Internalizing and externalizing problems in adolescence: general and dimension-specific effects of familial loadings and preadolescent temperament traits

BACKGROUND: We investigated the links between familial loading, preadolescent temperament, and internalizing and externalizing problems in adolescence, hereby distinguishing effects on maladjustment in general versus dimension-specific effects on either internalizing or externalizing problems.METHOD:In a population-based sample of 2230 preadolescents (10-11 years) familial loading (parental lifetime psychopathology) and offspring temperament were assessed at baseline by parent report, and offspring psychopathology at 2.5-years follow-up by self-report, teacher report and parent report. We used purified measures of temperament and psychopathology and partialled out shared variance between internalizing and externalizing problems.RESULTS:Familial loading of internalizing psychopathology predicted offspring internalizing but not externalizing problems, whereas familial loading of externalizing psychopathology predicted offspring externalizing but not internalizing problems. Both familial loadings were associated with Frustration, low Effortful Control, and Fear. Frustration acted as a general risk factor predicting severity of maladjustment; low Effortful Control and Fear acted as dimension-specific risk factors that predicted a particular type of psychopathology; whereas Shyness, High-Intensity Pleasure, and Affiliation acted as direction markers that steered the conditional probability of internalizing versus externalizing problems, in the event of maladjustment. Temperament traits mediated one-third of the association between familial loading and psychopathology. Findings were robust across different composite measures of psychopathology, and applied to girls as well as boys.CONCLUSIONS:With regard to familial loading and temperament, it is important to distinguish general risk factors (Frustration) from dimension-specific risk factors (familial loadings, Effortful Control, Fear), and direction markers that act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from both types of risk factors. About one-third of familial loading effects on psychopathology in early adolescence are mediated by temperament.     

The role of self-control in early escalation of substance use: a time-varying analysis

This research tested predictions about the role of temperament and self-control in early substance use (tobacco, alcohol, and marijuana). A sample of 1,526 participants was assessed in 6th grade (mean age = 11.5 years) and followed with yearly assessments through 9th grade. Latent growth models showed temperament dimensions were related to early substance use, and their effects were mediated through generalized self-control ability. Time-varying effects indicated rate of growth in substance use was higher among participants who showed increases in poor self-control and lower among participants who showed increases in good self-control. Results in self-report data were corroborated by independent teacher ratings. Findings are discussed with reference to epigenetic models of protection and vulnerability.     

Psychometric and Genetic Architecture of Substance Use Disorder and Behavioral Disinhibition Measures for Gene Association Studies

Using large twin, family, and adoption studies conducted at the Minnesota Center for Twin and Family Research, we describe our efforts to develop measures of substance use disorder (SUD) related phenotypes for targets in genome wide association analyses. Beginning with a diverse set of relatively narrow facet-level measures, we identified 5 constructs of intermediate complexity: nicotine, alcohol consumption, alcohol dependence, illicit drug, and behavioral disinhibition. The 5 constructs were moderately correlated (mean r = .57) reflecting a general externalizing liability to substance abuse and antisocial behavior. Analyses of the twin and adoption data revealed that this general externalizing liability accounted for much of the genetic risk in each of the intermediate-level constructs, though each also exhibited significant unique genetic and environmental risk. Additional analyses revealed substantial effects for age and sex, significant shared environmental effects, and that the mechanism of these shared environmental effects operates via siblings rather than parents. Our results provide a foundation for genome wide association analyses to detect risk alleles for SUDs as well as novel insights into genetic and environmental risk for SUDs.     

The high prevalence of bipolar II and associated cyclothymic and hyperthymic temperaments in HIV-patients

Background: Although recent studies have shown high rates of current and lifetime depression in HIV-infected patients, there is little systematic data on the occurrence of bipolarity in these patients. Method: We compared 46 HIV patients with index major depressive episode (MDE) to an equal number of age- and sex-matched seronegative MDE patients, and systematically examined rates of DSM-III-R bipolar subtypes (enriched in accordance with Akiskal's system of classifying soft bipolar disorders). Results: Although HIV and psychiatric clinic patients had comparable background in terms of familial affective loading, HIV patients had significantly higher familial rates for alcohol and substance use. The more important finding was the significantly higher proportion of HIV patients with lifetime bipolar II disorder (78%), and associated cyclothymic (52%) and hyperthymic (35%) temperaments; the findings were the same irrespective of HIV risk status (intravenous drug user vs. homosexual and other risk groups combined). Limitations: The major methodologic limitation of our study is that clinicians evaluating temperament were not blind to affective diagnoses and family history. The comparison affective group was a sample of convenience drawn from the same tertiary care university facility. Conclusion: The finding of a high rate of bipolar II disorder in HIV patients has treatment implications for seropositive patients presenting with depression. More provocatively, we submit that premorbid impulsive risk-taking traits associated with cyclothymic and hyperthymic temperaments may have played an important role in needle-sharing drug use and/or unprotected sexual behavior, leading ultimately to infection with HIV. Given their public health importance, these clinical findings and insights merit further investigation. In particular, systematic case-control studies, as well as other large scale studies with prospective methodology need to be conducted.     

The difficult temperament in adolescence: associations with substance use, family support, and problem behaviors

This study investigated interrelations between the number of difficult temperament factors (e.g., arrhythmicity, inflexibility, high distractibility) and substance use, perceived family support, and problem behaviors for a sample of 297 adolescents (M age = 15.7 years). The number of adolescent difficult temperament factors was associated significantly with more childhood behavior problems (e.g., hyperactivity, conduct disordered symptoms), which suggests some continuity of disordered behavior from childhood to adolescence. Number of adolescent difficult temperament factors also was associated with a higher percentage of substance users (for cigarettes, alcohol, marijuana, hard drugs), lower perceived family support, higher levels of depressive symptoms, and more delinquent activity. Number of difficult temperament factors was not associated significantly with gender or age of respondents.     

Genetic and Environmental Risk Factors for Illicit Substance Use and Use Disorders: Joint Analysis of Self and Co-twin Ratings

The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.     

A Twin Study of Drinking and Smoking Onset and Latencies from First Use to Regular Use

The early onset of alcohol and tobacco use has been associated with increased risk for later substance abuse and dependence problems. This study investigated genetic and environmental influences on age at onset of alcohol and tobacco use by examining twin resemblance for several retrospectively reported onset milestones including age at first use, age at first alcohol intoxication experience, and age at regular use. In addition, we also examined the latency between age at first use and age at regular use of tobacco and alcohol. The subjects were a volunteer sample of older adult twins 50 to 96 years of age. MZ twin correlations for age at first alcohol use and age at first tobacco use were .57 and .44, respectively, compared to .45 and .37 for DZ same-sex twins. MZ twins correlated .30 and .26 for the latencies between first use and regular use of alcohol and of tobacco, while DZ correlations were –.01 and .05, respectively. Biometrical model-fitting results confirmed that familial resemblance for age at first use for both alcohol and tobacco was largely the result of shared environmental factors, while the latencies between first use and regular patterns of use were more genetically influenced. These findings add to a growing body of literature suggesting that initiation of substance use is influenced primarily by environmental rather than genetic factors.     

The association between family history of asthma and the prevalence of asthma among US adults: National Health and Nutrition Examination Survey, 1999–2004

PurposeTo assess the overall prevalence of asthma and the association between family history of asthma and the prevalence of asthma among US adults.MethodsWe analyzed National Health and Nutrition Examination Survey data from 1999 to 2004 for 15,008 respondents aged 20 years or older with no history of emphysema. We divided respondents into three familial risk groups (high, moderate, and average) on the basis of the number and closeness of relatives, that they reported as having asthma and then assessed the asthma prevalence in each. We also assessed associations between asthma prevalence and age, sex, race/ethnicity, income, body mass index, smoking status, household smoking exposure, and physical activity.ResultsBy our definitions, 2.3% of respondents were at high, 13.0% at moderate, and 84.7% at average familial risk for asthma. The crude prevalence of self-reported lifetime asthma was 11.5% (95% confidence interval [CI]: 10.7–12.3%) among all respondents, and 37.6% (95% CI: 30.4–45.4%), 20.4% (95% CI: 18.2–22.7%), and 9.4% (95% CI: 8.7–10.2%) among those at high, moderate, and average familial risk, respectively. Among all risk factors we looked at, family history had the strongest association with lifetime asthma prevalence, and the association remained significant after adjustments for other risk factors. Compared with average familial risk, the adjusted odds ratios for lifetime asthma were 2.4 (95% CI: 2.0–2.8) for moderate and 4.8 (95% CI: 3.5–6.7) for high familial risk.ConclusionOur findings showed that a family history of asthma is an important risk factor for asthma and that familial risk assessments can help identify people at highest risk for developing asthma. Additional research is needed to assess how health care professionals can use family history information in the early detection and management of asthma.     

Genetic and Environmental Influences on Gambling and Substance Use in Early Adolescence

This study examined the genetic and environmental architecture of early gambling involvement and substance use to determine whether genetic or environmental factors that contribute to substance use also put young adolescents at risk for early involvement in gambling. Self-reports of substance use and gambling involvement were collected at age 13 years from 279 Monozygotic and Dizygotic twin pairs. Univariate ACE modeling revealed that genetic and nonshared environmental factors almost equally accounted for gambling involvement, with no contribution from shared environmental factors. In contrast, both shared and nonshared environmental factors played important roles in substance use; the contribution of genetic factors was also substantial. Bivariate analyses identified a significant, albeit modest, overlap between the genetic influence on gambling involvement and the genetic influence on substance use. The results shed light on the etiology of early gambling involvement and substance use, suggesting that preventive interventions targeting common risk factors may also need to be complemented by modules that are specific to each behavior.     

Familial rates of affective and substance use disorders in patients with first-episode mania

BACKGROUND: One explanation for the high co-occurrence between bipolar and substance use disorders is that substance abuse may precipitate affective symptoms in patients who otherwise may have not had the genetic risk for developing an affective illness. Previous studies comparing familial rates of affective illness between bipolar patients with and without alcohol use have provided conflicting results. We hypothesized that patients with bipolar disorder and antecedent alcohol abuse would have lower familial rates of affective illness than bipolar patients without antecedent alcohol abuse. METHODS: Family history data were obtained on 275 first-degree relatives of 51 patients hospitalized for a first manic episode using the Family History Research Diagnostic Criteria. RESULTS: Patients with bipolar disorder and antecedent alcohol abuse had lower familial rates of affective illness than patients with bipolar disorder without antecedent alcohol abuse (two-tailed Fisher's exact, P = 0.003). There was no statistically significant difference in the familial rates of affective illness between bipolar patients with and without antecedent drug abuse (other than alcohol). Patients with bipolar disorder and antecedent alcohol abuse had a significantly older age of onset of affective illness (27.6 years) than patients with bipolar disorder without antecedent alcohol abuse (20.6 years, z = 3.3, df = 1, P = 0.0009). There was no statistical difference in age of onset of affective illness between the patients with antecedent drug abuse and the patients without antecedent drug abuse. LIMITATIONS: Future studies with a larger number of bipolar patients, direct structured interviews of family members and better differentiation between substance abuse and dependence syndromes are needed to extend and replicate this pilot study. CONCLUSIONS: Our study suggests that there may be a subset of bipolar patients who have antecedent alcohol abuse and a subset who develop alcohol abuse after the onset of bipolar disorder. We further speculate that alcohol abuse may precipitate mania in some patients with bipolar disorder.     

Familial risks for asthma among twins and other siblings based on hospitalizations in Sweden

BACKGROUND: Asthma is a common disabling condition, with known environmental and familial risk factors and with their assumed interactions. We wanted to carry out a family study on asthma to address gene-environment interactions at a population level. METHODS: We conducted a nation-wide study on familial risks for asthma. An asthma database was constructed by linking the Multigeneration Register on 0-72-year-old subjects to the Hospital Discharge Register for diagnosed asthma cases in Sweden from years 1987 to 2004. Standardized incidence ratios (SIRs) were calculated for affected singleton siblings, twins and spouses by comparing with those whose siblings or spouses had no asthma. RESULTS: A total of 67 370 hospitalized cases and 5638 affected siblings were identified with a familial SIR of 3.70, which was independent of sex, diagnostic age and age differences between the siblings. The SIR for different-sex twins was 5.17 and for same-sex twins it was 13.38. There was a low correlation between spouses for asthma. CONCLUSIONS: Asthma shows a higher familial risk than many common diseases. The higher difference in familial excess risk between singleton siblings and different-sex twins provides strong genetic epidemiological evidence for gene-environment interactions in asthma. The concept of gene-environment interactions needs to be accommodated in future aetiological studies on asthma. Data on environmental factors and family history are important for clinical risk estimation.     

Suicide attempts among depressed adolescents in primary care.

Although depression is strongly associated with suicide attempts and suicide deaths, most depressed youth do not make an attempt, indicating the need to identify additional risk factors. We examined suicide attempts among 451 depressed primary care patients, 13 to 21 years of age. In bivariate analyses, youth classified as suicide attempters showed elevated levels of psychopathology, specifically depressive symptoms, externalizing behaviors, anxiety, substance use, mania, and posttraumatic stress disorder symptoms. Externalizing behaviors and depression severity uniquely contributed to the prediction of suicide attempts in multivariate analyses. High levels of environmental stress as well as a few key stressful events were associated with suicide attempts; a recent romantic breakup or being assaulted added to suicide attempt risk, beyond the effects of psychopathology. Implications of results for primary care preventive services and suicide attempt prevention are discussed.     

Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs

Although familial factors have been shown to influence drug use, abuse, and dependence, little is known about the common and specific factors that influence polysubstance use and misuse. Our objective was to assess whether there are genetic and environmental factors specific to each substance or whether there are factors that predispose an individual to use of illicit substances in general. Twins from female-female pairs from the Virginia Twin Registry were interviewed by phone to assess lifetime nonmedical use of cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Multivariate, biometrical model-fitting was applied to the data using the Mx computer package. In the best-fitting model, use of all classes of drugs was influenced by a single general genetic factor (common to all substances) and a general familial environmental factor. The magnitude of influence of the general genetic factor ranged from 3% of the variance for opiates to 59% of the variance for cannabis. Some differences were seen from the univariate results, indicating some of the parameter estimates were unstable due to small numbers of concordant pairs. However, generalizations could be made. In women, the substances examined share genetic and familial environmental factors which contribute to the vulnerability to use. Degree of influence of the factors differs for the substances examined. However, no specific genetic or familial environmental factors were found to contribute significantly to use of any of the illicit substances.     

Evaluation of family history as a risk factor and screening tool for detecting undiagnosed diabetes in a nationally representative survey population.

PURPOSE: We examined the utility of a three-level familial risk stratification system as a screening tool for diabetes in a nationally representative sample of the U.S. adult population. METHODS: National Health and Nutrition Examination Survey data were used to assess the prevalence and distribution of familial risk for diabetes, the association between three levels of familial risk and undiagnosed diabetes, and the use of familial risk as a screening tool for diabetes, alone and in combination with body mass index and age. RESULTS: The prevalence of undiagnosed diabetes was 3% and increased with increasing familial risk (average = 2%, moderate = 4%, high = 10%). High familial risk was significantly associated with undiagnosed diabetes (adjusted odds ratio = 4.6; 95% confidence interval: 1.9-11.3). The use of a three-tiered familial risk stratification for diabetes screening yielded higher specificity (94%) and positive predictive value (9.9%) for high familial risk than body mass index > or = 25 (specificity = 38%, positive predictive value = 4.2%). High familial risk and body mass index > or = 25 combined had higher specificity (97%) and positive predictive value (13.4%); the addition of age > or = 45 years further improved positive predictive value (21.0%) without reducing specificity. CONCLUSIONS: There was a strong and proportional association between familial risk and undiagnosed diabetes, suggesting that a three-tiered assessment of familial diabetes risk may increase the effectiveness of diabetes screening.     

Temperament and iq mediate the effects of family history of substance abuse and family dysfunction on academic achievement

In this study of sons of substance-abusing (n = 57) and normal (n = 71) fathers, it was hypothesized that sonS' positive affective temperament (PAT) and intellectual ability (FSIQ) would mediate the effects of paternal substance abuse and family dysfunction on sonS' reading achievement scores. Hierarchical, linear, and path analytic regression analyses were computed to test the hypotheses. It was found that (1) sonS' FSIQ and PAT each partially mediated the effects of paternal substance abuse on sonS' reading achievement scores and (2) that sonS' PAT mediated the relationship between family dysfunction and their reading achievement scores. Because reading achievement is pivotal to academic success and school failure is associated with early age substance use, the importance of identifying processes that promote academic success is discussed.     

Distinguishing early and late onset non-melancholic unipolar depression

AIM: We seek to determine whether unipolar non-melancholic major depression commencing early in life has a differing clinical picture, and whether it may have differing determinants. METHODS: We study a sample of such patients, comparing those with depression onset in their first 25 years against residual subjects, matching exactly by sex and controlling for age. RESULTS: There were no differences in current depression severity. Despite early onset subjects having a distinctly younger current mean age, they had a lifetime pattern of both greater depression chronicity and disability, and judged themselves as less likely to have benefited from any antidepressant medication or psychotherapy. 'Phenotypically' early onset subjects did not differ in terms of 'depressive' symptoms, but were distinguished by a greater irritability, which we interpret as reflecting a temperament dimension influencing symptom expression. Multivariate analyses indicated that the clinical pattern in those with an early onset was distinguished by more evident irritability and anxiety, that there was a distinct familial contribution to early onset depression, that its forerunners were an early personality style of behavioural inhibition or shyness, and that they were more likely to use alcohol and illicit drugs. CONCLUSIONS: While early onset unipolar depression is unlikely to be a pure depressive 'type', it may well be that certain familial temperament characteristics lead to an early onset of depression marked by irritability, a process that invokes a spectrum disorder concept linking temperament style and the depressive manifestations. Early onset depression is indicative of a poor prognosis, both in terms of response to interventions and in regard to chronicity and disability.     

Temperament and risky behaviors: a pathway to HIV?

BACKGROUND: Certain sexual behaviors and abuse of substances contribute to the risk of becoming HIV-infected. Because dispositional characteristics are likely to influence this process, we examined the association between temperament and HIV serostatus in subjects with heavy use of drugs and various sexual risk behaviors. METHODS: Two hundred and thirty individuals (81% of whom were HIV-infected) were assessed for underlying temperamental characteristics, substance use, and risky sexual behaviors. Toward this goal, a factor analysis was conducted on a new self-rated Temperament Autoquestionnaire (Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A)). MANOVA was used to examine overall associations between risky behaviors and temperament. Additionally, directed MANOVAs were conducted for each of six drugs of abuse (alcohol, marijuana, cocaine, opioids, other stimulants, and sedative hypnotics). RESULTS: Factor analysis confirmed the hypothesized temperament structure of five distinct factors: Cyclothymic, hyperthymic, anxious, irritable-explosive, and depressive. Heavy users of cocaine, other stimulants, and alcohol were more likely to have an irritable-explosive temperament. Interestingly, heavy users of opioids were more likely to show depressive and hyperthymic traits. The inclusion of HIV status as a predictor of temperament did not alter the results. Unlike a previous study, no direct significant relationships were found between risky sexual behaviors and specific temperaments. LIMITATIONS: Relatively small sample size for a factor analytic study, and cross-sectional design, which cannot determine a cause and effect relationship. CONCLUSIONS: We succeeded in studying and validating five distinct affective temperaments in a substance abuse population. Irritable-explosive, and to a lesser extent, depressive and hyperthymic traits, were associated with substance use, and may place individuals at risk for HIV infection via that mechanism. That current risky sexual practices were not directly linked to temperament may reflect modification in sexual behavior following the acquisition of HIV disease.     

Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores,Parental Knowledge,and Peer Substance Use

Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene–environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; M_age = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene–environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.

     

Risk factors for adolescent substance abuse and dependence: data from a national sample

A national household probability sample of 4,023 adolescents aged 12 to 17 years was interviewed by telephone about substance use, victimization experiences, familial substance use, and posttraumatic reactions to identify risk factors for Diagnostic and Statistical Manual of Mental Disorders--(4th ed.; American Psychiatric Association, 1994) defined substance abuse/dependence. Age and ethnicity data were available for 3,907 participants. Major findings were (a) adolescents who had been physically assaulted, who had been sexually assaulted, who had witnessed violence, or who had family members with alcohol or drug use problems had increased risk for current substance abuse/dependence; (b) posttraumatic stress disorder independently increased risk of marijuana and hard drug abuse/dependence; and (c) when effects of other variables were controlled, African Americans, but not Hispanics or Native Americans, were at approximately 1/3 the risk of substance abuse/dependence as Caucasians.     

Assessing community effects on adolescent substance use and delinquency

This study investigates community‐level prediction of adolescent substance use and problem behaviors using ratings by community leaders to assess the effects of four risk factors on levels of drug use and problem behaviors. Three questions are examined: (a) Can psychometrically sound measures of community leader perceptions of risk factors in their community be developed?; (b) What is the relationship between community leader ratings of the community and student perceptions of their community?; and (c) How are community leader ratings and student perceptions of the community related to community levels of current student substance use and serious delinquency? Results indicate that community leaders' perceptions of community risk factors demonstrate both internal validity and criterion validity. Community leaders and students demonstrate modest agreement in assessments of community risk factors. Community leaders' ratings of community norms favorable to substance use and community law enforcement permissive of substance use were related to levels of substance use reported by students. Leader ratings of low community attachment, community disorganization, and community law enforcement permissive of substance use were related to community levels of serious delinquency reported by students. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 925–946, 2007.