Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression
Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression
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DOI：
10.1016/j.biopsych.2015.10.023
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发表时间：
2017-05-01
影响因子：
10.6
通讯作者：
Penninx, Brenda W. J. H.
中科院分区：
文献类型：
--
作者：
Milaneschi, Yuri;Lamers, Femke;Penninx, Brenda W. J. H.
背景：与肥胖相关的瘦素信号传导失调（例如，中枢功能抵抗导致的高瘦素血症）可能会影响情绪。然而，重度抑郁症 (MDD) 中瘦素失调的证据是相互矛盾的。不确定的发现可能归因于 MDD 的异质性，聚集了生物学上不同的亚型。我们研究了瘦素与 MDD 的关系、其常见亚型（典型和非典型）以及临床特征。 方法：样本由来自荷兰抑郁和焦虑研究的参与者（年龄 18 至 65 岁）组成，患有当前（n = 1062）或缓解（n = 711）MDD 和健康对照受试者（n = 497）。 MDD 及其亚型的诊断基于 DSM-IV 症状。其他症状通过抑郁症状量表进行测量。评估了瘦素和肥胖指数（体重指数和腰围）的血液水平。 结果：与对照受试者相比，无论是缓解期（n=144，优势比=1.53，95%置信区间=1.16-2.03，p<5.003）还是当前（n=270，优势比=1.90，95%置信度），较高的瘦素与非典型MDD亚型相关。间隔=1.51-2.93，p=5.3e-8) 例。这种关联对于增加肥胖水平（瘦素与体重指数相互作用，p，.02）而言更为强烈，从而强化了瘦素抵抗参与的假设。没有发现瘦素与总体 MDD 或典型亚型相关。在目前的抑郁症患者中，较高的瘦素水平与非典型亚型的关键症状相关，例如食欲过盛、体重增加和铅样麻痹。结论：瘦素失调（抵抗）可能代表了将肥胖和 MDD 与非典型特征联系起来的潜在机制。开发有效针对瘦素抵抗的治疗方法可能有益于以肥胖相关代谢改变为特征的非典型抑郁症患者。
BACKGROUND: Obesity-related dysregulation of leptin signaling (e. g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features.METHODS: The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current (n=1062) or remitted (n=711) MDD and healthy control subjects (n=497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed.RESULTS: As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted (n=144, odds ratio=1.53, 95% confidence interval=1.16-2.03, p 5.003) and current (n=270, odds ratio=1.90, 95% confidence interval=1.51-2.93, p=5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p,.02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis.CONCLUSIONS: Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations.