Neurophysiological endophenotypes across bipolar and schizophrenia psychosis.
Neurophysiological endophenotypes across bipolar and schizophrenia psychosis.
复制标题
DOI：
10.1093/schbul/sbn049
复制
发表时间：
2007-11
影响因子：
6.6
通讯作者：
G. Thaker
中科院分区：
文献类型：
--
作者：
G. Thaker
寻找世界上两种主要的精神障碍，精神分裂症和双相情感障碍I（BP-I）的易感基因是非常困难的，尽管有证据表明这两种疾病都是高度遗传的。这种困难是由于这些疾病的复杂性和多因素性。它们包括几种中间表型，其中一些在2种精神病性障碍中重叠，共同和/或相互作用产生临床表现。过去几十年的研究已经确定了精神分裂症的几种神经生理缺陷，这些缺陷经常发生在精神病发作之前。这些异常包括平滑追踪眼球运动、P50感觉门控、前脉冲抑制、P300、负性失配和神经同步性。有证据表明，许多这些生理缺陷是彼此不同的。它们是稳定的，大多数独立于症状状态和药物（有一些例外），也可以在非患病亲属中观察到。这表明是家族性的，也许是遗传性的。在BP-I先证者及其亲属中也观察到一些缺陷，但程度较轻。这些生理指标的缺陷可能代表了指示基因（和/或环境因素）的小影响的中间表型。在遗传学研究中使用这些措施可能有助于寻找精神病易感基因，并澄清两种主要精神病性障碍共享病因病理生理学的程度。尽管有大量的工作描述了精神障碍的神经生理学指标，但挑战仍然存在：许多神经生理学表型仍然相对复杂，并且与低遗传性估计相关。需要进一步完善这些生理表型，以确定特定的潜在生理缺陷，从而提高其遗传力估计。这些神经生理学缺陷在何种程度上是独特的或在BP-I和精神分裂症之间重叠尚不清楚。最后，先证者及其亲属的神经生理缺陷的临床和功能后果没有得到很好的描述。
The search for liability genes of the world's 2 major psychotic disorders, schizophrenia and bipolar disorder I (BP-I), has been extremely difficult even though evidence suggests that both are highly heritable. This difficulty is due to the complex and multifactorial nature of these disorders. They encompass several intermediate phenotypes, some overlapping across the 2 psychotic disorders that jointly and/or interactively produce the clinical manifestations. Research of the past few decades has identified several neurophysiological deficits in schizophrenia that frequently occur before the onset of psychosis. These include abnormalities in smooth pursuit eye movements, P50 sensory gating, prepulse inhibition, P300, mismatch negativity, and neural synchrony. Evidence suggests that many of these physiological deficits are distinct from each other. They are stable, mostly independent of symptom state and medications (with some exceptions) and are also observed in non-ill relatives. This suggests a familial and perhaps genetic nature. Some deficits are also observed in the BP-I probands and to a lesser extent their relatives. These deficits in physiological measures may represent the intermediate phenotypes that index small effects of genes (and/or environmental factors). The use of these measures in genetic studies may help the hunt for psychosis liability genes and clarify the extent to which the 2 major psychotic disorders share etio-pathophysiology. In spite of the rich body of work describing these neurophysiological measures in psychotic disorders, challenges remain: Many of the neurophysiological phenotypes are still relatively complex and are associated with low heritability estimates. Further refinement of these physiological phenotypes is needed that could identify specific underlying physiological deficits and thereby improve their heritability estimates. The extent to which these neurophysiological deficits are unique or overlap across BP-I and schizophrenia is unclear. And finally, the clinical and functional consequences of the neurophysiological deficits both in the probands and their relatives are not well described.