Childhood adversity, characterized by the presence of sexual and physical abuse, is a global problem of significant proportions.^1,2 Epidemiologic studies^3-5 indicate prevalence rates for all forms of childhood sexual abuse and physical abuse ranging from 11% to 35%.Childhood sexual abuse and childhood physical abuse are among the strongest predictors of psychiatric pathology and severity of clinical course, including suicide.^2,4-14 The influence of childhood sexual abuse and childhood physical abuse on psychological development is thought to be mediated directly by changes in cognitive processing of threatening stimuli,^15-18 resulting in enhanced negative affect to daily life stressors.¹⁹ Although there is a clear link between early-life adversity and psychopathology, very little is known about the molecular mechanisms responsible for the long-lasting behavioral consequences of childhood abuse. Significant insight into this critical issue comes primarily from animal studies and from recent translation research in humans investigating epigenetic mechanisms.^20,21

Background: It is unclear whether the association between impulsive-aggressive behaviours and suicide exists across different ages.Method: Via psychological autopsy, we examined a total of 645 subjects aged 11–87 years who died by suicide. Proxy-based interviews were conducted using the SCID-I & SCID-II or K-SADS interviews and a series of behavioural and personality-trait assessments. Secondarily, 246 living controls were similarly assessed.Results: Higher levels of impulsivity, lifetime history of aggression, and novelty seeking were associated with younger age of death by suicide, while increasing levels of harm avoidance were associated with increasing age of suicide. This effect was observed after accounting for age-related psychopathology (current and lifetime depressive disorders, lifetime anxiety disorders, current and lifetime substance abuse disorders, psychotic disorders and cluster B personality disorders). Age effects were not due to the characteristics of informants, and such effects were not observed among living controls. When directly controlling for major psychopathology, the interaction between age, levels of impulsivity, aggression and novelty seeking predicted suicide status while controlling for the independent contributions of age and these traits.Conclusions: Higher levels of impulsive-aggressive traits play a greater role in suicide occurring among younger individuals, with decreasing importance with increasing age.

A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected second, third, and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated, given pedigree structures, and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (P = 0.02 after correcting for multiple tests). Family-based designs such as the one used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders.