To examine if maltreatment predicted increased risk of hospital-based treatment prior to age 18 y... more To examine if maltreatment predicted increased risk of hospital-based treatment prior to age 18 years for asthma, cardio-respiratory, and non-sexually transmitted infectious disease in a sample of low-income children. This study used administrative data from multiple systems to follow children for 12-18 years (N = 6,282). Cox regression was used to explore the risk of first hospital treatment by disease category. Negative binomial regression was used to explore the relationship between recurrent maltreatment and total hospital care episodes. Controlling for individual, family, and community factors, children with maltreatment reports had a 74-100% higher risk of hospital treatment. Recurrent reports predicted a higher count of hospital care episodes. The negative health impact of maltreatment prior to adulthood supports the need for early prevention and intervention to prevent initial and recurrent child abuse and improve capacity to meet healthcare needs of maltreated children.
Although motor impairment is frequently observed in children with autism spectrum disorders (ASD)... more Although motor impairment is frequently observed in children with autism spectrum disorders (ASD), the manner in which these impairments aggregate in families affected by autism is unknown. We used a standardized measure of motor proficiency to objectively examine quantitative variation in motor proficiency in sibling pairs concordant and discordant for ASD. Motor impairment of sibling pairs from 67 ASD-affected families comprising 29 concordant pairings and 48 discordant pairings were assessed using the Bruininks Oseretsky Test of Motor Proficiency, 2nd Edition, a standardized measure of motor proficiency. Motor skills were substantially impaired among ASD-affected children and highly correlated with autistic severity and IQ, whereas motor skills in unaffected siblings were essentially normal. Total motor composite scores of at least one standard deviation below the general population mean were seen in 83% of the affected group compared with 6% in the unaffected siblings. Findings indicate that motor impairment constitutes a core characteristic of ASD (not necessarily an ASD endophenotype), which has distinct implications for taxonomy, diagnosis, and approaches to intervention.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder frequently co-occur.... more Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder frequently co-occur. Several studies show increased risk of substance use disorders in ADHD, yet there is limited information related to how ADHD symptoms, autistic traits, and their combined effects are associated with nicotine, alcohol, and cannabis use and use disorders in the general population. Cross-sectional interview and self-report questionnaire data from 3,080 young adult Australian twins (mean age 31.9 years) were used to assess ADHD symptoms, autistic traits, substance use, and substance use disorders. Substance use disorders-based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria-were assessed in the full sample as well as in those who reported substance use. Logistic regression analyses were used for comparing the associations between ADHD symptoms, autistic traits, substance use, and substance misuse after conduct disorder, sex, age, and zygosity were controll...
We used surface-based morphometry to test for differences in cortical shape between children with... more We used surface-based morphometry to test for differences in cortical shape between children with simplex autism (n = 34, mean age 11.4 years) and typical children (n = 32, mean age 11.3 years). This entailed testing for group differences in sulcal depth and in 3D coordinates after registering cortical midthickness surfaces to an atlas target using 2 independent registration methods. We identified bilateral differences in sulcal depth in restricted portions of the anterior-insula and frontal-operculum (aI/fO) and in the temporoparietal junction (TPJ). The aI/fO depth differences are associated with and likely to be caused by a shape difference in the inferior frontal gyrus in children with simplex autism. Comparisons of average midthickness surfaces of children with simplex autism and those of typical children suggest that the significant sulcal depth differences represent local peaks in a larger pattern of regional differences that are below statistical significance when using coor...
Twin research and human genetics : the official journal of the International Society for Twin Studies, 2008
Recent clinic-based and population-based studies have shown evidence of association between ADHD ... more Recent clinic-based and population-based studies have shown evidence of association between ADHD and autistic symptoms in children and adolescents as well as evidence for genetic overlap between these disorders. The objective of the current study was to confirm the association between autistic and ADHD symptoms in a young adult twin sample assessed by self-report, and investigate whether shared genetic and/or environmental factors can explain the association. We performed twin-based structural equation modeling using self-report data from 11 Social Responsiveness Scale (SRS) items and 12 DSM-IV ADHD inattentive and impulsive symptom items obtained from 674 young adult Australian twins. Phenotypic correlation between autistic and ADHD symptoms was moderate. The most parsimonious univariate models for SRS and ADHD included additive genetic effects and unique environmental effects, without sex differences. ADHD and autistic traits were both moderately heritable. In a bivariate model, g...
Journal of autism and developmental disorders, 2003
Studies of the broader autism phenotype, and of subtle changes in autism symptoms over time, have... more Studies of the broader autism phenotype, and of subtle changes in autism symptoms over time, have been compromised by a lack of established quantitative assessment tools. The Social Responsiveness Scale (SRS-formerly known as the Social Reciprocity Scale) is a new instrument that can be completed by parents and/or teachers in 15-20 minutes. We compared the SRS with the Autism Diagnostic Interview-Revised (ADI-R) in 61 child psychiatric patients. Correlations between SRS scores and ADI-R algorithm scores for DSM-IV criterion sets were on the order of 0.7. SRS scores were unrelated to I.Q. and exhibited inter-rater reliability on the order of 0.8. The SRS is a valid quantitative measure of autistic traits, feasible for use in clinical settings and for large-scale research studies of autism spectrum conditions.
Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subc... more Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood. To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD. We performed a nested case-control study (pilot study: July 1, 2007, through June 30, 2009; full-scale study: September 15, 2008, through September 14, 2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116,430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses. The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status. Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised. A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR], 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (P < .001). These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits.
Journal of the American Academy of Child & Adolescent Psychiatry, 2008
To investigate the relation between parent reports of motor problems and clinically significant a... more To investigate the relation between parent reports of motor problems and clinically significant autistic symptoms in children with and without attention-deficit/hyperactivity disorder (ADHD). Subjects were male (n = 521) and female (n = 330) twins from an epidemiological study of ADHD, ages 7 to 19 years at assessment using the Child Behavior Checklist and semistructured psychiatric diagnostic interviews. Parent-rated Social Responsiveness Scale questionnaires were returned for 62% of 1,647 individuals who participated in interviews. After exclusion of subjects with incomplete data or evidence of mental retardation, 851 subjects (52%) were available for the present study analysis. Each subject was classified by DSM-IV ADHD subtype and assigned to one of seven population-defined ADHD subtypes based on latent class analysis of DSM-IV ADHD symptoms. Within each ADHD subtype, we examined the relation between Child Behavior Checklist motor problem endorsement and elevated autistic symptoms on the Social Responsiveness Scale. Motor problems and high levels of autistic traits were most common in individuals with combined-type ADHD. Within each of the clinically relevant DSM-IV and latent class ADHD subtypes, individuals with the combination of motor problems and ADHD were more likely to have high levels of autistic traits than those with ADHD alone. Children with the combination of ADHD and parent-reported motor coordination deficits have elevated levels of autistic symptoms. Targeted treatment and prevention interventions may be warranted. The exclusion criteria for DSM-IV ADHD should be revised to reflect these population-based findings.
To examine if maltreatment predicted increased risk of hospital-based treatment prior to age 18 y... more To examine if maltreatment predicted increased risk of hospital-based treatment prior to age 18 years for asthma, cardio-respiratory, and non-sexually transmitted infectious disease in a sample of low-income children. This study used administrative data from multiple systems to follow children for 12-18 years (N = 6,282). Cox regression was used to explore the risk of first hospital treatment by disease category. Negative binomial regression was used to explore the relationship between recurrent maltreatment and total hospital care episodes. Controlling for individual, family, and community factors, children with maltreatment reports had a 74-100% higher risk of hospital treatment. Recurrent reports predicted a higher count of hospital care episodes. The negative health impact of maltreatment prior to adulthood supports the need for early prevention and intervention to prevent initial and recurrent child abuse and improve capacity to meet healthcare needs of maltreated children.
Although motor impairment is frequently observed in children with autism spectrum disorders (ASD)... more Although motor impairment is frequently observed in children with autism spectrum disorders (ASD), the manner in which these impairments aggregate in families affected by autism is unknown. We used a standardized measure of motor proficiency to objectively examine quantitative variation in motor proficiency in sibling pairs concordant and discordant for ASD. Motor impairment of sibling pairs from 67 ASD-affected families comprising 29 concordant pairings and 48 discordant pairings were assessed using the Bruininks Oseretsky Test of Motor Proficiency, 2nd Edition, a standardized measure of motor proficiency. Motor skills were substantially impaired among ASD-affected children and highly correlated with autistic severity and IQ, whereas motor skills in unaffected siblings were essentially normal. Total motor composite scores of at least one standard deviation below the general population mean were seen in 83% of the affected group compared with 6% in the unaffected siblings. Findings indicate that motor impairment constitutes a core characteristic of ASD (not necessarily an ASD endophenotype), which has distinct implications for taxonomy, diagnosis, and approaches to intervention.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder frequently co-occur.... more Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder frequently co-occur. Several studies show increased risk of substance use disorders in ADHD, yet there is limited information related to how ADHD symptoms, autistic traits, and their combined effects are associated with nicotine, alcohol, and cannabis use and use disorders in the general population. Cross-sectional interview and self-report questionnaire data from 3,080 young adult Australian twins (mean age 31.9 years) were used to assess ADHD symptoms, autistic traits, substance use, and substance use disorders. Substance use disorders-based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria-were assessed in the full sample as well as in those who reported substance use. Logistic regression analyses were used for comparing the associations between ADHD symptoms, autistic traits, substance use, and substance misuse after conduct disorder, sex, age, and zygosity were controll...
We used surface-based morphometry to test for differences in cortical shape between children with... more We used surface-based morphometry to test for differences in cortical shape between children with simplex autism (n = 34, mean age 11.4 years) and typical children (n = 32, mean age 11.3 years). This entailed testing for group differences in sulcal depth and in 3D coordinates after registering cortical midthickness surfaces to an atlas target using 2 independent registration methods. We identified bilateral differences in sulcal depth in restricted portions of the anterior-insula and frontal-operculum (aI/fO) and in the temporoparietal junction (TPJ). The aI/fO depth differences are associated with and likely to be caused by a shape difference in the inferior frontal gyrus in children with simplex autism. Comparisons of average midthickness surfaces of children with simplex autism and those of typical children suggest that the significant sulcal depth differences represent local peaks in a larger pattern of regional differences that are below statistical significance when using coor...
Twin research and human genetics : the official journal of the International Society for Twin Studies, 2008
Recent clinic-based and population-based studies have shown evidence of association between ADHD ... more Recent clinic-based and population-based studies have shown evidence of association between ADHD and autistic symptoms in children and adolescents as well as evidence for genetic overlap between these disorders. The objective of the current study was to confirm the association between autistic and ADHD symptoms in a young adult twin sample assessed by self-report, and investigate whether shared genetic and/or environmental factors can explain the association. We performed twin-based structural equation modeling using self-report data from 11 Social Responsiveness Scale (SRS) items and 12 DSM-IV ADHD inattentive and impulsive symptom items obtained from 674 young adult Australian twins. Phenotypic correlation between autistic and ADHD symptoms was moderate. The most parsimonious univariate models for SRS and ADHD included additive genetic effects and unique environmental effects, without sex differences. ADHD and autistic traits were both moderately heritable. In a bivariate model, g...
Journal of autism and developmental disorders, 2003
Studies of the broader autism phenotype, and of subtle changes in autism symptoms over time, have... more Studies of the broader autism phenotype, and of subtle changes in autism symptoms over time, have been compromised by a lack of established quantitative assessment tools. The Social Responsiveness Scale (SRS-formerly known as the Social Reciprocity Scale) is a new instrument that can be completed by parents and/or teachers in 15-20 minutes. We compared the SRS with the Autism Diagnostic Interview-Revised (ADI-R) in 61 child psychiatric patients. Correlations between SRS scores and ADI-R algorithm scores for DSM-IV criterion sets were on the order of 0.7. SRS scores were unrelated to I.Q. and exhibited inter-rater reliability on the order of 0.8. The SRS is a valid quantitative measure of autistic traits, feasible for use in clinical settings and for large-scale research studies of autism spectrum conditions.
Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subc... more Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood. To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD. We performed a nested case-control study (pilot study: July 1, 2007, through June 30, 2009; full-scale study: September 15, 2008, through September 14, 2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116,430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses. The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status. Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised. A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR], 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (P < .001). These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits.
Journal of the American Academy of Child & Adolescent Psychiatry, 2008
To investigate the relation between parent reports of motor problems and clinically significant a... more To investigate the relation between parent reports of motor problems and clinically significant autistic symptoms in children with and without attention-deficit/hyperactivity disorder (ADHD). Subjects were male (n = 521) and female (n = 330) twins from an epidemiological study of ADHD, ages 7 to 19 years at assessment using the Child Behavior Checklist and semistructured psychiatric diagnostic interviews. Parent-rated Social Responsiveness Scale questionnaires were returned for 62% of 1,647 individuals who participated in interviews. After exclusion of subjects with incomplete data or evidence of mental retardation, 851 subjects (52%) were available for the present study analysis. Each subject was classified by DSM-IV ADHD subtype and assigned to one of seven population-defined ADHD subtypes based on latent class analysis of DSM-IV ADHD symptoms. Within each ADHD subtype, we examined the relation between Child Behavior Checklist motor problem endorsement and elevated autistic symptoms on the Social Responsiveness Scale. Motor problems and high levels of autistic traits were most common in individuals with combined-type ADHD. Within each of the clinically relevant DSM-IV and latent class ADHD subtypes, individuals with the combination of motor problems and ADHD were more likely to have high levels of autistic traits than those with ADHD alone. Children with the combination of ADHD and parent-reported motor coordination deficits have elevated levels of autistic symptoms. Targeted treatment and prevention interventions may be warranted. The exclusion criteria for DSM-IV ADHD should be revised to reflect these population-based findings.
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Papers by John Constantino