Risk factors for parental psychopathology: a study in families with children or adolescents with psychopathology.

The parents of children with psychopathology are at increased risk for psychiatric symptoms. To investigate which parents are mostly at risk, we assessed in a clinical sample of families with children with psychopathology, whether parental symptom scores can be predicted by offspring psychiatric diagnoses and other child, parent and family characteristics. Parental depressive, anxiety, avoidant personality, attention-deficit/hyperactivity (ADHD), and antisocial personality symptoms were measured with the Adult Self Report in 1805 mothers and 1361 fathers of 1866 children with a psychiatric diagnosis as assessed in a child and adolescent psychiatric outpatient clinic. In a multivariate model, including all parental symptom scores as outcome variables, all offspring psychiatric diagnoses, offspring comorbidity and age, parental age, parental educational attainment, employment, and relationship status were simultaneously tested as predictors. Both 35.7% of mothers and 32.8% of fathers scored (sub)clinical for at least one symptom domain, mainly depressive symptoms, ADHD symptoms or, only in fathers, avoidant personality symptoms. Parental psychiatric symptoms were predicted by unemployment. Parental depressive and ADHD symptoms were further predicted by offspring depression and offspring ADHD, respectively, as well as by not living together with the other parent. Finally, parental avoidant personality symptoms were also predicted by offspring autism spectrum disorders. In families with children referred to child and adolescent psychiatric outpatient clinics, parental symptom scores are associated with adverse circumstances and with similar psychopathology in their offspring. This signifies, without implying causality, that some families are particularly vulnerable, with multiple family members affected and living in adverse circumstances.

How to early recognize mood disorders in primary care: A nationwide, population-based, cohort study.

BACKGROUND: Mood disorders are managed predominantly in primary care. However, general practitioners' (GPs) ability to detect and diagnose patients with mood disorders is still considered unsatisfactory. The aim of the present study was to identify predictors for the early recognition of depressive disorder (DD) and bipolar disorder (BD) in general practice. METHODS: A cohort of 1,144,622 patients (605,285 women, 539,337 men) was investigated, using the Health Search IMS Health Longitudinal Patient Database. Predictors of DD or BD were identified at baseline encompassing somatization-related features, lifestyle variables, medical and psychiatric comorbidities. Patients were followed up as long as the following events occurred: diagnoses of DD or BD, death, end of the registration with the GP, end of the study period. RESULTS: We found an incidence rate of DD or BD of 53.61 and 1.5 per 10,000 person-years, respectively. For both the conditions, the incidence rate grew with age. Most of the lifestyle variables and medical comorbidities increased the risk of mood disorders. The strongest effect was found for migraine/headache (HR [95% CI]=1.32 [1.26-1.38]), fatigue (1.32 [1.25-1.39]) irritable bowel syndrome (1.15 [1.08-1.23]), and pelvic inflammation disease (1.28 [1.18-1.38]). CONCLUSIONS: Several predictors, in particular somatic symptoms, could be interpreted as an early sign of a mood disorder, and represent a valid indication for the GPs diagnostic process of mental disorders.

Spousal resemblance in psychopathology: A comparison of parents of children with and without psychopathology.

BACKGROUND: Spouses resemble each other for psychopathology, but data regarding spousal resemblance in externalizing psychopathology, and data regarding spousal resemblance across different syndromes (e.g. anxiety in wives and attention deficit/hyperactivity disorder [ADHD] in husbands) are limited. Moreover, knowledge is lacking regarding spousal resemblance in parents of children with psychiatric disorders. We investigated and compared spousal resemblance within and across internalizing and externalizing symptom domains in parents of children with and without psychopathology. METHODS: Symptoms of depression, anxiety, avoidant personality, ADHD, and antisocial personality were assessed with the Adult Self Report in 728 mothers and 544 fathers of 778 children seen in child and adolescent psychiatric outpatient clinics and in 2075 mothers and 1623 fathers of 2784 children from a population-based sample. Differences in symptom scores and spousal correlations between the samples were tested. RESULTS: Parents in the clinical sample had higher symptom scores than in the population-based sample. In both samples, correlations within and across internalizing and externalizing domains of psychopathology were significant. Importantly, correlations were significantly higher in the clinical sample (P=0.03). Correlations, within and across symptoms, ranged from 0.14 to 0.30 in the clinical sample and from 0.05 to 0.23 in the population-based sample. CONCLUSIONS: This large study shows that spousal resemblance is not only present within but also across symptom domains. Especially in the clinical sample, ADHD symptoms in fathers and antisocial personality symptoms in mothers were correlated with a range of psychiatric symptoms in their spouses. Clinicians need to be alert of these multiple affected families.

Regular exercise behaviour in youth is not related to current body mass index or body mass index at 7-year follow-up.

OBJECTIVE: This population-based study aimed (1) to test the presence of an association between regular voluntary exercise behaviour (EB) that is performed in leisure time and body mass index (BMI) in youth and (2) to investigate the causal nature of this association using a longitudinal design in genetically informative subjects. DESIGN AND METHODS: Both EB and BMI were assessed repeatedly over time in 21 458 twin individuals from the Netherlands Twin Register (47.5% male) - first by parental report (ages 7, 10 and 12) and subsequently through self-report surveys (ages 14, 16 and 18). EB was quantified as weekly metabolic equivalent of task hours. RESULTS: Correlations over time were higher for BMI than for EB (r ≈ 0.70 vs. r ≈ 0.35) across 12 different follow-up periods. Cross-sectionally, regular involvement in EB was not associated with lower BMI in childhood and in genetically identical twin pairs discordant for EB; the exercising twin did not have a lower BMI than the non-exercising twin. Longitudinally, linear and quadratic relationships between EB and BMI were non-significant. Changes in EB over time did not induce opposite changes in BMI. CONCLUSIONS: No consistent association between regular EB and BMI was observed from ages 7 to 18 years.

Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study.

Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene.

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L.

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.

Trajectories of maternal depressive symptoms predict child problem behaviour: the Generation R study.

BACKGROUND: It is unclear how the course of maternal depressive symptoms affects child development. We modelled trajectories of maternal depressive symptoms from mid-pregnancy to 3 years after childbirth to better determine their associations with child problem behaviour. METHOD: Mother-child dyads (n = 4167) participated in a population-based prospective cohort in The Netherlands. Depressive symptoms were assessed with the Brief Symptom Inventory during pregnancy and at 2, 6 and 36 months postnatally. When children were 3 years old, problem behaviour was assessed with the Child Behaviour Checklist completed by each parent. A group-based modelling technique was used to model trajectories of maternal depressive symptoms and to examine their association with child problem behaviour. The added value of trajectory modelling was determined with successive linear regressions. RESULTS: We identified four trajectories of maternal depressive symptoms; 'no' (34%), 'low' (54%), 'moderate' (11%) and 'high' (1.5%). Child problem behaviour varied as a function of maternal trajectory membership. Whether rated by mother or father, children of mothers assigned to higher trajectories had significantly more problem behaviours than children of mothers assigned to lower trajectories. The model including trajectories had additive predictive value over a model relying only on a summed repeated measure of severity and a predefined chronicity variable. CONCLUSIONS: Depending on their course, maternal depressive symptoms have different effects on child problem behaviour. More information is gained by studying trajectories of symptoms, than only predefined measures of severity and chronicity. Moreover, trajectories can help identifying clinically depressed mothers who are possible candidates for early interventions.

Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region.

A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been reported to confer relative risk for phenotypes (depression/anxiety) and endophenotypes (amygdala reactivity). In this report, we identify and characterize three rare 5-HTTLPR alleles not previously described in the human literature. The three novel alleles were identified while genotyping 5-HTTLPR in a family-based attention deficit hyperactivity disorder clinical population. Two of the novel alleles are longer than the common 16-repeat long (L) allele (17 and 18 repeats) and the third is significantly smaller than the 14-repeat short (S) allele (11 repeats). The sequence and genetic architecture of each novel allele is described in detail. We report a significant decrease in the expression between the XL17 (17r) allele and the L(A) (16r) allele. The XS11 (11r) allele showed similar expression with the S (14r) allele. A 1.8-fold increase in expression was observed with the L(A)(16r) allele compared with the L(G) (16r) allele, which replicates results from earlier 5-HTTLPR expression experiments. In addition, transcription factor binding site (TFBS) analysis was performed using MatInspector (Genomatix) that showed the presence or absence of different putative TFBSs between the novel alleles and the common L (16r) and S (14r) alleles. The identification of rare variants and elucidation of their functional impact could potentially lead to understanding the contribution that the rare variant may have on the inheritance/susceptibility of multifactorial common diseases.

Berberine and evodiamine influence serotonin transporter (5-HTT) expression via the 5-HTT-linked polymorphic region.

The aim of this study was to investigate the effect of berberine and evodiamine on serotonin transporter (5-HTT) expression and then test how allelic variations previously identified in the promoter region could modulate that effect in the serotonergic neuronal cell line RN46A. Both berberine and evodiamine, alone and in combination, increased 5-HTT mRNA and protein expression significantly across the various alleles. When tested against the S, XS(11), L(G), L(A), XL(17), and XL(18) alleles, respectively, 100 µM berberine increased 5-HTT promoter activities by 67%, 128.7%, 106.9%, 100.4%, 26.2% and 82%, 2 µM evodiamine increased 5-HTT promoter activities by 216.7%, 81.6%, 305.6%, 181.5%, 175.3% and 102.2%. Berberine and evodiamine increased 5-HTT promoter activity differently depending on the genetic variation of the 5-HTTLPR polymorphism. This study has provided a convincing example of how herbal compounds influence the expression of one of the most intensively studied psychiatric candidate genes, the serotonin transporter.

Neuroimaging of response interference in twins concordant or discordant for inattention and hyperactivity symptoms.

Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced by genetic factors, but environmental influences are considered important as well. To distinguish between functional brain changes underlying primarily genetically and environmentally mediated ADHD, we used functional magnetic resonance imaging (fMRI) to compare response interference in monozygotic twins highly concordant or discordant for attention problems (AP). AP scores were assessed longitudinally with the Child Behavior Check List attention problem scale (CBCL-AP). Response interference was measured during two executive function paradigms; a color-word Stroop and a flanker task. The neuroimaging results indicated that, across the entire sample, children with high CBCL-AP scores, relative to children with low CBCL-AP scores, showed decreased activation to response interference in dorsolateral prefrontal, parietal and temporal brain regions. Increased activation was noted in the premotor cortex and regions associated with visual selective attention processing, possibly reflecting compensatory mechanisms to maintain task performance. Specific comparisons of high and low scoring concordant twin pairs suggest that AP of genetic origin was characterized by decreased activation of the left dorsolateral prefrontal cortex during the Stroop task and right parietal lobe during the flanker task. In contrast, comparison of twins from discordant monozygotic pairs, suggests that AP of environmental origin was characterized by decreased activation in left and right temporal lobe areas, but only during Stroop interference. The finding of distinct brain activation changes to response interference in inattention/hyperactivity of "genetic" versus "environmental" origin, indicates that genetic and environmental risk factors for attention/hyperactivity problems affect the brain in different ways.

A structural MRI study in monozygotic twins concordant or discordant for attention/hyperactivity problems: evidence for genetic and environmental heterogeneity in the developing brain.

Several structural brain abnormalities have been reported in patients with Attention Deficit Hyperactivity Disorder (ADHD). However, the etiology of these brain changes is still unclear. To investigate genetic and environmental influences on ADHD related neurobiological changes, we performed Voxel-Based Morphometry on MRI scans from monozygotic (MZ) twins selected from a large longitudinal population database to be highly concordant or highly discordant for ratings on the Child Behavior Checklist Attention Problem scale (CBCL-AP). Children scoring low on the CBCL-AP are at low risk for ADHD, whereas children scoring high on this scale are at high-risk for ADHD. Brain differences between concordant high-risk twin pairs and concordant low-risk twin pairs likely reflect the genetic risk for ADHD; brain differences between the low-risk and high-risk twins from discordant MZ twin pairs reflect the environmental risk for ADHD. A major difference between comparisons of high and low-risk twins from concordant pairs and high/low twins from discordant pairs was found for the prefrontal lobes. The concordant high-risk pairs showed volume loss in orbitofrontal subdivisions. High-risk members from the discordant twin pairs exhibited volume reduction in the right inferior dorsolateral prefontal cortex. In addition, the posterior corpus callosum was compromised in concordant high-risk pairs, only. Our findings indicate that inattention and hyperactivity symptoms are associated with anatomical abnormalities of a distributed action-attentional network. Different brain areas of this network appear to be affected in inattention/hyperactivity caused by genetic (i.e., high concordant MZ pairs) vs. environmental (i.e., high-low discordant MZ pairs) risk factors. These results provide clues that further our understanding of brain alterations in ADHD.

Genetic analyses of maternal and teacher ratings on attention problems in 7-year-old Dutch twins.

The goal of the present study is to examine genetic and environmental influences on maternal and teacher ratings of Attention Problems (AP) in 7-year-old children. Teachers completed the Teacher Report Form (N=2259 pairs), and mothers the Child Behavior Checklist (N=2057 pairs). Higher correlations were found in twins rated by the same teacher than in twins rated by different teachers. This can be explained by rater bias or by a greater environmental sharing in twins, who are in the same classroom. We further found that 41% of the variation in maternal and teacher ratings is explained by a common factor. The heritability of this common factor is 78%. The heritabilities of the rater specific factors of mothers and teachers are 76% and 39%, respectively. Because Attention Problems that are persistent over situations may indicate more serious behavior problems than context dependent Attention Problems, we believe that gene finding strategies should focus on this common phenotype.

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register.

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.

A study of genetic and environmental influences on maternal and paternal CBCL syndrome scores in a large sample of 3-year-old Dutch twins.

BACKGROUND: There is increasing evidence that behavioral problems are common in very young children, yet little is known about the etiology of individual differences in these problems. It is unclear to what degree environmental and genetic factors influence the development of early child psychopathology. In this paper, we focus on the following issues. Firstly, to what degree do genetic and environmental factors influence variation in behavioral problems? Secondly, to what degree are these underlying etiological factors moderated by sex and informant? We investigate these issues by analyzing Child Behavior Checklist (CBCL) data on 9689 3-year-old twin pairs. METHODS: Rater Bias and Psychometric Models were fitted to CBCL/2-3 data obtained from mothers and fathers to determine the genetic and environmental contributions to the five CBCL syndromes:aggressive, oppositional, overactive, withdrawn, and anxious/depressed behavior. RESULTS: Parental ratings are influenced by aspects of the child's behavior that are experienced in the same way by both parents and by aspects of the child's behavior that are experienced uniquely by each parent. There is evidence for high genetic contributions to all CBCL syndromes. Shared and non-shared environmental influences play significant roles as well. One exception is overactive behavior, which is influenced by genetic and non-shared environmental influences only. CONCLUSIONS: Variation in behavior problems in the very young shows high heritability. Individual raters offer unique perspectives that can have an impact on estimates of problem behavior and genetic architecture. Therefore, multi-informant approaches in the assessment of the very young will be useful to clinicians and researchers alike.

Genetic and environmental mechanisms underlying stability and change in problem behaviors at ages 3, 7, 10, and 12.

Maternal ratings on internalizing (INT) and externalizing (EXT) behaviors were collected in a large, population-based longitudinal sample. The numbers of participating twin pairs at ages 3, 7, 10, and 12 were 5,602, 5,115, 2,956, and 1,481, respectively. Stability in both behaviors was accounted for by genetic and shared environmental influences. The genetic contribution to stability (INT: 43%; EXT: 60%) resulted from the fact that a subset of genes expressed at an earlier age was still active at the next time point. A common set of shared environmental factors operated at all ages (INT: 47%; EXT: 34%). The modest contribution of nonshared environmental factors (INT: 10%; EXT: 6%) could not be captured by a simple model. Significant age-specific influences were found for all components, indicating that genetic and environmental factors also contributed to changes in problem behavior.

Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12.

BACKGROUND: Twin studies of childhood behavior problems support the conclusion that individual differences in impulsivity, hyperactivity, and inattention are largely due to genetic influences. Non-genetic variation is due to environmental influences that are unique to the individual, and possibly to rater contrast effects. In the present longitudinal twin study, we report on the size of genetic and environmental effects on individual differences in attention problems at ages 3, 7, 10 and 12 years. METHODS: Mothers were asked to complete the CBCL for their twin offspring when the children were 3 (n = 11,938), 7 (n = 10,657), 10 (n = 6,192), and 12 years old (n = 3,124). We focus on the Overactivity (OA) scale in the Child Behavior Checklist (CBCL/2-3), and on the Attention Problem (AP) scale of the CBCL/4-18. The data were analyzed using longitudinal structural equation modeling. RESULTS: Broad heritability of OA and AP is estimated at nearly 75%, at each age. A contrast effect was observed at age 3 only. The results revealed less stability of OA at age 3 to AP at age 7 (r = .40), compared to the stability from AP at age 7 and beyond (r = .70). Genetic effects explained between 76% and 92% of the covariance between OA and AP. CONCLUSIONS: OA and AP are highly heritable at all ages in both genders. The same set of genes appears to be expressed in boys and girls. The size of genetic and environmental contributions remains the same across the ages studied. Stability in OA and AP is accounted for by genetic influences. Children who do not display OA or AP at a given age are unlikely to develop these problems at a subsequent age.

Individual differences in aggression: genetic analyses by age, gender, and informant in 3-, 7-, and 10-year-old Dutch twins.

Aggression in humans is associated with substantial morbidity and mortality. In this study we report on the aggressive behavior syndrome (AGG) in young children as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and 10 years. The purpose of this study was three-fold. First, we determined the number of children who are "clinically deviant" on the AGG scale. Second, we assessed the genetic and environmental contributions to AGG for the maternal, paternal, and teacher ratings at each age, for boys and girls. Third, we explored issues of rater bias by analyzing parental and teacher data simultaneously. CBCL data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and 2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old, 4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs from the Netherlands Twin Registry. Structural equation modeling was employed to obtain genetic and environmental estimates at each age. Analyses were conducted separately by age and informant, as well as simultaneously, for all informants. Differences in raw scores across gender were found, with boys being rated as more aggressive than girls by all informants. Mothers reported more symptoms than fathers, who reported more symptoms than teachers. Evidence for moderate to high genetic influence (51%-72%) was seen for AGG by all three informants at all ages with only small sex differences in heritability estimates. Best fitting models for AGG by parent reports also included a small contribution of common environment. The largest sex differences in heritabilities were seen at age 10. Contributions of common (13%-27%) and unique (16%-31%) environment were small to moderate. There was some evidence of genetic dominance by teacher report for 10-year-old girls.

Causes of stability of aggression from early childhood to adolescence: a longitudinal genetic analysis in Dutch twins.

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.

Co-occurrence of aggressive behavior and rule-breaking behavior at age 12: multi-rater analyses.

Aggressive Behavior (AGG) and Rule-Breaking Behavior (RB) are two of the eight CBCL syndromes. The phenotypic correlation between AGG and RB ranges from.48 to.76, and varies depending on the rater and the sex of the child. Prevalence of AGG and RB (i.e., T > or = 67) is in the range of 6%-7% in both boys and girls. Fifty percent to 60% of the children who are deviant on AGG are also deviant on RB and vice versa. Why so many children show problem behavior in the clinical range for both syndromes is unclear. This co-occurrence could be due to genetic factors influencing both traits, to environmental factors influencing both traits, or to both. The purpose of this study is to use a genetically informative sample to estimate genetic and environmental influences on AGG and RB and to investigate the etiology of the co-occurrence of both behaviors. We do this using multiple informants to take into account underlying sources of parental agreement and disagreement in ratings of their offspring. To this end, mother and father ratings of AGG and RB were collected by using the Child Behavior Checklist in a large sample of 12-year-old twins. Parental agreement is represented by an interparent correlation in the range of .53-.76, depending on phenotype (AGG or RB) and sex of the child. Genetic influences account for 79% and 69% of the individual differences in RB and AGG behavior (defined as AGG and RB on which both parents do agree) in boys. In girls 56% and 72% of the variance in RB and AGG are accounted for by genetic factors. Shared environmental influences are significant for RB in girls only, explaining 23% of the total variance. Eighty percent of the covariance between AGG and RB, similarly assessed by both parents, can be explained by genetic influences. So, co-occurrence in AGG and RB is mainly caused by a common set of genes. Parental disagreement seems to be a combination of so-called rater bias and of parental specific views.

Heritability of attention problems in children: I. cross-sectional results from a study of twins, age 3-12 years.

Multiple twin studies of attention problems (AP) from the Child Behavior Checklist or ADHD from the DSM criteria have reported on the genetic and environmental influences on these behaviors. The majority of these have studied AP and ADHD symptoms in twin samples combined across wide age spans, combined rater information and both genders. Thus, it is possible that the results are complicated by developmental, informant, and gender differences. The purpose of this study was to assess for the genetic and environmental contributions to overactive behavior (a syndrome highly related to AP in 7-, 10-, and 12-years olds) in 3-years olds (3,671 twin pairs), and attention problems in 7- (3,373 twin pairs), 10- (2,485 twin pairs), and 12-years olds (1,305 twin pairs) while controlling for developmental, gender and rater contrast contributions. Using a cross-sectional twin design, contributions from genetic additive, genetic dominance, unique environmental and rater contrast effects were estimated for CBCL maternal reports. We found that genetic influences on overactive behavior and attention problems are high across an age span that covers pre-school and elementary school age. Although girls display less problem behavior compared to boys, heritability estimates were found equal for both genders at each age. Environmental experiences that are unique to the individual accounted for the remaining influence. At the age of 3 years, a rater contrast effect was detected. We hypothesize that the contrast effect represents a maternal rater bias effect that is dependent on the age of the twins. The implications of these findings are discussed with reference to the clinical setting and in the context of future research.