Prenatal exposure to sex hormones determines important effects on the development and organization of the brain, which, consequently, will also influence its behavior (Collear and Hines, 1995). Subjects with high levels of testosterone present themselves as more prone to take risks, impulsive, with greater aggressiveness, while subjects with low levels of testosterone present themselves as more prone to reasoning and the study of logical subjects (Manning et al., 2000; Kilduff et al., 2013).

Several markers can detect the effects of prenatal androgens (Cohen-Bendahan et al., 2005), however, among the less invasive measures, the digit ratio allows to estimate prenatal exposure to androgens. It appears detectable in human fetuses as early as 10–40 weeks of gestation and assumes stable levels around 2 years of age (Manning et al., 1998; Manning, 2002a; Malas et al., 2006). It expresses the ratio of the length of the index finger to the ring finger of the right hand (Neyse and Brañas-Garza, 2014) which is measured from the midpoint of the lower crease (where the finger joins the hand) to the tip of the finger (D2:D4).

Generally, the digit ratio shows positive correlations with typical female behaviors and negative correlations with typical male behaviors (Putz et al., 2004). Specifically, it was observed that D2:D4 ratios appear to correlate with certain personological factors such as neuroticism, agreeableness, and openness (Fink et al., 2004, 2006). Moreover, D2:D4 can be a predictive factor of success among high financial brokers (Coates et al., 2009), of success in admission at Italian Medical Schools (Coco et al., 2011), of best performances in sports such as basketball (Tester and Campbell, 2007), skiing (Manning, 2002b), and soccer (Manning and Taylor, 2001), and of aggressive behavior in professional soccer players (Perciavalle et al., 2013) and of the risky decision making (Massimino et al., 2019; Rinella et al., 2019).

Many studies have attempted to verify possible correlations between digit ratio indices and impulsivity, while there are far fewer studies that have explored a possible correlation between the D2:D4 ratio and state and trait anxiety. Usually, the onset of anxiety disorders coincides with puberty, a period when the production of sex hormones is greatest (Yonkers and Kidner, 2002). It is shown that females are more than two times as likely as males to be afflicted with mood disorders (Shear et al., 2000; Pigott, 2003; Kessler et al., 2005; Bekker and van Mens-Verhulst, 2007; Fabio and Caprì, 2019). This disparity has been documented worldwide (Seedat et al., 2009) and would seem to suggest a potential role for gonadal hormones in the onset of anxiety and depressive disorders. In fact, several studies have confirmed that women are more likely to experience mood disorders during puberty, menopause, perimenstrual periods, and postpartum (Ahokas et al., 2001; Parker and Brotchie, 2004; Douma et al., 2005; Solomon and Herman, 2009).

Also, in women, an association is shown between D2:D4 and anxious behavior in childhood (Williams et al., 2003), and also with neuroticism (Fink et al., 2004), considered a precursor to anxiety (Ehrler et al., 1999; Khan et al., 2005).

Moreover, the relationship between testosterone levels, anxiety disorders, and major depressive disorder in humans is evident in males with hypogonadism, who exhibit a significantly higher prevalence of anxiety disorders and major depressive disorder, compared to those with normal physiological levels of androgens (Shores et al., 2004; Zarrouf et al., 2009). Despite a few inconsistent reports, the majority of studies support the case that testosterone yields beneficial effects on mood in men, especially in those with lower than normal levels (McHenry et al., 2014).

Even in the animal world, it has been shown that rhesus monkeys show sexually dimorphic D2:D4, with males having higher ratios than females (Baxter et al., 2017), and male rats deprived of androgens because of perinatal castration display female-typical patterns of anxious behavior (Lucion et al., 1996).

Few studies have used the D2:D4 ratio to explore a possible correlation between state and trait anxiety. Among these, it is possible to mention two. The first one actually identified a correlation between the D2:D4 ratio and anxiety in male university students, females excluded (Evardone and Alexander, 2009). The second instead investigated male subjects suffering from anxiety disorders (de Bruin et al., 2004). The results, whose scores indicated high values of the D2:D4 ratio, allowed us to suppose that these subjects may have been exposed to lower levels of prenatal testosterone. However, in this study female subjects were not assessed. From these observations, we hypothesize that there is a difference between males and females and that a higher digit ratio correlates with an increase in perceived state and trait anxiety.

Therefore, the main purpose of this study was to identify a possible correlation between the D2:D4 ratio and state and/or trait anxiety in adult healthy subjects, and, if so, whether it exists any difference between men and women. In addition, we also wanted to observe whether there is a relationship between participants' age and state and/or trait anxiety.

Anxiety is an uncomfortable feeling, such as worry or fear that can be mild or severe. Everyone experiences anxiety in their life, as for a job interview or an exam or a medical test. Some individuals cope with these situations without great difficulty, while others find it difficult to control their worries. In these individuals, their feelings of anxiety are more constant and can often affect their daily lives.

As said above, the main purpose of this study was to identify a possible correlation between the D2:D4 ratio and state and/or trait anxiety in adult healthy subjects, and, if so, whether it exists any difference between men and women. In addition, we also wanted to observe whether there is a relationship between participants' age and state and/or trait anxiety.

The observed results can be summarized as follows:

It should first be pointed out that the D2:D4 ratio measured in men was slightly lower (0.97 ± 0.039 SD) than that observed in women (0.99 ± 0.039 SD), and that this difference was statistically significant (P = 0.0028).

This study confirms what has already been highlighted in the literature (see Manning et al., 2014b), namely, that the D2:D4 ratio is related to the individual's ability to cope with unexpected and/or negative situations, the main cause of anxiety. This ability, although more evident in men, is also detectable in women. This well accords with findings in studies that have emphasized that the D2:D4 ratio tends to be negatively correlated with rates of female workforce participation and that this effect was greatest for the right hand (Manning et al., 2014a).

In summary, the present data allow us to conclude that a low D2:D4 ratio (<1) represents a protective factor against anxiety in both men and women and that this protection seems likely to act throughout life. Certainly, it would be interesting in the future to investigate the correlation of digit ratio with both cognitive performance and psychological protective variables of anxiety, to confer to an anthropometric variable such as digit ratio a predictive value with a social impact.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by University of Catania. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

SR, SM, MC, and VP contributed to the conception and design of the study. SR and SM were responsible for data collection and VP for statistical analysis. All the authors were responsible for the drafting and finalization of the manuscript, contributed to manuscript revision, and approved the submitted version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.