Howland R H
Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pa. 15213.
J Clin Psychiatry. 1993 Feb;54(2):47-54.
Many studies of thyroid augmentation in refractory depression are methodologically weak, have had mixed results, and often do not include biological measures of hormonal effects. In this paper, recent clinical and preclinical research on thyroid dysfunction in refractory depression is reviewed.
A search of MEDLINE for articles published from 1970 to the present was conducted, in addition to a search of the bibliographies of published papers in this area. The clinical studies chosen for review included those in which the patient population was identified as having refractory depression and where a specific measure of thyroid function was used, such as thyroid indices, thyroid-releasing hormone stimulation, or basal metabolic rate. Animal studies of depression using the learned helplessness experimental paradigm were also reviewed and included if they examined the factors involved in antidepressant treatment response.
Fifty-two percent of patients with refractory depression in six clinical studies evidenced subclinical hypothyroidism (range, 29%-100%), which can be contrasted with a prevalence of approximately 8% to 17% in unselected populations of depressed patients. Four studies investigating an animal model of refractory depression strongly implicate a pathophysiologic role for hypothyroidism, perhaps mediated by altered beta-adrenergic function.
These findings indicate that hypothyroidism is significantly associated with refractory depression, suggesting that this characterizes one biological subtype of refractory depression. Failure to rigorously investigate the effects of thyroid augmentation, including measures of thyroid and beta-adrenergic function, may partly explain the ambiguous results from many treatment studies, and future research should incorporate these measures in the study of refractory depression.
许多关于难治性抑郁症中甲状腺功能增强的研究在方法上存在缺陷，结果不一，且往往未纳入激素效应的生物学指标。本文综述了难治性抑郁症中甲状腺功能障碍的近期临床和临床前研究。
除了检索该领域已发表论文的参考文献外，还对MEDLINE中1970年至今发表的文章进行了检索。选择进行综述的临床研究包括那些将患者群体确定为难治性抑郁症且使用了特定甲状腺功能测量方法的研究，如甲状腺指标、促甲状腺激素释放激素刺激或基础代谢率。还对使用习得性无助实验范式进行的抑郁症动物研究进行了综述，若这些研究考察了抗抑郁治疗反应所涉及的因素则将其纳入。
六项临床研究中52%的难治性抑郁症患者存在亚临床甲状腺功能减退（范围为29%-100%），相比之下，未选择的抑郁症患者群体中该患病率约为8%至17%。四项针对难治性抑郁症动物模型的研究强烈表明甲状腺功能减退具有病理生理作用，可能由β-肾上腺素能功能改变介导。
这些发现表明甲状腺功能减退与难治性抑郁症显著相关，提示这是难治性抑郁症的一种生物学亚型特征。未能严格研究甲状腺功能增强的影响，包括甲状腺和β-肾上腺素能功能的测量，可能部分解释了许多治疗研究结果的模糊性，未来的研究应在难治性抑郁症研究中纳入这些测量方法。
