mediate the relationship between finger length ratio (2D4D), depression and physical health?

Personality and Individual Differences 113 (2017) 74–80

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Does life stress moderate/mediate the relationship between finger length ratio (2D4D), depression and physical health? Kimberly A. Rapoza Mercy College, 555 Broadway, Dobbs Ferry, NY 10522, United States

a r t i c l e

i n f o

Article history: Received 17 November 2016 Received in revised form 2 March 2017 Accepted 4 March 2017 Available online xxxx Keywords: 2D4D ratio Prenatal androgen Depression Physical health Life stress

a b s t r a c t Diseases with sex-dependent expressions may have an etiology in prenatal sex hormone exposure, specifically prenatal androgens. This study examined the relationship between prenatal hormone exposure (as evidenced by the 2D4D ratio), with life stress as a potential moderator/mediator, and adult depressive and/or physical health symptoms. Participants were n = 137 undergraduates from diverse backgrounds. Results indicated a more masculine 2D4D ratio was associated with poorer health in males, but the 2D4D ratio seemed to have little explanatory power for female physical/mental health. In males, a lower ratio (i.e., more masculine) ratio was linked to clinical cutoff scores for depression, higher levels of life stress, and greater depression scores. In addition, the relationship was mediated by life stress, indicating the link between a more masculine ratio and depression was dependent on levels of life stress. The 2D4D ratio was also moderated by life stress, such that at high levels of stress a more masculine ratio was associated with more physical symptoms. Overall, while life stress seemed to have the largest impact on physical and mental health for female participants, a more masculine ratio emerged as a risk factor for men, but was strongly governed by the context of reported stress levels. © 2017 Elsevier Ltd. All rights reserved.

1. Introduction

1.1. Explanation of 2D4D ratio

Far too little is known regarding the contributions of individual biological vulnerabilities to long-term physical and mental health consequences that stem from stressful life experiences. A vastly underexplored area is the way in which biological characteristics may interact with social experiences to increase or decrease the propensity for developing physical or mental illness. This study rest theoretically upon the diathesis- stress model, which notes that individuals vary widely in their susceptibility to physical and mental health disorders, and even a biological or genetic predisposed vulnerability does not mean any one individual will develop a specific disorder (Markward, Dozier, Hooks, & Markward, 2000). Markward and colleagues note the diathesis-stress model assumes the existence of an internal vulnerability (i.e., biogenetic, cognitive or psychosocial) that interacts with external environmental stressors; it is this synergistic combination of vulnerability and stress that is the catalyst for a particular disorder. This study provides a framework for understanding how the relationship between prenatal hormone exposure (as evidenced by the 2D4D ratio) and stressful adult life experiences synergistically interact to create risk for adult depressive symptoms and/or poorer physical health.

The ratio of the lengths of the 2D (index finger) and 4D (ring finger) digits is influenced by exposure to prenatal sex hormones and is also sexually dimorphic (Manning, Scott, Wilson, & Lewis-Jones, 1998). Zheng and Cohn (2011) examined the developmental basis of the 2D4D ratio utilizing mice, which also evidence the sexually dimorphic digit ratio. The authors found gender differences in the 2D4D ratio appeared during an early and specific window of prenatal limb development. The authors examined androgen and estrogen receptor activity during this developmental window and found males had greater differences in androgen receptor activity between 2D and 4D, while females had greater differences in estrogen receptor activity between 2D and 4D during the same interval. After a series of experiments involving manipulating prenatal exposure to sex hormones it was determine that 4D had higher levels of androgen and estrogen receptors than 2D and that receptor activity influenced the 2D4D ratio through gene expression and digit specific increases in cell numbers (modulating finger length). As described by Manning (2002) exposure to high levels of prenatal androgens (testosterone) and low levels of prenatal estrogen produces a lower (i.e., more masculine) 2D4D finger ratio (where the index finger is shorter than the ring finger). Exposure to low levels of prenatal androgens and high levels of prenatal estrogen produce a higher (i.e., more feminine) 2D4D ratio (where the index finger is the same length or longer than the ring finger). These patterns are found in varying degrees in

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K.A. Rapoza / Personality and Individual Differences 113 (2017) 74–80

both men and women, influenced by each individual's prenatal hormone exposure. On average males present with a lower 2D4D ratio than females (Manning, Churchill, & Peters, 2007). In addition, ethnic variations in ratio values were detected by Manning and colleagues, such that higher ratios were found for Caucasian, non-Chinese Asian, and Middle-Easterners and lower ratios were found for Chinese and Black participants. 1.2. Relationship of 2D4D ratio to physical health and depression Manning (2002) theorized that diseases with sex-dependent expression may have ties to and an etiology in prenatal sex hormone exposure. Depression is sexually dimorphic, in that rates of depression across large scale epidemiological studies have consistently been found to be 2–3 times higher among women than men (Klerman & Weissman, 1989). The inquiry into prenatal sex hormone exposure and depression is a new line of research and as of yet results have been equivocal. Bailey and Hurd (2005a) found that men with higher 2D4D finger digit ratios (i.e., more feminine) had higher trait depression scores than men with lower 2D4D finger length ratios. However, other studies did not find a relationship between depression and 2D4D digit ratio (Austin, Manning, McInroy, & Mathews, 2002; Martin, Manning, & Dowrick, 1999) or found a more masculine ratio was associated with increased reports of depression in boys (Vermeersch, T'sjoen, Kaufman, Vincke, & Van Houtte, 2010). Bailey and Hurd noted that prior studies suffered from some methodological shortcomings, such as the use measures designed to detect clinical depression, and not depression in non-clinical populations. Also that prior empirical studies did not controlled for birth control medication or menstrual cycle phase in female participants. Investigations into sex related variations in disease status, especially those that are sexually dimorphic and influenced by sex hormone exposure, point to a potential role for 2D4D digit ratio in the manifestation of physical illness and disease. A fair number of recent studies investigated 2D4D ratio as related to cardiovascular disease and found a higher (i.e., feminized) digit ratio in males was implicated as increasing risk for earlier myocardial infarction and coronary artery disease (Manning & Bundred, 2001; Ozdogmus et al., 2010; Wu et al., 2013). A more feminine ratio was also linked to an increased risk for breast cancer in women (Muller et al., 2012), and a more masculine digit ratio has been tied to prostate disease, prostate cancer and immune system dysfunction (Manning & Bundred, 2001; Rahman et al., 2011; Sudhakar, Manjunatha, & Madhusudhana, 2015). Whereas instigations into specific diseases have been informative, this study will explore a model of the relationship between the 2D4D ratio and general physical health. While general physical health is comprised of ailments from the less severe end of the disease spectrum, the frequency and severity of such illnesses can weigh heavily on an individual's sense of actual or perceived quality of life, impacting physical and/or social functioning (Portenoy et al., 1994).

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An intriguing, and as of yet unanswered question, is whether 2D4D digit ratio also influences levels of life stress. A more masculine ratio has been associated with socially positive masculine traits/behaviors, such as dominance and mating success (Manning & Fink, 2008; Neave, Laing, Fink, & Manning, 2003). However, research on other biologically influenced traits, such as extroversion has noted a cost benefits tradeoff where the tradeoff for greater mating and social success may be increased physical risk taking, romantic unfaithfulness, and having children by more than one partner (Nettle, 2005). While as noted a more masculine ratio is associated with socially positive outcomes, it is possible that socially traits/behaviors 2D4D ratio (especially a lower ratio) increases vulnerability by synergistically interacting with the environment to produce higher levels of stress, thus indirectly increasing risk for poorer health and depression. For example, in males a more masculine ratio was linked with greater risk for hyperactivity, impulsivity, physical aggression, general unprovoked aggression, criminal offenses and convictions, and risk taking behavior (Bailey & Hurd, 2005b; Hanoch, Gummerum, & Rolison, 2012; Martel, Gobrogge, Breedlove, & Nigg, 2008; McIntyre et al., 2007; Ronay & Von Hippel, 2010; Stenstrom, Saad, Nepomuceno, & Mendenhall, 2011). Also documented in females a lower 2D4D ratio was associated with greater reactive aggression (Benderlioglu & Nelson, 2004). Each of the above behavioral proclivities associated with a lower 2D4D ratio could reasonably increase stress or perceived stress through greater relationship, financial, medical, social, legal, and career difficulties. For example, Lenz et al. (2016) examined the digit ratio of 46 individuals that had completed suicide and the corpses of 25 non-suicide controls. The authors found a significantly more masculine 2D4D ratio for the group that completed suicide, which was primarily carried by the males in the sample. The authors noted the association between increased risk for suicide and a lower ratio may rest on the associations between a masculine 2D4D ratio and traits of greater physical aggression and impulsivity. Thus this exploratory question of whether 2D4D ratio impacts experiences of life stress, while speculative and exploratory, seems warranted. It is predicted that a lower 2D4D ratio will be associated with more reported physical symptoms. This study will explore whether the 2D4D ratio is related to depression (utilizing a measure designed to assess depression in community samples) and greater life stress. We will also explore whether levels of life stress will mediate and/or moderate the relationship between prenatal androgen exposure and adult physical and/or mental health. Given variations in the association of the 2D4D ratio to different emotional, personality and behavioral factors based on gender, models will be explored separately for males and females. 2. Method 2.1. Sample There were 137 participants (46.7% men and 52.6% women) with an average age of 34.80 (SD = 13.01). The most frequently reported race/ ethnicities were African American (21.2%), Caucasian (59.9%), and Latino (8.8%). The participants were predominately upper-middle (17.5%), middle (46%), or working (29.2%) class.

1.3. Stress, health and 2D4D ratio 2.2. Procedure There is a large and consistent body of empirical literature establishing the relationship between negative or stressful life events and the onset of depression (for a review see Brown & Harris, 1986). Underlying the etiology of immune related illnesses could be the impact of chronic life stress on the hypothalamic-pituitary-adrenal axis (HPA axis). The HPA axis plays a significant role in hormonal response to environmental stressors, activating the release of cortisol by the adrenal cortex. Melamed, Shirom, Toker, Berliner, and Shapira (2006) noted that hypo- or hyper-cortisol levels in the body may underlie a host of potential adverse health effects, such as diabetes, sleep disorders, chronic pain, cardiovascular disease and immune system disorders.

Participants were recruited from a college campus, with a sizable number of commuters. Students were approached and completed the measures in common areas (i.e., library, cafeteria, etc.) and in classrooms during break. The APA ethical code of conduct was followed and IRB approval attained. After completion of informed consent and the survey packet a digital camera with high pixel resolution capabilities was utilized to photograph each participant's hands. Measurements were taken with a tool function in centimeters using the GNU Image Manipulation Program (GIMP). The use of photo imaging software to provide digit measurement is a common technique (e.g., Bailey &

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K.A. Rapoza / Personality and Individual Differences 113 (2017) 74–80

Hurd, 2005a; Millet & Dewitte, 2007). In keeping with procedures developed by Manning et al. (1998) the digits were measured from the basal crease of the digit to the fingertip. When there were bands of creases at the base of the digit, the length was measured based on the most proximal of the creases. The length of the index finger (2D) was divided by the length of the ring finger (4D) to obtain the 2D4D ratio. The measurements were taken twice by either the PI or two research assistants, then averaged into one composite score.

2.3. Measures A demographic form with self-report questions assessing gender, age, ethnicity and social-class was included in the questionnaire packet and asked additional information on depression diagnoses and the use of oral contraceptives and the current phase of the menstrual cycle for women.

2.3.1. Physical health questionnaire This study utilized the Memorial Symptom Assessment Scale (Portenoy et al., 1994) to assess the frequency and distress caused by 32 symptoms over a 6 month period. Only the physical health subscale was examined and additional immune system related illness questions were added to the scale (i.e., colds & flu, fevers, sore throat, and infections). Portenoy and colleagues found reliability to be high overall. This study obtained a Cronbach's alpha of 0.88 for the newly developed physical symptom scale.

2.3.2. Stress questionnaire Chronic life stress over a 6-month period was assessed with the CRISYS stress measure (Shalowitz, Berry, Rasinski, & DannhausenBrun, 1998). The measure contains 11 content domains (financial, legal, career, relationship, safety in the home & community, medical & home issues, difficulty with authority and prejudice) and was found to have good test-retest reliability and strong face, content and construct validity. This study obtained a Cronbach's alpha of 0.80.

3. Results 3.1. Descriptive statistics The mean values for major study variables were: life stress (M = 6.74, SD = 5.22), depression (M = 14.50, SD = 9.58), and physical symptoms (M = 12.42, SD = 8.52). The average male right hand 2D4D ratio was (M = 0.961, SD = 0.07) and the average for females was (M = 0.963, SD = 0.07). The average male left hand 2D4D ratio was (M = 0.950 SD = 0.07) and the average for females was (M = 0.969, SD = 0.05). A series of t-tests were conducted on physical symptoms, life stress, depression and right and left hand 2D4D ratio by gender. Females scored higher than males on physical symptoms (M = 14.38, SD = 8.69 vs. M = 10.00, SD = 7.61; t(134) = 3.11, p b 0.01, CI: 95% CI (− 7.17, − 1.59); d = 0.54), life stress (M = 7.64, SD = 5.42 vs. M = 5.84, SD = 4.83; t(134) = 2.03, p b 0.05, CI: 95% CI (− 3.54, − 0.05); d = 0.42) and on depression (M = 15.99, SD = 9.54 vs. M = 12.73, SD = 9.46; t(134) = 1.99, p b 0.05, CI: 95% CI (− 6.48,− 0.02); d = 0.34). There were no significant differences between males and females on right or left hand 2D4D ratio. For males, those meeting the CES-D risk cutoff score for clinical depression (e.g., 16 or greater) had a more masculine right 2D4D ratio (M = 0.93, SD = 0.08) than those that did not (M = 0.97, SD = 0.07; F(1,57) = 4.50, p b 0.05, CI: 95% CI (0.94, − 0.98) d = 0.37), but no differences were detected in females or with the left hand 2D4D ratio for either gender. 3.2. Correlational analyses For males (Table 1) right hand 2D4D ratio was negatively associated with depression (r = −0.30, p b 0.05, CI: 95% CI (−0.52, −0.05) and life stress (r = −0.27, p b 0.05,CI: 95% CI (−0.49, −0.01), indicating a more masculine ratio was associated with greater depression and stress. Life stress was positively associated with depression (r = 0.55, p b 0.001,CI: 95% CI (0.35, 0.70) and physical symptoms (r = 0.35, p b 0.01, CI: 95% CI (0.11, 0.55). In the female sample life stress was associated with depression (r = 0.41, p b 0.001, CI: 95% CI (0.19, 0.58) and physical symptoms (r = 0.30, p ≤ 0.01, CI: 95% CI (0.08, 0.50). 3.3. Data analyses

2.3.3. Depression Depression was assessed using the CES-D, a measure developed for the screening of adult depression in community populations (Santor & Coyne, 1997). The measure contains twenty items that list symptoms of depression one might have during a week's time. The measure was found to have good internal consistency and concurrent validity by Santor and Coyne. This study obtained a Cronbach's alpha of 0.86.

The literature indicates the effects of prenatal androgen and digit ratio differentiation are stronger for the right hand in humans (as well as other species such as mice) and sex-linked behavioral and personality differences in 2D4D digit ratio show greater effects on the right hand than on the left (Bailey & Hurd, 2005b; Brown, Fin, & Breedlove, 2002; Manning et al., 1998; Zheng & Cohn, 2011). For these reasons, studies

Table 1 Inter-correlation among study variables for males and females. Physical health Physical health (M) Physical health (F) Depression (M) Depression (F) Right 2D4D ratio (M) Right 2D4D ratio (F) Left 2D4D ratio (M) Left 2D4D ratio (F) Life stress (M) Life stress (F) M = Male and F = Female. ⁎ p b 0.05. ⁎⁎ p ≤ 0.01. ⁎⁎⁎ p b 0.001.

Depression

Right 2D4D ratio

Left 2D4D ratio

Life stress

– – −0.30⁎ −0.05 0.22 0.22 0.55⁎⁎⁎ 0.41⁎⁎⁎

– – 0.10 0.02 −0.27⁎ −0.10

– – −0.07 0.07

– –

– – 0.46⁎⁎⁎ 0.36⁎⁎ −0.13 −0.09 0.23 0.08 0.35⁎⁎ 0.30⁎⁎

K.A. Rapoza / Personality and Individual Differences 113 (2017) 74–80

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Table 2 Summary of hierarchical regression analyses on physical health and depression for male participants. Variables entered

Physical symptoms Step 1

Step 1

Step 2 Step 3 Step 4 Model

African American Caucasian Latino 2D4D Life stress 2D4Dx Life Stress F value R2 ΔF value ΔR2

Depression

Step 2

Step 3

Step 4

Step 1

Step 2

Step 3

Step 4

β

t

β

t

β

t

β

t

β

t

β

t

β

t

β

t

0.06 −0.18 −0.18

0.21 −0.57 −0.80

0.07 −0.15 −0.20 −0.14

0.24 −0.47 −0.89 −0.99

−0.11 −0.10 −0.17 −0.04 0.43

−0.40 −0.34 −0.80 −0.30 2.87⁎⁎

−0.16 −0.16 −0.28 −0.25 0.34 −0.34 3.21⁎⁎ 0.27 5.41⁎ 0.08

−0.63 −0.58 −1.36 −1.60 2.31⁎

0.03 −0.18 −0.07

0.10 −0.58 −0.31

0.05 −0.11 −0.12 −0.30

0.17 −0.36 −0.55 −2.22⁎

−0.16 −0.06 −0.08 0.18 0.52

−0.65 −0.20 −0.41 −1.46 3.75⁎⁎⁎

−0.16 −0.06 −0.08 −0.19 0.52 −0.01 3.72⁎⁎ 0.30 0.007 0.00

−0.65 −0.21 −0.41 −1.23 3.57⁎⁎⁎

1.00 0.05 1.00 0.05

2.55⁎ 0.20 8.25⁎⁎ 0.13

0.99 0.07 0.97 0.02

−2.33⁎ 0.63 0.03 0.63 0.03

4.55⁎⁎ 0.30 14.08⁎⁎⁎ 0.19

1.74 0.12 4.92⁎ 0.08

−0.08

⁎ p b 0.05. ⁎⁎ p ≤ 0.01. ⁎⁎⁎ p ≤ 0.001.

the variables were significant. At Step 3, life stress (ß = 0.51, p b 0.001, CI: 95% CI (0.40, 1.59) was significant. At Step 4, there were no significant interactions.

have conducted analyses and modeling with right hand digit ratio data (Bailey & Hurd, 2005a; Evardone & Alexander, 2009; Manning, 2002). Our descriptive analyses evidenced few effects linked to the left hand 2D4D ratio and so modeling was conducted with only right hand measurements. Models with the criterion variables of depression and physical health were created separately for males and females. All continuous predictor variables were centered to control for multicollinearity. For all the regression equations Step 1 contained ethnicity (with three variables coded African American ethnicity {African American = 1/other group = 0}, Latino ethnicity {Latino = 1/other groups = 0} and {Caucasian = 1/other group = 0}, which made Other Ethnicity the reference group. This step contained use of birth control pills and days since last menstruation for female participants only. Step 2 contained the 2D4D ratio score, Step 3 contained life stress, and Step 4 evaluated the potential interactions between 2D4D ratio and life stress.

3.5. Mediated regression analyses for depression Based on the correlation matrix, only the relationship between depression, life stress and the 2D4D ratio in males met the initial criteria for potential mediation. Mediation procedures, as recommended by Baron and Kenny (1986) were followed. In the first regression equation 2D4D ratio was a significant predictor of life stress (ß = −0.30, p b 0.05). Second, 2D4D ratio was a significant predictor of depression (ß = − 0.27, p b 0.05). Third, life stress was a significant predictor of depression (ß = 0.55, p b 0.001). The last regression containing both 2D4D ratio and life stress was significant (F (2, 57) = 11.36, p b 0.001). 2D4D ratio was no longer significant (ß = −0.18, ns), while life stress was significant (ß = 0.47, p b 0.001) indicating that life stress mediated the relationship between 2D4D and depression. A Sobel test confirmed the indirect effect of 2D4D ratio via life stress was marginally different than zero (Z = − 1.85 p = 0.06).

3.4. Moderated regression analyses for depression In the male sample (Table 2), the regression model on depression was significant (F (6, 57) = 3.72, p b 0.01). At step 1, there were no significant variables. In Step 2, 2D4D ratio was significant (β = − 0.30, p b 0.05, CI: 95% CI (−0.72.26, −3.62). At Step 3, life stress (ß = 0.52, p b 0.00, CI: 95% CI (0.46, 1.51) was significant. At Step 4, there were no significant interactions. In the female sample (Table 3), the regression model on depression was significant (F (8, 44) = 2.30, p b 0.05). At Step 1 and Step 2, none of

3.6. Moderated regression analyses for physical health In the male sample (Table 2), the regression model on physical symptoms was significant F (6, 57) = 3.21, p ≤ 0.01. In Step 1 and Step 2 there were no significant predictors. In Step 3, life stress was

Table 3 Summary of hierarchical regression analyses on physical health and depression for female participants. Variables entered

Physical symptoms Step 1

Step 1

Step 2 Step 3 Step 4 Model

African American Caucasian Latino Birth Control Last Period 2D4D Life Stress 2D4Dx Life Stress F value R2 ΔF value ΔR2

⁎ p ≤ 0.05. ⁎⁎ p ≤ 0.01. ⁎⁎⁎ p ≤ 0.0.

Depression

Step 2

Step 3

Step 4

Step 1

Step 2

Step 3

Step 4

β

t

β

t

β

t

β

t

β

t

β

t

β

t

β

t

0.02 0.05 0.19 −0.29 −0.15

0.09 0.19 0.93 −1.72 −0.96

−0.02 0.04 0.17 −0.28 −0.14 −0.08

−0.08 0.18 0.83 −1.63 −0.90 −0.44

0.28 0.43 0.36 −0.25 −0.15 −0.05 0.58

1.32 1.88 2.02⁎ −1.73 −1.11 −0.32 4.04⁎⁎⁎

0.30 0.47 0.36 −0.30 −0.15 −0.15 0.60 −0.18 3.33⁎⁎

1.38 2.05⁎ 1.98 −1.98 −1.16 −0.84 4.18⁎⁎⁎

−0.34 −0.17 −0.12 −0.24 0.19

−1.51 −0.70 −0.57 −1.44 1.24

−0.37 −0.17 −0.13 −0.23 0.20 −0.06

−1.52 −0.70 −0.62 −1.35 1.26 −0.36

−0.10 0.17 0.04 −0.21 0.19 −0.04 0.51

−0.44 0.69 0.23 −1.36 1.38 −0.24 3.39⁎⁎

−0.10 0.18 0.04 −0.22 0.19 −0.07 0.52 −0.06 2.30⁎

−0.41 0.73 0.21 −1.38 1.35 −0.37 3.36⁎⁎

1.27 0.14 1.27 0.14

1.07 0.15 0.20 0.004

3.61⁎⁎ 0.41 16.28⁎⁎⁎ 0.26

0.43 1.22 0.02

−1.11 1.14 0.13 1.14 0.13

0.95 0.13 0.13 0.003

2.68⁎ 0.34 11.47⁎⁎ 0.21

0.34 0.11 0.002

−0.32

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K.A. Rapoza / Personality and Individual Differences 113 (2017) 74–80

significant (ß = 0.43, p b 0.01, CI: 95% CI (0.17, 0.97). In Step 4, the interaction between 2D4D ratio and life stress (ß = −0.34, p ≤ 0.05, CI: 95% CI (−15.41, −1.13) was significant. Based on the computational tools developed by Dawson (2014) significant interaction effects were probed by conducting a simple slopes analysis and graphs were plotted on the simple regression line for the low (−1SD) and high (+1SD) values of the moderator on the dependent variable against the low (−1SD) and high (+1SD) values of the predictor variable proposed to be moderated. The simple slope effects of the 2D4D ratio at conditional values of life stress were significant at +1SD. Graphical depiction of the interaction (see Fig. 1) indicated that at high levels of life stress, a lower 2D4D ratio (i.e. more masculine) was associated with more reported symptoms, whereas at low levels of life stress a higher 2D4D ratio (i.e., more feminine) was linked with more physical symptoms. In the female sample (Table 3), the regression model on physical health was significant (F (8, 44) = 3.33, p b 0.01). There were no significant variables at Step 1 or Step 2. In Step 3, life stress (ß = 0.58, p b 0.001, CI: 95% CI (0.48, 1.43) was significant. At Step 4, there were no significant interactions. 4. Discussion Evidence to date indicates that high levels of life stress place adults at increased risk for both depression and physical ailments. While some may have long-standing and pervasive health problems stemming from certain events, others may show resilience in the face of difficult life situations. What factors might contribute to such variability in health outcomes? Not all studies have found a relationship between prenatal androgen exposure and depression. Using the NEO-PI depression sub-scale (which measures depression as a personality trait) Bailey and Hurd (2005a) found that men with higher 2D4D finger digit ratios (i.e., more feminine) had higher trait depression scores than men with lower 2D4D finger length ratios. However, studies utilizing a clinical diagnostic measure of depression have not found any relationship with 2D4D digit ratio (Austin et al., 2002; Martin et al., 1999), but measure designed to assess depression in community samples have (Vermeersch et al., 2010). Bailey and Hurd noted previous studies have had some methodological limitations, such that the clinical measures utilized were perhaps not sensitive enough to detect small differences that may be present in non-clinical populations. This study provides evidence that prenatal androgen exposure, particularly for males, increases risk for poorer mental health. Based on the pattern of correlations, our study found support for a relationship between a lower 2D4D ratio (i.e., more masculine) and depression in males. Additionally, males meeting the cutoff score for a potential clinical diagnosis of depression had a significantly more masculine ratio than those that did not.

Fig. 1. Graphical depiction of the interaction between 2D4D ratio and life stress scores on physical symptoms.

This study found no evidence that 2D4D ratio was associated with depression or physical health symptoms in women. In fact, life stress was the most robust predictor of female physical and mental health. Prior research has also consistently failed to find an association between digit ratio and depression for women (Austin et al., 2002; Bailey & Hurd, 2005a; Martin et al., 1999; Vermeersch et al., 2010). We obtained this result, despite controlling for circulating hormonal variability, which could have masked a relationship between prenatal androgen exposure and depression in women. As previously noted depression is sexually dimorphic, with consistently higher rates of diagnoses in women compared to men (Klerman & Weissman, 1989). Yet prior research and the current study have only found significant associations between the 2D4D ratio and depression in males. Other studies, such as Evardone and Alexander (2009) examined the 2D4D ratio and anxiety, which also evidences greater risk for women and is sensitive to sexlinked post-pubertal hormones, but found an association between trait anxiety and a feminine ratio for males only. This lack of expected findings between 2D4D and mental health disorders that are sexually dimorphic and hormonally influenced in females has been perplexing. It is possible then that a variety of factors are involved in the development of depression in men and women, and the organization effects of prenatal androgen exposure on depression differ for males and females. Putz, Gaulin, Sporter, and McBurney (2004) noted sexual differentiation of behaviors or traits under the influence of hormones may have different developmental timing that may or may not match the timing of 2D4D development and differentiation. Hence, when the developmental windows are different 2D4D would not provide insight into certain traits that are sexually dimorphic. Additionally, explanations of sex differences in depression have noted hormonal differences in the etiology of depression (Hankin & Abramson, 2001). For example, in a review of the literature Piccinelli and Wilkinson (2000) noted that the manifestation of depression seems heavily tied to changes in gonadal hormones corresponding to puberty for females, who are then diagnosed at twice the ratio of males. Research has also found testosterone levels are a risk factor for depression in men, particularly later in life as testosterone levels decline (Manning, Bundred, Newton, & Flanagan, 2003). For example, depression in older men was associated with low levels of bioavailable testosterone and low levels of dihydrotestosterone (Barrett-Connor, Von Muhlen, & Kritz-Silverstein, 1999). While life stress and 2D4D ratio were significant variables in the regression model for males, a follow up mediation analysis indicated the effects of a lower 2D4D ratio were reduced and only marginally significant when life stress was accounted for in the mediation analysis. The empirical literature suggests that a more masculine 2D4D ratio was linked with characteristics (i.e., impulsivity, risk taking, aggression, etc.) that might reasonably be though to increase the propensity for difficult and stressful life circumstances (Bailey & Hurd, 2005b; Hanoch et al., 2012; McIntyre et al., 2007). Hence, the vulnerability for depression created by the 2D4D ratio seems more indirect and related to traits associated with a more masculine ratio. This study found no evidence that 2D4D ratio was associated with, or predictive of, physical health in women. Again, life stress was the strongest predictor in the regression model for women. A different pattern of results was obtained for males in the sample. The 2D4D ratio was not directly related to physical symptoms through correlational analyses. However, in the regression model on physical symptoms life stress and a more masculine 2D4D ratio were significant predictor of physical health symptoms. A follow up investigation of the interaction between life stress and the 2D4D ratio revealed that males with a lower ratio reported more physical symptoms under conditions of high life stress compared to men with higher (i.e., more feminine) ratios, and men with a higher ratio reported more symptoms under low levels of life stress. A lower ratio was empirically related by past studies to a variety of specific disease in males, such as cardiovascular problems, prostate cancer, and immune system dysfunction (Manning & Bundred, 2001; Rahman et al., 2011). This study provides evidence of a relationship

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between a lower 2D4D ratio and poorer general physical health, but that relationship might be more indirect and moderated by life stress, such that at higher levels of life stress males with a more masculine ratio have greater illness susceptibility and poorer health. It is generally known that stress can intensify or stimulate disease activity and/or acquisition, although the potential for gendered effects has been a more recent area of investigation. According to Kajantie and Phillips (2006) sex differences exist in physiological responses to stress, such that females from adolescence to menopause demonstrate lower HPA axis response to acute psychosocial stress as compared with males. This changes later in the life span after menopause and led the authors to infer that stress responses are also tied in with cycles of estrogen exposure as the dampened response is reversed during the luteal phase of menstruation and after menopause. Hence, this study provides evidence that greater exposure to prenatal testosterone in males may create a vulnerability for poorer general health, through interactions with life stress, but the parameters of this relationship are still vague. For example, it is unclear if susceptibility in either gender changes with developmental age. 4.1. Limitations and directions for future research The sample in this study was relatively young. Health complications tend to increase with age (Jousilahti, Vartiainen, Tuomilehto, & Puska, 1999) and it is unclear how a more masculine ratio is related to disease and aging. Future research might also consider exploring the relationship of 2D4D to other psychological disorders that have sexually dimorphic rates of diagnosis (i.e., anxiety, antisocial personality disorder, etc.), comorbid disorders, and other moderating social and biological factors. The current study also did not find significant differences between males and females on right hand 2D4D ratio. While other studies have also not found sex differences in 2D4D ratio within their samples on the right hand (Evardone & Alexander, 2009; Schwarz, Mustafic, Hassebrauck, & Jorg, 2011), this might underestimate relationships between the 2D4D ratio and health. In addition, the smaller sample size, while within range of that collected in published research on 2D4D and depression (Austin et al., 2002; Bailey & Hurd, 2005a, 2005b; Martin et al., 1999; Vermeersch et al., 2010) might underestimate some 2D4D relationships, which tend to be weak. 4.2. Conclusion The current study provides evidence that a more masculine 2D4D ratio was associated with poorer health in males, but has little explanatory power for female reports of physical and mental health. A more masculine ratio in males was linked to a clinical diagnosis of depression, higher levels of life stress, and greater depression scores. In addition, regression models found that while a lower ratio was associated with greater reports of depressive symptoms, life stress marginally mediated this relationship. That is, a more masculine ratio might create vulnerability by increasing exposure to life stress, which then underlies the relationship between a more masculine ratio and depression. A lower 2D4D ratio was found to be an indirect contributor to physical health, moderated by life stress. That is, at high levels of life stress a more masculine ratio was associated with more reported symptoms. Overall, while life stress, rather than 2D4D ratio seemed to have the largest impact on physical and mental health for female participants, a more masculine ratio emerged as a risk factor for men, but was strongly governed by the context of stress levels in the male participant's lives. Acknowledgements This research was funded by a National Institute of Health Extramural Associates Research Development Award (EARDA) (G11 HD035965). The funder had no role in study design, the collection/analysis of data, or publication. The author would also like to thank Kemesha

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