Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
J Psychiatr Res. 2011 Apr;45(4):519-25. doi: 10.1016/j.jpsychires.2010.08.001. Epub 2010 Aug 21.
In previous studies of the present patients with schizophrenia, aberrant tyrosine transport across the fibroblast membrane was found. A low K(m), a kinetic factor indicating high affinity between tyrosine and the binding site at the cell membrane, was found to be associated with poor cognitive functions in patients. The present study aimed at investigating possible relationships between patients with schizophrenia and their first-degree relatives in aberrant tyrosine transport indicating that it may be a biological marker for the genetic susceptibility.
Thirty-three parents, 13 fathers and 20 mothers, from 23 families with a schizophrenic patient agreed to enter the study. They underwent skin biopsies for fibroblast cultivation, neuropsychological and psychiatric investigations and were classified as family history positive or negative. Tyrosine transport kinetics (K(m) and V(max)) were calculated from in vitro trials of gradients of extracellular tyrosine concentrations in fibroblast cultures.
An association between patients with schizophrenia and their mothers were found for a low K(m) indicating maternal inheritance. Mothers displaying a low K(m) performed worse on the neuropsychological tests compared to mothers with normal K(m). Corresponding relationships between a low K(m) and neurocognitive dysfunction had previously been found for the patients.
An aberrant tyrosine transport across plasma membrane may constitute a biological marker for an endophenotype within the schizophrenia spectrum with low cognitive functioning. A plausible mode for genetic transmission is maternal inheritance.
在对本研究中精神分裂症患者的先前研究中,发现成纤维细胞膜上的酪氨酸转运出现异常。发现低 K(m)(一种动力学因素,表明酪氨酸与细胞膜结合位点之间的高亲和力)与患者认知功能差有关。本研究旨在研究精神分裂症患者及其一级亲属之间的酪氨酸转运异常,表明其可能是遗传易感性的生物学标志物。
23 个有精神分裂症患者的家庭中,有 33 位父母(13 位父亲和 20 位母亲)同意参与研究。他们接受了皮肤活检以培养成纤维细胞,进行神经心理学和精神病学调查,并分为有家族史阳性或阴性。从成纤维细胞培养中细胞外酪氨酸浓度梯度的体外试验中计算酪氨酸转运动力学(K(m)和 V(max))。
发现精神分裂症患者与其母亲之间存在低 K(m),表明存在母系遗传。表现出低 K(m)的母亲在神经心理学测试中的表现比 K(m)正常的母亲差。先前发现 K(m)低与神经认知功能障碍之间存在对应关系。
质膜上的酪氨酸转运异常可能构成精神分裂症谱系中认知功能低下的内表型的生物学标志物。遗传传递的合理模式是母系遗传。