Honesty mediates the relationship between serotonin and reaction to unfairness

Takahashi, Hidehiko; Takano, Harumasa; Camerer, Colin F.; Ideno, Takashi; Okubo, Shigetaka; Matsui, Hiroshi; Tamari, Yuki; Takemura, Kazuhisa; Arakawa, Ryosuke; Kodaka, Fumitoshi; Yamada, Makiko; Eguchi, Yoko; Murai, Toshiya; Okubo, Yoshiro; Kato, Masaaki; Ito, Hiroshi; Suhara, Tetsuya

doi:10.1073/pnas.1118687109

Cited by 44 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The work by Takahashi et al (1) recently reported a negative association between brainstem serotonin transporters and personality traits such as honesty and rejection to unfairness. They interpret their locus within brainstem to include the dorsal raphe nucleus (DRN) (1).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Challenges in the differentiation of midbrain raphe nuclei in neuroimaging research

Kranz

Hahn

Savli

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The work by Takahashi et al. (1) recently reported a negative association between brainstem serotonin transporters and personality traits such as honesty and rejection to unfairness. They interpret their locus within brainstem to include the dorsal raphe nucleus (DRN) (1). Other than DRN, the median raphe nucleus (MRN) also projects to the forebrain and may be equally important in the serotonergic modulation of cortical activity. Hence, several studies have focused on these two midbrain raphe nuclei with respect to receptor and transporter distributions or anatomical connections. Small nuclei such as DRN and MRN are, however, exceptionally difficult to localize in human imaging research in vivo, such as positron emission tomography (PET).The works of Baker et al. (2, 3) provided insight into the distribution and location of serotonergic neurons within MRN and DRN in the postmortem human brain ( Fig. 1 A and B). Rostrocaudally, the DRN extends at the level of accessory oculomotor nucleus to the motor trigeminal nucleus. At the level of the trochlear nucleus ∼7-5 mm above the isthmus, the DRN exhibits its fountain-shaped appearance in a transverse section with a ventrodorsal and mediolateral extension of about 5 mm. The DRN above the isthmus includes the majority of neurons, with its subparts containing the greatest number of serotonergic neurons. At the level of the isthmus, the DRN narrows extensively to just 0.5 mm in the mediolateral extension and nestles up against the fourth ventricle. Farther caudally, the DRN divides into two staves and extends 14 mm below the level of the isthmus. For reliably delineating the DRN, a circular region of interest (ROI) may be placed at the level between superior and inferior colliculus and not extending 6 mm in diameter in a transverse plain in two slices. The ROI then may include up to 14 voxels given a voxel size of 2 × 2 × 2 mm of a PET image in MNI (Montreal Neurological Institute) standard space (Fig. 1C). In comparison, the MRN in the pontine tegmentum extends rostrocaudally from the level of the decussation of the superior cerebellar peduncle (1 mm above isthmus) down to the motor trigeminal nucleus ∼18 mm below isthmus. Most serotonergic neurons of the MRN lie within the first 10 mm below the level of the isthmus. In a transverse plain, the MRN appears with a ventrodorsal extension of about 6 mm and a mediolateral extension of about 2 mm. A reliable delineation of MRN may, therefore, provide a ROI in two slices within the rostral one-third of the pons, not extending 8 voxels.Given figure 2a in the work by Takahashi et al. (1), we propose that they measured serotonin transporters within the MRN rather than the DRN and suggest that MRN may be easily mistaken in imaging studies as DRN. DRN and MRN differ in several aspects, including receptor distributions and afferent and efferent connections (4), which highlights the importance of differentiating and identifying them as two separate nuclei in neuroimaging research.

show abstract

mentioning

confidence: 99%

“…They interpret their locus within brainstem to include the dorsal raphe nucleus (DRN) (1). Other than DRN, the median raphe nucleus (MRN) also projects to the forebrain and may be equally important in the serotonergic modulation of cortical activity.…”

mentioning

confidence: 99%

Challenges in the differentiation of midbrain raphe nuclei in neuroimaging research

Kranz

Hahn

Savli

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…

Yang et al (1) argue that sex and age are confounding factors in our study (2). However, by definition, they actually are not.

…”

mentioning

confidence: 72%

Reply to Yang et al.: Gender is not a confounding factor of our result

Takahashi¹,

Takano²,

Ideno³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Yang et al (1) argue that sex and age are confounding factors in our study (2). However, by definition, they actually are not. Their sex difference argument does not have any influence on our result from a young Japanese male sample. In our article, we were interested in individual differences in reaction to unfairness observed in the ultimatum game. We were fully aware that sex and age are major factors to account for many brain functions and their disorders (3, 4). We also understand that sex difference in personalities is a major research topic. Therefore, we focused on young male volunteers. In addition, to prevent young females from unnecessary radiation exposure, we recruited only male volunteers as a first step. Sex difference was already addressed as a limitation. Needless to say, it is highly recommended to test this if a similar result could be observed in a female sample as well.As for mediation analysis, we have also tested a bootstrapping method. We generated 1,000 samples from our data and tested the significance of the indirect effect using the bootstrap biascorrected and accelerated bootstrap 95% confidence intervals (CI) (5). The indirect effect was considered significant if CI of the indirect effect did not include zero. The analysis revealed that both straightforwardness (CI −0.77 ∼ −0.0027) and trust (CI −0.49 ∼ −0.0046) were significant mediators of the relationship between serotonin transporter binding in the midbrain and rejection to unfair offers in the ultimatum game.

show abstract

“…In a recent article, Takahashi et al (1) described interesting work regarding the mediating effect of honesty in the relationship between serotonin and reaction to unfairness. After reading the article with interest, we have some concerns about the study.…”

mentioning

confidence: 99%

“…First, only male subjects were investigated in their study (1). Sex differences in the serotonin system and personalities would potentially confound the results.…”

mentioning

confidence: 99%