Neurochemical Effects of Omega-3 Fatty Acids in Adolescents at Risk for Mania

Omega-3 脂肪酸对有躁狂风险的青少年的神经化学影响

基本信息

批准号：
8054292
负责人：
Melissa P Delbello
金额：
$ 23.31万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-15 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8054292
关键词：
Adolescent Affect Age Amygdaloid structure Anterior Antidepressive Agents Applications Grants Applied Research Attention Autopsy Award Behavioral Symptoms Binding Biological Markers Bipolar Disorder Brain Brain region Brodmann&apos s area Chemistry Child Chronic Clinical Consumption DSM-IV Data Development Dietary Supplementation Disease Early treatment Epidemiology Erythrocytes Evidence based treatment Exhibits Family Study Fatty Acids Fishes Functional disorder General Population Glutamates Goals Grant Human Human Milk Image Inositol Intake Intervention Intervention Studies Intervention Trial Lead Magnetic Resonance Spectroscopy Major Depressive Disorder Manic Mediating Mediator of activation protein Mind Mood Disorders Moods N-acetylaspartate National Institute of Mental Health Neurobiology Neurosciences Research Omega-3 Fatty Acids Onset of illness Outcome Assessment Parents Patients Peripheral Pharmaceutical Preparations Pilot Projects Placebo Control Placebos Play Population Prefrontal Cortex Prevalence Prevention strategy Process Protons Psychopathology Randomized Recruitment Activity Relative (related person)Research Research Infrastructure Resources Risk Risk Factors Role Safety Seafood Severities Source Staging Stress Structure Supplementation Surveys Symptoms Techniques Testing Thalamic structure Therapeutic Effect Tissues Universities Work Youth adolescent offspring cingulate cortex cohort depressive symptoms high risk hypomania improved in utero meetings mental health center neurochemistry neuroimaging neurophysiology novel offspring placebo controlled study pre-clinical prevent psychosocial public health relevance research and development resilience therapy development treatment effect treatment response treatment trial young adult

项目摘要

DESCRIPTION (provided by applicant): Adolescent offspring of parents with bipolar disorder, particularly those with prominent depressive symptoms, have an elevated risk of developing mania, and by definition bipolar I disorder, compared with the general population. However, medications that are commonly used to treat depressive symptoms may accelerate the onset of mania or hypomania. Therefore, studies evaluating the efficacy, safety, and tolerability of potential treatments for depressive symptoms in adolescents with a bipolar parent are necessary, and may lead to early intervention, and ultimately prevention, strategies for incipient manic and hypomanic episodes. Preclinical and clinical evidence suggests that omega-3 fatty acid deficiency may represent a preventable risk factor for developing bipolar disorder. Indeed, findings from preliminary placebo-controlled trials indicate that omega-3 fatty acid supplementation reduces mood symptom severity in youth and adults with mood disorders. Additionally, postmortem studies reveal significant omega-3 fatty acid deficits in the prefrontal cortex of young bipolar patients. Recent neuroimaging studies indicate that symptoms of bipolar disorder may arise from dysfunction within the anterior limbic network, which includes the ventrolateral prefrontal and anterior cingulate cortices. Specifically, proton magnetic resonance spectroscopy (1H MRS) studies reveal that adolescents with and at high risk for developing bipolar disorder exhibit excessive glutamate and myo-inositol and decreased N- acetyl aspartate levels, suggesting that hypermetabolism may underlie the disruption in anterior limbic brain regions. These neurochemical changes may be useful biomarkers of treatment effects. With these considerations in mind, the goals of this study are: 1) To collect pilot data regarding the efficacy, safety, and tolerability of omega-3 fatty acid supplementation for the treatment of adolescents with active depressive symptoms and a high risk for developing mania (i.e. they have a bipolar parent and meet DSM-IV-TR criteria for major depressive disorder), and 2) To use 1H MRS (i.e. prefrontal neurochemistry) and red blood cell (RBC) omega-3 fatty acid levels to examine potential mediators of treatment response to omega-3 fatty acids in adolescents with a high risk for mania. To accomplish these aims, a total of 60 adolescents (ages 12-21 years) with active depressive symptoms and significant risk factors for developing mania will be randomized to treatment with omega-3 fatty acids or placebo for 12 weeks. The aims of this application are consistent with those of the NIMH R34 grant mechanism; "pilot testing of new or adapted interventions" and "development of novel interventions to target specific risk factors for psychopathology or etiologic factors identified through neuroscience research". Additionally, the proposed study will capitalize on the infrastructure of the NIMH supported Center for Interventions Development and Applied Research (CIDAR) grant; the University of Cincinnati Bipolar Disorder Imaging and Treatment Research Center (BITREC, P50MH077138). Public Health Relevance: Evidence-based treatments are urgently needed for mood disorders in youth at high risk for developing bipolar disorder. This proposal will combine novel neuroimaging techniques with a placebo-controlled double-bind treatment trial in order to examine the neurophysiologic and therapeutic effects of chronic omega-3 fatty acid supplementation in adolescents at high risk for developing bipolar disorder, as an initial step to establish early intervention and prevention strategies.

描述（由申请人提供）：与一般人群相比，患有双相情感障碍的父母的青春期后代，特别是那些具有显着抑郁症状的人，患躁狂症（根据定义为 I 型双相情感障碍）的风险较高。然而，常用于治疗抑郁症状的药物可能会加速躁狂或轻躁狂的发作。因此，有必要进行研究，评估双相情感障碍父母青少年抑郁症状的潜在治疗方法的有效性、安全性和耐受性，并可能导致对早期躁狂和轻躁狂发作的早期干预和最终预防策略。临床前和临床证据表明，omega-3 脂肪酸缺乏可能是罹患双相情感障碍的一个可预防的危险因素。事实上，初步安慰剂对照试验的结果表明，补充 omega-3 脂肪酸可降低患有情绪障碍的青少年和成人情绪症状的严重程度。此外，尸检研究显示，年轻双相情感障碍患者的前额皮质存在显着的 omega-3 脂肪酸缺乏。最近的神经影像学研究表明，双相情感障碍的症状可能是由前边缘网络内的功能障碍引起的，其中包括腹外侧前额叶和前扣带皮层。具体来说，质子磁共振波谱 (1H MRS) 研究表明，患有双相情感障碍和高风险的青少年表现出过量的谷氨酸和肌醇以及降低的 N-乙酰天冬氨酸水平，这表明代谢亢进可能是前边缘脑区域破坏的基础。这些神经化学变化可能是治疗效果的有用生物标志物。考虑到这些因素，本研究的目标是： 1) 收集关于补充 omega-3 脂肪酸治疗患有活动性抑郁症状和高躁狂风险青少年的有效性、安全性和耐受性的试点数据（即他们有双相情感障碍父母并符合 DSM-IV-TR 重度抑郁症标准），以及 2) 使用 1H MRS（即前额神经化学）和红细胞 (RBC) omega-3 脂肪酸水平，以检查躁狂高风险青少年对 omega-3 脂肪酸治疗反应的潜在调节因素。为了实现这些目标，共有 60 名患有活动性抑郁症状和显着的躁狂危险因素的青少年（年龄 12-21 岁）将被随机分配接受 omega-3 脂肪酸或安慰剂治疗，为期 12 周。本申请的目的与 NIMH R34 资助机制的目的一致； “对新的或适应的干预措施进行试点测试”和“针对通过神经科学研究确定的精神病理学或病因因素的特定危险因素开发新的干预措施”。此外，拟议的研究将利用 NIMH 支持的干预开发和应用研究中心 (CIDAR) 拨款的基础设施；辛辛那提大学双相情感障碍影像和治疗研究中心（BITREC，P50MH077138）。公共卫生相关性：对于患有双相情感障碍高风险青少年的情绪障碍，迫切需要循证治疗。该提案将新颖的神经影像技术与安慰剂对照的双结合治疗试验相结合，以检查长期补充 omega-3 脂肪酸对双相情感障碍高风险青少年的神经生理学和治疗效果，作为建立双相情感障碍高风险青少年的第一步。早期干预和预防策略。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DOI：
10.1016/j.jad.2021.05.086
发表时间：
2021-09-01
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
Li W;Lei D;Tallman MJ;Patino LR;Gong Q;Strawn JR;DelBello MP;McNamara RK
通讯作者：
McNamara RK

Investigation of postmortem brain polyunsaturated fatty acid composition in psychiatric disorders: limitations, challenges, and future directions.

精神疾病中死后大脑多不饱和脂肪酸成分的调查：局限性、挑战和未来方向。

DOI：
10.1016/j.jpsychires.2010.04.029
发表时间：
2011
期刊：
Journal of psychiatric research
影响因子：
4.8
作者：
McNamara,RobertK;Jandacek,Ronald
通讯作者：
Jandacek,Ronald

Effects of Fish Oil Monotherapy on Depression and Prefrontal Neurochemistry in Adolescents at High Risk for Bipolar I Disorder: A 12-Week Placebo-Controlled Proton Magnetic Resonance Spectroscopy Trial.

鱼油单一疗法对 I 型双相情感障碍高危青少年抑郁和前额神经化学的影响：为期 12 周的安慰剂对照质子磁共振波谱试验。

DOI：
10.1089/cap.2019.0124
发表时间：
2020
期刊：
Journal of child and adolescent psychopharmacology
影响因子：
1.9
作者：
McNamara,RobertK;Strawn,JeffreyR;Tallman,MaxJ;Welge,JeffreyA;Patino,LRodrigo;Blom,ThomasJ;DelBello,MelissaP
通讯作者：
DelBello,MelissaP

Role of Long-Chain Omega-3 Fatty Acids in Psychiatric Practice.