The Heritability of Psychopathology Symptoms in Early Adolescence: Moderation by Family Cultural Values in the ABCD Study.

Family cultural values that emphasize support, loyalty, and obligation to the family are associated with lower psychopathology in Hispanic/Latino/a youth, but there is a need to understand the implications of family cultural values for youth development in racially/ethnically heterogeneous samples. This study examined phenotypic associations between parent- and youth-reported family cultural values in late childhood on youth internalizing and externalizing symptoms in early adolescence, and whether family cultural values moderated genetic and environmental influences on psychopathology symptoms. The sample comprised 10,335 children (Mage=12.89 years; 47.9% female; 20.3% Hispanic/Latino/a, 15.0% Black, 2.1% Asian, 10.5% other) and their parents from the Adolescent Brain Cognitive Development (ABCD) Study, and biometric models were conducted in the twin subsample (n = 1,042 twin pairs; 43.3% monozygotic). Parents and youth reported on their family cultural values using the Mexican American Cultural Values Scale at youth age 11-12, and parents reported on youth internalizing and externalizing symptoms using the Child Behavior Checklist at youth ages 11-12 and 12-13. Greater parent- and youth-reported family cultural values predicted fewer youth internalizing and externalizing symptoms. Biometric models indicated that higher parent-reported family cultural values increased the nonshared environmental influences on externalizing symptoms whereas youth-reported family cultural values decreased the nonshared environmental influences on internalizing symptoms. This study highlights the need for behavior genetic research to consider a diverse range of cultural contexts to better understand the etiology of youth psychopathology.

Shifting goalposts: widening discrepancies between girls' actual and ideal bodies predict disordered eating from preadolescence to adulthood.

BACKGROUND: Little is known regarding how disordered eating (DE) relates to perceived actual body size, ideal body size, and their discrepancy. This study examined changes in perceived actual body size, ideal body size, and actual-ideal discrepancies over time, and their relationship with subsequent DE. METHODS: Participants were 759 female twins from the Minnesota Twin Family Study who reported on body image and DE every three to five years between approximately ages 11 to 29. We used multilevel modeling to examine developmental trajectories of body mass index (BMI) and Body Rating Scale Actual, Ideal, and Actual-Ideal discrepancy scores and compared the degree to which BMI, BRS body size perceptions, and body dissatisfaction predicted DE behaviors and attitudes over time. Participants were treated as singletons in analyses. RESULTS: Perceived Actual body sizes and BMIs increased from age 10 to 33, whereas Ideal body sizes remained largely stable across time, resulting in growing Actual-Ideal discrepancies. Body size perceptions and Actual-Ideal discrepancies predicted subsequent DE behaviors and attitudes more strongly than did body dissatisfaction as measured by self-report questionnaires. CONCLUSIONS: This research advances understanding of how female body size perceptions and ideals change across development and highlights their relationship with subsequent DE.

Maladaptive personality traits and older adult relationship satisfaction: A co-twin control approach to understanding associations.

OBJECTIVE: Maladaptive personality traits have been implicated in romantic relationship dissatisfaction, but the etiology of those links and the degree to which they extend to other types of relationships are unclear. The purpose of this study was to examine associations between maladaptive personality traits and satisfaction in various relationships using a co-twin control design to identify potential environmental contributions. METHOD: The sample consisted of 1340 older adult twin participants from the Minnesota Twin Registry (Mage = 70.3) that completed the Personality Inventory for DSM-5 Faceted Brief Form and Network of Relationships Inventory (Revised for Older Adults). RESULTS: Several maladaptive personality traits were phenotypically associated with relationship dissatisfaction, with detachment and negative affect having the largest effects. Further, within twin pair differences in detachment and negative affect were associated with greater relationship dissatisfaction, suggesting that observed associations were mediated partly by the unique environment, not solely the result of genetic and familial confounding. Both phenotypic and co-twin associations were strongest overall in the romantic partner relationship. CONCLUSION: These findings support the notion that maladaptive personality traits are implicated in interpersonal dysfunction across multiple domains.

Associations between adolescent cannabis use and young-adult functioning in three longitudinal twin studies.

Observational studies have linked cannabis use to an array of negative outcomes, including psychiatric symptoms, cognitive impairment, and educational and occupational underachievement. These associations are particularly strong when cannabis use occurs in adolescence. Nevertheless, causality remains unclear. The purpose of the present study was thus to examine associations between prospectively assessed adolescent cannabis use and young-adult outcomes (psychiatric, cognitive, and socioeconomic) in three longitudinal studies of twins (n = 3,762). Twins reporting greater cumulative cannabis use in adolescence reported higher levels of psychopathology as well as poorer socioeconomic outcomes in young adulthood. However, cannabis use remained associated only with socioeconomic outcomes (i.e., educational attainment, occupational status, and income) in monozygotic-cotwin control analyses, which account fully for shared genetic and environmental confounding. Follow-up analyses examining associations between twin differences in adolescent cannabis use and longitudinal change in academic functioning during the middle- and high-school years provided a possible mechanism for these associations, indicating that greater cannabis use during this period was associated with decreases in grade point average and academic motivation as well as increases in academic problem behavior and school disciplinary problems. Our findings thus suggest that cannabis use in adolescence has potentially causal, deleterious effects on adolescent academic functioning and young-adult socioeconomic outcomes despite little evidence suggesting a strong, causal influence on adult mental health or cognitive ability.

Testing the consequences of alcohol, cannabis, and nicotine use on hippocampal volume: a quasi-experimental cotwin control analysis of young adult twins.

BACKGROUND: Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences. METHODS: In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI. RESULTS: Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use. CONCLUSIONS: The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.

Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

BACKGROUND: Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset. METHODS: PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models. RESULTS: Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence. CONCLUSIONS: PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

Genotype Data and Derived Genetic Instruments of Adolescent Brain Cognitive Development Study® for Better Understanding of Human Brain Development.

The data release of Adolescent Brain Cognitive Development® (ABCD) Study represents an extensive resource for investigating factors relating to child development and mental wellbeing. The genotype data of ABCD has been used extensively in the context of genetic analysis, including genome-wide association studies and polygenic score predictions. However, there are unique opportunities provided by ABCD genetic data that have not yet been fully tapped. The diverse genomic variability, the enriched relatedness among ABCD subsets, and the longitudinal design of the ABCD challenge researchers to perform novel analyses to gain deeper insight into human brain development. Genetic instruments derived from the ABCD genetic data, such as genetic principal components, can help to better control confounds beyond the context of genetic analyses. To facilitate the use genomic information in the ABCD for inference, we here detail the processing procedures, quality controls, general characteristics, and the corresponding resources in the ABCD genotype data of release 4.0.

Pubertal timing and adolescent outcomes: investigating explanations for associations with a genetically informed design.

BACKGROUND: Psychopathology and risky behaviors increase during adolescence, and understanding which adolescents are most at risk informs prevention and intervention efforts. Pubertal timing relative to same-sex, same-age peers is a known correlate of adolescent outcomes among both boys and girls. However, it remains unclear whether this relation is better explained by a plausible causal process or unobserved familial liability. METHODS: We extended previous research by examining associations between pubertal timing in early adolescence (age 14) and outcomes in later adolescence (age 17) in a community sample of 2,510 twins (49% boys, 51% girls). RESULTS: Earlier pubertal timing was associated with more substance use, risk behavior, internalizing and externalizing problems, and peer problems in later adolescence; these effects were small, consistent with previous literature. Follow-up co-twin control analyses indicated that within-twin-pair differences in pubertal timing were not associated with within-twin-pair differences in most adolescent outcomes after accounting for shared familial liability, suggesting that earlier pubertal timing and adolescent outcomes both reflect familial risk factors. Biometric models indicated that associations between earlier pubertal timing and negative adolescent outcomes were largely attributable to shared genetic liability. CONCLUSIONS: Although earlier pubertal timing was associated with negative adolescent outcomes, our results suggests that these associations did not appear to be caused by earlier pubertal timing but were likely caused by shared genetic influences.

The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

Causal effects of cannabis legalization on parents, parenting, and children: A systematic review.

Medical and recreational cannabis legalization lead to increased cannabis use among adults. There is concern that legalization has negative implications for minors via effects on parents. We conducted a systematic review of studies examining legalization in the United States. Web of Science, PsycInfo, and PubMed were searched through May 2021, studies examining effects of legalization on maternal cannabis and other substance use during pregnancy and postpartum, perinatal outcomes, parental cannabis and other substance use and attitudes, parenting, and child outcomes were identified, and two independent reviewers extracted information on study designs, samples, and outcomes, and assessed classification of evidence and risk of bias. Forty-one studies met inclusion criteria; only 6 (15%) used the most causally informative study design (difference in differences). It is likely legalization increases maternal cannabis use during pregnancy and postpartum, parental cannabis use, and approval of adult cannabis use. Legalization may increase some adverse perinatal outcomes, though findings were inconsistent. It is likely legalization increases unintentional pediatric cannabis exposure. There is insufficient evidence for effects of legalization on child abuse and neglect, and there have been no studies examining effects of legalization on other aspects of parenting or on child adjustment. There is a critical lack of causally informative epidemiological studies examining effects of legalization on parenting and young children. Additional causally informative research is needed. Studies of parental cannabis use in a legal context are particularly needed. Commonsense guidelines must recognize the shifting national landscape around legalization while seeking to minimize potential harm to minors.

Commentary: Substance use and the brain: it is not straightforward to differentiate cause from consequence - a commentary on Kim-Spoon et al. (2020).

That substance abuse is associated with differences in brain structure and function, and related neurocognitive impairment is undisputed. Causally informative study designs, such as the prospective, longitudinal study leveraged by Kim-Spoon et al. (2020), as well as twin and family studies, are necessary for answering vexing but critical questions about substance use and the developing brain. Investigations that seek to differentiate cause from consequence and identify the factors that initiate the cycle of addiction have the potential to transform our understanding of the development of substance use and abuse, prompt revisions to current models of addiction, guide the most strategic preventive-intervention efforts, and ultimately improve the lives of millions of affected individuals and their families.

Internalizing-externalizing comorbidity and regional brain volumes in the ABCD study.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability - mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

A developmental perspective on personality and psychopathology across the life span.

Taking a developmental perspective, guided by core principles of developmental science and developmental psychopathology, is necessary to move the fields of personality science and psychopathology forward. Personality and psychopathology can be delineated using hierarchical models of individual differences, as evidenced by decades of converging evidence across community and psychiatric samples, countries and cultures, and ages and developmental periods. A large body of empirical research likewise documents associations between personality and various forms of psychopathology. Cross-sectional investigations of personality-psychopathology links in samples of adults now yield diminishing returns. Prospective, longitudinal investigations that assess personality, psychopathology, and their co-development across the life span are needed to determine their temporal ordering, capture dynamic associations over time and development, and elucidate causal origins and underlying mechanisms. We lay out a developmental framework that integrates across the developmental, personality, and psychopathology literatures in order to further understanding and guide future investigations of the nature of personality-psychopathology links.

Close relationships and depression: A developmental cascade approach.

Previous research has shown that problematic parent-child, peer, and romantic partner relationships are associated with an increased likelihood for major depressive disorder (MDD). Less research has evaluated the developmental unfolding of how these interpersonal relationship features are both an antecedent versus a consequence of MDD symptoms from adolescence through young adulthood. These gaps were evaluated using a large community sample (N = 1,127; 54% female, 96% white) via a developmental cascade model. Results showed support for significant antecedent effects, as greater parent-child relationship problems at ages 11 and 17 predicted rank-order increases in MDD symptoms at ages 14 and 20. Supporting a developmental cascade of problematic social relationships, greater parent-child relationship problems at ages 11 and 14 also predicted greater subsequent rank-order increases in antisocial peer affiliation at ages 14 and 17. Greater affiliation to antisocial peers at age 20 predicted greater rank-order increases in romantic relationship problems at age 24, which in turn predicted greater MDD symptoms at age 29. Cross-effects were generally small (ßs ≤ .16), illustrating other factors may be relevant to the development or consequences of MDD. Nonetheless, findings support the importance of efforts to strengthen social support networks to offset risk as well as potentially treat depression.

Trait neuroticism and emotion neurocircuitry: Functional magnetic resonance imaging evidence for a failure in emotion regulation.

Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala-ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.

Minnesota Center for Twin and Family Research.

The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.

Problematic alcohol use and hippocampal volume in a female sample: disentangling cause from consequence using a co-twin control study design.

BACKGROUND: Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure. METHODS: The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging. RESULTS: Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase. CONCLUSIONS: The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts.

Mediating pathways from childhood ADHD to adolescent tobacco and marijuana problems: roles of peer impairment, internalizing, adolescent ADHD symptoms, and gender.

BACKGROUND: We examined whether increased risk for adolescent tobacco and marijuana problems associated with childhood ADHD is explained by key intermediary influences during adolescence and differs by gender. METHODS: Longitudinal structural equation models examined mediating effects on problems with both substances (or each substance separately) through age-14 peer impairment, internalizing, and adolescent ADHD symptoms in two twin samples, prospectively assessed since age 11 (N = 2,164). Whether these mediators contributed beyond mediating effects of early-adolescent substance use was also considered. Twin difference analyses further illuminated which mediators might be potentially causal. RESULTS: Direct effects of childhood ADHD on age-17 tobacco and marijuana problems (i.e., independent of included mediators) as well as effects of adolescent ADHD symptoms were significant only for females. By contrast, mediation by peer impairment, evident particularly for marijuana, was relatively stronger for males than females. Depression and anxiety were not prospectively associated with age-17 substance problems when earlier substance problems were considered. Consistent with causal influence of early substance use on later problems, monozygotic twins with more severe tobacco or marijuana problems at age 14 than their co-twins were also more likely to have substance problems later in adolescence. CONCLUSIONS: Mediation through peer impairment, continued presence of ADHD symptoms, and early substance use may alter development so that childhood ADHD indirectly contributes to problems with tobacco and marijuana. Targeting gender-sensitive interventions prior to mid-adolescence, before these patterns become established, is essential.