Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit͞hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD. Dopamine plays an important role in normal attention (1) and disorders of attention (2, 3). Recently, this role of dopamine has stimulated molecular genetic studies (4) of attention deficit͞ hyperactivity disorder (ADHD), the most prevalent psychiatric disorder of childhood recognized in the United States. The dopamine receptor genes (5) have been investigated in other psychiatric disorders (e.g., schizophrenia; see refs. 6 and 7), and the background from this work set the stage for our molecular genetic investigations of ADHD.In our program of research, we adopted a candidate gene approach, focusing on the dopamine receptor D4 (DRD4) gene on chromosome 11p15.5. This gene has a polymorphism in a coding region-a variable number of tandem repeats of a 48-base pair sequence in exon 3 (8) that codes for variation in the third intracellular loop of the D4 receptor, which may have functional significance. In vitro studies suggest that the receptor encoded by the DRD4 7-repeat allele may be subsensitive to endogenous dopamine compared with the receptor encoded by the 2-repeat allele (9), although this apparently is not due merely to the length of the third intracellular loop (10). Initially, in our clinical studies we used population-based (11) and family-based (12) association designs, which suggested that the DRD4 7-repeat allele is associated with ADHD, but with a small relative risk (about 1.5). A review of the recent literature (4) revealed that two independent groups have confirmed this association in children (13,14), but one group did not (15). The pattern of replication has held up in several other case studies not yet published.The presence of the DRD4, 7-repeat allele is not a necessary condition (about half of the ADHD cases did not have a 7-repeat allele) (11, 12) or a sufficient condition (about 20% of ethnically matched control subjects d...

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Background: Child maltreatment can cause significant physical and psychological problems. The present study aimed to investigate the prevalence and determinants of child maltreatment in Guangzhou, China, where such issues are often considered a taboo subject.