[Developmental disorders].
Developmental disorders, which are usually diagnosed in infancy, childhood, or adolescence, include mental retardation, learning disorders, motor skills disorder, communication disorders, pervasive developmental disorders (PDD), attention-deficit hyperactivity disorder (ADHD), and tic disorders. Epidemiological studies have indicated that these disorders are characterized not only by high heritability (e.g., 0.80 for PDD) but also by their shared genetic etiology. Furthermore, retrospective or prospective longitudinal studies have revealed that adult psychiatric disorders are often preceded either by their juvenile counterparts (homotypic continuity) or by different disorders (heterotypic continuity). Recent genetic studies have detected copy number variants (CNVs; e.g., deletions on 1q21.1, 3q29, and 22q.11.21 and duplications on 16p11.2) as shared genetic factors for PDD, mental retardation, and schizophrenia. While these CNVs are generally very rare (<1%), their effect size is much larger than that of single nucleotide polymorphisms. Although the mechanism by which CNVs cause these abnormalities remains unclear, pleiotropic effect of CNVs may provide insights into the high rate of comorbidity among developmental disorders and heterotypic continuity between developmental disorders and adult disorders. In addition, longitudinal neuroimaging studies have provided evidence for irregularities in the typical trajectories in developmental disorders. For instance, retarded cortical development is identified in ADHD in cortical trajectory, and early acceleration of brain growth is identified in PDD. Finally, we outlined several research topics as the future direction for investigation of developmental disorders: a longitudinal clinical study in subjects with specific disorder-related CNVs; detailed analysis of genetic factors relevant to developmental disorders, including smaller CNVs and INDELs; and functional analysis of genetic factors by using induced pluripotent stem cell technology or non-human primate animal models.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagaya, Japan.
Itaru
I
Kushima
Takashi
T
Okada
Norio
N
Ozaki
D000328:Adult; D002648:Child; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D003952:Diagnostic Imaging; D006801:Humans