Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene-environment study.

To investigate similarities and differences in the serotonergic diathesis for mood disorders and suicide attempts, we conducted a study in a cohort followed longitudinally for 22 years. A total of 1255 members of this cohort, which is representative of the French-speaking population of Quebec, were investigated. Main outcome measures included (1) mood disorders (bipolar disorder and major depression) and suicide attempts by early adulthood; (2) odds ratios and probabilities associated with 143 single nucleotide polymorphisms in 11 serotonergic genes, acting directly or as moderators in gene-environment interactions with childhood sexual or childhood physical abuse (CPA), and in gene-gene interactions; (3) regression coefficients for putative endophenotypes for mood disorders (childhood anxiousness) and suicide attempts (childhood disruptiveness). Five genes showed significant adjusted effects (HTR2A, TPH1, HTR5A, SLC6A4 and HTR1A). Of these, HTR2A variation influenced both suicide attempts and mood disorders, although through different mechanisms. In suicide attempts, HTR2A variants (rs6561333, rs7997012 and rs1885884) were involved through interactions with histories of sexual and physical abuse whereas in mood disorders through one main effect (rs9316235). In terms of phenotype-specific contributions, TPH1 variation (rs10488683) was relevant only in the diathesis for suicide attempts. Three genes contributed exclusively to mood disorders, one through a main effect (HTR5A (rs1657268)) and two through gene-environment interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)). Childhood anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders, nor did childhood disruptiveness mediate the effects of TPH1 on suicide attempts. Of the serotonergic genes implicated in mood disorders and suicidal behaviors, four exhibited phenotype-specific effects, suggesting that despite their high concordance and common genetic determinants, suicide attempts and mood disorders may also have partially independent etiological pathways. To identify where these pathways diverge, we need to understand the differential, phenotype-specific gene-environment interactions such as the ones observed in the present study, using suitably powered samples.

The influence of genetic factors and life stress on depression among adolescent girls.

BACKGROUND: The possible causes of greater depression among adolescent girls were investigated by examining variation in the influence of genetic and environmental risk factors among 182 prepubertal female, 237 prepubertal male, 314 pubertal female, and 171 pubertal male twin pairs from the Virginia Twin Study of Adolescent Behavioral Development. OBJECTIVES: To compare the trajectory of depressive symptoms among boys and girls from childhood to adolescence; to analyze the role of genetic, shared, and unique environmental factors in depression among prepubertal and pubertal male and female twins; and to investigate a possible link between liability to depression and one salient index of the child's environment: past-year life events. METHODS: Child-reported depression was assessed using the Child and Adolescent Psychiatric Interview and ratings of past-year life events and pubertal status obtained by maternal questionnaire and interview, respectively. RESULTS: The impact of life events on depression was particularly evident in the adolescent girls. The results from model fitting indicate increased heritability for depression in this group, and its long-term consistency was mediated primarily by latent genetic factors. Model fitting also showed that at least part of the liability to depression and to life events can be linked to a common set of genes in the adolescent girls, and there is a notable developmental increase in the genetic variance for life events. CONCLUSIONS: The greater heritability for depression in pubertal girls, its genetic mediation over time, and the increase in genetic variance for life events may be one possible explanation for the emergence of increased depression among pubertal girls and its persistence through adolescence.

Personal and familial characteristics of resilient sons of male alcoholics.

This study compared sons of male alcoholics (SOMAs) who had no problems with those who were abusing substances, those who had school problems, those who were delinquent and those who were multiproblem. Corresponding groups of non-SOMAs were also included. Groups were compared at ages 6, 10, 12 and 14 years on teacher- and peer-rated aggressiveness, hyperactivity, inattention, anxiety and prosociality; parent-rated temperament; parents' disciplinary practices; school performance; family socio-economic status; self-reported substance (ab)use and delinquency; and school performance (from school records). Differences between SOMAs and non-SOMAs were small. According to teachers and peers, no problem SOMAs and non-SOMAs were less aggressive-oppositional, inattentive and hyperactive than problem SOMAs and non-SOMAs. These effects differed as a function of age, however. Also, no problem SOMAs and non-SOMAs performed better in school than boys in the problem groups. We discuss the relevance of these findings for identifying factors that render children resilient and for early screening to select truly at risk SOMAs for prevention programs.

Recovering components of variance from differential ratings of behavior and environment in pairs of relatives.

Evidence from genetic studies underscores the importance of examining the within-family environment and its association with genetic differences among siblings in influencing children's development. Simulated and published data are analyzed to illustrate the contribution of genetic and environmental factors to differential ratings of behavioral and environmental differences within families. Comparison of the mean differential ratings within various types of pairs is not an adequate index of the underlying genetic and environmental variance components. However, on the assumption that differential ratings are a linear function of underlying trait differences, it is a simple matter to recover within-family statistics that offer a more legitimate basis for estimating genetic and environmental components of variance within families. The assumptions and dangers underlying any analysis of differential ratings are noted.

Paternal alcoholism, paternal absence and the development of problem behaviors in boys from age six to twelve years.

OBJECTIVE: The purpose of this study was to examine the association between paternal alcoholism, paternal absence, and the development and stability of behavioral problems in boys, from kindergarten to the end of elementary school. METHOD: A sample of 642 boys originating from low socioeconomic status (SES) families was used. Paternal alcoholism was established using the Short Michigan Alcohol Screening Test. Behavioral problems (opposition, hyperactivity, inattention, physical aggression and anxiety) were assessed by teachers' reports when the boys were 6 and 12 years old. Four groups of boys were created on the basis of paternal alcoholism (nonalcoholic, alcoholic) and family structure (intact families, nonintact/father-absent families). RESULTS: Consistent with personality theories of alcoholism, results showed that a propensity for physical aggression and low anxiety best distinguished sons of male alcoholics (SOMAs) from non-SOMAs at both ages (6 and 12 years), even when SES was controlled. In addition, SOMAs were more oppositional and hyperactive than non-SOMAs at both ages. No significant effects were observed for family structure or age, or an interaction between these factors and paternal alcoholism in the multivariate analysis. CONCLUSIONS: The results suggest that problem behaviors in SOMAs begin early and persist over time, and that paternal alcoholism and family structure are not associated with changes in boys' behaviors between kindergarten and the end of elementary school in this population, at least in the sample used.

Tobacco, alcohol and drug use in eight- to sixteen-year-old twins: the Virginia Twin Study of Adolescent Behavioral Development.

OBJECTIVE: This study reports prevalences of lifetime and current alcohol, tobacco and drug use in adolescents; examines associations between substance use and a number of putative risk factors; and estimates the contribution of genetic, shared and unique environmental influences on substance use. METHOD: Substance use data were collected using the Child and Adolescent Psychiatric Assessment on a population sample of 1,412 male and female monozygotic and dizygotic twin pairs, aged 8 through 16, from the Virginia Twin Study of Adolescent Behavioral Development. RESULTS: Heritabilities were estimated to be 84% and 82% for liability to lifetime and current tobacco use, respectively. For alcohol use the role of genes and environment varied according to the context of reporting. Liability to lifetime alcohol use was estimated to be under environmental control, with 71% of the variation shared by members of a twin pair and 29% unique to individual twins. Lifetime alcohol use without the permission of a parent or guardian and current use of alcohol were predominantly explained by genetic factors (h2 = 72% and 74%). The role of genetic factors increased and that of unique environmental factors decreased with increasing severity of alcohol use. Lifetime use of any drug showed a heritability of 45%, with the shared environment accounting for 47% of the variation. Shared environmental factors explained most of the variation in marijuana use. CONCLUSIONS: Genetic factors explained a significant proportion of the variation in the use of tobacco, alcohol and other drugs. Shared environmental factors contributed significantly to lifetime alcohol use and other drug use.

Hemodialysis treatment of methanol intoxication.

Hemodialysis was undertaken to treat methanol intoxication in a patient with intravascular hemolysis, myoglobinuria, systemic acidosis, renal insufficiency, retinal abnormalities, and a blood methanol level of 400 mg/dl, 29 h after methanol ingestion. Sixteen hours of treatment were required to achieve safe blood levels. Calculated methanol removal was 218 g, or 73% of the ingested dose, and extraordinarily large volumes of ethanol were required to maintain blood levels greater than 100 mg/dl. All the manifestations of methanol poisoning were reversed and there were no permanent sequelae. It is concluded that, if methanol levels remain high, even significantly delayed institution of hemodialysis can be beneficial. The treatment may need to be quite prolonged, and the amount of ethanol administered should be individualized according to the patient's blood levels.

Assessment of genetic and environmental influences on differential ratings of within-family experiences and relationships in twins.

BACKGROUND: Although there is evidence that genetic factors influence individual differences in environmental risk exposure, there are few findings on genetic effects on differential parenting. The present study sought to examine this issue. METHODS: The sample comprised 1,117 pairs of like-sex male and female twins, aged 8-16 years, and their parents, recruited from the school population of Virginia. Differential ratings of the within-family experiences were provided by the Twin Inventory of Relationships and Experiences (TIRE). RESULTS: Dimensions describing the within-family environment based on differential ratings contrasting the twins with one another, were influenced, to an approximately equal extent, by both genetic and environmental factors. CONCLUSIONS: The findings suggest that genetic differences between like-sex siblings lead them to experience their family environment differently, but also that environmental influences significantly affect interactions within the family.

Parietal pleural changes in empyema: appearances at CT.

The parietal pleura bordering pleural space collections was analyzed with computed tomography (CT) in 35 patients with thoracic empyema, 30 patients with malignant effusion, and 20 patients with transudatory effusion. Enhancement of the parietal pleura was present in 96% of the 25 patients with empyema who underwent contrast material-enhanced examinations. Of the 35 patients with empyema, 86% showed thickening of the parietal pleura, 60% showed thickening of the extrapleural subcostal tissues, and 35% showed increased attenuation of the extrapleural fat. None of the 20 patients with transudatory effusion showed these findings. Of the 30 patients with malignant effusion, eight patients (27%) showed chest wall changes similar to those of the patients with empyema. However, two-thirds of these patients had a recognized superimposed complication (ie, sclerotherapy). Contrast-enhanced CT appears to be sensitive to chest wall changes in patients with empyema. CT study of the parietal pleura may help suggest occult pleural space infections and may influence therapeutic decisions that vary with the stage of empyema.