Immunological and neurotrophic markers of risk status and illness development in high-risk youth: understanding the neurobiological underpinnings of bipolar disorder.
Immunological and neurotrophic markers of risk status and illness development in high-risk youth: understanding the neurobiological underpinnings of bipolar disorder.
复制标题
DOI：
10.1186/2194-7511-2-4
复制
发表时间：
2014-12
影响因子：
4
通讯作者：
Young LT
中科院分区：
文献类型：
--
作者：
Duffy A;Horrocks J;Doucette S;Keown-Stoneman C;Grof P;Andreazza A;Young LT
双相情感障碍是一种高度可遗传的疾病，发病于青春期和青壮年。我们检测了双相父母特征良好的后代中候选免疫和神经营养标记物的基因表达(MRNA)和蛋白水平，以确定疾病风险状态和疾病发展的早期临床阶段的可靠指标。检测候选免疫(肿瘤坏死因子-α、白介素1-β、白介素10、干扰素-δ)和神经营养(脑源性神经营养因子)标志物的基因表达和蛋白水平。高危子女是从父母中有一人确认患有双相情感障碍的家庭中确定的。对照子女来自父母双方都没有达到重大精神障碍终生标准的家庭。所有的父母诊断和统计手册第四版(DSM-IV)的诊断都是基于情感障碍终生版(SADS-L)访谈的时间表和盲目共识审查。作为正在进行的研究的一部分，使用KSADS-PL格式的访谈和盲目共识审查确认的诊断对所有后代进行了前瞻性评估。与对照组相比，高危子代的IL-6(p = 0.050)和脑源性神经营养因子(p = 0.006)蛋白水平显著升高。与较晚的临床阶段相比，高危子女的IL-6(p = 0.050)和脑源性神经营养因子(p = 0.045)蛋白水平较高。调整后，只有脑源性神经营养因子蛋白水平的差异仍然显著。与对照组相比，BDNF基因对高危儿童的基因表达和蛋白质水平均有调节作用。BDNF基因还调节了高危子代的临床分期和基因表达水平之间的关系。这些发现支持在患双相情感障碍的高危人群中候选免疫和神经营养标记物的可检测到的差异，以及在疾病发展的临床阶段可检测到的变化。这些关联似乎受到遗传变异的影响。本文的在线版本(DOI：10.1186/2194-7511-2-4)包含补充材料，可供授权用户使用。
Bipolar disorder is a highly heritable illness that onsets in adolescence and young adulthood. We examined gene expression (mRNA) and protein levels of candidate immune and neurotrophic markers in well-characterized offspring of bipolar parents in order to identify reliable indicators of illness risk status and the early clinical stages of illness development. We measured mRNA expression and protein levels in candidate immune (TNF-α, IL-1β, IL-10, IFN-δ) and neurotrophic (brain-derived neurotrophic factor (BDNF)) markers from plasma. High-risk offspring were identified from families in which one parent had confirmed bipolar disorder. Control offspring were identified from families in which neither parent met lifetime criteria for a major psychiatric disorder. All parental Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses were based on Schedule for Affective Disorders - Lifetime Version (SADS-L) interviews and blind consensus review. As part of an ongoing study, all offspring were prospectively assessed using KSADS-PL format interviews and diagnoses confirmed on blind consensus review. High-risk offspring had significantly increased IL-6 (p = 0.050) and BDNF (p = 0.006) protein levels compared to controls. Those high-risk offspring in earlier compared to later clinical stages of illness development had higher IL-6 (p = 0.050) and BDNF (p = 0.045) protein levels. After adjustments, only differences in BDNF protein levels remained significant. There was a moderating effect of the BDNF genotype on both gene expression and protein levels in high-risk compared to control offspring. The BDNF genotype also moderated the association between clinical stage and gene expression levels in high-risk offspring. These findings provide support for detectable differences in candidate immune and neurotrophic markers in individuals at high risk of developing bipolar disorder and for detectable changes over the clinical stages of illness development. These associations appear to be moderated by genetic variants. The online version of this article (doi:10.1186/2194-7511-2-4) contains supplementary material, which is available to authorized users.