Cytokines, PUFA Tissue Concentrations and Treatment Selection in Antenatal MMD

产前 MMD 的细胞因子、PUFA 组织浓度和治疗选择

• 批准号: 8265810
• 负责人: William Henry Coryell
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8265810
• 关键词: Acute; Adverse effects; Antidepressive Agents; Case-Control Studies; Characteristics; Depressed mood; Depressive disorder; Development; Eicosapentaenoic Acid; Erythrocytes; Fetus; First Pregnancy Trimester; Fishes; Goals; Grant; High Risk Woman; Individual; Inflammatory; Intake; Lead; Left; Major Depressive Disorder; Measures; Mental Depression; Mercury; Meta-Analysis; Mono-S; Mothers; Newborn Infant; Nutritional; Nutritional status; Omega-3 Fatty Acids; Outcome; Perinatal; Pharmaceutical Preparations; Placebos; Polyunsaturated Fatty Acids; Pregnancy; Pregnancy Trimesters; Pregnant Women; Prophylactic treatment; Recurrence; Risk; Risk Factors; Sampling; Sampling Studies; Screening procedure; Second Pregnancy Trimester; Selection for Treatments; Supplementation; Symptoms; Testing; Tissues; Woman; control trial; conventional therapy; cytokine; depressive symptoms; design; experience; high risk; immune function; inflammatory marker; inflammatory modulation; placebo controlled study; pregnant; response; single episode major depressive disorder; tool

DESCRIPTION (provided by applicant): Pregnancy does not reduce the risk of recurrence among women who have previously experienced depressive illness and the advent of new episodes during pregnancy raises particular problems. Concerns over the possible teratogenicity of medications in general leave many women reluctant to continue preexisting antidepressant prophylaxis or to accept new trials of conventional antidepressant treatment and there is accumulating evidence that the SSRIs have short-term adverse effects on the newborn. The antidepressant effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation may offer a particularly appropriate alternative to conventional therapy for depressive episodes that occur during pregnancy. The nutritional needs of the fetus increase the likelihood of omega-3 PUFA deficits in the mother but access to adequate omega-3 PUFAs but fish intake is limited due to concerns over mercury levels. Antidepressant trials of omega-3 supplementation that have described significant benefits over placebo include one that targeted pregnant women and yielded a large effect size. Other trials, however, have failed to show clear antidepressant effects and meta-analyses have yielded no explanations for these inconsistencies. A clear possibility is that the studies with positive results involved subjects who more likely to benefit from omega-3 supplementation but the characteristics of such individuals are entirely unknown. Numerous case-control studies have associated depressive illness with lower tissue concentration of omega-3 PUFAs and with higher ratios of omega-6 to omega-3. Such measures may well identify individuals likely show antidepressant effects from supplementation. The likelihood that omega-3 PUFAs exert antidepressant effects via modulation of the inflammatory cascade, and the extensive evidence that high levels of cytokines characterize individuals with depressive disorders, indicate that these measures too may help to select those most likely to benefit from treatment with omega-3 PUFAs. The above considerations lead us to propose a developmental (R21) grant with two goals involving two overlapping subject groups. The larger would consist of 120 women in their first trimester of pregnancy who are not currently in major depressive episodes but who are at high risk of recurrence; they would be used to identify measures of PUFA tissue concentration and inflammatory marker status as risk factors for later onsets of major depressive episodes. A second group would consist of 60 women who begin pregnancy in depressive episodes or who develop episodes in their first two trimesters but who choose not to take conventional antidepressant therapy; they would be used to test PUFA tissue concentration and inflammatory measures as predictors of response to omega-3 supplementation mono- therapy. Together the results allow for the personalization both of acute antidepressant treatment and of omega-3 prophylaxis for women at high risk for perinatal depressive disorder and would provide important information for the design of larger controlled trials of omega-3 supplementation.

描述（由申请人提供）：对于之前患有抑郁症的女性来说，怀孕并不会降低复发的风险，而且怀孕期间新的抑郁症发作会带来特殊的问题。由于担心药物可能致畸，许多妇女不愿意继续使用已有的抗抑郁药物预防或接受传统抗抑郁药物治疗的新试验，而且越来越多的证据表明 SSRIs 对新生儿有短期不良影响。补充 omega-3 多不饱和脂肪酸 (PUFA) 的抗抑郁作用可能为妊娠期间发生的抑郁发作提供传统疗法的特别合适的替代方案。胎儿的营养需求增加了母亲 omega-3 PUFA 缺乏的可能性，但母亲可以获得足够的 omega-3 PUFA，但由于对汞含量的担忧，鱼的摄入量受到限制。补充 omega-3 的抗抑郁试验表明，与安慰剂相比具有显着益处，其中一项针对孕妇并产生了较大的效果。然而，其他试验未能显示出明显的抗抑郁作用，荟萃分析也没有对这些不一致给出任何解释。一个明显的可能性是，取得积极结果的研究涉及更有可能受益于 omega-3 补充剂的受试者，但这些人的特征完全未知。许多病例对照研究表明抑郁症与较低的 omega-3 PUFA 组织浓度以及较高的 omega-6 与 omega-3 比率相关。这些措施可以很好地识别可能因补充剂而表现出抗抑郁作用的个体。 omega-3 PUFA 通过调节炎症级联发挥抗抑郁作用的可能性，以及高水平细胞因子是抑郁症患者特征的大量证据表明，这些措施也可能有助于选择那些最有可能从 omega-3 PUFA 治疗中受益的人。上述考虑促使我们提出一项发展性 (R21) 资助，其两个目标涉及两个重叠的学科组。更大的规模将由 120 名处于怀孕前三个月的女性组成，她们目前没有重度抑郁发作，但复发的风险很高；它们将用于确定 PUFA 组织浓度和炎症标志物状态的测量结果，作为重度抑郁发作后期发作的危险因素。第二组由 60 名女性组成，她们在怀孕时患有抑郁症或在妊娠前两个三个月出现抑郁症，但选择不接受传统的抗抑郁治疗；它们将用于测试 PUFA 组织浓度和炎症指标，作为 omega-3 补充单一疗法反应的预测因子。总之，这些结果可以为围产期抑郁症高危女性提供个性化的急性抗抑郁治疗和 omega-3 预防，并将为设计更大规模的 omega-3 补充剂对照试验提供重要信息。