Anne L. Glowinski

Suicide attempts in an adolescent female twin sample.

OBJECTIVE To examine suicide attempts in an epidemiologically and genetically informative youth sample. METHOD 3,416 Missouri female adolescent twins (85% participation rate) were interviewed from 1995 to 2000 with a telephone version of the Child Semi-Structured Assessment for the Genetics of Alcoholism, which includes a detailed suicidal behavior section. Mean age was 15.5 years at assessment. RESULTS At least one suicide attempt was reported by 4.2% of the subjects. First suicide attempts were all made before age 18 (and at a mean age of 13.6). Major depressive disorder, alcohol dependence, childhood physical abuse, social phobia, conduct disorder, and African-American ethnicity were the factors most associated with a suicide attempt history. Suicide attempt liability was familial, with genetic and shared environmental influences together accounting for 35% to 75% of the variance in risk. The twin/cotwin suicide attempt odds ratio was 5.6 (95% confidence interval [CI] 1.75-17.8) for monozygotic twins and 4.0 (95% CI 1.1 -14.7) for dizygotic twins after controlling for other psychiatric risk factors. CONCLUSIONS In women, the predisposition to attempt suicide seems usually to manifest itself first during adolescence. The data show that youth suicide attempts are familial and possibly influenced by genetic factors, even when controlling for other psychopathology.

A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

CONTEXT The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy. OBJECTIVE To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects. DESIGN A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures. SETTING Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009. PARTICIPANTS Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91). MAIN OUTCOME MEASURE Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression). RESULTS At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders. CONCLUSIONS Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.

Social phobia in a population-based female adolescent twin sample: co-morbidity and associated suicide-related symptoms

BACKGROUND This report attempted to replicate and extend prior work examining social phobia (SP), co-morbid psychiatric illnesses, and the risk of suicidal ideation and suicide attempts incurred by their adolescent sufferers. METHODS SP, alcohol dependence (ALD) and major depressive disorder (MDD) diagnoses, and suicide-related symptoms, were assessed in a population-based adolescent female twin sample. The differentiation of risks as a function of co-morbidity was explored. A trivariate model was fitted to estimate sharing of genetic and environmental vulnerability between SP and co-morbid disorders. RESULTS The lifetime prevalence of SP was 16.3 %. Significant risk for co-morbid MDD (OR = 3.2) and ALD (OR = 2.1) was observed. Strong evidence for shared genetic vulnerability between SP and MDD (respective heritabilities 28%, 45%; genetic r = 1.0) was observed with moderate support noted for similar sharing between SP and ALD (genetic r = 0.52, heritability for ALD 63%). SP with co-morbid MDD was associated with elevated risk for ALD and for suicide-related symptoms. CONCLUSIONS SP is a common illness often followed by co-morbid MDD and ALD. SP with comorbid MDD predicts a substantially elevated risk of ALD and suicide-related symptoms, stressing the need for early SP detection.

Ascertainment of a mid-western US female adolescent twin cohort for alcohol studies: assessment of sample representativeness using birth record data.

Female twin pairs were identified from birth records, and their families invited to participate in a prospective study of the determinants of alcohol problems in women. We investigated sampling biases arising because of failure to locate families, or non-cooperation of families. Out of 2644 families with a live-born pair (born between July 1975 and December 1986) who survived beyond infancy, contact was established and a brief screening interview completed with 90% (N = 2380). Fewer than 6% of located families declined to participate in the initial screening interview. Predictors of failure to locate a family or to obtain a screening interview were identified from information recorded in birth records, and from neighborhood characteristics identified from 1990 US Census block group data for the family residence when the twins were born. African-American families were under-represented in the final sample, but this effect was barely significant when other variables were controlled for. Under-represented were families where the mother was 19 or younger at the birth of the twins, where the mother herself was born out-of-state, or where information about biological father was not reported in the birth record. Non-participating families on average came from neighborhoods with a higher proportion of residents living in poverty, and with a higher proportion of African-American residents. Sampling biases were however small. The unusual cooperativeness in research of families with twins persists.

Genetic epidemiology of self-reported lifetime DSM-IV major depressive disorder in a population-based twin sample of female adolescents

BACKGROUND In adults, about 40% of the variance in risk of Major Depressive Disorder (MDD) is due to genetic factors, but little data exist on the heritability of youth MDD. The goal of this study was the genetic analysis of MDD in an epidemiologically and genetically representative sample of adolescent female twins. METHODS A sample of 3416 female adolescent twins systematically ascertained from birth records was assessed using a structured telephone interview that included a comprehensive DSM-IV-based section for the diagnostic assessment of MDD. Mean subject age at time of assessment was 15.5 and participation rate exceeded 85%. Genetic modeling was conducted taking into consideration the problem of censoring, i.e., that younger adolescents were not through their period of risk for adolescent onset of MDD. RESULTS Lifetime self-reported MDD prevalence ranged from 1% under age 12 to 17.4% at age 19 and older. The genetic variance in risk of MDD was 40.4% (95% confidence interval (CI): 23.9-55.1), with the remaining variance explained by non-shared environmental effects 59.6% (95%CI: 44.9-76.1). Shared environmental effects were not significant. A significant recall bias was observed with older respondents on average reporting later onsets for their first episode of MDD. CONCLUSIONS The genetic and environmental contributions to risk of MDD in this representative sample of female adolescent twins are remarkably analogous to findings from adult samples. These results are congruent with a conceptualization of adolescent MDD and adult MDD as having very similar etiologic determinants.

A 3p26-3p25 genetic linkage finding for DSM-IV major depression in heavy smoking families.

OBJECTIVE The authors tested for genetic linkage of DSM-IV-diagnosed major depressive disorder in families that were ascertained for cigarette smoking. METHOD Within a study that targeted families characterized by a history of smoking, analyses derived a subset of 91 Australian families with two or more offspring with a history of DSM-IV major depressive disorder (affected sibling pairs, N=187) and 25 Finnish families (affected sibling pairs, N=33). Within this affected sibling pairs design, the authors conducted nonparametric linkage analysis. RESULTS In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25). CONCLUSIONS Genome-wide significant linkage was detected for major depressive disorder on chromosome 3p in a sample ascertained for smoking. A linkage peak at this location was also observed in an independent study of major depressive disorder.

Teaching Pediatric Residents to Assess Adolescent Suicide Risk With a Standardized Patient Module

OBJECTIVE: We hypothesized that a suicide risk assessment (SRA) training module incorporating standardized patients (SPs) would enhance pediatric resident SRA performance. METHODS: We conducted an educational survey of pediatric residents regarding SRA (N = 80). In addition, we tested the performance of a SRA training module among pediatric interns who received SRA practice with SPs simulating suicidality scenarios, with (n = 6) or without (n = 6) SRA lecture, or SRA lecture only (n = 12) and control interns (n = 10). We examined postintervention confidence in SRA and self-reported and objectively measured knowledge of suicidal risk factors. RESULTS: Resident confidence and knowledge regarding SRA were low, compared with assessment of medical illness. Interns in the SP plus lecture group had significantly greater confidence in screening adolescents for suicide risk factors and assessing suicidal adolescents (screening, 4.2 ± 0.4; assessing, 4.2 ± 0.4), compared with subjects in either the lecture-only (screening, 2.9 ± 0.8; P = .005; assessing, 2.9 ± 1.1; P = .01) or control (screening, 3.1 ± 0.7; P = .025; assessing, 2.6 ± 0.8; P = .003) group. In addition, only the SP plus lecture group demonstrated significantly greater objective knowledge of suicide risk factors (92% vs 25% correct; P = .008) than the control group. Neither the lecture-only group nor the SP-only group was significantly better than the control group in terms of knowledge or confidence relevant to SRA. CONCLUSION: This SRA training module was significantly more effective than lecture alone in enhancing pediatric intern knowledge and confidence in SRA.

Infant viewing of social scenes is under genetic control and is atypical in autism

Long before infants reach, crawl or walk, they explore the world by looking: they look to learn and to engage, giving preferential attention to social stimuli, including faces, face-like stimuli and biological motion. This capacity—social visual engagement—shapes typical infant development from birth and is pathognomonically impaired in children affected by autism. Here we show that variation in viewing of social scenes, including levels of preferential attention and the timing, direction and targeting of individual eye movements, is strongly influenced by genetic factors, with effects directly traceable to the active seeking of social information. In a series of eye-tracking experiments conducted with 338 toddlers, including 166 epidemiologically ascertained twins (enrolled by representative sampling from the general population), 88 non-twins with autism and 84 singleton controls, we find high monozygotic twin–twin concordance (0.91) and relatively low dizygotic concordance (0.35). Moreover, the characteristics that are the most highly heritable, preferential attention to eye and mouth regions of the face, are also those that are differentially decreased in children with autism (χ2 = 64.03, P < 0.0001). These results implicate social visual engagement as a neurodevelopmental endophenotype not only for autism, but also for population-wide variation in social-information seeking. In addition, these results reveal a means of human biological niche construction, with phenotypic differences emerging from the interaction of individual genotypes with early life experience.

Parental separation and early substance involvement: results from children of alcoholic and cannabis dependent twins

BACKGROUND Risks associated with parental separation have received limited attention in research on children of parents with substance use disorders. We examined early substance involvement as a function of parental separation during childhood and parental alcohol and cannabis dependence. METHOD Data were drawn from 1318 adolescent offspring of monozygotic (MZ) or dizygotic (DZ) Australian twin parents. Cox proportional hazards regression analyses were conducted predicting age at first use of alcohol, first alcohol intoxication, first use and first regular use of cigarettes, and first use of cannabis, from parental separation and both parent and cotwin substance dependence. Parent and cotwin alcohol and cannabis dependence were initially modeled separately, with post hoc tests for equality of effects. RESULTS With few exceptions, risks associated with parental alcohol versus cannabis dependence could be equated, with results largely suggestive of genetic transmission of risk from parental substance (alcohol or cannabis) dependence broadly defined. Controlling for parental substance dependence, parental separation was a strong predictor for all substance use variables, especially through age 13. CONCLUSION Together, findings underscore the importance of parental separation as a risk-factor for early substance involvement over and above both genetic and environmental influences specific to parental alcohol and cannabis dependence.

Nicotine addiction in light smoking African American mothers

Background:Although African Americans (AAs) smoke fewer average cigarettes per day (CPD) than European Americans (EAs), they carry a disproportionate tobacco-related morbidity and mortality burden. The objective of this study was to evaluate the ethnic differences in markers of nicotine addiction, including rates of lifetime nicotine dependence (ND) symptoms, current smoking, and smoking during pregnancy across different levels of peak lifetime cigarette consumption. Methods:Data from 237 EA (N = 118) and AA (N = 119) mothers participating in the Missouri Family Study (2003–2005), an ethnically diverse family study of offspring outcomes in high and low risk families, were used to contrast prevalence of ND symptoms and other smoking behaviors between EA and AA women at low (1–10 CPD), moderate (11–19 CPD), and high (≥20 CPD) levels of lifetime peak daily cigarette consumption. Results:Compared with EA smokers, AAs had lower lifetime prevalence of DSM-IV ND (68% vs 54%, P < 0.05), consumed fewer CPD during their heaviest lifetime consumption (18% EA vs 58% AA smoked ≤10 CPD, P < 0.0001), but did not differ in overall rates of smoking during pregnancy or current smoking. However, stratifying by categories of peak lifetime daily cigarette use, AA mothers who smoked ≤10 CPD reported greater lifetime ND symptoms and current smoking than their EA counterparts. In addition, nearly two thirds of AA mothers in this smoking category smoked during pregnancy, and 30% smoked throughout an entire pregnancy. The respective prevalence estimates in EA mothers were 38% and 0%. Conclusions:Stratifying the sample into categories of lifetime peak daily cigarette use revealed significant ethnic or racial differences in smoking prevalence during pregnancy, which were obscured in overall analysis. Substantial public health risks warranting clinical attention exist among light smokers, particularly AA women.