Department of Psychiatry, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
CNS Drugs. 2010 Dec;24(12):983-96. doi: 10.2165/11539700-000000000-00000.
Bipolar disorder is a chronic and typically recurring illness with significant psychosocial morbidity. Although the aetiological factors that contribute to the onset of mania, and by definition bipolar I disorder, are poorly understood, it most commonly occurs during the adolescent period. Putative risk factors for developing bipolar disorder include having a first-degree relative with a mood disorder, physical/sexual abuse and other psychosocial stressors, substance use disorders, psychostimulant and antidepressant medication exposure and omega-3 fatty acid deficiency. Prominent prodromal clinical features include episodic symptoms of depression, anxiety, hypomania, anger/irritability and disturbances in sleep and attention. Because prodromal mood symptoms precede the onset of mania by an average of 10 years, and there is low specificity of risk factors and prodromal features for mania, interventions initiated prior to onset of the disorder (primary prevention) or early in the course of the disorder (early or secondary prevention) must be safe and well tolerated upon long-term exposure. Indeed, antidepressant and psychostimulant medications may precipitate the onset of mania. Although mood stabilizers and atypical antipsychotic medications exhibit efficacy in youth with bipolar I disorder, their efficacy for the treatment of prodromal mood symptoms is largely unknown. Moreover, mood stabilizers and atypical antipsychotics are associated with prohibitive treatment-emergent adverse effects. In contrast, omega-3 fatty acids have neurotrophic and neuroprotective properties and have been found to be efficacious, safe and well tolerated in the treatment of manic and depressive symptoms in children and adolescents. Together, extant evidence endorses a clinical staging model in which subjects at elevated risk for developing mania are treated with safer interventions (i.e. omega-3 fatty acids, family-focused therapy) in the prodromal phase, followed by pharmacological agents with potential adverse effects for nonresponsive cases and secondary prevention. This approach warrants evaluation in prospective longitudinal trials in youth determined to be at ultra-high risk for bipolar I disorder.
双相障碍是一种慢性且通常反复发作的疾病，具有显著的社会心理发病率。尽管导致躁狂发作和定义为双相 I 型障碍的病因因素了解甚少，但它最常发生在青少年时期。发生双相障碍的潜在风险因素包括有一级亲属患有心境障碍、身体/性虐待和其他社会心理应激源、物质使用障碍、精神兴奋剂和抗抑郁药物暴露以及欧米伽-3 脂肪酸缺乏。突出的前驱临床特征包括间歇性抑郁、焦虑、轻躁狂、愤怒/易怒和睡眠及注意力障碍。由于前驱情绪症状比躁狂发作平均提前 10 年，并且风险因素和前驱特征对躁狂的特异性低，因此必须在疾病发作前（一级预防）或疾病早期（早期或二级预防）开始干预，而且必须长期暴露时安全且耐受良好。事实上，抗抑郁药和精神兴奋剂可能会引发躁狂发作。虽然心境稳定剂和非典型抗精神病药物在双相 I 型障碍的青少年中显示出疗效，但它们治疗前驱情绪症状的疗效在很大程度上尚不清楚。此外，心境稳定剂和非典型抗精神病药物与禁止的治疗后出现的不良反应相关。相比之下，欧米伽-3 脂肪酸具有神经营养和神经保护特性，已被发现对儿童和青少年的躁狂和抑郁症状有效、安全且耐受良好。综上所述，现有的证据支持一种临床分期模型，即处于躁狂发作风险升高的患者在前驱阶段用更安全的干预措施（即欧米伽-3 脂肪酸、以家庭为中心的治疗）进行治疗，然后对无反应的病例和二级预防使用可能有不良反应的药物进行治疗。这种方法值得在被确定为具有极高双相 I 型障碍风险的青年中进行前瞻性纵向试验评估。
