May 14, 2014

Do We Frown Because We Are Depressed or Are We Depressed Because We Frown?

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Michelle Magid, MD

University of Texas Southwestern, Austin, Texas


Smiling makes us feel better! In a TED talk, researcher Ron Gutman discussed the facts that people with bigger smiles tended to live longer lives, have happier marriages, and appear more competent to others.1 In addition, smiling can reduce stress levels by decreasing cortisol, and improve mood by increasing endorphins.1 Gutman’s talk received criticism as it was unclear whether the link between smiling and success was correlative or causative.2

According to evolutionary theorist Charles Darwin and philosopher/psychologist William James, the relationship is causative—we are happy because we smile, we are sorry because we cry, and we are angry because we clench our teeth, not the other way around.3,4 In other words, changes in facial expression create and enhance emotion and are not merely a consequence of that emotion.

If facial expression can influence emotional experience, then what would happen if depressed patients were no longer able to frown?

Three recent studies5–7 (with sample sizes of 30 to 85) set out to answer this question. Male and female participants with major depressive disorder were injected with botulinum toxin A (BTA) into the forehead region, causing a reduced ability to frown (ie, paralysis of the corrugator and procerus muscles, which control expressions of fear, anxiety, and anguish). In all 3 double-blind, placebo-controlled trials, BTA was associated with a statistically significant reduction in depressive symptoms compared with placebo. More interestingly, in our 24-week trial,7 the antidepressant effects of BTA continued even after the cosmetic effects had worn off.

If botulinum toxin in the frown muscles improves symptoms of depression, why?

Some may argue that looking aesthetically better leads to feeling better, but our study7 excluded those with concern about their frown lines. Others argue that the more pleasant and less depressed we look, the more inviting we are to others, leading to improved social interactions and, subsequently, improved mood. These arguments, however, do not explain why mood continues to improve even when the BTA is no longer cosmetically active.

A final argument is that BTA in the forehead alters peripheral feedback to the brain. A recent study8 showed that people who were given BTA in the frown muscles had reduced activity in the left amygdala on functional magnetic resonance imaging (fMRI) when mimicking angry facial expressions. In theory, paralysis of the forehead muscles reduces sensory information from the trigeminal tract to the brainstem, which then alters activity between the brainstem and left amygdala. These findings are important as hyperactivity in the left amygdala has been linked to anxiety, depression, posttraumatic stress disorder, and heightened fear responses.9 In one study,10 20 depressed patients exhibited exaggerated left amygdala activity when shown pictures of emotional faces, especially fearful faces. After antidepressant treatment, left amygdala hyperactivity returned to normal.

Is botulinum toxin a viable treatment option for major depressive disorder?

Regardless of whether one subscribes to a more behavioral or biological mechanism of action, further trials are warranted to determine if BTA is indeed a viable therapeutic option for depression and if specific patient populations are more likely to respond (eg, a recent study11 showed that higher agitation scores are predictive of response). If larger trials can replicate the findings of the 3 small trials, BTA may become a novel treatment in the management of major depressive disorder.

Financial disclosure:Dr Magid received grant/research support from the Brain and Behavior Institute, Young Investigator Award, to fund this study. After completion and as a result of the study, Dr. Magid became a consultant for Allergan.


1. Gutman R. The hidden power of smiling. TED Talks. March 2011.

2. Grohol J. Ron Gutman: smiling while confusing correlation with causation.

3. Darwin, C. The Expression of the Emotions in Man and Animals. London, England: John Murray; 1872.

4. James, William. The Principles of Psychology. New York, NY: Henry Holt & Co; 1890.

5. Wollmer MA, de Boer C, Kalak N, et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012;46(5):574–581. PubMed

6. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxin A: a randomized, double-blind, placebo controlled trial [published online ahead of print December 16, 2013]. J Psychiatr Res. Abstract

7. Magid M, Reichenberg JS, Poth PE, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry [published online ahead of print May 13, 2014]. Abstract

8. Hennenlotter A, Dresel C, Castrop F, et al. The link between facial feedback and neural activity within central circuitries of emotion—new insights from botulinum toxin-induced denervation of frown muscles. Cereb Cortex. 2009;19(3):537–542. PubMed

9. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1):169–191. PubMed

10. Sheline YI, Barch DM, Donnelly JM, et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001;50(9):651–658. PubMed

11. Wollmer MA, Kalak N, Jung S, et al. Agitation predicts response of depression to botulinum toxin treatment in a randomized controlled trial. Front Psychiatry. 2014;5:36. PubMed

Category: Depression
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9 thoughts on “Do We Frown Because We Are Depressed or Are We Depressed Because We Frown?

  1. One question that I haven’t seen answered is how “true” the placebo control can be given that the sam injection doesn’t produce the same, highly identifiable physiological response. If I see I’m frowning I KNOW I didn’t get an active compound. If I see a wrinkle-free forehead I KNOW I got botox. This is a methodological flaw, unless the “sham injection” can also produce the same physical appearance.
  2. very interesting approach! I consider that the beginning is the question: one whole entity or is soma- psychic? and now we all agree that the human is only on entity. If so, if what is inside the head is also outside in muscle expression then the result must be the goal of this study. Maybe..
  3. I think the argument about correlation vs causality is simplistic; complex adaptive systems are non-linear and recursive. That’s why different psychotherapeutic approaches work equally well. A behaviorist tells us to do some something different (smile, not frown) and then we will feel better. The dynamic therapist works with us first to feel better, and then our behavior will change (more smiles, less frowns). Two roads lead to the same place, and linear causality becomes an illusion.
  4. Somatic Experiencing practicioners, Hakomi practicioners, and Sensorimotor psychotherapists heve known about this type of phenomena for years. The mind and body are one. Just as the cortex and limbic can influence the body, the body can influence the limbic. Example – try holding your head up straight and you will not be able to experience shame. Shame is associated with a stereotyped body posture. The emotions and body posture must match. Try hanging you head down, look at the floor and then itis possible to experience shame. If the face can’t frown it gives that feedback to the brain. Depression is acompanied often by a certain facial expression. If one cannot make that expression then it will be harder to experience depressed mood.
  5. So difficult to know where to enter the causal loop. The willingness to maintain the physiological expression and/or posture begins subjectively. so too even the participation in a study and as mentioned one’s read on the effects, i.e. no wrinkles, along with the consequent “emotional contagion” and reciprocal social empathy mirroring of others (let alone the mirror response to seeing one’s face in the mirror) 🙂
  6. Botulism injection has a role in migraine headaches. Do people get less headaches because they can’t frown. No, there is retrograde effects which inhibit depolarization of nerves.
  7. This is interesting. Links in with Somatic experiencing and Neurolinguistic programming though not specifically linked to frowning. Body posture has a big influence on felt mood. Depressed people often slump and look down worsening feelings. My great grandmother used to say “Chin up” – if you lift your head it is very difficult to feel down. Try feeling down with a pencil between your teeth.
    A lot of mediation techniques rely in part on similar mechanisms. I am researching the use of tongue pressure on roof of mouth or thumb suckling ( thumb pressure on roof of mouth) to block anxiety and panic attacks. Works great!
    There is so much we dont know about how we work!!

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