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Objective: Callous-unemotional (CU) behaviors and quantitative autistic traits (QATs), heritable domains implicated in social development, are both associated with reduced prosocial behavior and increased aggression at their clinical extremes. However, they are hypothesized to contribute to aggression through separate mechanisms. This study tested whether CU behaviors and QATs exhibited distinct profiles of heritable influences as well as independent contributions to early childhood aggression in a general population sample with enhanced sensitivity to clarify these relationships., Method: Parents of 3- to 4-year-old epidemiologically representative twins ascertained from birth records (N = 113 pairs) completed questionnaires measuring CU behaviors, QATs, and aggression. Correlation coefficients indexed overlap across behaviors. Intraclass correlations were compared between monozygotic and dizygotic twins to characterize relative genetic and environmental influences. Generalized estimating equations tested contributions of CU subdomains, verified via factor analysis, and QATs to aggression., Results: Total CU scores strongly correlated with QATs ( r  = 0.54) and aggression ( r  = 0.55), while QATs correlated moderately with aggression ( r  = 0.38). Among 3 identified CU factors, the uncaring factor strongly correlated with QATs ( r  = 0.52), while unemotional and callous factors showed small correlations ( r  = 0.25 and r  = 0.16, respectively). QATs, aggression, and all CU factors except the callous factor showed heritable influences. Uncaring and callous factors as well as QATs demonstrated unique and shared contributions to aggression, with the callous factor being moderated by sex., Conclusion: Partially overlapping relations support distinct mechanisms whereby CU behaviors, in particular the callous factor, and QATs contribute to early aggression. In-depth social developmental assessment may enhance personalized intervention for aggression in early childhood., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science., (© 2023 The Authors.)

Objective: To assess the extent to which articles examining telepsychiatry after the start of the COVID-19 pandemic provided racial and sociodemographic characteristics for people receiving audiovisual (video) versus audio-only telepsychiatry., Data Sources, Study Selection, and Data Extraction: We employed the keyword telepsychiatry and screened all peer-reviewed articles in PubMed published from March 1, 2020, until November 23, 2022, prior to the federal government's announcement of the impending end to the COVID-19 public health emergency. We retrieved and reviewed the full-text articles of 553 results for potential inclusion, of which 266 were original research articles., Results: We found that 106 of 553 articles had any mention of differences between audio-only and audiovisual telepsychiatry. Twenty-nine of 553 articles described potential socioeconomic differences in the distribution of people receiving audio-only versus audiovisual telepsychiatry, and 20 of 553 described potential racial/ethnic differences. Among research articles, most (213/266) did not differentiate between videoconferencing and audio-only/telephone-based telehealth services. A total of 4 research articles provided racial and sociodemographic characteristics of individuals who received audio-only versus audiovisual telepsychiatry services during the COVID-19 pandemic, all of which were conducted in relatively small regional samples that could not be generalized to the US as a whole., Conclusions: Overall, this analysis underscores that empirical data are lacking on racial and sociodemographic distribution of audio-only versus audiovisual telepsychiatry services since the COVID-19 pandemic., Prim Care Companion CNS Disord 2023;25(6):23r03563 ., Author affiliations are listed at the end of this article., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12-21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two 'conflict classes' perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics., (Published by Elsevier Ltd.)

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability., (Copyright © 2019. Published by Elsevier B.V.)

Previous research has suggested that behavioral comorbidity is the rule rather than the exception in autism. The present study aimed to trace the respective origins of autistic and general psychopathologic traits-and their association-to infancy. Measurements of autistic traits and early liability for general psychopathology were assessed in 314 twins at 18 months, ascertained from the general population using birth records. 222 twins were re-evaluated at 36 months. Standardized ratings of variation in social communication at 18 months were highly heritable and strongly predicted autistic trait scores at 36 months. These early indices of autistic liability were independent from contemporaneous ratings of behavior problems on the Brief Infant-Toddler Social and Emotional Assessment (which were substantially environmentally-influenced), and did not meaningfully predict internalizing or externalizing scores on the Achenbach Scales of Empirically Based Assessment at 36 months. In this general population infant twin study, variation in social communication was independent from variation in other domains of general psychopathology, and exhibited a distinct genetic structure. The commonly-observed comorbidity of specific psychiatric syndromes with autism may arise from subsequent interactions between autistic liability and independent susceptibilities to other psychopathologic traits, suggesting opportunities for preventive amelioration of outcomes of these interactions over the course of development.

Reciprocal social behavior (RSB), an early-emerging capacity to engage in social contingency-which is foundational for both social learning and social competency-is hypothesized to be disrupted in autism spectrum disorder (ASD). The ability to quantify the full range of RSB during the toddler period, when core symptoms of ASD often arise, is pivotal for evaluating early risk for ASD, characterizing social development, and tracking response to early interventions. However, important parameters of variation in RSB-especially prior to the development of verbal language-can be nuanced and difficult to characterize using questionnaire-based methods. To address this challenge, we developed a system for measuring quantitative variation in RSB in toddlers (ages 18 - 30 months) that incorporated not only standard questionnaire data from caregivers but also a novel set of video-referenced items, through which a respondent compares the behavior of a subject to that observed in a short video of a young child manifesting a highly competent level of social communication. Testing of this measure in a general population sample of twins confirmed that both the video-referenced items and the RSB Total Score (video-referenced items plus non-video-referenced items) displayed unimodal, continuous distributions, strong internal consistency, marked preservation of individual differences, and extremely high heritability. In addition, video-referenced items were particularly sensitive to quantifying incremental changes in social communication, a major element of RSB, over the course of early childhood development. Scores on the vrRSB clearly differentiated children with and without ASD and these data comprise an initial validation of this promising method for quantifying early RSB-cross-sectionally, over time, and as a function of early intervention.

Objective: Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls)., Method: Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score., Results: After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041)., Conclusion: BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized., Methods: We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006-2011. Youth offspring/relatives ("Relatives of BD probands;" n=267; mean age=16.8years; ±2.9S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands ("relatives of control probands;" n=149; mean age=17.4years; ±2.9S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes., Results: Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p=0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR=2.80-3.17; p<0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves., Conclusion: Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 (χ 2  = 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.

Background: Reciprocal social behavior (RSB) is a developmental prerequisite for social competency, and deficits in RSB constitute a core feature of autism spectrum disorder (ASD). Although clinical screeners categorically ascertain risk of ASD in early childhood, rapid methods for quantitative measurement of RSB in toddlers are not yet established. Such measurements are critical for tracking developmental trajectories and incremental responses to intervention., Methods: We developed and validated a 20-min video-referenced rating scale, the video-referenced rating of reciprocal social behavior (vrRSB), for untrained caregivers to provide standardized ratings of quantitative variation in RSB. Parents of 252 toddler twins [Monozygotic (MZ) = 31 pairs, Dizygotic (DZ) = 95 pairs] ascertained through birth records, rated their twins' RSB at two time points, on average 6 months apart, and completed two developmental measures, the Modified Checklist for Autism in Toddlers (M-CHAT) and the MacArthur Communicative Development Inventory Short Form (MCDI-s)., Results: Scores on the vrRSB were fully continuously distributed, with excellent 6-month test-retest reliability ([intraclass correlation coefficient] ICC = 0.704, p < .000). MZ twins displayed markedly greater trait concordance than DZ twins, (MZ ICC = 0.863, p < .000, DZ ICC = 0.231, p < .012). VrRSB score distributions were highly distinct for children passing versus failing the M-CHAT (t = -8.588, df = 31, p < .000), incrementally improved from 18-24 months, and were inversely correlated with receptive and expressive vocabulary on the MCDI-s., Conclusions: Like quantitative autistic trait ratings in school-aged children and adults, toddler scores on the vrRSB are continuously distributed and appear highly heritable. These ratings exhibited minimal measurement error, high inter-individual stability, and developmental progression in RSB as children matured from 18-24 months, supporting their potential utility for serially quantifying the severity of early autistic syndromes over time and in response to intervention. In addition, these findings inform the genetic-environmental structure of RSB in early typical development., (© 2015 Association for Child and Adolescent Mental Health.)

Background: Self-harm has considerable societal and economic costs and has been extensively studied in relation to alcohol involvement. Although early onset alcohol use (EAU) has been causally linked to maladaptive clinical outcomes, its association with self-harm is less well characterized. This study aimed to further examine the link between EAU and both nonsuicidal self-injury (NSSI) and suicide attempt (SA), and elucidate shared familial and causal/individual-specific pathways that explain this co-occurrence., Methods: Using data from 6,082 Australian same-sex twin pairs (1,732 monozygotic [MZ] and 1,309 dizygotic [DZ]), ages 23 to 40, we examined prevalence rates of NSSI and SA among twin pairs concordant and discordant for EAU. Conditional logistic regression, controlling for early clinical covariates and the influence of zygosity on EAU, was used to examine the odds ratio (OR) of self-harm within twin pairs discordant for EAU., Results: Prevalence rates of both NSSI and SA were highest among twin pairs concordant for EAU and for twins who reported EAU within discordant twin pairs. Results from discordant twin analyses revealed nearly 4-fold increased odds of SA for the twin who endorsed EAU, and this OR was equal across MZ and DZ twins. EAU also was associated with elevated odds of NSSI (OR = 7.62), although this was only the case for DZ twins in discordant pairs., Conclusions: The equivalent increase in odds of SA for both MZ and DZ twins suggests that causal or individual-specific influences explain the link between EAU and SA. For NSSI, elevated odds for DZ twins and nonsignificant findings for MZ twins implicate correlated genetic factors in the association between EAU and NSSI. Future studies should test mechanisms through which EAU may causally influence SA, as well as examine whether genetic risk for third variables (e.g., negative urgency, stress reactivity) may explain the genetic overlap between EAU and NSSI., (Copyright © 2015 by the Research Society on Alcoholism.)

Recent studies have revealed the polygenic nature of bipolar disorder (BP), and identified common risk variants associated with illness. However, the role of common polygenic risk in multiplex families has not previously been examined. The present study examined 249 European-ancestry families from the NIMH Genetics Initiative sample, comparing subjects with narrowly defined BP (excluding bipolar II and recurrent unipolar depression; n = 601) and their adult relatives without BP (n = 695). Unrelated adult controls (n = 266) were from the NIMH TGEN control dataset. We also examined a prospective cohort of young (12-30 years) offspring and siblings of individuals with BPI and BPII disorder (at risk; n = 367) and psychiatrically screened controls (n = 229), ascertained from five sites in the US and Australia and assessed with standardized clinical protocols. Thirty-two disease-associated SNPs from the PGC-BP Working Group report (2011) were genotyped and additive polygenic risk scores (PRS) derived. We show increased PRS in adult cases compared to unrelated controls (P = 3.4 × 10(-5) , AUC = 0.60). In families with a high-polygenic load (PRS score ≥32 in two or more subjects), PRS distinguished cases with BPI/SAB from other relatives (P = 0.014, RR = 1.32). Secondly, a higher PRS was observed in at-risk youth, regardless of affected status, compared to unrelated controls (GEE-χ(2) = 5.15, P = 0.012). This report is the first to explore common polygenic risk in multiplex families, albeit using only a small number of robustly associated risk variants. We show that individuals with BP have a higher load of common disease-associated variants than unrelated controls and first-degree relatives, and illustrate the potential utility of PRS assessment in a family context., (© 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.)

Background: The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders., Method: A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998-2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA., Results: The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives., Conclusions: The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.

Objective: Although prior studies have demonstrated that depression is associated with an overeating-binge eating dimension (OE-BE) phenotypically, little research has investigated whether familial factors contribute to the co-occurrence of these phenotypes, especially in community samples with multiple racial/ethnic groups. We examined the extent to which familial (i.e., genetic and shared environmental) influences overlapped between Major Depressive Disorder (MDD) and OE-BE in a population-based sample and whether these influences were similar across racial/ethnic groups., Method: Participants included 3,226 European American (EA) and 550 African American (AA) young adult women from the Missouri Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD and OE-BE. Quantitative genetic modeling was used to estimate familial influences between both phenotypes; all models controlled for age., Results: The best-fitting model, which combined racial/ethnic groups, found that additive genetic influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%, 54%) for OE-BE, with the remaining variances due to non-shared environmental influences. Genetic overlap was substantial (rg  = .61 [.39, .85]); non-shared environmental influences on MDD and OE-BE overlapped weakly (re  = .26 [.09, .42])., Discussion: Results suggest that common familial influences underlie MDD and OE-BE, and the magnitude of familial influences contributing to the comorbidity between MDD and OE-BE is similar between EA and AA women. If racial/ethnic differences truly exist, then larger sample sizes may be needed to fully elucidate familial risk for comorbid MDD and OE-BE across these groups., (© 2014 Wiley Periodicals, Inc.)

Background: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology., Methods: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI., Results: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI., Conclusions: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18-28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67-1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29-78% vs. 41%, 95% CI: 29-52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33-53% and E = 57%, 47-67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.

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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Borderline personality disorder (BPD) and substance use disorders frequently co-occur; their dual presence predicts poor prognosis. The genetic underpinnings of BPD have not been well-characterized and could offer insight into comorbidity. The current report focuses on the association of neurexin 3 (NRXN3) single nucleotide polymorphisms (SNPs) with BPD symptoms in heroin dependent cases and controls., Methods: The sample of the Comorbidity and Trauma Study, a genetic association study of heroin dependence, consists of Australian heroin dependent cases ascertained from opioid replacement therapy clinics and controls ascertained in nearby economically disadvantaged neighborhoods. The assessment included a screening instrument for BPD, used previously in Australian population surveys. Genotypic and BPD phenotypic data were available for 1439 cases and 507 controls. We examined the association of 1430 candidate gene SNPs with BPD phenotypes., Results: One or more NRXN3 SNPs were nominally associated with all BPD phenotypes; however, none met the conservative significance threshold we employed to correct for multiple testing. The most strongly associated SNPs included rs10144398 with identity disturbance (p=4.9×10(-5)) and rs10151731 with affective instability (p=8.8×10(-5)). The strongest association with screening positive for BPD was found for the NRXN3 SNP, rs10083466 (p=.0013). Neither the correlation of BPD phenotypes nor the linkage disequilibrium relationships of the SNPs account for the number of observed associations involving NRXN3 SNPs., Conclusions: Our findings provide intriguing preliminary evidence for the association of NRXN3 with BPD phenotypes. The strongest associations were found for traits (i.e., affective instability; identity disturbance) also observed with other disorders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Although routine adolescent depression and suicide risk assessment (ADSRA) is recommended, primary care physician (PCP) ADSRA training is needed for successful ADSRA implementation. This study examined the effect of an intervention using standardized patients (SPs) on PCP ADSRA confidence, knowledge, and practices., Methods: The intervention consisted of a 60-minute seminar followed by a 60-minute SP session to practice ADSRA skills in simulated clinical situations., Intervention: PCPs (n = 46) completed pre- and postintervention assessments. Untrained PCPs interested in the intervention (n = 58) also completed assessments. Assessments evaluated ADSRA self-reported confidence and practices and objectively assessed knowledge. The main outcomes were (1) changes in pre-/postintervention PCP ADSRA confidence and knowledge, and (2) ADSRA practices in untrained versus postintervention PCPs., Results: Compared with untrained PCPs, PCPs 5-10 months postintervention were more likely to screen most adolescents for depression (40% vs. 22%, p = .05), to use a depression screening tool (50% vs. 19%, p = .001), to have diagnosed at least one adolescent with depression in the past 3 months (96% vs. 78%, p = .013), and to have screened depressed adolescents for suicide risk factors, including access to weapons (51% vs. 25%; p = .007) or an impulsive violence history (27% vs. 11%; p = .037). PCP confidence and knowledge about depression assessment and treatment also significantly improved postintervention., Conclusions: This study supports the use of an SP intervention to improve PCP ADSRA confidence, knowledge, and practices. Widespread implementation of similar educational efforts has the potential to dramatically improve adolescent morbidity and mortality., (Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although there is a long tradition in alcoholism research of using family history ratings, the interpretability of family history reports of alcoholism from general community samples has yet to be established., Methods: Telephone interview data obtained from a large cohort of female like-sex twins (N = 3,787, median age 22) and their biological parents (N = 2,928, assessed at twins' median age 15) were analyzed to determine agreement between parent self-report, parent ratings of coparent, and twin narrow (alcohol problems) and broad (problem or excessive drinking) ratings of each parent., Results: In European ancestry (EA) families, high tetrachoric correlations were observed between twin and cotwin ratings of parental alcohol problems, between twin and parent ratings of coparent alcohol problems using symptom-based and single-item assessments, as well as moderately high correlations between twin and both mother and father self-reports. In African American (AA) families, inter-rater agreement was substantially lower than for EA families, with no cases where father ratings of maternal alcohol problems agreed with either twin ratings or mother self-report, and both cotwin agreement and mother-twin agreement were reduced. Differences between EA and AA families were not explained by differences in years of cohabitation with father or mother's education; however, underreporting of problems by AA parents may have contributed., Conclusions: Results support the use of family history ratings of parental alcoholism in general community surveys for EA families, but suggest that family history assessment in AA families requires improved methods., (Copyright © 2012 by the Research Society on Alcoholism.)

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.

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.

Unlabelled: Although African Americans (AA) smoke fewer average cigarettes per day (CPD) than European Americans (EA), they carry a disproportionate tobacco related morbidity and mortality burden., Objective: To evaluate 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% v. 54%, p<.05), consumed fewer CPD during their heaviest lifetime consumption (18% EA v. 58% AA smoked ≤ 10 CPD, p<.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/racial differences in smoking prevalence during pregnancy that were obscured in overall analysis. Substantial public health risks warranting clinical attention exist among light smokers, particularly AA women.

Objective: To investigate the course of alcoholism in males and females in a 14-year follow-up of persons with DSM-III alcoholism compared to very heavy drinkers and unaffected controls in a community sample., Methods: Case-control study based on data from the 1997 Health Services Use and Cost study, a 14-year follow-up survey of 442 individuals who participated in two waves of the 1981-1983 St. Louis Epidemiologic Catchment Area study. Cases met criteria for DSM-III alcohol abuse (AA) or dependence (AD) at both waves of the ECA: "Two-times Alcohol Use Disorder Positives (ECA 2t-AUDPs)." Two comparison groups were frequency matched to 2t-AUDPs: (1) ECA Very Heavy Drinkers/One-time Alcohol Use Disorder Positives (ECA VHD/1t-AUDPs) and (2) ECA alcohol-unaffecteds. Lifetime and past year alcohol use disorders, patterns of drinking and recovery among males and females are reported., Results: 84.6% of 2t-AUDPs again met lifetime DSM-III criteria at 14-year follow-up. At follow-up, only 9.3% male 2t-AUDPs and 20.7% female 2t-AUDPs met past year DSM-IV AUD criteria. Past year drinking patterns, however, revealed higher rates of DSM-IV AA or AD, problem or risk drinking among 2t-AUDPs (61.7%) compared to both ECA VHD/1t-AUDPs (41.2%) and ECA alcohol-unaffecteds (22.1%)., Conclusions: In a community sample, the rate of past year DSM-IV alcohol dependence was lower among male 2t-AUDPs than females, though both groups showed past year rates substantially lower than lifetime rates. However, less than half of ECA 2t-AUDPs exhibited low-risk or abstinent alcohol use behaviors, indicating that while remission from diagnosis is common, clinical relevance persists.

Introduction: In substance abusing families, sources of familial comorbidity are potentially confounded by genetic-environmental (GE) interplays. The children-of-twins (COT) design can be used to elucidate the association of a parental trait and an offspring outcome such as the association of parental alcoholism and offspring suicidality., Methods: We examined the association of paternal alcoholism and offspring suicidal behaviors in an adolescent and young adult COT sample of 'Vietnam Era Twins' offspring who had completed an interview including a comprehensive assessment of lifetime suicidal behaviors. We stratified the COT sample into four groups contingent upon paternal zygosity, MZ versus DZ, and lifetime paternal alcohol dependence history (AD), positive versus negative. We examined whether the relationship of paternal alcoholism and offspring suicidality was best explained by genetic predispositions common to alcoholism and suicidality or by GE interplay--environmental influences correlated with parental alcoholism or the interaction of genetic and environmental factors., Results: Our results suggest a main effect of paternal alcoholism on offspring suicide attempt; COT analyses do not support a purely genetic explanation for this association., Discussion: Suicide attempts probably result from GE interplays and must be studied in genetically informative samples of offspring of substance abusing parents.

Background: Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD., Objective: To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences., Design: Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use., Setting: General population sample of twins (median age, 30 years)., Participants: Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years)., Main Outcome Measures: Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt., Results: Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs., Conclusions: Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and environmental vulnerabilities, although it remains possible that early-onset cannabis use may predispose to suicide attempt.

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.

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.

Background: Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders., Methods: Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors., Results: The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects., Conclusions: There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

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.