Department of Child and Adolescent Psychology and Psychiatry, Erasmus MC, University Medical Center Rotterdam-Sophia Children's Hospital, PO Box 2040, Rotterdam, CA 3000, the Netherlands; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA; Center for Precision Psychiatry, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA.
Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
Dev Cogn Neurosci. 2024 Dec;70:101443. doi: 10.1016/j.dcn.2024.101443. Epub 2024 Sep 23.
Thanks to methodological advances, large-scale data collections, and longitudinal designs, psychiatric neuroimaging is better equipped than ever to identify the neurobiological underpinnings of youth mental health problems. However, the complexity of such endeavors has become increasingly evident, as the field has been confronted by limited clinical relevance, inconsistent results, and small effect sizes. Some of these challenges parallel those historically encountered by psychiatric genetics. In past genetic research, robust findings were historically undermined by oversimplified biological hypotheses, mistaken assumptions about expectable effect sizes, replication problems, confounding by population structure, and shared biological patterns across disorders. Overcoming these challenges has contributed to current successes in the field. Drawing parallels across psychiatric genetics and neuroimaging, we identify key shared challenges as well as pinpoint relevant insights that could be gained in psychiatric neuroimaging from the transition that occurred from the candidate gene to (post) genome-wide "eras" of psychiatric genetics. Finally, we discuss the prominent developmental component of psychiatric neuroimaging and how that might be informed by epidemiological and omics approaches. The evolution of psychiatric genetic research offers valuable insights that may expedite the resolution of key challenges in psychiatric neuroimaging, thus potentially moving our understanding of psychiatric pathophysiology forward.
由于方法学的进步、大规模数据集的收集和纵向设计,精神病神经影像学比以往任何时候都更有能力确定青年心理健康问题的神经生物学基础。然而,随着该领域面临临床相关性有限、结果不一致和效应量小等问题,这种复杂性变得越来越明显。其中一些挑战与精神病遗传学中历史上遇到的挑战相似。在过去的遗传研究中,历史上由于过于简单的生物学假设、对预期效应大小的错误假设、复制问题、群体结构混杂以及跨疾病的共同生物学模式,强有力的发现被削弱了。克服这些挑战为该领域目前的成功做出了贡献。通过在精神病遗传学和神经影像学之间进行类比,我们确定了关键的共同挑战,并指出了从候选基因到(后)全基因组“时代”的精神病遗传学的转变中,可以从精神病遗传学中获得的相关见解。最后,我们讨论了精神病神经影像学中突出的发展成分,以及流行病学和组学方法如何为其提供信息。精神病遗传学研究的发展提供了有价值的见解,这可能会加速解决精神病神经影像学中的关键挑战,从而有可能推动我们对精神病理生理学的理解向前发展。