Heinz A, Mascarell Maricic L, Liu S, Walter H, Schumann G, Beck A
Klinik für Psychiatrie und Psychotherapie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.
Psychiatrische Universitätsklinik der Charité im St. Hedwig Krankenhaus, Berlin, Deutschland.
Nervenarzt. 2021 Mar;92(3):228-233. doi: 10.1007/s00115-020-01034-4. Epub 2020 Nov 27.
Genetic risk factors for major mental disorders identified in psychiatric research show a substantial overlap. Therefore, it has been suggested that neurobiological research should focus on intermediate phenotypes that reflect shared aspects of different mental disorders due to overlapping genetic effects and environmental factors. Longitudinal studies are required to assess the interaction between genetic variability and modifying environmental factors and to investigate the effects on intermediate phenotypes and (mediated by them) on the expression of individual mental disorders.
Discussion of the possibilities and limitations of longitudinal cohort studies using the IMAGEN study as an example.
The results of the European IMAGEN study are presented with a focus on addiction.
The longitudinal assessments of the IMAGEN cohort revealed that neuroimaging data indicating a low activation of the dopaminergic reinforcement system detected at the age of 14 years are predictive for increased drug use. In addition to genetic factors, environmental influences such as maternal smoking during pregnancy were correlated with this low activation.
Longitudinal neurobiological basic research can validate the effects of candidate genes and reveal relevant environmental factors. Relevant modifiable factors indicated by the IMAGEN study and related datasets include drug use during pregnancy, trauma and other experiences of violence, social disadvantage and exclusion.
精神病学研究中确定的主要精神障碍的遗传风险因素显示出大量重叠。因此，有人建议神经生物学研究应关注中间表型，这些表型反映了由于重叠的遗传效应和环境因素导致的不同精神障碍的共同方面。需要进行纵向研究来评估遗传变异性与环境修饰因素之间的相互作用，并研究其对中间表型以及（通过中间表型介导）对个体精神障碍表达的影响。
以IMAGEN研究为例，讨论纵向队列研究的可能性和局限性。
介绍了欧洲IMAGEN研究的结果，重点是成瘾问题。
IMAGEN队列的纵向评估显示，14岁时检测到的多巴胺能强化系统激活水平较低的神经影像学数据可预测药物使用增加。除遗传因素外，孕期母亲吸烟等环境影响也与这种低激活有关。
纵向神经生物学基础研究可以验证候选基因的作用，并揭示相关环境因素。IMAGEN研究及相关数据集表明的相关可改变因素包括孕期药物使用、创伤及其他暴力经历、社会劣势和排斥。
