Children with high CBCL-DP values are at risk for later severe, psychiatric symptomatology. The different developmental trajectories suggest that the CBCL-DP is not simply an early manifestation of a single disease process but might rather be an early developmental risk marker of a persisting deficit of self-regulation of affect and behavior.

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Our results support a psychological perspective for the development of psychiatric symptoms in PKU. Thus, optimizing medical treatment necessary to prevent brain damage should be accompanied by psychiatric monitoring and psychological support for the families.

Research in animals and first results in adolescents have indicated that genetic variation in the corticotropin-releasing hormone receptor 1 (CRHR1) is associated with heavy alcohol consumption related to stress. The purpose of this study was to determine whether two haplotype-tagging single nucleotide polymorphisms covering the CRHR1 gene (rs242938, rs1876831) interact with stressful life events affecting age at drinking initiation and alcohol consumption in young adults. Participants were drawn from the Mannheim Study of Children at Risk, an epidemiological cohort study following the outcome of early risk factors. Structured interviews were administered to 270 participants (125 males, 145 females) at 15 yr and 19 yr to assess age at first drinking and, at 19 yr, to assess current drinking and recent stressful life events. Life events during childhood and child psychopathology were measured using standardized parent interviews. Results indicated that, even after control for a range of confounders, higher numbers of stressful life events prior to drinking onset were significantly related to earlier age at first drink only among homozygotes for the C allele of rs1876831. Earlier age at drinking onset was significantly associated with higher consumption levels in 19-yr-olds. Furthermore, homozygotes of the rs1876831 C allele as well as carriers of the rs242938 A allele, when exposed to stress, exhibited significantly higher drinking activity than carriers of other alleles. These findings extend previous reports by demonstrating that the CRHR1 gene and stressful life events interact to predict both drinking initiation in adolescence and progression of heavy alcohol use in young adulthood.

BackgroundClock genes govern circadian rhythms and shape the effect of alcohol use on the physiological system. Exposure to severe negative life events is related to both heavy drinking and disturbed circadian rhythmicity. The aim of this study was 1) to extend previous findings suggesting an association of a haplotype tagging single nucleotide polymorphism of PER2 gene with drinking patterns, and 2) to examine a possible role for an interaction of this gene with life stress in hazardous drinking.MethodsData were collected as part of an epidemiological cohort study on the outcome of early risk factors followed since birth. At age 19 years, 268 young adults (126 males, 142 females) were genotyped for PER2 rs56013859 and were administered a 45-day alcohol timeline follow-back interview and the Alcohol Use Disorders Identification Test (AUDIT). Life stress was assessed as the number of severe negative life events during the past four years reported in a questionnaire and validated by interview.ResultsIndividuals with the minor G allele of rs56013859 were found to be less engaged in alcohol use, drinking at only 72% of the days compared to homozygotes for the major A allele. Moreover, among regular drinkers, a gene x environment interaction emerged (p = .020). While no effects of genotype appeared under conditions of low stress, carriers of the G allele exhibited less hazardous drinking than those homozygous for the A allele when exposed to high stress.ConclusionsThese findings may suggest a role of the circadian rhythm gene PER2 in both the drinking patterns of young adults and in moderating the impact of severe life stress on hazardous drinking in experienced alcohol users. However, in light of the likely burden of multiple tests, the nature of the measures used and the nominal evidence of interaction, replication is needed before drawing firm conclusions.