Kersting Anette, Kroker Kristin, Horstmann Julia, Baune Bernhard T, Hohoff Christa, Mortensen Lena Sünke, Neumann Lisa C, Arolt Volker, Domschke Katharina
Department of Psychiatry, University of Munster, Münster, Germany.
Neuropsychobiology. 2007;56(4):191-6. doi: 10.1159/000120624. Epub 2008 Mar 13.
BACKGROUND/AIMS: It has been suggested that monoamine oxidase A (MAO-A) activity is involved in the pathogenesis of major depression. Bereavement-related complicated grief significantly increases the risk of major depression and has been shown to be influenced by serotonergic tonus, possibly conferred by MAO-A activity. Complicated grief--whose inclusion in DSM-V as a separate mental disorder is under discussion--has been shown to be a distinct syndrome with symptoms not seen in depression. Therefore, in the present study, genetic variation in the MAO-A gene was investigated for its influence on complicated grief in major depression.
Sixty-six unrelated Caucasian patients (41 female, 25 male) with major depression and a history of bereavement were evaluated for complicated grief using the Inventory of Complicated Grief (ICG), the posttraumatic stress reaction after the loss by means of the Impact of Event Scale (IES-R) and further psychopathological measures. Patients were additionally genotyped for the functional variable number tandem repeat (VNTR) in the promoter region of the MAO-A gene.
The more active longer allele of the MAO-A VNTR was significantly associated with complicated grief in the female subgroup of patients (chi(2) = 9.471, p = 0.002, OR = 9.208, 95% CI 2.129-38.899, Bonferroni-corrected p = 0.012), whereas there was no such effect in male patients. Higher posttraumatic stress reaction was only nominally associated with the more active longer allele of the MAO-A VNTR in the female subgroup of patients (genotypes: chi(2) = 5.939, p = 0.015, OR = 5.333, 95% CI 1.366-20.557, Bonferroni-corrected p = 0.087). No significant associations of MAO-A VNTR with the severity of depressive symptoms (Beck Depression Inventory), anxiety symptoms (Spielberger State-Trait Anxiety Inventory), general mental health (Brief Symptom Inventory), or perceived social support (F-SozU) were found (all p > 0.10).
The present pilot study for the first time suggests a gender-specific contribution of the more active MAO-A VNTR variant to an increased vulnerability for complicated grief as a potential intermediate phenotype of major depression.
背景/目的：有研究表明，单胺氧化酶A（MAO-A）活性与重度抑郁症的发病机制有关。丧亲相关的复杂性悲伤会显著增加患重度抑郁症的风险，并且已被证明受血清素能张力的影响，而血清素能张力可能由MAO-A活性赋予。复杂性悲伤——其作为一种单独的精神障碍纳入《精神疾病诊断与统计手册》第五版（DSM-V）正在讨论中——已被证明是一种独特的综合征，具有抑郁症中未出现的症状。因此，在本研究中，研究了MAO-A基因的遗传变异对重度抑郁症中复杂性悲伤的影响。
对66名患有重度抑郁症且有丧亲史的无亲缘关系的白种人患者（41名女性，25名男性），使用复杂性悲伤量表（ICG）评估复杂性悲伤，通过事件影响量表（IES-R）评估丧亲后的创伤后应激反应以及其他精神病理学指标。此外，对患者进行MAO-A基因启动子区域功能性可变数目串联重复序列（VNTR）的基因分型。
MAO-A VNTR中活性更高的较长等位基因与女性亚组患者的复杂性悲伤显著相关（χ² = 9.471，p = 0.002，OR = 9.208，95%可信区间2.129 - 38.899，经Bonferroni校正的p = 0.012），而在男性患者中未发现这种效应。在女性亚组患者中，较高的创伤后应激反应仅名义上与MAO-A VNTR活性更高的较长等位基因相关（基因型：χ² = 5.939，p = 0.015，OR = 5.333，95%可信区间1.366 - 20.557，经Bonferroni校正的p = 0.087）。未发现MAO-A VNTR与抑郁症状严重程度（贝克抑郁量表）、焦虑症状（斯皮尔伯格状态-特质焦虑量表）、总体心理健康（简明症状量表）或感知到的社会支持（F-SozU）有显著关联（所有p > 0.10）。
本初步研究首次表明，活性更高的MAO-A VNTR变体对作为重度抑郁症潜在中间表型的复杂性悲伤易感性增加存在性别特异性影响。
