Skip to main content

Testing the prenatal hormone hypothesis of tic-related disorders: Gender identity and gender role behavior

  • GERIANNE M. ALEXANDER (a1) (a2) and BRADLEY S. PETERSON (a2) (a3)

The hypothesis that prenatal masculinization of the brain increases risk of tic disorders in postnatal life was tested by measuring gender and gender role behavior in 89 children and adults with a clinical diagnosis of Tourette syndrome or obsessive compulsive disorder and 67 healthy, unaffected children and adults. Consistent with this hypothesis, a tic disorder in females was associated with more gender dysphoria, increased masculine play preferences, and a more typically “masculine” pattern of performance on two sex-typed spatial tasks. Males with tic disorders reported increased masculine play preferences, and the strength of these preferences was positively associated with the severity of tic symptoms. In addition, unlike their female counterparts, males with tic disorders showed a relative impairment in mental rotation ability. These behavioral profiles are consistent with those of children who have verifiable elevations in prenatal androgen levels. These findings therefore support the hypothesis that an altered androgen-dependent process of sexual differentiation during prenatal life may contribute to the development of tic-related disorders.This work was supported by National Institutes of Health Grants MH01232 (B. P.) and MH59139 (B. P.) and the Suzanne Crosby Murphy endowment in Pediatric Neuropsychiatry, College of Physicians and Surgeons, Columbia University. The authors thank Amy Basile and Shibani Mukerji for their valuable assistance with behavioral testing.

Corresponding author
Address correspondence and reprint requests to: Gerianne M. Alexander, PhD, Department of Psychology, Texas A&M University, TAMU 4235, College Station, TX 77843; E-mail:
Hide All


Alexander, G. M., Packard, M. G., & Peterson, B. S. (2002). Sex and spatial position effects on object location memory following intentional learning of object identities. Neuropsychologia 40, 15161522.
Alexander, G. M., & Peterson, B. S. (2001). Sex steroids and human behavior: Implications for developmental psychopathology. CNS Spectrum 6, 7588.
Arnold, A. P., & Breedlove, S. M. (1985). Organizational and activational effects of sex steroids on brain and behavior: A reanalysis. Hormones & Behavior 19, 469498.
Bakan, P., Dibb, G., & Reed, P. (1973). Handedness and birth stress. Neuropsychologia 11, 363366.
Baron–Cohen, S., & Hammer, J. (1997). Is autism an extreme form of the male brain? Advances in Infancy Research 11, 193217.
Benenson, J. F., Liroff, E. R., Pascal, S. J., & Cioppa, G. D. (1997). Propulsion: A behavioural expression of masculinity. British Journal of Developmental Psychology 15, 3750.
Berenbaum, S. A. (1999). Effects of early androgens on sex-typed activities and interests in adolescents with congenital adrenal hyperplasia. Hormones & Behavior 35, 102110.
Berenbaum, S. A., & Hines, M. (1992). Early androgens are related to childhood sex-typed toy preferences. Psychological Science 3, 203206.
Berenbaum, S. A., & Resnick, S. M. (1997). Early androgen effects on aggression in children and adults with congenital adrenal hyperplasia. Psychoneuroendocrinology 22, 505515.
Breedlove, S. M., Cooke, B. M., & Jordan, C. L. (1999). The orthodox view of brain sexual differentiation. Brain, Behavior & Evolution 54, 814.
Brown, W. M., Hines, M., Fane, B. A., & Breedlove, M. (2002). Masculinized finger length patterns in human males and females with congenital adrenal hyperplasia. Hormones & Behavior 42, 380386.
Campbell, D. W., & Eaton, W. O. (1999). Sex differences in the activity level of infants. Infant & Child Development 8, 117.
Carson, D. J., Okuno, A., Lee, P. A., Stetton, G., Didolkar, S. M., & Migeon, C. J. (1982). Amniotic fluid steroid levels: Fetuses with adrenal hyperplasia, 46, XXY fetuses, and normal fetuses. American Journal of Diseases of Children 136, 218222.
Collaer, M. L., & Hines, M. (1995). Human behavioral sex differences: A role for gonadal hormones during early development? Psychological Bulletin 118, 55107.
Collins, D. W., & Kimura, D. (1997). A large sex difference on a two-dimensional mental rotation task. Behavioral Neuroscience 111, 845849.
Comings, D. E., & Comings, B. G. (1987). A controlled study of Tourette syndrome. VI. Early development, sleep problems, allergies, and handedness. American Journal of Human Genetics 41, 822838.
DuPaul, G. J. (1991). Parent and teacher ratings of ADHD symptoms: Psychometric properties in a community-based sample. Journal of Clinical Child Psychology 20, 245253.
Eals, M., & Silverman, I. (1994). The hunter-gatherer theory of spatial sex differences: Proximate factors mediating the female advantage in location memory. Ethology and Sociobiology 15, 95105.
Eaton, W. O., & Enns, L. R. (1986). Sex differences in human motor activity level. Psychological Bulletin 100, 1928.
Ehrhardt, A. A., & Baker, S. W. (1974). Fetal androgens, human central nervous system differentiation, and behavior sex differences. In R. C. Friedman, R. M. Richart, & R. L. van the Wiele (Eds.), Sex differences in behavior (pp. 3352). New York: Wiley.
Ehrhardt, A. A., Epstein, R., & Money, J. (1968). Fetal androgens and female gender identity in the early-treated adrenogenital syndrome. Johns Hopkins Medical Journal 122, 165167.
Ehrhardt, A. A., & Money, J. (1967). Progestin-induced hermaphroditism: IQ and psychosexual identity in a study of ten girls. The Journal of Sex Research 3, 83100.
Gorski, R. A. (1979). The neuroendocrinology or reproduction: An overview. Biology of Reproduction 20, 111127.
Gouchie, C., & Kimura, D. (1991). The relationship between testosterone levels and cognitive ability patterns. Psychoneuroendocrinology 16, 323334.
Green, R., Fuller, M., & Rutley, B. (1972). It-Scale for children and Draw-A-Person Test: 30 feminine vs. 25 masculine boys. Journal of Personality Assessment 36, 349352.
Hampson, E., Rovet, J. F., & Altmann, D. (1998). Spatial reasoning in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Developmental Neuropsychology 14, 299320.
Herman, R. A., Jones, B., Mann, D. R., & Wallen, K. (2000). Timing of prenatal androgen exposure: Anatomical and endocrine effects on juvenile male and female rhesus monkeys. Hormones and Behavior 38, 5266.
Hines, M. (2002). Sexual differentiation of the human brain and behavior. In D. W. Pfaff, A. P. Arnold, A. M. Etgen, S. E. Fahrback, & R. T. Ruben (Eds.), Hormones, brain and behavior (Vol. 4, pp. 425462). San Diego, CA: Academic Press.
Hines, M., Fane, B. A., Pasterski, V. L., Mathews, G. A., Conway, G. S., & Brooke, C. (2003). Spatial abilities following prenatal androgen abnormality: Targeting and mental rotations performance in individuals with congenital adrenal hyperplasia. Psychneuroendocrinology 28, 10101026.
Hines, M., & Gorski, R. A. (1985). Hormonal influences on the development of neural asymmetries. In D. F. Benson & E. Zaidel (Eds.), The dual brain: Hemispheric specialization in humans (pp. 7596). New York: Guilford Press.
Hines, M., & Kaufman, F. R. (1994). Androgen and the development of human sex-typical behavior: Rough-and-tumble play and sex of preferred playmates in children with congenital adrenal hyperplasia (CAH). Child Development 65, 10421053.
Hyde, J. S., & Linn, M. C. (1988). Gender differences in verbal ability: A meta-analysis. Psychological Bulletin 104, 5369.
James, T. W., & Kimura, D. (1997). Sex differences in remembering the locations of objects in an array: Location-shifts versus location-exchanges. Evolution & Human Behavior 18, 155163.
King, J. A., Barkley, R. A., Delville, Y., & Ferris, C. G. (2000). Early androgen treatment decreases cognitive function and catecholamine innervation in an animal model of ADHD. Behavioral Brain Research 107, 3543.
Leckman, J. F., Riddle, M. A., Hardin, M. T., Ort, S. I., Swartz, K. L., Stevenson, J., & Cohen, D. J. (1989). The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child & Adolescent Psychiatry 28, 566573.
Leckman, J. F., & Scahill, L. (1990). Possible exacerbation of tics by androgenic steroids [Letter]. New England Journal of Medicine, 322, 1674.
Maccoby, E. E. (1998). The two sexes: Growing up apart, coming together. Cambridge, MA: Belknap Press/Harvard University Press.
Manning, J. T., Baron–Cohen, S., Wheelwright, S., & Sanders, G. (2001). The 2nd to 4th digit ratio and autism. Developmental Medicine & Child Neurology 43, 160164.
Manning, J. T., Scott, D., Wilson, J., & Lewis–Jones, D. I. (1998). The ratio of 2nd to 4th digit length: A predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Human Reproduction 13, 30003004.
McClure, E. B. (2000). A meta-analytic review of sex differences in facial expression processing and their development in infants, children, and adolescents. Psychological Bulletin 126, 424453.
Meaney, M. J. (1988). The sexual differentiation of social play. Trends in Neuroscience 11, 5458.
Miller, G. A., & Chapman, J. P. (2001). Misunderstanding analysis of covariance. Journal of Abnormal Psychology 110, 4048.
Moffat, S. D., & Hampson, E. (1996). A curvilinear relationship between testosterone and spatial cognition in humans: Possible influence of hand preference. Psychoneuroendocrinology 21, 323337.
Peterson, B. S. (1996). Considerations of natural history & pathophysiology in the psychopharmacology of Tourette's syndrome. Journal of Clinical Psychiatry, 57(Suppl. 9), 2434.
Peterson, B. S., Leckman, J. F., Scahill, L., Naftolin, F., Keefe, D., Charest, N. J., & Cohen, D. J. (1992). Steroid hormones and CNS sexual dimorphisms modulate symptom expression in Tourette's syndrome. Psychoneuroendocrinology 17, 553563.
Peterson, B. S., Leckman, J. F., Scahill, L., Naftolin, F., Keefe, D., Charest, N. J., King, R. A., Hardin, M. T., & Cohen, D. J. (1994). Steroid hormones and Tourette's syndrome: Early experience with antiandrogen therapy. Journal of Clinical Psychopharmacology 14, 131135.
Peterson, B. S., Pine, D. S., Cohen, P., & Brook, J. (2001). A prospective, longitudinal study of tic, obsessive–compulsive, and attention deficit-hyperactivity disorders in an epidemiological sample. Journal of the American Academy of Child & Adolescence Psychiatry 40, 685694.
Peterson, B. S., Riddle, M. A., Cohen, D. J., Katz, L. D., Smith, J. C., Hardin, M. T., & Leckman, J. F. (1993). Reduced basal ganglia volumes in Tourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. Neurology 43, 941949.
Peterson, B. S., Staib, L., Scahill, L., Zhang, H., Anderson, C., Leckman, J. F., Cohen, D. J., Gore, J. C., Albert, J., & Webster, R. (2001). Regional brain and ventricular volumes in Tourette syndrome. Archives of General Psychiatry 58, 427440.
Peterson, B. S., Zhang, Z., Anderson, G. A., & Leckman, J. F. (1998). A randomized, placebo-controlled, crossover trial of the use of an adrogen receptor antagonist in the treatment of Tourette's syndrome. Journal of Clinical Psychopharmacology 18, 324331.
Quadagno, D. M., Briscoe, R., & Quadagno, J. S. (1977). Effects of perinatal gonadal hormones on selected nonsexual behavior patterns: A critical assessment of the nonhuman and human literature. Psychological Bulletin 84, 6280.
Reinisch, J. M., & Sanders, S. A. (1986). A test of sex differences in aggressive response to hypothetical conflict situations. Journal of Personality and Social Psychology 50, 10451049.
Reinisch, J. M. (1981). Prenatal exposure to synthetic progestins increases potential for aggression in humans. Science 211, 11711173.
Resnick, S. M., Berenbaum, S. A., Gottesman, I. I., & Bouchard, T. J. (1986). Early hormonal influences on cognitive functioning in congenital adrenal hyperplasia. Developmental Psychology 22, 191198.
Ruble, D. N., & Martin, C. L. (1998). Gender development. In N. Eisenberg (Ed.), Handbook of child psychology (5th ed., Vol. 3, pp. 9331016). New York: Wiley.
Rutter, M., & Garmezy, N. (1983). Developmental psychopathology. In E. M. Hetherington (Ed.), Socialization, personality and social development (Vol. 4). New York: Wiley.
Scahill, L., Riddle, M. A., McSwiggin–Hardin, M., Ort, S. I., King, R. A., Goodman, W. K., Cicchetti, D., & Leckman, J. F. (1997). Children's Yale–Brown Obsessive Compulsive Scale: Reliability and validity. Journal of the American Academy of Child & Adolescent Psychiatry 36, 844852.
Schultz, R. T., Carter, A. S., Gladstone, M., Scahill, L., Leckman, J. F., Peterson, B. S., Heping, A., Cohen, D. J., & Pauls, D. (1998). Visual–motor integration functioning in children with Tourette syndrome. Neuropsychology 12, 134145.
Silverman, I., & Eals, M. (1992). Sex differences in spatial abilities: Evolutionary theory and data. In J. H. Barkow, L. Cosmides, & J. Tooby (Eds.), The adapted mind (pp. 533549). New York: Oxford University Press.
Singer, H. S., Reiss, A. L., Brown, J. E., Aylward, E. H., Shih, B., Chee, E., Harris, E. L., Reader, M. J., Chase, G. A., Bryan, R. N., & Denckla, M. B. (1993). Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. Neurology 43, 950956.
Skilbeck, W. M., Bates, J. E., & Bentler, P. M. (1975). Human figure drawings of gender-problem and school-problem boys. Journal of Abnormal Child Psychology 3, 191199.
Smith, L. L., & Hines, M. (2000). Language lateralization and handedness in women prenatally exposed to diethylstilbestrol (DES). Psychoneuroendocrinology 25, 497512.
Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence (WASI). San Antonio, TX: Psychological Corporation/Harcourt Brace.
Willcutt, E. G., Pennington, B. F., Boada, R., Ogline, J. S., Tunick, R. A., Chhabildas, N. A., & Olson, R. K. (2001). A comparison of cognitive deficits in reading disability and attention-deficit/hyperactivity disorder. Journal of Abnormal Psychology 110, 157172.
Williams, C. L., & Meck, W. H. (1991). The organizational effects of gonadal steroids on sexually dimorphic spatial ability. Psychoneuroendocrinology 16, 155176.
Wudy, S. A., Dorr, H. G., Sollender, C., Djalali, M., & Homoki, J. (1999). Profiling steroid hormones in amniotic fluid of midpregnancy by routine stable isotope dilution/gas chromatography-mass spectrometry: Reference values and concentrations in fetuses at risk for 21-hydroxylase deficiency. Journal of Clinical Endocrinology and Metabolism 84, 27242728.
Yazgan, M. Y., Peterson, B., Wexler, B. E., & Leckman, J. F. (1995). Behavioral laterality in individuals with Gilles de la Tourette's syndrome and basal ganglia alterations: A preliminary report. Biological Psychiatry 38, 386390.
Zucker, K. J., Bradley, S. J., Oliver, G., Blake, J., Fleming, S., & Hood, J. (1996). Psychosexual development of women with congenital adrenal hyperplasia. Hormones and Behavior 30, 300318.
Zucker, K. J., Finegan, J. K., Doering, R. W., & Bradley, S. J. (1983). Human figure drawings of gender-problem children: A comparison to sibling, psychiatric and normal controls. Journal of Abnormal Child Psychology 11, 287298.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Development and Psychopathology
  • ISSN: 0954-5794
  • EISSN: 1469-2198
  • URL: /core/journals/development-and-psychopathology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed