Department of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden; Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
Psychoneuroendocrinology. 2022 Jul;141:105765. doi: 10.1016/j.psyneuen.2022.105765. Epub 2022 Apr 14.
Hypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration.
This study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.
ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups.
Quality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge - the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05).
EA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.
性欲亢进障碍（HD）-一种伴有冲动成分的非性癖性性欲障碍-被评估为纳入 DSM-5 的诊断标准，而强迫性性行为障碍的诊断则被纳入 ICD-11 的冲动控制障碍。下丘脑-垂体-肾上腺（HPA）轴的过度活跃被认为会影响细胞衰老，并与 HD 有关。以前没有研究调查过 HD 或 HPA 轴失调与表观遗传年龄（EA）加速的关系。
本研究报告了一项基于特征明确的队列的病例对照研究，对比了 60 名 HD 患者、33 名健康志愿者（HV）和 19 名混合 HD/HV 的 EA 预测指标，这些患者表现为地塞米松抑制试验（DST）不抑制，而 73 名混合 HD/HV 的 DST 对照组则表现为抑制。使用 Illumina Infinium Methylation EPIC BeadChip 测量了 94 名受试者的全血基因组甲基化模式，并根据适用于表观遗传年龄估计的专门方案进行了预处理。实施了在线 DNAm Age Calculator（https://dnamage.
ucla.edu/）来获取各种 EA 预测指标，并在模拟生成的亚组之间进行比较。
质量控制分析表明，在所有亚组中，EA 测量 DNA 甲基化 GrimAge（与死亡率风险最相关的 EA 时钟）与实际年龄之间存在强烈的相关性。该研究有足够的能力检测到与 HD 和 HPA 轴失调分别相关的 2.5 和 3.0 年的 DNAm GrimAge-年龄差异。在所有样本中，基线 DNAm GrimAge 平均比实际年龄大 2.8 岁。没有 EA 加速标志物与 HD 或 DST 抑制状态相关（p>0.05）。
显示出与生理失调和死亡风险高度相关的 EA 加速标志物，与 HD 或 DST 不抑制状态（在 0.5mg 地塞米松后测量）无关。HPA 轴失调与 EA 加速的独立性不支持在患有 HD 的患者中应用该剂量方案的生物学相关性。这些发现不支持 HD 中细胞衰老加速的观点。需要根据躯体环境中的既定剂量方案对 DST 不抑制者进行分层研究，以充分阐明 HPA 轴失调对 EA 的潜在贡献。
