Clinical genomic psychiatry comes of age in the evaluation and treatment of developmental disabilities: is our nation prepared to make the benefits available to all who need them?
Clinical genomic psychiatry comes of age in the evaluation and treatment of developmental disabilities: is our nation prepared to make the benefits available to all who need them?
复制标题
临床基因组精神病学在评估和治疗发育障碍方面已经成熟：我们的国家是否准备好为所有需要它们的人提供福利？
DOI：
10.1007/s11920-007-0073-z
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发表时间：
2007
影响因子：
6.7
通讯作者：
Cubells,JosephF
中科院分区：
文献类型：
--
作者：
Cubells,JosephF
In 2001, when simultaneous issues of Nature and Science reported the (almost) complete sequence of the human genome, many writers in the popular and professional literature proclaimed that this historic achievement would revolutionize medical practice. Without question, the Genome Project has radically altered the world of biomedical research forever. Techniques that sprang directly from the Project, such as whole-genome comparative hybridization, have enabled truly revolutionary discoveries. For example, it is now clear that local variations in the presence or number of large stretches of identical or highly similar sequence, now referred to as copy-number variants, constitute a previously unappreciated form of polymorphic genetic variation in the human population. Thus, at the level of research, the enthusiasm that greeted completion of the Project has already been, and will continue to be, born out in spades. Similarly, some fields of clinical medicine, most notably oncology, are already applying new and more effective diagnostic and therapeutic methods enabled by modern genomics, such as gene expression profile-guided chemotherapy. How is the field of genomics going to impact clinical psychiatry? My hunch is that for many of the complex adult disorders we manage, such as schizophrenia and depression, the major role of genomics will remain in research for quite some time. Although the benefits of such research are certain to be enormous, they will most probably derive from genomics-based advances in our understanding of human neurobiology rather than from direct application of genomic tools in the clinic. For example, persuasive evidence now implicates several novel genes (DISC1, NRG1, DTNBP1, and RGS4, to name a few) as important contributors to risk for schizophrenia in some families and individuals. These discoveries have propelled unanticipated directions of investigation into pathogenesis (having little or nothing to do with dopamine!) that promise to produce new preventive and therapeutic strategies. Many aspects of the emerging pattern of genetic discoveries also add support to the pharmacologic evidence implicating glutamate-mediated neurotransmission as an essential target for therapeutics. Finally, incontrovertible evidence supporting locus heterogeneity in schizophrenia strongly suggests that Blueler was correct when he inferred that dementia praecox represented a “group of schizophrenias.” The rapid advances in psychiatric research catalyzed by the Genome Project suggest that at some point, genomics will be directly applicable to clinical psychiatry. Are there examples of such applications in current practice? In my view, the articles in this issue make a compelling case that genomic approaches have begun to establish a role in the clinical evaluation and treatment of developmental disabilities. We learn in this issue that multiple genetically defined developmental disorders are associated with distinct behavioral phenotypes. Features of autism have now been documented in several genetically defined chromosomal disorders (see Martin and Ledbetter’s review), including Fragile X syndrome (Martin and Ledbetter), trisomy 21 (Visootsak and Sherman), Prader-Willi syndrome (Dimitropoulos and Schultz), and 22q11 deletion syndrome (22q11DS; Ousley et al.). The behavioral profile of Williams syndrome (Paterson and Schultz) highlights dramatically that autistic features are not invariable artifacts of intellectual disability or disordered brain development. Patients with the latter disorder, in marked contrast to
