Neuropsychol Rev. 2009 Sep;19(3):385-98. doi: 10.1007/s11065-009-9114-1.
In this review, we describe neuropsychological and brain imaging findings in the early stages of psychosis and schizophrenia. We focus on recent clinical high-risk studies and consider whether the evidence supports these as 'endophenotypes' of a vulnerability to the illness or as 'biomarkers' of illness onset and transition. The findings suggest that there are a number of processes at psychosis onset that may represent biomarkers of incipient illness. These neurobiological indices particularly implicate the integrity of frontal and temporal cortices, which may or may not be related to the genetics of psychosis (i.e. potential 'endophenotypes'). However, these brain regions are dynamically changing during normal maturation, meaning that any putative neurobiological markers identified at the earliest stages of illness may be relatively unstable.We suggest that, while such measures maybe readily identified as potential neurobiological markers of established illness, they are inconsistent at (or around) the time of illness onset when assessed cross-sectionally. Instead,identification of more valid risk markers may require longitudinal assessment to ascertain normal or abnormal trajectories of neurodevelopment. Accordingly, we assert that the current conceptualisations of potential biomarkers and/or 'endophenotypes' for schizophrenia may need to be reconsidered in the context of normal and abnormal brain maturational processes at the time of onset of psychotic disorders.
在这篇综述中，我们描述了精神病和精神分裂症早期的神经心理学和脑成像研究结果。我们专注于最近的临床高风险研究，并考虑这些研究结果是否支持这些结果作为疾病易感性的“内表型”或作为疾病发作和转变的“生物标志物”。研究结果表明，在精神病发作时有许多可能代表疾病初期的生物标志物的过程。这些神经生物学指标特别涉及额叶和颞叶皮质的完整性，这些完整性可能与精神病的遗传学（即潜在的“内表型”）有关，也可能无关。然而，这些脑区在正常成熟过程中是动态变化的，这意味着在疾病的最早阶段识别出的任何潜在的神经生物学标志物可能相对不稳定。我们认为，虽然这些措施可以很容易地被识别为既定疾病的潜在神经生物学标志物，但在横断面评估时，它们在疾病发作时（或接近时）并不一致。相反，确定更有效的风险标志物可能需要进行纵向评估，以确定神经发育的正常或异常轨迹。因此，我们断言，在精神障碍发作时，正常和异常大脑成熟过程的背景下，需要重新考虑精神分裂症潜在生物标志物和/或“内表型”的当前概念。
