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

Vermeersch, Hans; T’Sjoen, Guy; Kaufman, Jean; Vincke, Johny; Houtte, Mieke Van

doi:10.1530/eje-10-0090

Cited by 61 publications

(53 citation statements)

References 48 publications

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“…It is proposed that longer CAG repeat length causes lower transcriptional activity of genes activated by testosterone binding (43). A longer (>23) and a shorter (≤20) than average amount of CAG triplets have been suggested as risk alleles (44). Longer CAG repeat length is associated with more depressive symptoms (45).…”

Section: Genetic Risk Constellationmentioning

confidence: 99%

Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior

et al. 2017

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Epidemiological studies show low rates of diagnosed depression in men compared to women. At the same time, high rates of alcohol use disorders (AUDs) and completed suicide are found among men. These data suggest that a male-specific pattern for depression may exist that is linked to AUDs and suicidal behavior. To date, no underlying neuroendocrine model for this specific pattern of male depression has been suggested. In this paper, we integrate findings related to this specific pattern of depression with underlying steroid secretion patterns, polymorphisms, and methylation profiles of key genes in order to detail an original neuroendocrine model of male-specific depression. Low circulating levels of sex steroids seem to increase the vulnerability for male depression, while concomitant high levels of glucocorticoids further intensify this vulnerability. Interactions of hypothalamus–pituitary–gonadal (HPG) and hypothalamus–pituitary–adrenocortical (HPA) axis-related hormones seem to be highly relevant for a male-specific pattern of depression linked to AUDs and suicidal behavior. Moreover, genetic variants and the epigenetic profiles of the androgen receptor gene, well-known depression related genes, and HPA axis-related genes were shown to further interact with men’s steroid secretion and thus may further contribute to the proposed male-specific pattern for depression. This mini-review points out the multilevel interactions between the HPG and HPA axis for a male-specific pattern of depression linked to AUDs and suicidal behavior. An integration of multilevel interactions within the three-hit concept of vulnerability and resilience concludes the review.

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Section: Genetic Risk Constellationmentioning

confidence: 99%

Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior

et al. 2017

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“…A CAG repeat polymorphism within the AR gene was found to influence the transactivation of androgendependent genes (17,18). The length of the CAG repeats varies between w12 and 30 repeats with an average length of 22 in Caucasian populations (19)(20)(21)). An inverse relationship exists between AR CAG repeat length and the transcriptional activity of testosterone target genes (18).…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men

Möhlig

Arafat²,

Osterhoff³

et al. 2011

European Journal of Endocrinology

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Objective: Low circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described in women. Objective: We investigated such a putative interaction between testosterone and the CAG length with respect to IR in men with normal glucose tolerance. Design: Cross-sectional study. Methods: In 113 non-diabetic men calculated free testosterone, the CAG length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR, as indicated by homeostasis model assessment (HOMA %S). Results: In a multivariate regression analysis adjusted for age and body mass index, free testosterone, CAG length, and a multiplicative interaction term were significantly associated with IR (PZ0.001, PZ0.001, PZ0.01 respectively). The model explained 36.6% of the variation of IR and predicted that in carriers with a CAG length of 23, changes in testosterone would only minimally affect IR. For CAG lengths longer than 23, however, an increase in testosterone would improve IR, namely the longer the CAG length, the greater the effect. In contrast, in the case of CAG lengths shorter than 23, the effect of increasing testosterone would be the opposite. Conclusions: In men, testosterone and the AR CAG repeat length polymorphism interacted with respect to IR. The interpretation of the association between testosterone and IR seems to require consideration of the AR CAG repeat polymorphism.

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“…10,11,14,21,22 Previous studies have identified a relationship between a smaller number of CAG repeats and increased impulsivity in males. 21–24 Impulsivity has also been associated with an increased risk of developing alcoholism in males and increased alcoholism severity, but a paucity of data exists regarding females. 11,12 To our knowledge, there are no reports examining the influence of the CAG repeat length of the AR gene on psychiatric outcomes in females.…”

Section: Discussionmentioning

confidence: 99%

“…The length of the polyglutamine tract and impulsivity have been inversely related in males, 21,24 but to our knowledge, no data are available describing the relationship between the size of the AR allele and impulsivity or the AR CAG repeat length and alcoholism in females. We sought to provide additional insight into the correlation between CAG repeat length of the AR gene and alcoholism by comparing the repeat lengths with measures of alcoholism and psychiatric severity, in a cohort of well-characterized African–American and Caucasian alcoholic females.…”

Section: Introductionmentioning

confidence: 98%

A preliminary case study of androgen receptor gene polymorphism association with impulsivity in women with alcoholism

Mettman¹,

Butler²,

Poje³

et al. 2014

AGG

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ObjectiveThe androgen receptor (AR) gene, located on the X chromosome, contains a common polymorphism involving cytosine–adenine–guanine (CAG) repeats, which impacts disease and could contribute to the unequal sex ratio in alcoholism. CAG repeats in the AR gene are known to correlate with impulsivity in males. We report the first preliminary study examining the association between the number of CAG repeats and measures of impulsivity in females with chronic alcoholism.MethodsA total of 35 women and 85 men with chronic alcoholism were previously recruited for a nutritional clinical trial, and 26 well-characterized females (19 African–American and seven Caucasian) with alcoholism agreed to participate for genetic testing. Genomic deoxyribonucleic acid (DNA) was isolated from peripheral blood and CAG repeats determined by analyzing polymerase chain reaction (PCR)-amplified products, using the polymorphic AR gene assay. CAG repeat length was correlated with raw scores from the Barratt Impulsivity Scale, version 11 and the Alcoholism Severity Scale.ResultsCAG repeat lengths were significantly longer in Caucasian alcoholic women compared with African–Americans, and the average number of CAG repeats were significantly, positively correlated (P<0.05) with impulsivity scores. Women with average CAG repeat length (CAGave) ≥18, representing the upper quartile of the repeat range, showed significantly greater mean raw impulsivity scores. CAG repeat length appeared to have less effect in African–American compared with Caucasian women, possibly due to a shorter average repeat length.ConclusionWe found an association between the number of CAG repeats and impulsivity in females with chronic alcoholism, specifically in women with CAGave ≥18, seen more commonly in Caucasian compared with African–American women.

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

Cited by 61 publications

References 48 publications

Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior

Neuroendocrinology of a Male-Specific Pattern for Depression Linked to Alcohol Use Disorder and Suicidal Behavior

Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men

A preliminary case study of androgen receptor gene polymorphism association with impulsivity in women with alcoholism

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