Effect of serotonin transporter genotype on self-reported efficacy and activity changes of brain prefrontal area in response to placebo

M. Isawa, R. Tashiro, C. Naruse, Y. Yamaguchi, H. Itoh, Tomohiro Nishimura, Masatoshi Tomi, H. Shimada, H. Saito, M. Mochizuki, E. Nakashima

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Abstract

Patients benefit from drug therapy not only through pharmacological mechanisms, but also through non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of the brain. We consider that the difference between responders and non-responders to placebo might be related to polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine and lactose (placebo). Activity in the prefrontal area of the brain was measured in terms of blood flow by means of near-infrared spectroscopy (NIRS) as an objective indicator. Self-reported feelings of drowsiness on established scales were used as subjective indicators. Twenty-one subjects in block A took caffeine on the first day and placebo on the third day, and 21 in block B took placebo on the first day and placebo on the third day. After placebo administration, improvement of sleepiness was significantly enhanced, a similar extent to that after caffeine medication. Among the 42 subjects, 22 showed S/S type polymorphism in the serotonin transporter (52.4 %), 17 showed S/L type (40.5 %) and 3 showed L/L type (7.10 %). Statistical analysis of the results indicate that subjects with L/L genotype showed a significantly greater placebo response in terms of both self-reported feeling of drowsiness and blood flow in the prefrontal area of the brain associated with working memory (46 area). Our results indicate that the L/L genotype of 5-HTTLPR, which is rare in Japanese (3.2 %) but common in Americans (32.2 %), may be associated with a greater placebo effect.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalPharmazie
Volume73
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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ASJC Scopus subject areas

  • Pharmaceutical Science

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Isawa, M., Tashiro, R., Naruse, C., Yamaguchi, Y., Itoh, H., Nishimura, T., Tomi, M., Shimada, H., Saito, H., Mochizuki, M., & Nakashima, E. (2018). Effect of serotonin transporter genotype on self-reported efficacy and activity changes of brain prefrontal area in response to placebo. Pharmazie, 73(1), 35-41. https://doi.org/10.1691/ph.2018.7740