Light Treatment for Winter-SAD: Prediction of Response by Immediate Improvement

描述(申请人提供)：季节性情感障碍冬季类型(SAD)包括冬季的主要抑郁发作，春季和夏季缓解。悲伤的症状包括烦躁不安、食欲增加、食物摄入量和体重增加以及能量和动力下降，这些都与功能和生活质量的季节性急剧下降有关。强光治疗SAD已被证明是安全有效的。4例患者中有3例在强光治疗后好转，2例中只有1例在强光治疗下完全缓解。因此，预测谁会缓解和谁不会缓解在临床上非常重要；然而，预测仍然是难以捉摸的。长期目标是评估一项简单的治疗测试的有用性，该测试可以在医生的办公室进行，以预测在整个疗程的光治疗后的抗抑郁反应。短期目标是将在高度人工环境中(在PET扫描仪中)获得的初步数据扩展到更自然的环境，并测试在一次光疗后抑郁的立即改善是否与整个光疗后更实质性的抗抑郁反应有关。最后，由于心血管危险因素(即胆固醇、体重指数、脂肪百分比和分布、血压、胰岛素抵抗、C反应蛋白)在冬季恶化，由于上述心血管危险因素反映了饮食和运动，并且由于冬季SAD患者进食更多、体重增加和活动减少，我们将评估强光是否也降低了SAD抑郁患者的心血管危险因素。光可能会以两种不同的方式减少食欲和体重：a)通过其抗抑郁作用；b)考虑到光暴露对光周期哺乳动物的强烈代谢影响，光不依赖于抑郁。80名患有SAD的抑郁症患者将被随机分为强光或暗红光干预，第一次在实验室进行，其余的在家里进行，在基线、治疗4周和6周时测量他们的抑郁评分和心血管风险因素，并在第一次1小时的强光治疗后进行额外的抑郁评估。抑郁评分和心血管危险因素(体重、血脂、胰岛素抵抗、炎症标记物、血压)的变化将在亮红光和暗红光之间以及与时间变化相关的方法(如t检验、相关、线性回归、卡方和纵向方法)中进行比较。与R34应用程序的任务一致，将初步探索潜在的中介或混杂变量(如食欲、食物摄入量、体力活动、睡眠)的影响，并为未来更明确的应用提供更复杂的预测模型。季节性情感障碍，也被称为SAD或冬季抑郁症，是一种影响数百万美国人的严重疾病。强光疗法有助于治疗抑郁症，但与药物治疗一样，并不是每个人对治疗都有很好的反应。我们建议研究一个人在治疗一小时后情绪的改善(就像在医生的办公室里一样)是否有助于预测谁会改善。如果这被证明是真的，未来我们将不必等待数周就可以决定是否需要在光的基础上或替代光的情况下接受另一种治疗。在冬天，许多SAD患者渴望甜食和淀粉，吃得更多，运动更少，体重增加。因此，我们建议找出强光是否可以降低食欲、食物摄入量、体重增加、增加体力活动，并在下游改善胆固醇、血糖、炎症标志物和血压，这些都是心脏病和中风的重要风险因素。

DESCRIPTION (provided by applicant): Seasonal affective disorder winter type (SAD) consists of episodes of major depression in winter with remission in spring and summer. SAD symptoms include dysphoria, increased appetite, food intake and weight gain and reduced energy and motivation, which are associated with drastic seasonal decrements in functioning and quality of life. Bright light treatment has been shown to be safe and effective for SAD. While 3 out of 4 patients improve with bright light treatment, only 1 in 2 completely remits with bright light. Thus, predicting who will remit and who will not is clinically very important; however forecasting this remains elusive. The long term objective is to estimate the usefulness of a simple therapeutic test which could be performed in a doctor's office in predicting an antidepressant response after a full course of six weeks of light treatment. The short term objective is to extend the preliminary data which were obtained in a highly artificial setting (in the PET scanner) to a more naturalistic setting, and test if immediate improvement of depression after a session of light treatment is associated with to a more substantial antidepressant response after a full course of light treatment. Finally, because cardiovascular risk factors (i.e., cholesterol, body mass index, fat % and distribution, blood pressure, insulin resistance, C reactive protein) worsen during winter, because the above cardiovascular risk factors are reflective of diet and exercise, and because patients with SAD eat more, gain weight and have reduced activity in the winter, we will evaluate if bright light also reduces cardiovascular risk factors in depressed patients with SAD. Light might reduce appetite and weight in two distinct ways: a) via its antidepressant effect and b) independent of depression, considering the robust metabolic effects of light exposure on photoperiodic mammals. 80 depressed patients with SAD will be randomized to bright light or dim red light intervention, with the first session in the lab and the remainder at home, and their depression scores and cardiovascular risk factors measured at baseline, 4 weeks and 6 weeks of treatment, with an additional depression evaluation after the first 1 hour session of bright light treatment. Changes in depression scores and cardiovascular risk factors (weight, lipids, insulin resistance, inflammatory markers, blood pressure) will be compared between bright vs. dim red light and changes in time related with methods such as t-tests, correlations, linear regressions, chi squares, and longitudinal methods. The effect of potential mediating or confounding variables (such as appetite, food intake, physical activity, sleep) will be preliminarily explored, consistent with the mission of an R34 application, and inform more complex predictive models for a future more definitive application. Seasonal affective disorder, also called SAD or winter depression, is a serious condition that affects millions of Americans. Bright light treatment helps with depression, but, as with medications, not everyone responds well to treatment. We propose to study if improvement in one's mood after one hour of treatment (as it would be in a doctor's office) would help anticipate who will improve or not. If this proves true, in the future we would not have to wait many weeks before deciding if one would need to get another treatment in addition or instead of light. During winter many patients with SAD crave sweets and starches, eat more, exercise less and gain weight. We thus propose to find out if bright light could reduce food cravings, food intake, weight gain, increase physical activity, and downstream improve cholesterol, blood sugar, inflammatory markers and blood pressure, which are important risk factors for heart disease and stroke.