Nicole L. Schmidt

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.

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.

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.

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.

Mapping White Matter Microstructure in the One Month Human Brain

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Investigation of brain structure in the 1-month infant

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

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.

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.

Correction to: Investigation of brain structure in the 1-month infant.

The authors regret that, in this article, there was an error in the analyses comparing infant male and female regional brain volume differences.