Adolescent substance use, externalizing and attention problems, and early life stress (ELS) commonly co-occur. These psychopathologies show overlapping neural dysfunction in the form of reduced recruitment of reward processing neuro-circuitries. However, it is unclear to what extent these psychopathologies show common v. different neural dysfunctions as a function of symptom profiles, as no studies have directly compared neural dysfunctions associated with each of these psychopathologies to each other.

In study 1, a latent profile analysis (LPA) was conducted in a sample of 266 adolescents (aged 13–18, 41.7% female, 58.3% male) from a residential youth care facility and the surrounding community to investigate substance use, externalizing and attention problems, and ELS psychopathologies and their co-presentation. In study 2, we examined a subsample of 174 participants who completed the Passive Avoidance learning task during functional magnetic resonance imaging to examine differential and/or common reward processing neuro-circuitry dysfunctions associated with symptom profiles based on these co-presentations.

In study 1, LPA identified profiles of substance use plus rule-breaking behaviors, attention-deficit hyperactivity disorder, and ELS. In study 2, the substance use/rule-breaking profile was associated with reduced recruitment of reward processing and attentional neuro-circuitries during the Passive Avoidance task (p < 0.05, corrected for multiple comparisons).

Findings indicate that there is reduced responsivity of striato-cortical regions when receiving outcomes on an instrumental learning task within a profile of adolescents with substance use and rule-breaking behaviors. Mitigating reward processing dysfunction specifically may represent a potential intervention target for substance-use psychopathologies accompanied by rule-breaking behaviors.

People who tend to impulsively choose smaller, sooner rewards over larger, later rewards are at increased risk for addiction and psychiatric disorders. A neurobiological measure of the tendency to overvalue immediate gratification could facilitate the study of individuals who are susceptible to these mental disorders. The objective of this research was to develop a cortical assay of impulsive choice for immediate rewards.

A cortex-based assay of impulsive choice was developed using 1105 healthy adults from the Human Connectome Project, and then cross-validated in two independent samples of adults with elevated rates of psychiatric disorders.

Study 1: Cortical delay discounting (C-DD) was developed using a multivariate additive model of gray matter thickness across both hemispheres. Higher C-DD corresponded to thinner cortex and greater impulsive choice for immediate rewards. It also predicted cannabis use beyond established risk factors for drug use, including familial substance use, childhood conduct problems, personality traits, and cognitive functioning. Study 2: C-DD replicated the association with delay discounting performance from study 1. Structural equation modeling showed C-DD covaried with symptoms of externalizing, but not internalizing disorders. Study 3: C-DD positively predicted future delay discounting behavior (6–34 months later).

Across three studies, a cortical assay of impulsive choice evidenced consistent associations with drug use and delay discounting task performance. It was also uniquely associated with psychiatric disorders that share impulsivity as a core feature. Together, findings support the utility of C-DD as a neurobiological assay of impulsive decision-making and a possible biomarker of externalizing disorders.

Resting pulse is robustly and inversely associated with the risk for externalizing disorders and may be positively associated with internalizing disorders. We know little about the causal nature of these associations.

We examined resting pulse at conscription examination in 369 301 males born 1960–80 with a mean (s.d.) follow-up of 29.1 (7.7) years. From pulse rates, we predicted, using Cox models, the risk for criminal behavior (CB), drug abuse (DA), alcohol use disorder (AUD), major depression (MD), and anxiety disorders (AD), assessed from medical, criminal, and pharmacy registries. Co-relative analyses were conducted on the general population, cousin, half-sibling, full-sibling, and monozygotic pairs discordant for the outcome. Twin/sibling modeling for pulse was performed using OpenMX.

Familial resemblance for pulse resulted entirely from genetic factors. In the general population, the risk for externalizing disorders (CB, DA, and AUD) and internalizing disorders (MD and AD) were, respectively, significantly associated with low and high resting pulse rate. For CB, DA, and AUD, co-relative analyses showed that the inverse association with pulse resulted entirely from familial common causes (aka ‘confounders’). By contrast, co-relative analyses found that the association between higher pulse and MD and AD resulted from direct causal effects.

Resting pulse has a negative and positive association with, respectively, the risk for externalizing and for internalizing disorders. Co-relative analyses indicate that the nature of these associations differ, suggesting that elevated pulse appears to directly increase the risk for internalizing disorders while the reduced pulse is a risk index for underlying traits that predispose to externalizing disorders.

Research suggests that personality traits have both direct and indirect effects on the development of psychological symptoms, with indirect effects mediated by stressful or traumatic events. This study models the direct influence of personality traits on residualized changes in internalizing and externalizing symptoms following a stressful and potentially traumatic deployment, as well as the indirect influence of personality on symptom levels mediated by combat exposure.

We utilized structural equation modeling with a longitudinal prospective study of 522 US National Guard soldiers deployed to Iraq. Analyses were based on self-report measures of personality, combat exposure, and internalizing and externalizing symptoms.

Both pre-deployment Disconstraint and externalizing symptoms predicted combat exposure, which in turn predicted internalizing and externalizing symptoms. There was a significant indirect effect for pre-deployment externalizing symptoms on post-deployment externalizing via combat exposure (p < 0.01). Negative Emotionality and pre-deployment internalizing symptoms directly predicted post-deployment internalizing symptoms, but both were unrelated to combat exposure. No direct effects of personality on residualized changes in externalizing symptoms were found.

Baseline symptom dimensions had significant direct and indirect effects on post-deployment symptoms. Controlling for both pre-exposure personality and symptoms, combat experiences remained positively related to both internalizing and externalizing symptoms. Implications for diagnostic classification are discussed.

Cross-sectional and longitudinal studies have shown a positive association between attention deficit hyperactivity disorder (ADHD) and problematic alcohol use in adults. To what extent this association is explained by genetic and environmental factors is largely unknown.

Data on ADHD and alcohol consumption were collected by self-report in 6024 adult Dutch twins. ADHD symptoms were assessed by three subscales of the Conners' Adult ADHD Rating Scales – Self-Report: Screening Version (CAARS–S:SV): inattentiveness, hyperactivity and the ADHD index (ADHD-I). Problem drinking was defined as at least two self-reported alcohol-related problems on the CAGE questionnaire. Structural equation modelling was applied to the bivariate twin data to estimate genetic and environmental influences.

Heritability of ADHD symptoms ranged between 32% and 40% and heritability of problem drinking was 50%. The positive correlation between ADHD symptoms and problem drinking was confirmed in this general population sample, with phenotypic correlations between 0.20 and 0.28 and genetic correlations between 0.39 and 0.50. Phenotypic correlations are primarily (61–100%) explained by genetic influences with non-shared environmental influences explaining the remaining covariance. No significant quantitative or qualitative gender differences in covariance structure were found.

This study convincingly shows that ADHD symptoms and problem drinking are moderately but significantly correlated in adults and that genetic correlations are primarily underlying this association. This suggests that early interventions are required to prevent adolescents with ADHD from developing problematic levels of alcohol use. Furthermore, clinicians who treat alcohol-dependent patients should be aware that the patient may have a co-morbid condition of ADHD; integrated interventions are required.

Individuals with borderline personality disorder (BPD) frequently display co-morbid mental disorders. These disorders include ‘internalizing’ disorders (such as major depressive disorder and anxiety disorders) and ‘externalizing’ disorders (such as substance use disorders and antisocial personality disorder). It is hypothesized that these disorders may arise from latent ‘internalizing’ and ‘externalizing’ liability factors. Factor analytic studies suggest that internalizing and externalizing factors both contribute to BPD, but the extent to which such contributions are familial is unknown.

Participants were 368 probands (132 with BPD; 134 without BPD; and 102 with major depressive disorder) and 885 siblings and parents of probands. Participants were administered the Diagnostic Interview for DSM-IV Personality Disorders, the Revised Diagnostic Interview for Borderlines, and the Structured Clinical Interview for DSM-IV.

On confirmatory factor analysis of within-person associations of disorders, BPD loaded moderately on internalizing (factor loading 0.53, s.e. = 0.10, p < 0.001) and externalizing latent variables (0.48, s.e. = 0.10, p < 0.001). Within-family associations were assessed using structural equation models of familial and non-familial factors for BPD, internalizing disorders, and externalizing disorders. In a Cholesky decomposition model, 84% (s.e. = 17%, p < 0.001) of the association of BPD with internalizing and externalizing factors was accounted for by familial contributions.

Familial internalizing and externalizing liability factors are both associated with, and therefore may mutually contribute to, BPD. These familial contributions account largely for the pattern of co-morbidity between BPD and internalizing and externalizing disorders.

Epidemiological research is believed to underestimate the lifetime prevalence of mental illness due to recall failure and a lack of rapport between researchers and participants.

In this prospective study, we examined lifetime prevalence and co-morbidity rates of substance use disorders, antisocial personality disorder (ASPD) and major depressive disorder (MDD) in a representative, statewide Minnesota sample (n = 1252) assessed four times between the ages of 17 and 29 years with very low attrition.

Lifetime prevalence rates of all disorders more than doubled between the ages of 17 and 29 years in both men and women, and our prospective rates at the age of 29 years were consistently higher than rates from leading epidemiological surveys. Although there was some variation, the general trend was for lifetime co-morbidity to increase between the ages of 17 and 29 years, and this trend was significant for MDD–alcohol dependence, MDD–nicotine dependence, and ASPD–nicotine dependence.

Overall, our results show that emerging adulthood is a high-risk period for the development of mental illness, with increases in the lifetime prevalence and co-morbidity of mental disorders during this time. More than a quarter of individuals had met criteria for MDD and over a fifth had experienced alcohol dependence by the age of 29 years, indicating that mental illness is more common than is estimated in cross-sectional mental health surveys. These findings have important implications for the measurement of economic burden, resource allocation toward mental health services and research, advocacy organizations for the mentally ill, and etiological theories of mental disorders.

The distribution and co-morbidity of common psychiatric disorders can be largely explained as manifestations of two broad psychopathological spectra of internalizing and externalizing disorders. Twin studies suggest that these spectra arise from genetic factors.

Structural equation twin modeling was applied to interview and questionnaire data on personality traits and lifetime psychiatric disorders on more than 5300 members of male–male (MM) and female–female (FF) twin pairs.

The best-fitting models for both the externalizing and internalizing spectra differed significantly in males and females. In males, the externalizing genetic common factor was best indexed by four disorders in the following order: antisocial personality disorder (ASPD), drug abuse/dependence (DAD), alcohol abuse dependence (AAD) and conduct disorder (CD). In females, the four disorders most closely related to the externalizing common factor were, in order: DAD, AAD, nicotine dependence (ND) and ASPD. Personality traits of novelty seeking (NS) and extraversion (E) better indexed the genetic externalizing spectrum in females than in males. In both males and females, major depression (MD) and generalized anxiety disorder (GAD) best indexed the genetic internalizing common factor. Panic disorder (PD) and agoraphobia (AgP) better reflected the internalizing genetic common factor in women, and neuroticism (N) in men. Genetic correlations between the two spectra were estimated at + 0.53 in males and + 0.52 in females.

The disorders that optimally index the genetic liability to externalizing and internalizing disorders in the general population differ meaningfully in men and women. In both sexes, these genetic spectra are better assessed by psychiatric disorders than by personality traits.

We examined the relationship between the onset and pattern of childhood mental health disorders and subsequent current smoking status at age 17 years.

Data were from a prospective cohort study of 2868 births of which 1064 supplied information about their current smoking at 17 years of age. The association between the onset and pattern of clinically significant mental health disorders in the child and subsequent smoking at age 17 years was estimated via multivariable logistic regression.

Relative to 17 year olds who never had an externalizing disorder, 17-year-olds who had an externalizing disorder at age 5, 8 or 14 years were, respectively, 2.0 times [95% confidence interval (CI) 1.24–3.25], 1.9 (95% CI 1.00–3.65) or 3.9 times (95% CI 1.73–8.72) more likely to be a current smoker. Children with an ongoing pattern of externalizing disorder were 3.0 times (95% CI 1.89–4.84) more likely to be smokers at the age of 17 years and those whose mothers reported daily consumption of 6–10 cigarettes at 18 weeks' gestation were 2.5 times (OR 2.46, 95% CI 1.26–4.83) more likely to report smoking at 17 years of age. Associations with early anxiety and depression in the child were not found.

Current smoking in 17-year-olds may be underpinned by early emergent, and then, ongoing, externalizing disorder that commenced as young as age 5 years as well as exposure to early prenatal maternal smoking. The associations documented in adults and adolescents that link tobacco smoking and mental health are likely to be in play at these early points in development.

Previous research indicates that alcohol and drug dependence constitute aspects of a general vulnerability to externalizing disorders that accounts for much of the parent-offspring resemblance for these and related disorders. This study examined how adolescent offspring risk for externalizing psychopathology varies with respect to parental alcoholism and illicit drug dependence.

Data from the Minnesota Twin Family Study, a community-based investigation of adolescents (age 17 years, n=1252) and their parents, were used. Lifetime diagnoses of alcohol and drug dependence (among both parents and offspring) and offspring attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, adult antisocial behavior, and nicotine dependence were assessed via structured interviews.

Parental alcohol dependence and parental drug dependence were similarly associated with increased risk for nearly all offspring disorders, with offspring of alcohol and drug-dependent parents having approximately 2–3 times the odds for developing a disorder by late adolescence compared to low-risk offspring. Compared to parental dependence on other illicit drugs, parental cannabis dependence was associated with weaker increased risk for offspring externalizing disorders.

Both parental alcohol and drug dependence are independently associated with an increased risk for a broad range of externalizing psychopathology among late-adolescent offspring.