- Email: [email protected]
Prenatal testosterone and stuttering
Early Human Development 91 (2015) 43–46
Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Prenatal testosterone and stuttering Christian Montag a,⁎, Benjamin Bleek b, Svenja Breuer b, Holger Prüss c, Kirsten Richardt c, Susanne Cook d, J. Scott Yaruss e, Martin Reuter b,f a
Department of Psychology, University of Ulm, Ulm, Germany Department of Psychology, University of Bonn, Bonn, Germany Department for the Treatment of Stuttering, LVR Clinic Bonn, Bonn, Germany d Alexandria, VA, USA e Department of Communication Science & Disorders, University of Pittsburgh, PA, USA f Center for Economics & Neuroscience, University of Bonn, Bonn, Germany b c
a r t i c l e
i n f o
Article history: Received 6 October 2014 Received in revised form 4 November 2014 Accepted 6 November 2014 Available online xxxx Keywords: Stuttering Prenatal testosterone OASES 2D:4D ratio Case control
a b s t r a c t Background: The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. Aims: The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more “male” characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. Study design, subjects, outcome measures: We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. Results: In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. Conclusions: The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Stuttering is a neurodevelopmental disorder affecting the fluency of speech, with a prevalence of about 1% among adults and a skewed sex ratio [1]. People who stutter are more likely to be male than female. The sex ratios range from about 2:1 in younger children to roughly 4:1 in adolescents and adults [2]. This change in sex ratio over time indicates a much higher rate of spontaneous recovery in girls who stutter [3]. As with many other predominantly male phenotypes and disorders, it has been often speculated that developmental effects of sex hormones like testosterone or estrogen could account for the sex biases in stuttering [1,4,5]. A very prominent and pioneering but nevertheless contentious theory that addresses the possible biological underpinnings of stuttering in this context is the so-called Geschwind-Behan-Galaburda (GBG) ⁎ Corresponding author at: Molecular Psychology, Department of Psychology, University of Ulm, Helmholtzstr. 8/1, D-89081 Ulm, Germany. E-mail address: [email protected] (C. Montag).
http://dx.doi.org/10.1016/j.earlhumdev.2014.11.003 0378-3782/© 2014 Elsevier Ireland Ltd. All rights reserved.
model of cerebral lateralization [4]. The authors hypothesized that many predominantly male disorders might result from a high level of testosterone during embryonic development, such that it delays lefthemisphere growth, causes right-hemisphere dominance for speech and language, and results in left-handedness. On this basis, the GBG model hypothesizes relationships among maleness, prenatal testosterone exposure, cerebral lateralization, left-handedness, and disorders such as dyslexia, autism, delayed speech and language development, and also stuttering. Of note, handedness is also discussed to be associated with stuttering [6,7]. The GBG model has been extensively debated and criticized during the last decades, but there are also findings that seem to confirm a relationship among prenatal testosterone exposure and cerebral lateralization in general [8–10]. The relationship between prenatal testosterone and (language) lateralization is of interest in the context of the aetiology and pathogenesis of stuttering, because atypical hemispheric language processing is characteristic for adults who stutter. In the 1920s, Orton and Travis discussed a lack of hemispheric dominance and a resulting conflict in the
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C. Montag et al. / Early Human Development 91 (2015) 43–46
neuromotor control of speech as one of the multiple causes of stuttering [7]. Moreover, newer brain imaging studies commonly reported results that suggest increased right hemisphere participation in speech production of people who stutter [e. g. 11–13]. This right hemispheric overactivity was considered to be compensatory because it is associated with decreased functional and anatomical anomalies in the left hemisphere of people who stutter [13,14, see also review 15]. Taking all these findings together, it is possible that prenatal testosterone could influence the aetiology and the development of stuttering. To the best knowledge of the authors of the present article, there are no studies that have investigated these relationships in the context of stuttering. There are only anecdotal case reports that indicate a potential association between testosterone and stuttering. For example, Kartalci et al. [16] showed an association between testosterone administration for treating hypogonadism and stuttering in an adolescent boy. Because of the lack of empirical evidence in the field, the present study sought to explore whether prenatal testosterone could be linked to the occurrence and/or the symptomatology of stuttering. As it is difficult to assess early prenatal testosterone levels in humans (e.g., at the end of 1st Trimester or beginning of 2nd Trimester), and because it is unknown if a person will stutter in the future, indirect measures are required. One of the most often-used indirect indicators of prenatal testosterone is the 2D:4D ratio of the hand (D = digit or finger). Longer ring fingers (4D), as compared to the index finger (2D;), characterize the typical male hand (lower 2D:4D ratio). This pattern is associated with higher prenatal testosterone levels. In contrast, longer index fingers, as compared to ring fingers, characterize a more typical female hand. This pattern is associated with lower prenatal testosterone levels (note that the ratio is not related to actual testosterone levels in adolescence/adulthood; it only reflects the prenatal environment). The robust statistical difference in 2D:4D between male and female hands has been abundantly researched and confirmed in a large number of samples [e. g. 17]. Hönekopp et al. [18], Breedlove [19] and Manning et al. [20] have summarized the sizable body of evidence linking digit ratio to prenatal testosterone. Given the above-mentioned evidence on males being more affected in the context of stuttering, as well as the laterality issues indicating that prenatal testosterone might be involved in stuttering, we hypothesized in a first step of this study that people who stutter would be more likely to exhibit male hand characteristics (lower 2D:4D ratio – hence higher prenatal testosterone) than people who do not stutter. In a second step, we were interested in linking 2D:4D to the individual degree of the multifaceted symptomatology within the stuttering group. Here, we hypothesized that a lower 2D:4D (higher prenatal testosterone levels) would be linked with a higher symptomatology, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES) [21]. Besides the two mentioned research hypotheses, we aimed to replicate the classical sex effect of the 2D:4D ratio, with females being associated with higher ratios compared to males.
and at a self-help congress for stuttering in 2012. The persons who do not stutter reported no lifetime history of stuttering and no occurrence of stuttering in their families. They were recruited at the university and in the personal environment of the researchers. No significant betweengroup differences were found with respect to age (F(1,72) = .13, p = .72) or sex (Chi2 = .44, df =1, p = .51). The present study was approved by the local ethics' committee of the university and all participants gave written consent. In the second part of the study, the association between 2D:4D and experiences due to stuttering in everyday life were investigated in the group of people who stutter. In addition to the original described sample described above, 6 additional participants who stutter were recruited. Thus, the total sample of persons who stuttered examined in the second part of this study consisted of 44 individuals (34 males and 10 females). The mean-age of the participants was 31.95 years (SD =11.90). 2.2. Questionnaire The German translation of the Overall Assessment of the Speaker's Experience of Stuttering (OASES, [21]; translation by [24]) was administered to all persons who stutter. This questionnaire includes 100 items that examine the overall impact of stuttering on people's lives. Each item is assessed as a self-report with a five-point Likert scale. The questionnaire is divided into four subscales: (I) general perspectives about stuttering, (II) affective, behavioral and cognitive reactions to stuttering, (III) functional communication difficulties, and (IV) the impact of stuttering on the speaker's quality of life. The German version has been externally validated with the NEO-FFI, a measure for human personality [25]. High neuroticism and low extraversion was associated with high OASES scores (hence high negative experience of stuttering in everyday life). 2.3. 2D:4D ratio All participants were first asked if one of their index or ring fingers had been broken. If so, the afflicted hand was excluded from the analysis. There were four instances of a broken left ring finger, one instance of a broken right ring finger, and instance of a broken right hand. Therefore, different sample sizes (degrees of freedom) can be observed in the statistical analysis reported below. Scans of both the left and right hand were conducted with a Canon Scanner. Every scan was implemented in the software GIMP 2.0 to calculate 2D:4D. A line was drawn from the middle of the lowest crease from the index and ring finger to the tip of each finger. Each hand was measured by two independent raters in pixels. The inter-raterreliability between the two measures for the left and right 2D/4D fingers was high and ranged from .978 to .998. The correlations between measures was r = .85 for the left 2D:4D ratio and r = .86 for the right 2D:4D ratio. 2.4. Statistical analyses
2. Methods 2.1. Participants In the first part of the study, 38 persons who stutter (28 males and 10 females) and 36 persons who do not stutter (24 males and 12 females) were invited. This sample size, which is comparable to other studies also investigating the 2D:4D marker in patient groups such as schizophrenia [e. g. 22,23], represents a starting point to investigate the link between prenatal testosterone and stuttering. We aimed to achieve the same number of males and females in the non-stuttering group after the persons who stutter were recruited. The mean age of persons who stutter was 30.63 years (SD = 10.65). The mean age of the non-stuttering group was 31.53 years (SD = 10.54). The persons who stutter were recruited in speech therapy settings in 2012-2013
An analysis of variance (ANOVA) was used to investigate potential differences in the 2D:4D ratio by subject group (persons who stutter/ persons who do not stutter) and sex (male/female). In a second step, partial correlations were computed between the 2D:4D measures of the left/right hand and the OASES scores, controlling for age, because this variable correlated significantly (though not strongly) with the OASES total scale, (r = −.30, p b .05) and the subscale I (r = −.33, p b .05). The other correlations between OASES subscales and age barely missed significance. Sex was not associated with significant differences in the OASES. All analyses were conducted for the total sample and for the male/female subsamples independently. Considering a potential link between the four subscales of the OASES and 2D:4D, the alpha to be reached for significance was adjusted to .0125 for these analyses (.05 divided by four tests).
C. Montag et al. / Early Human Development 91 (2015) 43–46
3. Results
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Table 2 Partial Correlation of 2D:4D ratios (right hand) with OASES scores in the stutter group.
3.1. Comparison of 2D:4D between participant groups No significant main effects were observed on the left 2D:4D ratio for sex (male vs. female; F(1,65) = 2.11, p = .15) or participant group (people who stutter vs. people who do not stutter; F(1,65) = 0.01, p = .93). Also, no interaction effect was observed (F(1,65) = 0.01, p = .94). A significant main effect of sex on the right 2D:4D ratio was observed (F(1,67) = 5.78, p = .02), with males showing lower ratios compared to women. No main effect of the participant group (F(1,67) = 0.28, p = .60) or interaction effect (F(1,67) = 0.84, p = .36) was observed. 3.2. Correlation of the 2D:4D ratio with the OASES scores in persons who stutter No significant sex differences in the total OASES scale or the OASES subscales could be observed. As shown in Tables 1 and 2, several significant negative correlations were observed between the 2D:4D ratio and the OASES total score and its subscales. These effects were most prominent in females. The strongest correlations (about r N −.70; p b .05) were between the left 2D:4D ratio and both subscale IV of the OASES and the total OASES score in females. The association between left 2D:4D and OASES (suggesting that higher prenatal testosterone is linked to reported higher negative experiences due to stuttering) in females is shown in Fig. 1. 4. Discussion As a strong skewed sex ratio in persons who stutter is welldocumented, we hypothesized that a measure reflecting prenatal testosterone (2D:4D) could be of relevance for understanding the biological basis and experience of stuttering. In line with the literature, we observed the expected statistical difference in 2D:4D between males and females for the right hand. Descriptive results for the left hand showed findings in the expected direction, but the difference did not reach significance. Fittingly, Manning et al. [17] described that the effect of sex on 2D:4D ratio to be stronger for the right compared to the left hand. We did not find a difference between the 2D:4D ratio when comparing persons who stutter with persons who do not stutter. Therefore, an influence of prenatal testosterone as indirectly measured via 2D:4D on the occurrence of stuttering cannot be observed. While a direct assessment of prenatal testosterone could result in different findings, such a study would require measurement of prenatal testosterone in the uterus while the mother is pregnant [26] and, later, the child would have to be investigated in a longitudinal design with respect to the development of stuttering. However, we cannot rule out a 2D:4D group
Males
Females
Total Sample
OASES I
OASES II
OASES III
OASES IV
OASES Total
r = −.04 p = .83 df =30 n =33 r = −.51, p = .16 df =7 n =10 r = −.15 p = .36 df =40 n =43
r = −.17 p = .34 df =30 n =33 r = −.70, p = .04 df =7 n =10 r = −.22 p = .16 df =40 n =43
r = −.12 p = .50 df =30 n =33 r = −.64, p = .07 df =7 n =10 r = −.19 p = .22 df =40 n =43
r = −.18 p = .31 df =30 n =33 r = −.53, p = .14 df =7 n =10 r = −.21 p = .19 df =40 n =43
r = −.16 p = .38 df =30 n =33 r = −.68, p = .04 df =7 n =10 r = −.23 p = .15 df =40 n =43
difference between persons who stutter and persons who do not stutter because the sample size of the present study is rather small making it difficult to detect small effect size due to reduced statistical power. The other hypothesis of interest was whether there is a link between the 2D:4D ratio and a speaker's experiences due to stuttering. Here, a moderate correlation appeared for the total sample, linking higher prenatal testosterone levels (lower 2D:4D) to higher scores on the OASES (left hand). In detail, a stronger influence of prenatal testosterone on the evolving human organism is associated with greater problems in coping with stuttering. Of note, the observed association between 2D:4D ratio and the OASES scores seems to be largely driven by the female subsample of the present sample. Specifically, a large correlation was observed for the left hand (r = -.75, p = .02) explaining 56% of the variance in the OASES scale. Effects in the same direction can be observed for the right hand. Therefore, prenatal testosterone as reflected by 2D:4D might be of special importance for predicting experiences associated with stuttering in females. Although the present finding is hard to interpret at present (given the scarce literature), recent studies on testosterone and emotionality in females can illuminate the present association between 2D:4D and the OASES in females. Bos et al. [27] observed that females under influence of exogenous administered testosterone showed higher neural response in the thalamocingulate region and insula to crying infants. Moreover, the same research group [28] showed that females under testosterone administration respond more strongly with their amygdala to happy and fearful faces. In interpreting the stronger activity of the basolateral and superficial amygdala under the influence of testosterone, the authors suggested that testosterone might be a promotor of
Table 1 Partial Correlation of 2D:4D ratios (left hand) with OASES scores in the stutter group.
Males
Females
Total Sample
OASES I
OASES II
OASES III
OASES IV
OASES Total
r = −.19 p = .30 df =29 n =32 r = −.47 p = .20 df =7 n =10 r = −.23 p = .15 df =39 n =42
r = −.26 p = .16 df =29 n =32 r = −.59 p = .09 df = 7 n =10 r = −.30 p = .06 df =39 n =42
r = −.24 p = .19 df =29 n =32 r = −.72 p = .03 df =7 n =10 r = −.33 p = .04 df =39 n =42
r = −.36 p = .04 df =29 n =32 r = −.79⁎ p = .01 df =7 n =10 r = −.43⁎ p = .005 df =39 n =42
r = −.31 p = .09 df =29 n =32 r = −.75 p = .02 df =7 n =10 r = −.38 p = .01 df =39 n =42
⁎ These results hold for Bonferroni adjustment as discussed in the statistical analyses section. Here Bonferroni adjustments have been applied for the subscales. In general bold printed results show the most relevant statistics.
Fig. 1. Negative correlation between the 2D:4D ratio of the left hand and the OASES score in females who stutter (partial correlation: p = −.75, df =7, p = .02; R2 = .56). Of note: The Y-axis describes the mean-answer on the OASES items technically ranging from 1 to 5 (and not the mean-total score). We depict a smaller range on the Y-axis for reasons of better visibility.
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C. Montag et al. / Early Human Development 91 (2015) 43–46
“preferential processing of salient stimuli in the context of social challenges” (p. 815). Clearly, one's own speech difficulties, along with the reactions of others, represents a salient stimuli with which the person who stutters needs to cope. Females might react more emotionally to their own speech difficulties and the responses of their environments when under the influence of testosterone, though again, the present study examined only a marker of prenatal testosterone and not testosterone at the time of the assessment. The generalization of the present finding is of course limited due to the small sample of females who stutter in the current study (n = 10), although our sample (34 males and 10 females) is consistent with the male-to-female ratio reported in the overall population of individuals who stutter [see also 2]. Of additional importance, a potential involvement of the 2D:4D marker in stuttering would not reflect an exclusive influence of prenatal testosterone on stuttering, because this morphological marker has already been associated with a wide range of phenotypes, including disorders such as autism, ADHD [e. g. 29] and schizophrenia/schizotypal personality [e. g. 30]. Therefore, the influence of prenatal testosterone on the brain and behavior is rather broad. Summarizing, the present study shows that the inclusion of the 2D:4D ratio in stuttering research could represent an interesting research avenue to a better understanding of the biological basis of individual differences in coping with speech disorders. Future research should explore how individual differences in this marker of prenatal testosterone might relate to observed differences in neural structure and the occurrence of stuttering. Contributions CM designed the study. BB, SB, HP and KR recruited the participants. SB measured the 2D:4D ratios. CM, BB, SC, SY and MR drafted the manuscript. CM, BB and MR conducted the statistical analyses. Conflict of Interest None. Acknowledgement The position of CM is funded by a Heisenberg grant by the German Research Foundation (MO 2363/3-1). We thank Thomas Grünhage for measuring the 2D:4D ratios (as a second person). References [1] Bloodstein O, Bernstein Ratner N. A handbook on stuttering. 6th ed. Clifton Park, NY: Thomson Delmar; 2008. [2] Van Borsel J, Moeyaert J, Mostaert C, Rosseel R, Van Loo E, Van Renterghem T. Prevalence of stuttering in regular and special school populations in Belgium based on teacher perceptions. Folia Phoniatr Logop 2006;58:289–302. [3] Yairi E, Ambrose NG. Early childhood stuttering I: persistency and recovery rates. J Speech Lang Hear Res 1999;42:1097–112. [4] Geschwind N, Galaburda AM. Cerebral lateralization: biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Arch Neurol 1985; 42:428–59.
[5] Starkweather CW. A simple theory of stuttering. J Fluency Disord 1995;20:91–116. [6] Manning JT, Peters M. Digit ratio (2D:4D) and hand preference for writing in the BBC Internet Study. Laterality 2009;14:1–13. [7] Kushner HI. Retraining left-handers and the aetiology of stuttering: the rise and fall of an intriguing theory. Laterality 2012;17:673–93. [8] Bryden MP, Mcmanus IC, Bulmanfleming MB. Evaluating the empirical support for the Geschwind-Behan-Galaburda model of cerebral lateralization. Brain Cogn 1994;26:103–67. [9] Beaton AA, Rudling N, Kissling C, Taurines R, Thome J. Digit ratio (2D:4D), salivary testosterone and handedness. Laterality 2011;16:136–55. [10] Kalmady SV, Agarwal SM, Shivakumar V, Jose D, Venkatasubramanian G, Reddy YCJ. Revisiting Geschwind's hypothesis on brain lateralisation: a functional MRI study of digit ratio (2D:4D) and sex interaction effects on spatial working memory. Laterality 2013;18:625–40. [11] Braun AR, Varga M, Stager S, Schulz G, Selbie S, Maisog JM, et al. Altered patterns of cerebral activity during speech and language production in developmental stuttering. An H2 (15) O positron emission tomography study. Brain 1997;120: 761–84. [12] Sommer M, Koch MA, Paulus W, Weiller C, Büchel C. Disconnection of speechrelevant brain areas in persistent developmental stuttering. Lancet 2002;360:380–3. [13] Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, et al. How the brain repairs stuttering. Brain 2009;132:2747–60. [14] Preibisch C, Neumann K, Raab P, Euler HA, von Gudenberg AW, Lanfermann H, et al. Evidence for compensation for stuttering by the right frontal operculum. Neuroimage 2003;20:1356–64. [15] Büchel C, Sommer M. What causes stuttering? PLoS Biol 2004;2:e46. [16] Kartalci S, Erbay LG, Ozcan OO, Yuksel T, Unal S. Stuttering after testosterone administration: a case report. Anadolu Psikiyatri Derg 2012;13:82–4. [17] Manning JT, Churchill AJ, Peters M. The effects of sex, ethnicity, and sexual orientation on self-measured digit ratio (2D: 4D). Arch Sex Behav 2007;36:223–33. [18] Hönekopp J, Bartholdt L, Beier L, Liebert A. Second to fourth digit length ratio (2D: 4D) and adult sex hormone levels: new data and a meta-analytic review. Psychoneuroendocrinology 2007;32:313–21. [19] Breedlove SM. Mini review: organisation hypothesis: instances of the fingerpost. Endocrinology 2010;151:4116–22. [20] Manning J, Kilduff L, Cook C, Crewther B, Fink B. Digit ratio (2D:4D) a biomarker for prenatal sex steroids and adult sex steroids in challenge situations. Front Endocrinol (Lausanne) 2014;5:9. [21] Yaruss JS, Quesal RW. Overall Assessment of the Speaker's Experience of Stuttering (OASES): documenting multiple outcomes in stuttering treatment. J Fluency Disord 2006;31:90–115. [22] Walder DJ, Andersson TL, McMillan AL, Breedlove SM, Walker EF. Sex differences in digit ratio (2D: 4D) are disrupted in adolescents with schizotypal personality disorder: altered prenatal gonadal hormone levels as a risk factor. Schizophr Res 2006;86: 118–22. [23] Venkatasubramanian G, Arasappa R, Rao NP, Gangadhar BN. Digit ratio (2D: 4D) asymmetry and Schneiderian first rank symptoms: Implications for cerebral lateralisation theories of schizophrenia. Laterality 2011;16:499–512. [24] Metten C, Schulte K, Rosenberger S. EESE (Erfassung der Erfahrungen von stotternden Erwachsenen): Deutsche Übersetzung des Fragebogens OASES (The Overall Assessment of The Speaker's Experience of Stuttering); 2006. [25] Bleek B, Reuter M, Yaruss JS, Cook S, Faber J, Montag C. Relationships between personality characteristics of people who stutter and the impact of stuttering on everyday life. J Fluency Disord 2012;37:325–33. [26] Lust JM, Geuze RH, Van de Beek C, Cohen-Kettenis PT, Groothuis AGG, Bouma A. Sex specific effect of prenatal testosterone on language lateralization in children. Neuropsychologia 2010;48:536–40. [27] Bos PA, Hermans EJ, Montoya ER, Ramsey NF, Van Honk J. Testosterone administration modulates neural responses to crying infants in young females. Psychoneuroendocrinology 2010;35:114–21. [28] Bos PA, van Honk J, Ramsey NF, Stein DJ, Hermans EJ. Testosterone administration in women increases amygdala responses to fearful and happy faces. Psychoneuroendocrinology 2013;38:808–17. [29] De Bruin EI, Verheij F, Wiegman T, Ferdinand RF. Differences in finger length ratio between males with autism, pervasive developmental disorder-not otherwise specified, ADHD, and anxiety disorders. Dev Med Child Neurol 2006;48:962–5. [30] Zhu YK, Li CB, Jin J, Wang JJ, Lachmann B, Sariyska R, et al. The 2D: 4D ratio of the hand and schizotypal personality traits in schizophrenia patients and healthy control persons. Asian J Psychiatr 2014;9:67–72.
Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Prenatal testosterone and stuttering Christian Montag a,⁎, Benjamin Bleek b, Svenja Breuer b, Holger Prüss c, Kirsten Richardt c, Susanne Cook d, J. Scott Yaruss e, Martin Reuter b,f a
Department of Psychology, University of Ulm, Ulm, Germany Department of Psychology, University of Bonn, Bonn, Germany Department for the Treatment of Stuttering, LVR Clinic Bonn, Bonn, Germany d Alexandria, VA, USA e Department of Communication Science & Disorders, University of Pittsburgh, PA, USA f Center for Economics & Neuroscience, University of Bonn, Bonn, Germany b c
a r t i c l e
i n f o
Article history: Received 6 October 2014 Received in revised form 4 November 2014 Accepted 6 November 2014 Available online xxxx Keywords: Stuttering Prenatal testosterone OASES 2D:4D ratio Case control
a b s t r a c t Background: The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. Aims: The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more “male” characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. Study design, subjects, outcome measures: We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. Results: In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. Conclusions: The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Stuttering is a neurodevelopmental disorder affecting the fluency of speech, with a prevalence of about 1% among adults and a skewed sex ratio [1]. People who stutter are more likely to be male than female. The sex ratios range from about 2:1 in younger children to roughly 4:1 in adolescents and adults [2]. This change in sex ratio over time indicates a much higher rate of spontaneous recovery in girls who stutter [3]. As with many other predominantly male phenotypes and disorders, it has been often speculated that developmental effects of sex hormones like testosterone or estrogen could account for the sex biases in stuttering [1,4,5]. A very prominent and pioneering but nevertheless contentious theory that addresses the possible biological underpinnings of stuttering in this context is the so-called Geschwind-Behan-Galaburda (GBG) ⁎ Corresponding author at: Molecular Psychology, Department of Psychology, University of Ulm, Helmholtzstr. 8/1, D-89081 Ulm, Germany. E-mail address: [email protected] (C. Montag).
http://dx.doi.org/10.1016/j.earlhumdev.2014.11.003 0378-3782/© 2014 Elsevier Ireland Ltd. All rights reserved.
model of cerebral lateralization [4]. The authors hypothesized that many predominantly male disorders might result from a high level of testosterone during embryonic development, such that it delays lefthemisphere growth, causes right-hemisphere dominance for speech and language, and results in left-handedness. On this basis, the GBG model hypothesizes relationships among maleness, prenatal testosterone exposure, cerebral lateralization, left-handedness, and disorders such as dyslexia, autism, delayed speech and language development, and also stuttering. Of note, handedness is also discussed to be associated with stuttering [6,7]. The GBG model has been extensively debated and criticized during the last decades, but there are also findings that seem to confirm a relationship among prenatal testosterone exposure and cerebral lateralization in general [8–10]. The relationship between prenatal testosterone and (language) lateralization is of interest in the context of the aetiology and pathogenesis of stuttering, because atypical hemispheric language processing is characteristic for adults who stutter. In the 1920s, Orton and Travis discussed a lack of hemispheric dominance and a resulting conflict in the
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neuromotor control of speech as one of the multiple causes of stuttering [7]. Moreover, newer brain imaging studies commonly reported results that suggest increased right hemisphere participation in speech production of people who stutter [e. g. 11–13]. This right hemispheric overactivity was considered to be compensatory because it is associated with decreased functional and anatomical anomalies in the left hemisphere of people who stutter [13,14, see also review 15]. Taking all these findings together, it is possible that prenatal testosterone could influence the aetiology and the development of stuttering. To the best knowledge of the authors of the present article, there are no studies that have investigated these relationships in the context of stuttering. There are only anecdotal case reports that indicate a potential association between testosterone and stuttering. For example, Kartalci et al. [16] showed an association between testosterone administration for treating hypogonadism and stuttering in an adolescent boy. Because of the lack of empirical evidence in the field, the present study sought to explore whether prenatal testosterone could be linked to the occurrence and/or the symptomatology of stuttering. As it is difficult to assess early prenatal testosterone levels in humans (e.g., at the end of 1st Trimester or beginning of 2nd Trimester), and because it is unknown if a person will stutter in the future, indirect measures are required. One of the most often-used indirect indicators of prenatal testosterone is the 2D:4D ratio of the hand (D = digit or finger). Longer ring fingers (4D), as compared to the index finger (2D;), characterize the typical male hand (lower 2D:4D ratio). This pattern is associated with higher prenatal testosterone levels. In contrast, longer index fingers, as compared to ring fingers, characterize a more typical female hand. This pattern is associated with lower prenatal testosterone levels (note that the ratio is not related to actual testosterone levels in adolescence/adulthood; it only reflects the prenatal environment). The robust statistical difference in 2D:4D between male and female hands has been abundantly researched and confirmed in a large number of samples [e. g. 17]. Hönekopp et al. [18], Breedlove [19] and Manning et al. [20] have summarized the sizable body of evidence linking digit ratio to prenatal testosterone. Given the above-mentioned evidence on males being more affected in the context of stuttering, as well as the laterality issues indicating that prenatal testosterone might be involved in stuttering, we hypothesized in a first step of this study that people who stutter would be more likely to exhibit male hand characteristics (lower 2D:4D ratio – hence higher prenatal testosterone) than people who do not stutter. In a second step, we were interested in linking 2D:4D to the individual degree of the multifaceted symptomatology within the stuttering group. Here, we hypothesized that a lower 2D:4D (higher prenatal testosterone levels) would be linked with a higher symptomatology, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES) [21]. Besides the two mentioned research hypotheses, we aimed to replicate the classical sex effect of the 2D:4D ratio, with females being associated with higher ratios compared to males.
and at a self-help congress for stuttering in 2012. The persons who do not stutter reported no lifetime history of stuttering and no occurrence of stuttering in their families. They were recruited at the university and in the personal environment of the researchers. No significant betweengroup differences were found with respect to age (F(1,72) = .13, p = .72) or sex (Chi2 = .44, df =1, p = .51). The present study was approved by the local ethics' committee of the university and all participants gave written consent. In the second part of the study, the association between 2D:4D and experiences due to stuttering in everyday life were investigated in the group of people who stutter. In addition to the original described sample described above, 6 additional participants who stutter were recruited. Thus, the total sample of persons who stuttered examined in the second part of this study consisted of 44 individuals (34 males and 10 females). The mean-age of the participants was 31.95 years (SD =11.90). 2.2. Questionnaire The German translation of the Overall Assessment of the Speaker's Experience of Stuttering (OASES, [21]; translation by [24]) was administered to all persons who stutter. This questionnaire includes 100 items that examine the overall impact of stuttering on people's lives. Each item is assessed as a self-report with a five-point Likert scale. The questionnaire is divided into four subscales: (I) general perspectives about stuttering, (II) affective, behavioral and cognitive reactions to stuttering, (III) functional communication difficulties, and (IV) the impact of stuttering on the speaker's quality of life. The German version has been externally validated with the NEO-FFI, a measure for human personality [25]. High neuroticism and low extraversion was associated with high OASES scores (hence high negative experience of stuttering in everyday life). 2.3. 2D:4D ratio All participants were first asked if one of their index or ring fingers had been broken. If so, the afflicted hand was excluded from the analysis. There were four instances of a broken left ring finger, one instance of a broken right ring finger, and instance of a broken right hand. Therefore, different sample sizes (degrees of freedom) can be observed in the statistical analysis reported below. Scans of both the left and right hand were conducted with a Canon Scanner. Every scan was implemented in the software GIMP 2.0 to calculate 2D:4D. A line was drawn from the middle of the lowest crease from the index and ring finger to the tip of each finger. Each hand was measured by two independent raters in pixels. The inter-raterreliability between the two measures for the left and right 2D/4D fingers was high and ranged from .978 to .998. The correlations between measures was r = .85 for the left 2D:4D ratio and r = .86 for the right 2D:4D ratio. 2.4. Statistical analyses
2. Methods 2.1. Participants In the first part of the study, 38 persons who stutter (28 males and 10 females) and 36 persons who do not stutter (24 males and 12 females) were invited. This sample size, which is comparable to other studies also investigating the 2D:4D marker in patient groups such as schizophrenia [e. g. 22,23], represents a starting point to investigate the link between prenatal testosterone and stuttering. We aimed to achieve the same number of males and females in the non-stuttering group after the persons who stutter were recruited. The mean age of persons who stutter was 30.63 years (SD = 10.65). The mean age of the non-stuttering group was 31.53 years (SD = 10.54). The persons who stutter were recruited in speech therapy settings in 2012-2013
An analysis of variance (ANOVA) was used to investigate potential differences in the 2D:4D ratio by subject group (persons who stutter/ persons who do not stutter) and sex (male/female). In a second step, partial correlations were computed between the 2D:4D measures of the left/right hand and the OASES scores, controlling for age, because this variable correlated significantly (though not strongly) with the OASES total scale, (r = −.30, p b .05) and the subscale I (r = −.33, p b .05). The other correlations between OASES subscales and age barely missed significance. Sex was not associated with significant differences in the OASES. All analyses were conducted for the total sample and for the male/female subsamples independently. Considering a potential link between the four subscales of the OASES and 2D:4D, the alpha to be reached for significance was adjusted to .0125 for these analyses (.05 divided by four tests).
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3. Results
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Table 2 Partial Correlation of 2D:4D ratios (right hand) with OASES scores in the stutter group.
3.1. Comparison of 2D:4D between participant groups No significant main effects were observed on the left 2D:4D ratio for sex (male vs. female; F(1,65) = 2.11, p = .15) or participant group (people who stutter vs. people who do not stutter; F(1,65) = 0.01, p = .93). Also, no interaction effect was observed (F(1,65) = 0.01, p = .94). A significant main effect of sex on the right 2D:4D ratio was observed (F(1,67) = 5.78, p = .02), with males showing lower ratios compared to women. No main effect of the participant group (F(1,67) = 0.28, p = .60) or interaction effect (F(1,67) = 0.84, p = .36) was observed. 3.2. Correlation of the 2D:4D ratio with the OASES scores in persons who stutter No significant sex differences in the total OASES scale or the OASES subscales could be observed. As shown in Tables 1 and 2, several significant negative correlations were observed between the 2D:4D ratio and the OASES total score and its subscales. These effects were most prominent in females. The strongest correlations (about r N −.70; p b .05) were between the left 2D:4D ratio and both subscale IV of the OASES and the total OASES score in females. The association between left 2D:4D and OASES (suggesting that higher prenatal testosterone is linked to reported higher negative experiences due to stuttering) in females is shown in Fig. 1. 4. Discussion As a strong skewed sex ratio in persons who stutter is welldocumented, we hypothesized that a measure reflecting prenatal testosterone (2D:4D) could be of relevance for understanding the biological basis and experience of stuttering. In line with the literature, we observed the expected statistical difference in 2D:4D between males and females for the right hand. Descriptive results for the left hand showed findings in the expected direction, but the difference did not reach significance. Fittingly, Manning et al. [17] described that the effect of sex on 2D:4D ratio to be stronger for the right compared to the left hand. We did not find a difference between the 2D:4D ratio when comparing persons who stutter with persons who do not stutter. Therefore, an influence of prenatal testosterone as indirectly measured via 2D:4D on the occurrence of stuttering cannot be observed. While a direct assessment of prenatal testosterone could result in different findings, such a study would require measurement of prenatal testosterone in the uterus while the mother is pregnant [26] and, later, the child would have to be investigated in a longitudinal design with respect to the development of stuttering. However, we cannot rule out a 2D:4D group
Males
Females
Total Sample
OASES I
OASES II
OASES III
OASES IV
OASES Total
r = −.04 p = .83 df =30 n =33 r = −.51, p = .16 df =7 n =10 r = −.15 p = .36 df =40 n =43
r = −.17 p = .34 df =30 n =33 r = −.70, p = .04 df =7 n =10 r = −.22 p = .16 df =40 n =43
r = −.12 p = .50 df =30 n =33 r = −.64, p = .07 df =7 n =10 r = −.19 p = .22 df =40 n =43
r = −.18 p = .31 df =30 n =33 r = −.53, p = .14 df =7 n =10 r = −.21 p = .19 df =40 n =43
r = −.16 p = .38 df =30 n =33 r = −.68, p = .04 df =7 n =10 r = −.23 p = .15 df =40 n =43
difference between persons who stutter and persons who do not stutter because the sample size of the present study is rather small making it difficult to detect small effect size due to reduced statistical power. The other hypothesis of interest was whether there is a link between the 2D:4D ratio and a speaker's experiences due to stuttering. Here, a moderate correlation appeared for the total sample, linking higher prenatal testosterone levels (lower 2D:4D) to higher scores on the OASES (left hand). In detail, a stronger influence of prenatal testosterone on the evolving human organism is associated with greater problems in coping with stuttering. Of note, the observed association between 2D:4D ratio and the OASES scores seems to be largely driven by the female subsample of the present sample. Specifically, a large correlation was observed for the left hand (r = -.75, p = .02) explaining 56% of the variance in the OASES scale. Effects in the same direction can be observed for the right hand. Therefore, prenatal testosterone as reflected by 2D:4D might be of special importance for predicting experiences associated with stuttering in females. Although the present finding is hard to interpret at present (given the scarce literature), recent studies on testosterone and emotionality in females can illuminate the present association between 2D:4D and the OASES in females. Bos et al. [27] observed that females under influence of exogenous administered testosterone showed higher neural response in the thalamocingulate region and insula to crying infants. Moreover, the same research group [28] showed that females under testosterone administration respond more strongly with their amygdala to happy and fearful faces. In interpreting the stronger activity of the basolateral and superficial amygdala under the influence of testosterone, the authors suggested that testosterone might be a promotor of
Table 1 Partial Correlation of 2D:4D ratios (left hand) with OASES scores in the stutter group.
Males
Females
Total Sample
OASES I
OASES II
OASES III
OASES IV
OASES Total
r = −.19 p = .30 df =29 n =32 r = −.47 p = .20 df =7 n =10 r = −.23 p = .15 df =39 n =42
r = −.26 p = .16 df =29 n =32 r = −.59 p = .09 df = 7 n =10 r = −.30 p = .06 df =39 n =42
r = −.24 p = .19 df =29 n =32 r = −.72 p = .03 df =7 n =10 r = −.33 p = .04 df =39 n =42
r = −.36 p = .04 df =29 n =32 r = −.79⁎ p = .01 df =7 n =10 r = −.43⁎ p = .005 df =39 n =42
r = −.31 p = .09 df =29 n =32 r = −.75 p = .02 df =7 n =10 r = −.38 p = .01 df =39 n =42
⁎ These results hold for Bonferroni adjustment as discussed in the statistical analyses section. Here Bonferroni adjustments have been applied for the subscales. In general bold printed results show the most relevant statistics.
Fig. 1. Negative correlation between the 2D:4D ratio of the left hand and the OASES score in females who stutter (partial correlation: p = −.75, df =7, p = .02; R2 = .56). Of note: The Y-axis describes the mean-answer on the OASES items technically ranging from 1 to 5 (and not the mean-total score). We depict a smaller range on the Y-axis for reasons of better visibility.
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“preferential processing of salient stimuli in the context of social challenges” (p. 815). Clearly, one's own speech difficulties, along with the reactions of others, represents a salient stimuli with which the person who stutters needs to cope. Females might react more emotionally to their own speech difficulties and the responses of their environments when under the influence of testosterone, though again, the present study examined only a marker of prenatal testosterone and not testosterone at the time of the assessment. The generalization of the present finding is of course limited due to the small sample of females who stutter in the current study (n = 10), although our sample (34 males and 10 females) is consistent with the male-to-female ratio reported in the overall population of individuals who stutter [see also 2]. Of additional importance, a potential involvement of the 2D:4D marker in stuttering would not reflect an exclusive influence of prenatal testosterone on stuttering, because this morphological marker has already been associated with a wide range of phenotypes, including disorders such as autism, ADHD [e. g. 29] and schizophrenia/schizotypal personality [e. g. 30]. Therefore, the influence of prenatal testosterone on the brain and behavior is rather broad. Summarizing, the present study shows that the inclusion of the 2D:4D ratio in stuttering research could represent an interesting research avenue to a better understanding of the biological basis of individual differences in coping with speech disorders. Future research should explore how individual differences in this marker of prenatal testosterone might relate to observed differences in neural structure and the occurrence of stuttering. Contributions CM designed the study. BB, SB, HP and KR recruited the participants. SB measured the 2D:4D ratios. CM, BB, SC, SY and MR drafted the manuscript. CM, BB and MR conducted the statistical analyses. Conflict of Interest None. Acknowledgement The position of CM is funded by a Heisenberg grant by the German Research Foundation (MO 2363/3-1). We thank Thomas Grünhage for measuring the 2D:4D ratios (as a second person). References [1] Bloodstein O, Bernstein Ratner N. A handbook on stuttering. 6th ed. Clifton Park, NY: Thomson Delmar; 2008. [2] Van Borsel J, Moeyaert J, Mostaert C, Rosseel R, Van Loo E, Van Renterghem T. Prevalence of stuttering in regular and special school populations in Belgium based on teacher perceptions. Folia Phoniatr Logop 2006;58:289–302. [3] Yairi E, Ambrose NG. Early childhood stuttering I: persistency and recovery rates. J Speech Lang Hear Res 1999;42:1097–112. [4] Geschwind N, Galaburda AM. Cerebral lateralization: biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. Arch Neurol 1985; 42:428–59.
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