Matt McGue

Etiologic Connections Among Substance Dependence, Antisocial Behavior, and Personality: Modeling the Externalizing Spectrum

A hierarchical biometric model is presented of the origins of comorbidity among substance dependence, antisocial behavior, and a disinhibited personality style. The model posits a spectrum of personality and psychopathology, united by an externalizing factor linked to each phenotype within the spectrum, as well as specific factors that account for distinctions among phenotypes within the spectrum. This model fit self-report and mother-report data from 1,048 male and female 17-year-old twins. The variance of the externalizing factor was mostly genetic, but both genetic and environmental factors accounted for distinctions among phenotypes within the spectrum. These results reconcile evidence for general and specific causal factors within the externalizing spectrum and offer the externalizing factor as a novel target for future research.

Adjustment of twin data for the effects of age and sex

For most psychological, physiological, and medical variables there are substantial age and sex effects. In assessing twin similarity for these variables, one can either fail to adjust for the effects of age and sex, adjust for these effects using normative data, or use information in the twin sample to define an age-sex adjustment. It is shown that failing to correct for age and sex effects when they exist will result in overestimation of the twin intraclass correlation. Using normative data to define an age-sex adjustment will also result in overestimation of the twin intraclass correlation, although the magnitude of this overestimation is slight for moderate-sized normative samples and virtually nonexistent for large normative samples. Using a twin-based age-sex adjustment will lead to an underestimation of the twin intraclass correlation, but this underestimation can be corrected for through proper specification of the degrees of freedom for the between-pairs mean square. Illustration of the effects of age-sex adjustment are provided as well as the results of a computer simulation comparison of the various approaches. It is concluded that, even with moderately sized samples, the effects of age and sex can best be adjusted for through a twin-based approach.

The heritability of human longevity: A population-based study of 2872 Danish twin pairs born 1870–1900

The aim of this study was to explore, in a large and non-censored twin cohort, the nature (i.e., additive versus non-additive) and magnitude (i.e., heritability) of genetic influences on inter-individual differences in human longevity. The sample comprised all identified and traced non-emigrant like-sex twin pairs born in Denmark during the period 1870–1900 with a zygosity diagnosis and both members of the pairs surviving the age of 15 years. A total of 2872 pairs were included. Age at death was obtained from the Danish Central Person Register, the Danish Cause-of-Death Register and various other registers. The sample was almost non-censored on the date of the last follow-up (May 1, 1994), all but 0.6% had died, leaving a total of 2872 pairs for analysis. Proportions of variance attributable to genetic and environmental factors were assessed from variance-covariance matrices using the structural equation model approach. The most parsimonious explanation of the data was provided by a model that included genetic dominance (non-additive genetic effects caused by interaction within gene loci) and non-shared environmental factors (environmental factors that are individual-specific and not shared in a family). The heritability of longevity was estimated to be 0.26 for males and 0.23 for females. The small sex-difference was caused by a greater impact of non-shared environmental factors in the females. Heritability was found to be constant over the three 10-year birth cohorts included. Thus, longevity seems to be only moderately heritable. The nature of genetic influences on longevity is probably non-additive and environmental influences non-shared. There is no evidence for an impact of shared (family) environment.

Behavioral disinhibition and the development of substance-use disorders: Findings from the Minnesota Twin Family Study

One variant of substance-use disorder is characterized by behavioral disinhibition. In this report, we martial evidence for a model for the development of this variant. We hypothesize that genetic liability for this variant is reflected in a spectrum of risk indicators linked to the inability or unwillingness to inhibit behavioral impulses. Included in this spectrum are personality traits suggesting low constraint, and externalizing psychopathology, including conduct, oppositional defiant, and attention-deficit disorder in children and antisocial personality disorder and behavior in adults. We further hypothesize that these individual differences in behavioral disinhibition are manifestations of underlying central nervous system processes associated with various psychophysiological anomalies, some of which may index genetic risk for substance abuse. Support for the model is derived from the analysis of findings from the Minnesota Twin Family Study, an epidemiological investigation of approximately 2,700 adolescent twins and their parents.

Personality Stability and Change in Early Adulthood: A Behavioral Genetic Analysis.

Seventy-nine monozygotic and 48 same-sex dizygotic twin pairs completed the Multidimensional Personality Questionnaire twice, averaging 20 years of age at first and 30 years at second testing. There were significant mean decreases in measures of Negative Emotionality (NE), increases in measures of Constrain t (CO), but no significant mean changes for measures of Positive Emotionality (PE). Variance decreased for measures of NE but remained stable for measures of PE and CO. Biometrical analyses revealed that (a) NE variance reduction was due to diminishing genetic influences, (b) personality stability was due largely to genetic factors, and (c) although some evidence for genetic influence on personality change was observed, change was determined largely by environmental factors. It is concluded that the stable core of personality is strongly associated with genetic factors but that personality change largely reflects environmental factors.

Behavioral Disinhibition and the Development of Early-Onset Addiction: Common and Specific Influences

Research on substance use disorders is often compartmentalized, focused on understanding addiction to one substance or substance class at a time. Although this approach has contributed significantly to knowledge about addictions, early-onset substance use disorders appear to share common etiology with each other and with other disorders, traits, behaviors, and endophenotypes associated with behavioral disinhibition. We propose that a common genetic liability to behavioral disinhibition underlies the co-occurrence of these externalizing attributes. This liability is expressed in part through brain mechanisms related to cognitive control, impulsivity, and sensitivity to reward, all of which are maturing during adolescence. During this important transitional period, problem behaviors emerge, including the initiation of substance use. Exposure to various environmental risks further amplifies the risk associated with the common liability, increasing the likelihood of addiction generally. Specific environmental and genetic factors ultimately contribute to the differentiation among externalizing disorders.

A Developmental Perspective on Alcohol and Youths 16 to 20 Years of Age

Late adolescence (ie, 16–20 years of age) is a period characterized by escalation of drinking and alcohol use problems for many and by the onset of an alcohol use disorder for some. This heightened period of vulnerability is a joint consequence of the continuity of risk from earlier developmental stages and the unique neurologic, cognitive, and social changes that occur in late adolescence. We review the normative neurologic, cognitive, and social changes that typically occur in late adolescence, and we discuss the evidence for the impact of these transitions on individual drinking trajectories. We also describe evidence linking alcohol abuse in late adolescence with neurologic damage and social impairments, and we discuss whether these are the bases for the association of adolescent drinking with increased risks of mental health, substance abuse, and social problems in adulthood. Finally, we discuss both the challenges and successes in the treatment and prevention of adolescent drinking problems.

Sex and Age Effects on the Inheritance of Alcohol Problems: A Twin Study

Male monozygotic cotwins of probands with Alcohol Abuse-Dependence (n = 85) were more likely than male same-sex dizygotic cotwins (n = 96) to report alcohol, drug, and conduct disorder problems. For women, rates of problem behavior did not differ between monozygotic (n = 44) and same-sex dizygotic (n = 43) cotwins. Opposite-sex dizygotic twin data (n = 88) revealed significant cross-sex transmission; alcohol problems were greatest among male cotwins of female probands. For men, proportion of liability variance associated with additive genetic factors was significantly greater when proband had an early (h2 = .73 +/- .18) rather than late (h2 = .30 +/- .26) age of onset. For women, heritability did not vary as a function of probands age of onset, and the pooled estimate suggested little genetic influence (h2 = .00, SE not computable). Findings suggest that genetic influences may be substantial only in the etiology of early-onset male alcoholism.

The heritability of general cognitive ability increases linearly from childhood to young adulthood

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite lifes ‘slings and arrows of outrageous fortune’, do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype–environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.

The higher-order structure of common DSM mental disorders : internalization, externalization, and their connections to personality

Abstract Comorbidity among mental disorders is commonly observed in clinical and epidemiological samples. Can comorbidity be understood as meaningful covariance, and is this covariance structure linked with personality? We addressed this question in a sample of 634 female and 549 male, middle-aged participants in the Minnesota Twin-Family Study (MTFS). Mental disorders were assessed using the Structured Clinical Interview for DSM-III-R, the Substance Abuse Module from the Composite International Diagnostic Interview, and a specially-designed interview for the assessment of antisocial personality disorder. Personality was assessed using the Multidimensional Personality Questionnaire. Relations among symptom scales for eight common DSM disorders were compatible with hypothesized underlying bivariate normal distributions. Polychoric correlations among these scales were well-fit by a two-factor model positing internalizing and externalizing factors, which, in turn, were correlated with broad personality dimensions. Internalizing was positively correlated with negative emotionality (and negatively with positive emotionality in women) and externalizing was negatively correlated with constraint. These findings suggest that internalization, externalization, and their links to personality may provide a useful framework for understanding covariance among common adult mental disorders.