Hirtz Raphael, Libuda Lars, Hinney Anke, Föcker Manuel, Bühlmeier Judith, Holterhus Paul-Martin, Kulle Alexandra, Kiewert Cordula, Hebebrand Johannes, Grasemann Corinna
Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Psychiatry. 2021 Oct 20;12:732759. doi: 10.3389/fpsyt.2021.732759. eCollection 2021.
There is a distinct increase in the prevalence of depression with the onset of puberty. The role of peripubertal testosterone levels in boys in this context is insufficiently understood and may be modulated by a functional polymorphism of the androgen receptor gene (AR), a variable number of CAG repeats. Moreover, there is preliminary evidence that the relationship between testosterone, CAG repeat length, and the severity of depressive symptoms may differ between subclinical and overt depression, but this has neither been studied in a clinical sample of adolescents with depression nor compared between subclinical and overt depression in an adequately powered study. To investigate the relationship between free testosterone, CAG repeat length of the AR, depression status (subclinical vs. overt), and the severity of depressive symptoms, 118 boys treated as in- or daycare patients at a single psychiatric hospital were studied. Of these, 73 boys had at least mild depressive symptoms according to the Beck Depression Inventory-II (BDI-II > 13). Higher-order moderation analysis in the multiple regression framework revealed a constant relationship between free testosterone and depression severity irrespective of the number of CAG repeats in adolescents with a BDI-II score ≤ 13. In adolescents with a BDI-II score > 13, however, there was a significant negative relationship between free testosterone and BDI-II score in patients with <19 CAG repeats and a significant positive relationship regarding free testosterone and BDI-II score in those with more than 28 CAG repeats, even when considering important covariates. These results suggest that the effects of testosterone on mood in male adolescents with depression depend on the genetic make-up of the AR as well as on depression status. This complex relationship should be considered by future studies addressing mental health issues against an endocrine background and may, moreover, contribute to tailored treatment concepts in psychiatric medicine, especially in adults.
随着青春期的开始，抑郁症的患病率显著增加。在这种情况下，青春期男孩围青春期睾酮水平的作用尚未得到充分了解，可能会受到雄激素受体基因（AR）功能多态性（CAG重复序列数量可变）的调节。此外，有初步证据表明，睾酮、CAG重复序列长度与抑郁症状严重程度之间的关系在亚临床抑郁和显性抑郁之间可能有所不同，但这在青少年抑郁症临床样本中尚未得到研究，也未在一项有足够效力的研究中对亚临床抑郁和显性抑郁进行比较。为了研究游离睾酮、AR的CAG重复序列长度、抑郁状态（亚临床与显性）以及抑郁症状严重程度之间的关系，对一家精神病医院作为住院或日间护理患者接受治疗的118名男孩进行了研究。其中，根据贝克抑郁量表第二版（BDI-II>13），73名男孩至少有轻度抑郁症状。多元回归框架下的高阶调节分析显示，在BDI-II评分≤13的青少年中，无论CAG重复序列数量如何，游离睾酮与抑郁严重程度之间存在恒定关系。然而，在BDI-II评分>13的青少年中，CAG重复序列<19的患者中游离睾酮与BDI-II评分之间存在显著负相关，而在CAG重复序列超过28的患者中，游离睾酮与BDI-II评分之间存在显著正相关，即使考虑了重要的协变量也是如此。这些结果表明，睾酮对患有抑郁症的男性青少年情绪的影响取决于AR的基因构成以及抑郁状态。未来针对内分泌背景下心理健康问题的研究应考虑这种复杂关系，此外，这可能有助于精神医学领域的个性化治疗理念，尤其是在成年人中。
