Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males.

OBJECTIVES Androgen activity has been implicated in a range of traits and behaviours that have well-documented sex differences. However, the results of the studies on the relationship between testosterone and these traits and behaviours are inconsistent. This study has analyzed i) whether CAG repeat length, a presumed modulator of androgen receptor sensitivity, is associated with sex-dimorphic traits and behaviours (aggressive and non-aggressive risk-taking (ART and NART), dominance, depressive symptoms and self-esteem), and ii) whether CAG repeat length interacts with free testosterone (FT) with respect to these traits and behaviours. DESIGN AND METHODS Data obtained from a group of adolescent boys (n=301; mean age: 14.4 years) were analyzed using multivariate general linear modelling (SPSS, Chicago, IL, USA 15.0). RESULTS We found no direct correlation between CAG repeat length and dependent variables. We found significant interactions between CAG repeat length and testosterone, indicating that FT was more positively related to ART and NART with a shorter repeat length, and that an inverse association of FT with depressive symptoms and a positive association with self-esteem were stronger in boys with a longer CAG repeat length. CONCLUSION Our findings indicate the importance of studying FT and CAG repeat length simultaneously with respect to sex-dimorphic traits, taking into account the possible interactions between the two.

[1]  T. Hickey,et al.  The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. , 2002, The Journal of clinical endocrinology and metabolism.

[2]  E. Costello,et al.  Testosterone, antisocial behavior, and social dominance in boys: pubertal development and biosocial interaction , 2004, Biological Psychiatry.

[3]  E. Nieschlag,et al.  Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharmacogenetic study. , 2003, The Journal of clinical endocrinology and metabolism.

[4]  W. Willett,et al.  Sex Steroid Hormones and the Androgen Receptor Gene CAG Repeat and Subsequent Risk of Prostate Cancer in the Prostate-Specific Antigen Era , 2005, Cancer Epidemiology Biomarkers & Prevention.

[5]  Nina L. Colwill,et al.  The psychology of sex differences , 1978 .

[6]  A. Aromäki,et al.  Testosterone, Aggressiveness, and Antisocial Personality , 1999 .

[7]  A. Iranmanesh,et al.  Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. , 2000, The Journal of clinical endocrinology and metabolism.

[8]  J. Stanford,et al.  Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. , 1997, Cancer research.

[9]  E. Nieschlag,et al.  Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs. , 2001, European journal of endocrinology.

[10]  W. Vogel,et al.  (CAG)nCAA and GGN repeats in the human androgen receptor gene are not associated with prostate cancer in a French–German population , 1999, European Journal of Human Genetics.

[11]  D. Baird,et al.  7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. , 1999, The Journal of clinical endocrinology and metabolism.

[12]  K. Abromeit Music Received , 2023, Notes.

[13]  R. Kessler,et al.  Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. , 1993, Journal of affective disorders.

[14]  J. Kaufman,et al.  Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism. , 2007, The Journal of clinical endocrinology and metabolism.

[15]  L. S. Liben,et al.  Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents. , 1997, The Journal of clinical endocrinology and metabolism.

[16]  A. von Eckardstein,et al.  The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men , 2002, Diabetologia.

[17]  E. Nieschlag,et al.  X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. , 2004, The Journal of clinical endocrinology and metabolism.

[18]  S. Easteal,et al.  Association of dopamine-β-hydroxylase and androgen receptor gene polymorphisms with Eysenck's P and other personality traits , 2004 .

[19]  J. Kaufman,et al.  The role of testosterone in aggressive and non-aggressive risk-taking in adolescent boys , 2008, Hormones and Behavior.

[20]  A. Araujo,et al.  Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men , 2001, Biological Psychiatry.

[21]  J. Kaufman,et al.  Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men? , 2007, European journal of endocrinology.

[22]  S. Tsai,et al.  Association study of androgen receptor CAG repeat polymorphism and male violent criminal activity , 2006, Psychoneuroendocrinology.

[23]  Michael Zitzmann,et al.  The CAG repeat polymorphism within the androgen receptor gene and maleness. , 2003, International journal of andrology.

[24]  J. Archer,et al.  Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men , 2002, Physiology & Behavior.

[25]  J. Loehlin,et al.  Eysenck’s Psychoticism and the X-linked androgen receptor gene CAG polymorphism in additional Australian samples , 2005 .

[26]  E. Riboli,et al.  Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) , 2009, Cancer Causes & Control.

[27]  H. Brutsaert Co-educatie. Studiekansen en kwaliteit van het schoolleven. , 2001 .

[28]  William D. Schafer,et al.  Gender differences in risk taking: A meta-analysis. , 1999 .

[29]  L. Arseneault,et al.  Testosterone, Physical Aggression, Dominance, and Physical Development in Early Adolescence , 1998 .

[30]  A. Feingold,et al.  Gender differences in personality: a meta-analysis. , 1994, Psychological bulletin.

[31]  L. Singh,et al.  Reduced CAG repeats length in androgen receptor gene is associated with violent criminal behavior , 2008, International Journal of Legal Medicine.

[32]  D. Comings,et al.  Association of the androgen receptor gene (AR) with ADHD and conduct disorder. , 1999, Neuroreport.

[33]  K. Jackson,et al.  Incidence of major depressive disorder and dysthymia in young adolescents. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[34]  D. J. Lee Society and the Adolescent Self-Image , 1969 .

[35]  J. Albu,et al.  Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in men. , 1987, The Journal of clinical investigation.

[36]  H. Gough,et al.  CPI, California Psychological Inventory : manual , 1996 .

[37]  K. Van Steen,et al.  Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men. , 2009, European journal of endocrinology.

[38]  D. Kupfer,et al.  Screening for anxiety and depression in early adolescence. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[39]  J. Tanner,et al.  Growth at adolescence : with a general consideration of the effects of hereditary and environmental factors upon growth and maturation from birth to maturity , 1962 .

[40]  E. Wilson,et al.  Trinucleotide repeats in the human androgen receptor: a molecular basis for disease. , 1998, Journal of molecular endocrinology.

[41]  E. Nieschlag,et al.  Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. , 2007, The Journal of clinical endocrinology and metabolism.

[42]  M. Luxen Gender Differences in Dominance and Affiliation During a Demanding Interaction , 2005, The Journal of psychology.

[43]  A. Shalita,et al.  Androgen Receptor Polymorphisms (CAG Repeat Lengths) in Androgenetic Alopecia, Hirsutism, and Acne , 1998, Journal of cutaneous medicine and surgery.

[44]  Staffan Nilsson,et al.  Influence of androgen receptor repeat polymorphisms on personality traits in men. , 2009, Journal of psychiatry & neuroscience : JPN.

[45]  P. Kantoff,et al.  The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia. , 1999, Urology.

[46]  L. Bauman,et al.  Content Validity of the Psychiatric Symptom Index, CES-Depression Scale, and State-Trait Anxiety Inventory from the Perspective of DSM-IV , 1996, Psychological reports.

[47]  K. Lindblad-Toh,et al.  Androgen receptor trinucleotide repeat polymorphism and personality traits , 2001, Psychiatric genetics.

[48]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[49]  J. Benichou,et al.  Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. , 2000, Cancer research.