Longitudinal effects of family psychopathology and stress on pubertal maturation and hormone coupling in adolescent twins.

Adolescents experience profound neuroendocrine changes, including hormone "coupling" between cortisol, testosterone, and dehydroepiandrosterone. Emerging research has only begun to elucidate the role of hormone coupling, its genetic and environmental etiology, and the extent to which coupling is impacted by gender, puberty, and family context. We included measures on parent and child mental health, parenting stress, and family conflict of 444 twin pairs and their parents across two timepoints, when youth were on average 8 and 13 years old, respectively. Structural equation models examined the impact of family context effects on coupling during adolescence. Biometric twin models were then used to probe additive genetic, shared, and non-shared environmental effects on hormone coupling. Hormones were more tightly coupled for females than males, and coupling was sensitive to parental depression and co-twin psychopathology symptoms and stress exposure in females. The association between family context and coupling varied across specific neuroendocrine measures and was largely distinct from pubertal maturation. Biometric models revealed robust shared and non-shared environmental influences on coupling. We found that family antecedents modify the strength of coupling. Environmental influences account for much of the variation on coupling during puberty. Gender differences were found in genetic influences on coupling.

GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO POSITIVE AFFECT: INSIGHTS FROM ADOLESCENT TWINS.

Disturbances in positive affect and reductions in social reward/interpersonal pleasure are common across a range of clinical disorders and are often related. We examined the relationship between the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS-A), and other measures of positive affect in adolescents in a genetically informative research design. The sample consisted of 177 MZ and 136 same sex DZ twins drawn from a study of adolescent twins (M = 16.4 ± .97 years) who were part of the Wisconsin Twin Project. The self-report questionnaires included the Behavioral Activation Scale (BAS), Psychological Well-Being Scale, revised Early Adolescent Temperament Questionnaire (EATQR) and the adolescent version of the ACIPS (ACIPS-A). Structural equation modeling estimated the relative contribution of genetic and environmental factors to the phenotypic variance in each of the measures. Follow-up bivariate analyses parsed the genetic and environmental contributions to the phenotypic covariances between the ACIPS-A and each of the other measures of positive affect. We found evidence of moderate heritability for the ACIPS-A scale scores. Overall, models specifying additive genetic and unique environmental effects (AE models) were the most parsimonious models for each of the measures. Several of the measures showed moderate positive phenotypic intercorrelations, and all but one of these intercorrelations showed significant partial genetic underpinnings. Moreover, the bivariate biometric analyses indicated that the ACIPS-A also captures unique heritable variation. Thus, the ACIPS-A captures unique heritable contributions to social/interpersonal pleasure, as well as shared genetic variance with other measures of positive affectivity.

Wisconsin Twin Project Overview: Temperament and Affective Neuroscience.

The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989-2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.

Longitudinal Research at the Interface of Affective Neuroscience, Developmental Psychopathology, Health and Behavioral Genetics: Findings from the Wisconsin Twin Project.

The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene-environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.

Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure.

Importance: Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions. Objective: To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age. Design, Setting, and Participants: This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep. Main Outcomes and Measures: Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings. Results: In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period. Conclusions and Relevance: These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms.

The Shared Etiology of Attentional Control and Anxiety: An Adolescent Twin Study.

We investigated the etiology of attentional control (AC) and four different anxiety symptom types (generalized, obsessive-compulsive, separation, and social) in an adolescent sample of over 400 twin pairs. Genetic factors contributed to 55% of the variance in AC and between 43 and 58% of the variance in anxiety. Negative phenotypic associations between AC and anxiety indicated that lower attentional ability is related to increased risk for all 4 anxiety categories. Genetic correlations between AC and anxiety phenotypes ranged from -.36 to -.47, with evidence of nonshared environmental covariance between AC and generalized and separation anxiety. Results suggest that AC is a phenotypic and genetic risk factor for anxiety in early adolescence, with somewhat differing levels of risk depending on symptomatology.

Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins.

Stress and emotion involve diverse developmental and individual differences. Partially attributed to the development of the prefrontal cortex (PFC), the amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and experiential contributions remain unknown. In previous work, childhood basal cortisol function predicted adolescent resting-state functional connectivity (rs-FC) and psychopathology. To parse experience-driven (non-genetic) contributions, we investigated these relations with a monozygotic (MZ) twin design. Specifically, we examined whether intrapair differences in childhood afternoon cortisol levels predicted cotwin differences in adolescent brain function and coping. As expected, intrapair differences in childhood cortisol forecast amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery also predicted coping styles. These data highlight experience-dependent change in childhood and adolescence.

Wisconsin Twin Research: early development, childhood psychopathology, autism, and sensory over-responsivity.

The Wisconsin Twin Research Program comprises multiple longitudinal studies that utilize a panel recruited from statewide birth records for the years 1989 through 2004. Our research foci are the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, autism, sensory over-responsivity, and related topics. A signature feature of this research program is the breadth and depth of assessment during key periods of development. The assessments include extensive home- and laboratory-based behavioral batteries, recorded sibling and caregiver interactions, structured psychiatric interviews with caregivers and adolescents, observer ratings of child behavior, child self-report, cognitive testing, neuroendocrine measures, medical records, dermatoglyphics, genotyping, and neuroimaging. Across the various studies, testing occasions occurred between 3 months and 18 years of age. Data collection for some aspects of the research program has concluded and, for other aspects, longitudinal follow-ups are in progress.

Is sensory over-responsivity distinguishable from childhood behavior problems? A phenotypic and genetic analysis.

BACKGROUND: Although impaired sensory processing accompanies various clinical conditions, the question of its status as an independent disorder remains open. Our goal was to delineate the comorbidity (or lack thereof) between childhood psychopathology and sensory over-responsivity (SOR) in middle childhood using phenotypic and behavior-genetic analyses. METHOD: Participants (N = 970) were drawn from the Wisconsin Twin Project, a population-based sample of twins and their families. Mothers completed a sensory responsivity checklist when their offspring were on average 7 years old, followed by a diagnostic interview (Diagnostic Interview Schedule for Children; DISC) within 6-12 months. We examined the incidence of DISC diagnoses - attention deficit hyperactivity disorder, conduct disorder, oppositional defiant disorder, agoraphobia, general anxiety, obsessive-compulsive disorder, panic disorder, separation anxiety, social phobia, specific phobia, depression, enuresis, trichtollomaniatics, selective mutism, and pica - among children with SOR, and vice versa. Children with autism or pervasive developmental disorders were excluded from the present study. In addition, we examined parent-reported physical health diagnoses among nondiagnosed children and three groups of children with SOR and/or DISC diagnoses. Biometric models explored common underlying genetic and environmental influences on symptoms of SOR and psychopathology. RESULTS: A majority of individuals who screened positive for SOR did not qualify for a DISC diagnosis (58.2%), and vice versa (68.3%). Children who screened positive for SOR only and typical children had similar rates of physical health problems. Turning to a dimensional approach, multivariate twin models demonstrated that modest covariation between SOR and DISC symptoms could be entirely accounted for by common underlying genetic effects. CONCLUSIONS: Our results suggest that SOR occurs independently of recognized childhood psychiatric diagnoses but is also a relatively frequent comorbid condition with recognized diagnoses. Genetic sources of this comorbidity are implicated.

Sensory overresponsivity: prenatal risk factors and temperamental contributions.

OBJECTIVE: The study addresses risk factors and cause of pediatric sensory over-responsivity (SOR) in a large sample of twins. At age 2 years, (a) the association of temperamental traits with concurrent SOR; (b) the association of prenatal complications with SOR; (c) the association of having a male cotwin with female SOR; and (d) the common and unique genetic causes of temperament and SOR symptoms are examined. METHODS: The sample included 1026 twin pairs (mean age = 2 years 2 months) from a population-based longitudinal study. Auditory and tactile SOR symptom domains were partially independent and thus were examined separately. RESULTS: Temperamental negative affect and fear were moderately correlated with auditory and tactile SOR symptoms. Prenatal complications significantly predicted tactile symptoms after controlling for child characteristics. In addition, females with a male cotwin showed greater SOR at age 2 years than same-sex female dizygotic twins, suggesting a possible risk associated with in utero testosterone exposure. Both auditory and tactile SOR domains were heritable. Bivariate genetic analyses showed that each SOR domain had a similar genetic relationship with fear and negative affect. CONCLUSION: The findings suggest partially nonoverlapping causes and risk factors for tactile versus auditory SOR and indicate that prenatal factors warrant further investigation.

The limited effects of obstetrical and neonatal complications on conduct and attention-deficit hyperactivity disorder symptoms in middle childhood.

OBJECTIVE: The purpose of this study was to examine the effects of a wide range of obstetrical and neonatal complications as well as socioeconomic variables on the behaviors characterized by attention-deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder. METHOD: Data were collected on 7- to 8-year old twins, using multiple instruments assessing many areas of individual and family functioning. The influence of several aspects of prenatal care, labor and delivery, and early life were considered as well as indicators of socioeconomic status, such as family income and maternal education. RESULTS: The observed associations were stronger for attention-deficit hyperactivity disorder than conduct disorder symptoms and stronger for females than males. Family income and gender significantly predicted both behavioral outcomes, whereas birth weight predicted attention-deficit hyperactivity disorder symptoms only. However, the presence of attention-deficit hyperactivity disorder and conduct symptom behaviors were not associated with an occurrence of more obstetrical or neonatal complications as indicated by hierarchical linear modeling analyses. CONCLUSIONS: By school age, behavioral problems related to inattention, impulsivity, hyperactivity, defiance, and conduct are relatively unaffected by general adversity in the neonatal and perinatal periods.

Assessing internalizing, externalizing, and attention problems in young children: validation of the MacArthur HBQ.

OBJECTIVE: To test the validity of the MacArthur Health and Behavior Questionnaire (HBQ) using receiver operating characteristic (ROC) analysis to determine optimal thresholds for the HBQ in predicting Diagnostic Interview Schedule for Children Version-IV (DISC-IV) diagnoses. The roles of child sex, level of impairment, and physical health in understanding of psychopathology were also considered. METHOD: A sample of 814 8-year-old twin children was recruited from birth records. Mothers were interviewed over the telephone using the HBQ and were also interviewed in person using the DISC-IV. Fathers also completed the HBQ; children completed the parallel module of the Berkeley Puppet Interview. RESULTS: The HBQ identified more cases overall than the DISC-IV. Sex did not contribute to prediction of diagnosis. Impairment, DISC-IV symptom counts, father HBQ, child Berkeley Puppet Interview, and physical health significantly distinguished the HBQ low and high symptom groups. CONCLUSIONS: The HBQ is a valid new screening measure of psychopathology for use with children under 9 years of age. It is sensitive to internalizing disorders, which may aid the understanding of depression and anxiety disorders that are often underappreciated in young children.

Longitudinal analyses of affect, temperament, and childhood psychopathology.

The Wisconsin Twin Panel utilizes the resources of state birth records to study the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, the autism spectrum, and related psychobiological and behavioral phenotypes. The panel currently supports 5 active research studies which involve twins from birth to early adolescence. A range of research methods are employed, including questionnaires and structured interviews with caregivers, home and laboratory-based behavioral batteries, observer ratings, child self-report, psychophysiology, neuroendocrine measures, birth records, genotyping, and cognitive testing. The panel is in the early stages of generating longitudinal findings.