Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia

doi:10.1016/j.yhbeh.2006.02.006

Hormones and Behavior

Volume 50, Issue 1, June 2006, Pages 148-153

https://doi.org/10.1016/j.yhbeh.2006.02.006 Get rights and content

Abstract

Testosterone promotes male-typical neural and behavioral development in non-human mammals. There is growing evidence that testosterone exerts similar influences on human development, although the range of behaviors affected is not completely known. This study examined the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by congenital adrenal hyperplasia (CAH). Sixty individuals with CAH (34 female, 26 male) and 49 unaffected relatives (24 female, 25 male) completed the Autism Spectrum Quotient (AQ). Females with CAH scored significantly higher than unaffected females on total AQ score, largely due to enhanced scores on subscales measuring social skills and imagination. These results suggest that prenatal exposure to high levels of testosterone influences some autistic traits and that hormonal factors may be involved in vulnerability to autism.

Section snippets

Participants

Sixty individuals with classical CAH (34 females, 26 males), and 49 unaffected relatives (24 females, 25 males), ages 12 to 45 years, participated in the study. Unaffected relatives were recruited for the control group because they provide a partial control for genetic constitution (other than the genes for CAH) and socioeconomic background (Hines, 1982). All unaffected relative controls were siblings of CAH participants, except one, who was a first cousin. All participants were

The AQ

Table 1 shows means and standard deviations for total AQ scores and subscale scores by sex and diagnosis. Table 2 shows effect sizes (d values), and t test results for comparisons of unaffected males versus unaffected females, females with CAH versus those without CAH and males with versus without CAH. As expected, unaffected males had significantly higher total AQ scores than unaffected females. In addition, females with CAH scored higher on total AQ than unaffected females. Total AQ scores of

Discussion

This study tested the hypothesis that prenatal levels of androgens influence autistic traits, by measuring these traits in individuals with CAH, a disorder causing increased adrenal androgen production, beginning prenatally. We predicted that AQ scores would be higher in control males than in control females, and in females with CAH compared to unaffected females.

Our findings for sex differences on the AQ and its subscales resemble prior findings. A prior study of 76 males and 98 females from

Acknowledgments

Rebecca Knickmeyer, Autism Research Centre, Department of Psychiatry, Cambridge University; Simon Baron-Cohen, Autism Research Centre, Department of Psychiatry, Cambridge University; Briony A. Fane, Department of Psychology, City University, London; Sally Wheelwright, Autism Research Centre, Department of Psychiatry, Cambridge University; Greta A. Mathews, Department of Psychology, City University, London; Gerard S. Conway, London Centre for Paediatric Endocrinology, Great Ormond Street and The

References (34)

W.M. Brown et al.
Masculinized finger length patterns in human males and females with congenital adrenal hyperplasia
Horm. Behav.
(2002)
R.W. Dittmann et al.
Congenital adrenal hyperplasia I: gender-related behavior and attitudes in female patients and sisters
Psychoneuroendocrinology
(1990)
R.W. Dittmann et al.
Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia
Psychoneuroendocrinology
(1992)
M. Hines et al.
Spatial abilities following prenatal androgen abnormality: targeting and mental rotations performance in individuals with congenital adrenal hyperplasia (CAH)
Psychoneuroendocrinology
(2003)
G.A. Mathews et al.
Androgenic influences on neural asymmetry: Handedness and language lateralization in congenital adrenal hyperplasia (CAH)
Psychoneuroendocrinology
(2004)
J. Money et al.
Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46 XX congenital virilizing adrenal hyperplasia and 46 XY androgen-insensitivity syndrome compared
Psychoneuroendocrinology
(1984)
P. White et al.
Long-term consequences of childhood-onset congenital adrenal hyperplasia
Best Pract. Res. Clin. Endocr. Metab.
(2002)
K.J. Zucker et al.
Psychosexual development of women with congenital adrenal hyperplasia
Horm. Behav.
(1996)
American Psychiatric Association
Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR: Fourth Edition Text Revision
(2000)
S. Baron-Cohen et al.
The autism spectrum quotient (AQ): evidence from Asperger syndrome/high functioning autism, males and females, scientists and mathematicians
J. Autism Dev. Disord.
(2001)

S. Baron-Cohen et al.

Prenatal Testosterone in Mind: Amniotic Fluid Studies

(2004)

J. Cohen

Statistical Power Analysis for the Behavioral Sciences

(1988)

A.B. Dessens et al.

Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia

Arch. Sex. Behav.

(2005)

R.W. Goy et al.

Sexual Differentiation of the Brain

(1980)

M.M. Grumbach et al.

Disorders of sex differentiation

M. Hines

Prenatal gonadal hormones and sex differences in human behavior

Psychol. Bull.

(1982)

M. Hines

Brain Gender

(2004)

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Thousands of non-human mammal experiments have demonstrated that early androgen exposure exerts long-lasting effects on neurobehavioural sexual differentiation. In humans, females with classic congenital adrenal hyperplasia (CAH) are exposed to unusually high concentrations of androgens prenatally, whereas prenatal concentrations of androgens in males with CAH are largely normal. The current meta-analysis included 20 independent samples and employed multi-level meta-analytic models. Consistently across all 7 male-typical and female-typical play outcomes, in the expected directions, the present study found significant and large average differences between control males and control females (gs = 0.83–2.78) as well as between females with CAH and control females (gs = 0.95–1.08), but differences between males with CAH and control males were mostly negligible and were non-significant for 6 of the 7 outcomes (gs = 0.04–0.27). These meta-analytic findings suggest that prenatal androgen exposure masculinises and defeminises play behaviour in humans. Broader implications in relation to sex chromosomes, brain development, oestrogens, socio-cognitive influences, other aspects of sex-related behavioural development, and gender nonconformity are discussed.
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The syndromes of congenital adrenal hyperplasia (CAH), particularly their classical variants, present diverse medical and psychosocial challenges to the affected individual at all stages of life from the prenatal phase through old age. This chapter reviews the psychological outcomes in terms of gender, general cognitive development, psychopathology, sexuality, and quality of life, the factors that contribute to these outcomes including neuroanatomy and brain function, and the implications for the clinician and for the organization of health services.
Is there an association between prenatal testosterone and autistic traits in adolescents?
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Prenatal testosterone (pT) is a crucial component in physiological masculinization in humans. In line with the Prenatal Sex Steroid Theory of autism, some studies have found a positive correlation between pT and autistic traits in childhood. However, effects in adolescence have not been explored. Hormonal and environmental changes occurring during puberty may alter the strength or the nature of prenatal effects on autistic traits. The current study examines if pT relates to autistic traits in a non-clinical sample of adolescents and young adults (N = 97, 170 observations; age 13–21 years old). It also explores pT interactions with pubertal stage and timing. PT concentrations were measured from amniotic fluid extracted in the 2nd trimester of gestation via amniocentesis conducted for clinical purposes. Autistic traits were measured by self- and parent-reports on the Autism Spectrum Quotient (AQ) which provides a total score and 5 sub-scores (social skills, communication, imagination, attention switching and attention to detail). Self-reported pubertal stage was regressed on age to provide a measure of relative timing. We found no statistical evidence for a direct association between pT and autistic traits in this adolescent sample (males, females or full sample). Exploratory analyses suggested that pT correlated positively with autistic traits in adolescents with earlier puberty-onset, but statistical robustness of this finding was limited. Further exploratory post-hoc tests suggested the pT-by-pubertal timing interaction was stronger in males relative to females, in self-reported compared to parent-reported AQ and specifically for social traits. These findings require replication in larger samples. Findings have implications for understanding the effects of pT on human behavior, specifically existence of effects in adolescence.
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We systematically reviewed evidence for the androgen theory which proposes exposure to elevated levels of androgens in early development predisposes to autistic behaviour.
MEDLINE, EMBASE and Pubmed were searched for studies measuring androgens in mother or child during pregnancy or the first year of life and examined autistic behaviours (including social ability and repetitive behaviour) and language measured up to age 24 years.
Twenty-five of 3,041 publications met inclusion criteria, exploring 11 unique cohorts. Overall quality of evidence was very low as studies were non-experimental and most had high risk of bias. Only one research group found significant associations between autistic behaviour and androgens in amniotic fluid. There were mixed findings across the studies reviewed. Meta-analysis indicated a small significant pooled association between autistic behaviour and androgens in amniotic fluid (males and females combined; 3 studies), 0.28 [95 % CI 0.14, 0.41], also significant in males and females separately.
Despite interest in this topic, of studies exploring direct measures of early androgens and later autistic traits, there is only a small amount of low-quality evidence from independent cohorts. The androgen theory of autism is neither confirmed nor refuted by the existing association studies included in this review.

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Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia

Abstract

Section snippets

Participants

The AQ

Discussion

Acknowledgments

Horm. Behav.

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Psychoneuroendocrinology

Best Pract. Res. Clin. Endocr. Metab.

Horm. Behav.

Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR: Fourth Edition Text Revision

The autism spectrum quotient (AQ): evidence from Asperger syndrome/high functioning autism, males and females, scientists and mathematicians

J. Autism Dev. Disord.

Prenatal Testosterone in Mind: Amniotic Fluid Studies

Statistical Power Analysis for the Behavioral Sciences

Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia

Arch. Sex. Behav.

Sexual Differentiation of the Brain

Disorders of sex differentiation

Prenatal gonadal hormones and sex differences in human behavior

Psychol. Bull.

Brain Gender