Akiskal Hagop S, Benazzi Franco
International Mood Center, University of California at San Diego, V.A. Hospital, 3350 La Jolla Village Dr. 116-A, La Jolla, San Diego, CA 92161, USA.
J Affect Disord. 2005 Feb;84(2-3):209-17. doi: 10.1016/j.jad.2004.05.004.
Although increasing data link atypical depression (AD) to the bipolar spectrum, controversies abound about the extent of the overlap. In particular, the Columbia group, which has pioneered in providing data on operational clarity and pharmacological specificity of atypical depressions, has nonetheless consistently avoided studying its discriminatory validity from bipolar II (BP-II). Accordingly, we undertook a full scale validation of such a link in a large clinical sample of BP-II and unipolar (UP) major depressive disorder (MDD).
Consecutive 348 BP-II and 254 MDD outpatients presenting with major depressive episodes (MDE) were interviewed off psychoactive drugs with a modified Structured Clinical Interview for DSM-IV, the structured Family History Screen and the Hypomania Interview Guide. We used the DSM-IV criteria for "atypical features" specifier. Depressive mixed state was defined as > or =3 concurrent hypomanic signs and symptoms during MDE. Bipolar validators were age at onset, high depressive recurrence, depressive mixed state and bipolar family history (types I and II). Univariate and multivariate logistic regression were used to examine associations and control for confounding variables.
Frequency of AD was 43.0% in the combined BP-II and MDD sample. AD, versus non-AD, had significantly higher rates of BP-II. AD was significantly associated with all bipolar validators, among which family history was the most robust. A dose-response relationship was found between number of atypical symptoms during MDE and bipolar family history loading. The association between bipolar family history and number of atypical symptoms remained significant after controlling for the confounding effect of BP-II. Bipolar family history was strongly associated with the atypical symptoms of leaden paralysis and hypersomnia.
These results confirm a strong link between AD and bipolar validators along psychopathologic and familial grounds. From a practical standpoint, AD is best viewed as a variant of BP-II. Clinicians confronted with MDE patients presenting with atypical features should strongly consider a BP-II diagnosis. In a more hypothetical vein, atypicality-or some associated features thereof-might serve as a nosologic bridge between UP and BP-II.
尽管越来越多的数据将非典型抑郁症（AD）与双相谱系联系起来，但关于重叠程度的争议仍然很多。特别是，哥伦比亚研究小组率先提供了关于非典型抑郁症的操作清晰度和药理学特异性的数据，但仍然一直避免研究其与双相II型障碍（BP-II）的鉴别效度。因此，我们在一个大型的BP-II型和单相（UP）重度抑郁症（MDD）临床样本中对这种联系进行了全面验证。
对连续就诊的348例BP-II型和254例患有重度抑郁发作（MDE）的MDD门诊患者进行访谈，访谈时患者停用精神活性药物，采用改良的DSM-IV结构化临床访谈、结构化家族史筛查和轻躁狂访谈指南。我们使用DSM-IV标准来确定“非典型特征”说明符。抑郁混合状态定义为在MDE期间同时出现≥3种轻躁狂体征和症状。双相障碍验证指标包括发病年龄、高抑郁复发率、抑郁混合状态和双相家族史（I型和II型）。采用单变量和多变量逻辑回归来检验关联并控制混杂变量。
在BP-II型和MDD样本合并组中，AD的发生率为43.0%。与非AD相比，BP-II型的AD发生率显著更高。AD与所有双相障碍验证指标均显著相关，其中家族史最为显著。在MDE期间非典型症状的数量与双相家族史负荷之间发现了剂量反应关系。在控制了BP-II型的混杂效应后，双相家族史与非典型症状的数量之间的关联仍然显著。双相家族史与铅样麻痹和嗜睡的非典型症状密切相关。
这些结果从精神病理学和家族学角度证实了AD与双相障碍验证指标之间的紧密联系。从实际角度来看，AD最好被视为BP-II型的一种变体。面对具有非典型特征的MDE患者的临床医生应强烈考虑BP-II型诊断。从更具假设性的角度来看，非典型性——或其一些相关特征——可能作为UP和BP-II之间的一种疾病分类桥梁。
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