In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.
In memory of Professor Iain Wilkinson: cognitive and neuroimaging endophenotypes in a consanguineous schizophrenia multiplex family.
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DOI：
10.1017/s0033291721005250
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发表时间：
2023-05
影响因子：
6.9
通讯作者：
Woodruff, Peter W.
中科院分区：
文献类型：
--
作者：
Wilkinson, Iain D.;Mahmood, Tariq;Yasmin, Sophia Faye;Tomlinson, Anneka;Nazari, Jamshid;Alhaj, Hamid;el Din, Soumaya Nasser;Neill, Joanna;Pandit, Chhaya;Ashraf, Shahzad;Cardno, Alastair G.;Clapcote, Steven J.;Inglehearn, Chris F.;Woodruff, Peter W.
精神分裂症内表型可能有助于阐明遗传风险变异的功能影响，在多重影响的血缘家庭，分离隐性风险等位基因的大效应大小。我们研究了精神分裂症的风险基因座之间的关联，涉及染色体13 q22 -31上的6.1 Mb纯合区域在一个血缘的多重家庭和认知功能，血液动力学反应和白色物质的完整性，使用神经影像学。我们对四名受影响的家庭成员进行了CANTAB神经心理测试（所有风险基因座纯合子），10名未受影响的家庭成员（7个纯合子和3个杂合子）和10个健康志愿者，并在n-back工作记忆任务期间测试fMRI上的神经元反应，和白色物质的完整性的扩散张量成像（DTI）对四个受影响的和六个未受影响的家庭成员（四个纯合子和两个杂合子）和三个健康志愿者。对于认知比较，我们使用线性混合模型（Kruskal-Wallis）检验，然后使用Bonferroni调整的posthoc Dunn成对检验。对于fMRI分析，我们对超过p < 0.05校正阈值的体素进行计数。DTI分析是观察性的。与健康对照组相比，精神分裂症家族成员和风险单倍型纯合子的未受影响的家族成员表现出注意力（p <0.01）和工作记忆缺陷（p < 0.01）;神经激活偏侧性偏向右侧前额叶皮层（体素达到p < 0.05，校正），并观察到前扣带皮层和左侧背外侧前额叶皮层的各向异性分数较低。在这个家族中，13 q风险基因座的纯合性与认知功能受损、白色物质完整性和神经激活偏侧性改变相关。
Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging. We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational. Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex. In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.
影响因子：
3.7
作者：
Whalley HC;Dimitrova R;Sprooten E;Dauvermann MR;Romaniuk L;Duff B;Watson AR;Moorhead B;Bastin M;Semple SI;Giles S;Hall J;Thomson P;Roberts N;Hughes ZA;Brandon NJ;Dunlop J;Whitcher B;Blackwood DH;McIntosh AM;Lawrie SM
通讯作者：
Lawrie SM