“Sometimes your joy is the source of your smile, but sometimes your smile can be the source of your joy,” said Nobel Peace Prize nominee and peace activist Thich Nhat Hanh. His comment may have a literal biological basis.

Research points to a “facial feedback hypothesis,”1,2,3 which suggests that facial expressions feed information back to the brain, thereby influencing emotions positively or negatively.4

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Some studies have shown that voluntary contraction of facial muscles into a smile or frown can induce feelings of happiness or sadness respectively or influence emotional appraisal of events.5,6 Thus, the more commonly held viewpoint that emotions are expressed by the face may in fact be only half of the story—the face may actually impact emotion.

It is known that the corrugator muscles contract as a response to negative emotions (eg, fear, sadness, or anger).4 Research has supported a role for the corrugator muscles in depression.

For example, a study of depressed subjects showed that their corrugator activity was greater and did not decrease normally, even when they viewed happy imagery.7 Conversely, non-depressed subjects who viewed unhappy imagery had an increase not only in depressed mood but also in corrugator activity.8

Botulinum Toxin to Erase Corrugator Frowns

The aforementioned studies of this phenomenon have generally focused on voluntary activity of facial muscles. A recent study explored the potential role of onabotulinumtoxinA (OBA), a subtype of botulinum toxin, in reversing negative corrugator affect.

This is one of several commercially available botulinum toxin subtypes that are FDA-approved for reversing “frown lines” in the procerus (between-eyebrow) and corrugator muscles.4

Finzi and Rosenthal4 analyzed data of 74 subjects with major depression, who were randomized to receive either OBA (n = 41) or placebo (n = 44). Subjects were rated at screening, then three and six weeks after OBA treatment. The primary outcome measure was the response rate to OBA, as defined by a > 50 percent decrease in score on the Montgomery-Asberg Depression Rating Scale (MADRS).

The researchers found dramatic differences between the two groups at six-week follow-up.

Response rates from the date of injection were 52% in the OBA group versus 15% in the placebo group. [χ2 (1) = 11.2, P<0.001, Fisher p<0.001]. The secondary outcome measure of remission rate (MADRS score of 10 or less) was 27 percent with OBA and 7 percent with placebo [χ2(1) = 5.1, P<0.02, Fisher P<0.03].

Six weeks after a single treatment, MADRS scores of subjects were reduced on average by 47 percent in those given OBA, versus 21 percent in those given placebo (P< 0.0005).

Psychiatrists who saw photographs of the subjects taken before and after the study were able to guess correctly in about three-quarters of cases which treatment had been given. While this is not a foolproof indication of the success of OBA, it is still a powerful statement of potential effectiveness.

Why Is OBA Helpful With Depression?

The authors suggest several potential mechanisms of action by which OBA might help to alleviate depression. One is that frowning “may affect the way people feel about themselves and how others respond to them.”

Additionally, in line with the facial feedback hypothesis that inspired the study, “frowning may in and of itself be depressogenic. Thus, reduction in frowning may be in and of itself therapeutic.”

The authors term this “emotional proprioception,” meaning that the brain “continuously monitors the relative valence of facial expression and that mood responds accordingly.” Corrugator muscle tension may be “part of a neuronal circuit involving the brain stem, with motor input from the facial nerve and sensory afferents from facial and trigeminal cranial nerves.”

Thus, OBA treatment of the corrugator muscle would “interrupt the normal circuitry, reduce distress signals to the brain, and thereby influence mood in a favorable way.”

Potential Advantages and Disadvantages of OBA Treatment for Depression

The authors list several advantages of OBA treatment for major depression, including an excellent safety record for OBA injections into the corrugator and procerus muscles, increased adherence (treatment is required only once every three months), cost-effectiveness (due to the relative infrequency of treatment) and the absence of adverse interactions with psychotropic medications.

Potential disadvantages not mentioned by the authors include cost. As the treatments apparently need to be continued indefinitely at three-month intervals to have ongoing effectiveness, and treatment would not be covered by third-party payers, the cost might discourage people from availing themselves.

Additionally, several questions remain unanswered, including whether OBA should be used as monotherapy or adjunctive therapy to antidepressants, and whether the necessity to travel to a facility for a three-monthly injection would indeed increase adherence.

Still, this is a novel approach to treatment of depression. Since more than 30% of patients with major depression do not achieve remission, even with pharmacotherapy,9 a nonpharmacologic agent with potential to treat depression is definitely worth pursuing.


  1. Strack F, Martin LL, Stepper S. Inhibiting and facilitating conditions of the human smile: a nonobtrusive test of the facial feedback hypothesis. J Pers Soc Psychol. 1988;54(5):768-777.
  2. Adelmann PK, Zajonc RB. Facial efference and the experience of emotion. Annu Rev Psychol. 1989;40:249-280.
  3. Larsen RJ, Kasimatis M, Frey K. Facilitating the furrowed brow: an unobtrusive test of the facial feedback hypothesis applied to unpleasant affect. Cognition and Emotion. 1992;6:321-338.
  4. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA: A randomized, double-blind, placebo controlled trial. J Psychiatr Res. 2013 Dec 1 [Epub ahead of print]
  5. Soussignan R. Duchenne smile, emotional experience, and autonomic reactivity: a test of the facial feedback hypothesis. Emotion. 2002;2(1):52-74.
  6. Lewis MB. Exploring the positive and negative implications of facial feedback. Emotion. 2012;12(4):852-859.
  7. Schwartz GE, Fair PL, Salt P, et al. Facial muscle patterning to affective imagery in depressed and nondepressed subjects. Science. 1976;192(4238):489-491.
  8. Teasdale JD, Bancroft J. Manipulation of thought content as a determinant of mood and corrugator electromyographic activity in depressed patients. J Abnorm Psychol. 1977;86(3):235-241.
  9. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Am J Psychiatry. 2006;163(11):1905–1917.

This article originally appeared on MPR