two areas (the amygdala and the PreFrontal Cortex) during depression provides an important clue toward preventing and curing of the disease. The PFC functions as a center of logic, perception (including self-perception) or understanding in the brain, while the amygdala, as a core part of the limbic system processes emotions. The findings from fMRI studies by the authors is that talk therapy helps to right the faulty interaction by giving the PreFrontal Cortex what it needs to 'set things right', and Anti-Depressant Medications ('ADM') give the amygdala what it needs to set its end of the communication 'to rights'.

The Wizard behind the curtain

The figure below shows more of how those 2 parts of the brain interact, and how the two types of treatment are involved in bringing life back onto an even keel. During depression, the amygdala gets too 'uppity' (overactive), and the PFC too underactive -- it loses its 'assertiveness' or its ability to monitor the knee-jerk emotional reactions of the amygdala. The PFC is hindered from providing a reality check to the emotions engendered by the amygdala, particularly emotions in reaction to stressful events.

So each of the two treatment options goes at the disease from opposite ends: anti-depressant medications treat depression by decreasing the hyperactivity of the amygdala (the 'emotional' part of the brain), whereas cognitive therapy ('talk therapy') treats it by increasing the under-activity of the 'logical' part of the brain - the PreFrontal Cortex.

image: the additive effect of talk therapy and antidepressants in abating depression

Well, you say, "This is a convenient simplicity, but is there real evidence for it?"

Consider this:

On repetitive negative thinking, depression, and the amygdala

"..Aspects of emotional information processing that are often observed in patients with depression, such as repetitive negative thinking, have been associated with increased limbic activity and decreased activity in the prefrontal cortex." [1]
"Alterations in amygdala volume and activity have been observed in samples of depressed patients [43], with the most-consistent evidence suggesting increased and relatively unmodulated amygdala activity".[1, citing 44, 45, 46]

On talk therapy and the PreFrontal Cortex

"... Depressed individuals have decreased prefrontal activity compared with healthy individuals."[1, citing 46, 52, 63 and 64]

"The existence of inhibitory connections from the orbital prefrontal cortex (OFC) and [other regions] to the amygdala [56] suggests that these regions might exert a 'damping' effect on the amygdala, and therefore on emotional reactivity." [1]

"..CT [Cognitive Therapy] might thus increase inhibitory executive control, helping to interrupt or dampen automatic limbic reactions....ADM might target limbic regions directly, rather than relying on inhibition through the prefrontal cortex." [1]

A reality check, to press for finding the key 'trees' in the forest

Of course this figure is a gross simplification of the number of areas of the brain affected by depression and its cures. As the authors of this study say themselves, "The amygdala and the prefrontal cortex are but two of the brain regions for which there is evidence of dysfunction in depression" [1]

This article for example, discusses the significant number of areas below [insert thumbnails] affected by both Prozac (fluoxitine) and placebos for Prozac.

A simple complexity?

Nonetheless, the elegance of the complementarity between AntiDepressant Medications and Cognitive Therapy as a treatment is beguiling, simply because it allows one to keep an eye out for just key areas of the brain when foraging through the overwhelming complexity of this disease. And it may provide a very important clue to future reseach on the disease as a key puzzle-piece to its inner-workings and eventual banishment.


[1] Robert J. DeRubeis1, Greg J. Siegle2 & Steven D. Hollon, Nature Reviews Neuroscience 9, 788-796 (October 2008) | doi:10.1038/nrn2345 Opinion: Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. PubMed

[2] Luiz Pessoa, Nature Reviews Neuroscience 9, 148-158 (February 2008) |doi:10.1038/nrn2317, Opinion: On the relationship between emotion and cognition. PubMed

[43] Abercrombie, H. et al. Metabolic rate in the right amygdala predicts negative affect in depressed patients. Neuroreport 9, 3301–3307 (1998). PubMed

[44] Siegle, G. J., Steinhauer, S. R., Thase, M. E., Stenger, V. A. & Carter, C. S. Can't shake that feeling: fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol. Psychiatry 51, 693–707 (2002). PubMed

[45] Drevets, W. C. Prefrontal cortical amygdalar metabolism in major depression. Ann. NY Acad. Sci. 877, 614–637 (1999). PubMed

[46] Siegle, G. J., Thompson, W., Carter, C. S., Steinhauer, S. R. & Thase, M. E. Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biol. Psychiatry 61, 198–209 (2007). PubMed

[52] Mayberg, H. S. et al. Reciprocal limbic cortical function and negative mood: converging PET findings in depression and normal sadness. Am. J. Psychiatry 156, 675–682 (1999). PubMed

[56] Ghashghaei, H. T. & Barbas, H. Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience 115, 1261–1279 (2002). PubMed

[64] Baxter, L. et al. Reduction of prefrontal glucose metabolism common to three types of depression. Arch. Gen. Psychiatry 46, 243–250 (1989). PubMed

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