A Longitudinal Examination of Early-Life Sex Hormone and Vitamin D Levels as Predictors of Handedness in Childhood and Adolescence

What is already known about this subject:

• Most humans prefer using their right hand, though there is variability both in terms of direction (whether it is the right hand or the left hand that is preferred) and strength (how much and/or how consistently one hand is preferred over the other, regardless of direction). Studying handedness is thought to provide insights into how the two hemispheres of the human brain are organised. For instance, although speech function is typically located in the left hemisphere, this is not always the case, and the likelihood of right-hemisphere speech developing is higher in left-handers than right-handers. Observations such as this have led many researchers to exclude left-handers from scientific research studies, although the nature and origins of such differences remain poorly understood.
• It has been hypothesised that certain hormones (i.e., chemical substances that act as messengers within the body) to which a person is exposed before birth can influence the development of their handedness. In particular, there has been interest in the effects of sex hormones, such as testosterone and estradiol, which are known to play key roles in the development and maintenance of certain male-typical and female-typical characteristics (e.g., testosterone is central to developmental of the male reproductive system; estradiol is important for maintaining the menstrual cycle and female fertility). However, whereas the Geschwind-Behan-Galaburda (GBG) theory (Geschwind & Behan, 1982; Geschwind & Galaburda, 1987) and the sexual differentiation hypothesis (Hines & Shipley, 1984; Levy & Gur, 1980) each propose that higher testosterone levels before birth increase the chances of left-handedness, the callosal hypothesis (Witelson & Nowakowski, 1991; Witelson & Goldsmith, 1991) predicts that this increases the chances of right-handedness, and yet others (Lust et al., 2011) suggest that early testosterone levels influence the strength of a person’s handedness rather than the direction. There are also indications that the amount of estradiol to which a person is exposed during early life is influential, though this hormone remains under-research in this context. Likewise, as some studies suggest that the likelihood of being left-handed is related to one’s month of birth, it is possible that Vitamin D plays a role. This is because concentrations of this chemical exhibit seasonal fluctuation (i.e., Vitamin D levels tend to be highest during summer) and because it is known to affect many different types of cell found throughout the human body. However, despite being considered within the scientific literature for nearly half a century, research examining early levels of testosterone in relation to handedness has produced inconsistent results, very few studies have examined estradiol, and no studies so far have considered Vitamin D.
• In this manuscript, we present the largest study to date that uses actual measures of hormones measured before (or shortly after) birth as predictors of handedness measured later in life. More specifically, we aim to test whether testosterone and estradiol measured from umbilical cord blood collected immediately after birth, and Vitamin D levels measured from the mother’s blood during pregnancy, predict handedness at 10- and/or-16 years of age in the Raine Study cohort.