Goldstein Benjamin I, Lotrich Francis, Axelson David A, Gill Mary Kay, Hower Heather, Goldstein Tina R, Fan Jieyu, Yen Shirley, Diler Rasim, Dickstein Daniel, Strober Michael A, Iyengar Satish, Ryan Neal D, Keller Martin B, Birmaher Boris
Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, FG53, Toronto, Ontario, M4N-3M5
J Clin Psychiatry. 2015 Nov;76(11):1556-63. doi: 10.4088/JCP.14m09395.
Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study.
Subjects were 123 adolescents and young adults (mean [SD] = 20.4 ± 3.8 years; range, 13.4-28.3 years) in COBY, enrolled between October 2000 and July 2006. DSM-IV diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Clinical characteristics during the preceding 6 months, including mood, comorbidity, and treatment, were evaluated using the Longitudinal Interval Follow-Up Evaluation (LIFE). Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were assayed. Primary analyses examined the association of PIMs with bipolar disorder characteristics during the preceding 6 months.
Several lifetime clinical characteristics were significantly associated with PIMs in multivariable analyses, including longer illness duration (P = .005 for IL-6; P = .0004 for hsCRP), suicide attempts (P = .01 for TNF-α), family history of suicide attempts or completion (P = .01 for hsCRP), self-injurious behavior (P =.005 for TNF-α), substance use disorder (SUD) (P < .0001 for hsCRP), and family history of SUD (P = .02 for TNF-α; P = .01 for IL-6). The following bipolar disorder characteristics during the preceding 6 months remained significantly associated with PIMs in multivariable analyses that controlled for differences in comorbidity and treatment: for TNF-α, percentage of weeks with psychosis (χ(2) = 5.7, P =.02); for IL-6, percentage of weeks with subthreshold mood symptoms (χ(2)= 8.3, P = .004) and any suicide attempt (χ(2) = 6.1, P = .01); for hsCRP, maximum severity of depressive symptoms (χ(2) = 8.3, P =.004).
Proinflammatory markers may be relevant to bipolar disorder characteristics as well as other clinical characteristics among adolescents and young adults with bipolar disorder. Traction toward validating PIMs as clinically relevant biomarkers in bipolar disorder will require repeated measures of PIMs and incorporation of relevant covariates.
尽管关于中年成年人的文献不断涌现,但对于双相情感障碍青少年和青年中的促炎标志物(PIMs)却知之甚少。同样,在研究PIMs与双相情感障碍特征之间的关联时,很少有先前的研究考虑到潜在的混杂因素。因此,我们在双相情感障碍青少年病程及转归(COBY)研究中对这些主题进行了回顾性研究。
研究对象为2000年10月至2006年7月期间纳入COBY研究的123名青少年和青年(平均[标准差]=20.4±3.8岁;范围为13.4 - 28.3岁)。使用学龄儿童情感障碍和精神分裂症量表(K-SADS)确定DSM-IV诊断。使用纵向间隔随访评估(LIFE)评估前6个月的临床特征,包括情绪、共病情况和治疗情况。检测血清白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和高敏C反应蛋白(hsCRP)水平。主要分析研究了PIMs与前6个月双相情感障碍特征之间的关联。
在多变量分析中,几种终生临床特征与PIMs显著相关,包括病程较长(IL-6的P = 0.005;hsCRP的P = 0.0004)、自杀未遂(TNF-α的P = 0.01)、自杀未遂或自杀完成的家族史(hsCRP的P = 0.01)、自伤行为(TNF-α的P = 0.005)、物质使用障碍(SUD)(hsCRP的P < 0.0001)以及SUD家族史(TNF-α的P = 0.02;IL-6的P = 0.01)。在控制了共病和治疗差异的多变量分析中,前6个月的以下双相情感障碍特征仍与PIMs显著相关:对于TNF-α,有精神病症状的周数百分比(χ(2)= = 5.7,P = 0.02);对于IL-6,有阈下情绪症状的周数百分比(χ(2)= 8.3,P = 0.004)和任何自杀未遂情况(χ(2)= 6.1,P = 0.01);对于hsCRP,抑郁症状的最大严重程度(χ(2)= 8.3,P = 0.004)。
促炎标志物可能与双相情感障碍青少年和青年的双相情感障碍特征以及其他临床特征相关。要使PIMs作为双相情感障碍中具有临床相关性的生物标志物得到验证,需要对PIMs进行重复测量并纳入相关协变量。