Neuropsychopharmacology: 脑结构连接有助于预测双相情感障碍药物治疗效果

2021-04-10 MedSci原创 MedSci原创

测量脑结构连接可能有助于预测双相情感障碍青年患者的药物治疗结果。

双相情感障碍是一种常见的衰弱疾病,通常在青春期发病。研究患有双相情感障碍的青少年,可以明确发病时疾病的神经生物学,并识别预测和跟踪既往有限药物暴露的个人治疗后临床变化的生物改变。

MRI的功能和结构成像不仅对了解疾病生物学很有用,而且对评估药物效果和预测治疗反应也很有用。虽然解剖学在成人生活中通常被认为是相对静止的,但最近的证据表明,行为训练和精神药物的急性治疗都可以明显改变灰质结构。这包括精神分裂症和双相情感障碍患者的抗精神病药物和锂的研究。最近,基于种子的功能连接已被用于预测接受情绪稳定剂治疗的双相情感障碍患者的治疗反应。此外,有证据表明,双相情感障碍的病理生理学涉及网络连接障碍,因此检查大脑连接体可能是促进疾病理解和生物标记物开发的一种有前途的策略。

基于图形的分析为描述大脑网络(即连接体)的拓扑属性及其在精神疾病中的变化提供了一个强有力的工具。在这种方法中,大脑被建模为由多个节点和连接这些节点的边组成的网络。节点代表单独的皮质和皮质下区域,边缘反映了它们的连通性,这是这些区域之间信息传输所必需的,这是更高大脑功能的基础。基于图论分析,大脑结构连通性的完整性可以用一系列量化网络拓扑分离和整合特征的网络测度来表示。最近,高分辨率结构MRI已越来越多地用于通过评估区域间灰质(GM)体积测量的模式来描绘全脑连接模式。这样的测量可以帮助理解网络解剖学的改变如何塑造功能和行为特征,例如与双相情感障碍相关的特征。

除了研究疾病机制,这种方法还可以用来识别预测治疗反应的生物标记物,并确定广泛使用的疗法对大脑连接体的影响程度。锂是治疗躁狂症最古老和最有效的疗法之一。奎硫平对躁狂发作也是有效的,在一些躁狂青少年中,奎硫平可能比广泛使用的情绪稳定剂更有效。尽管研究人员已经提出了理解锂对双相情感障碍疗效的模型,但很少有关于锂或奎硫平对躁狂患者灰质网络特性标志物的体内影响的研究。华西医院Du Lei等在患有双相情感障碍的年轻人中进行了一项随机的安慰剂对照临床试验,并使用基于图表的方法来表征灰质连接组的指标。研究成果发表在Neuropsychopharmacology杂志。

该研究的目的是进行病例对照比较,以评估双相青年的结构连接体改变,在随机临床试验中确定锂和奎硫平对GM网络的影响,并确定基线指标是否可以预测治疗反应。首先,由于之前的功能磁共振研究已经在未用药和未用药的BD患者中发现了突显网络(SN)的网络异常,假设与健康对照青年相比,双相情感障碍青年也会在全球和区域水平上表现出预处理GM脑网络异常,特别是在SN中。其次,由于先前的结构MRI研究没有发现锂盐组和奎硫平组在灰质体积方面的纵向治疗效果有显著差异,不能假设锂盐和奎硫平组对GM网络特性的治疗效果会不同。鉴于锂和奎硫平对大脑解剖和功能的影响在以前的研究中都有报道,Du Lei等假设锂或奎硫平治疗6周会引起SN网络关键脑区(包括岛叶和前扣带回皮层)的全脑拓扑指标和区域节点中枢的变化,这些变化将与躁狂症状严重程度的减轻有关。第三,预测治疗前的GM网络矩阵将预测治疗后躁狂症状的减轻。

患有双相情感障碍的青年被随机分成奎硫平或锂双盲治疗组,每周评估一次。高分辨率磁共振成像来自经历混合或躁狂发作的双相情感障碍儿童和青少年(n = 100)和健康青年(n = 63)。基于区域间形态特征的相似性构建了脑网络,并用图论方法对其进行了分析。测试了双相情感障碍青年和健康青年在治疗前的解剖学差异,以及双相情感障碍青年治疗后神经解剖网络指标的变化。

图表显示双相情感障碍患者和健康对照组在不同时间点的全局拓扑属性的差异。两组的聚类系数(Cp)(p=0.009)和特征路径长度(Lp)在基线时有显著性差异(p=0.04)。治疗1周后CP升高,仍有显著性差异(p=0.045)。星号表示具有显著差异的网络指标(p<0.05)

图表显示了与健康对照组相比,双相情感障碍患者在不同时间点大脑结构连接体的结节中心明显改变的区域。使用BrainNet Viewer软件包(http://www.nitrc.org/projects/bnv).)将节点映射到皮质表面。DCG中扣带回和旁扣带回;IFGoperc额下回顶盖部;INS岛叶;PCL中央旁小叶;PHG海马旁回;SMA辅助运动区;SPG顶上回。

患有双相情感障碍的青少年在基线时集群系数(C)和特征路径长度(L)显著增加(p = 0.009.0 5和p = 0.0 4),并改变了岛叶、额下回和辅助运动区的结节中心。治疗后,患者脑岛的C、L和结节中心性均恢复正常。这些神经解剖学参数的改变与躁狂症状的改善相关,但在两种药物疗法之间没有区别。基线结构网络矩阵显著区分药物应答者和无应答者,准确率为80%。

双相情感障碍患者脑网络参数在治疗过程中的改变。CPLP (AB),以及区域水平的右岛叶结节效率、程度 (CD),都观察到了显著的分组时间效应。

图表显示了脑网络参数的变化与临床症状严重程度变化的相关性。AB显示基线时脑网络参数与症状严重程度的关系。C-F显示6周时临床症状严重程度的改变与改变的脑网络参数正常化之间的关系。

该研究表明,与健康青少年相比,躁狂青年双相情感障碍患者的整体和节点网络都发生了改变。治疗后,结构连接的一些基线改变明显减少。此外,基线结构连接数据成功预测了喹硫平或锂治疗6周后的治疗反应。这些结果表明,测量脑结构连接可能有助于预测双相情感障碍青年患者的药物治疗结果。

原文出处:

Lei Du,Li Wenbin,Tallman Maxwell J et al. Changes in the brain structural connectome after a prospective randomized clinical trial of lithium and quetiapine treatment in youth with bipolar disorder.[J] .Neuropsychopharmacology, 2021, undefined: undefined.

 

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  4. 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
  5. 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
  6. 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
    2021-10-24 yb6560
  7. 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1787710, encodeId=b3341e8771033, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Thu Oct 07 06:30:41 CST 2021, time=2021-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1788420, encodeId=a2aa1e8842026, content=<a href='/topic/show?id=38e014162e2' target=_blank style='color:#2F92EE;'>#Pharmacol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sun Oct 24 22:30:41 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1301803, encodeId=306d1301803ad, content=<a href='/topic/show?id=c34e3e53295' target=_blank style='color:#2F92EE;'>#双相情感障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37532, encryptionId=c34e3e53295, topicName=双相情感障碍)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7ca4300, createdName=wodejia-dayu, createdTime=Mon Apr 12 11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556523, encodeId=a54e1556523eb, content=<a href='/topic/show?id=ab7e85001cf' target=_blank style='color:#2F92EE;'>#脑结构#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85001, encryptionId=ab7e85001cf, topicName=脑结构)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4f3114785325, createdName=wmr116, createdTime=Mon Apr 12 11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568737, encodeId=53ad1568e3762, content=<a href='/topic/show?id=8b7d53129cc' target=_blank style='color:#2F92EE;'>#情感障碍#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53129, encryptionId=8b7d53129cc, topicName=情感障碍)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=afcb15435989, createdName=天堂的云, createdTime=Mon Apr 12 11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
    2021-04-12 wmr116
  9. [GetPortalCommentsPageByObjectIdResponse(id=1787710, encodeId=b3341e8771033, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Thu Oct 07 06:30:41 CST 2021, time=2021-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1788420, encodeId=a2aa1e8842026, content=<a href='/topic/show?id=38e014162e2' target=_blank style='color:#2F92EE;'>#Pharmacol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14162, encryptionId=38e014162e2, topicName=Pharmacol)], attachment=null, authenticateStatus=null, createdAvatar=, 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
  10. 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11:30:41 CST 2021, time=2021-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032869, encodeId=1f16103286972, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Sat Apr 10 23:30:41 CST 2021, time=2021-04-10, status=1, ipAttribution=)]
    2021-04-10 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

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