Thalia C. Eley

Sex Differences in the Etiology of Aggressive and Nonaggressive Antisocial Behavior: Results from Two Twin Studies

Recent theory and results from twin and adoption studies of children and adolescents suggest greater genetic influence on aggressive as compared to nonaggressive antisocial behavior. In addition, quantitative or qualitative differences in the etiology of these behaviors in males and females have been indicated in the literature. The Child Behavior Checklist was completed by the parents of 1022 Swedish twin pairs aged 7-9 years and of 501 British twin pairs aged 8-16 years. Genetic factors influenced aggressive antisocial behavior to a far greater extent than nonaggressive antisocial behavior, which was also significantly influenced by the shared environment. There was a significant sex difference in the etiology of nonaggressive antisocial behavior. Bivariate analyses supported the conclusion that the etiologies of aggressive and nonaggressive antisocial behavior differ for males and females.

Co-occurrence of ADHD and low IQ has genetic origins

Previous studies show that the symptoms of attention deficit hyperactivity disorder (ADHD) and lower intelligence quotient (IQ) covary in children. We investigated the aetiology of this association in a large population‐based sample of 5‐year‐old twins. The twins were individually assessed on an IQ test, and data on ADHD symptoms were obtained from mother interviews and teacher ratings. Confirming previous studies, the phenotypic correlation between ADHD symptom scores and IQ was −0.3 and, in a categorical analysis, children with a Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) ADHD research diagnosis obtained IQ scores nine points lower, on average, than comparison children. We show here that the co‐occurrence of ADHD and lower IQ has genetic origins: 86% of the association between ADHD symptom scores and IQ, and 100% of the association between ADHD diagnosis and IQ, was accounted for by genetic influences that are shared by ADHD and IQ. Some candidate genes for ADHD could also contribute to variation in IQ or vice versa.

A longitudinal behavioral genetic analysis of the etiology of aggressive and nonaggressive antisocial behavior

Developmental studies of antisocial behavior (ASB) have found two subgroups of behaviors, roughly described as aggressive and nonaggressive ASB. Theoretical accounts predict that aggressive ASB, which shows greater stability, should have high heritability. In contrast, nonaggressive ASB is very common in adolescence, shows less continuity, and should be influenced both by genes and shared environment. This study explored the genetic and environmental influences on aggressive and nonaggressive ASB in over 1,000 twin pairs aged 8-9 years and again at 13-14 years. Threshold models were fit to the data to incorporate the skew. In childhood, aggressive ASB was highly heritable and showed little influence of shared environment, whereas nonaggressive ASB was significantly influenced both by genes and shared environment. In adolescence, both variables were influenced both by genes and shared envirnmment. The continuity in aggressive antisocial behavior symptoms from childhood to adolescence was largely mediated by genetic influences, whereas continuity in nonaggressive antisocial behavior was mediated both by the shared environment and genetic influences. These data are in agreement with the hypothesis that aggressive ASB is a stable heritable trait as compared to nonaggressive behavior, which is more strongly influenced by the environment and shows less genetic stability over time.

Genetic influence on language delay in two-year-old children

Previous work suggests that most clinically significant language difficulties in children do not result from acquired brain lesions or adverse environmental experiences but from genetic factors that presumably influence early brain development. We conducted the first twin study of language delay to evaluate whether genetic and environmental factors at the lower extreme of delayed language are different from those operating in the normal range. Vocabulary at age two was assessed for more than 3000 pairs of twins. Group differences heritability for the lowest 5% of subjects was estimated as 73% in model-fitting analyses, significantly greater than the individual differences heritability for the entire sample (25%). This supports the view of early language delay as a distinct disorder. Shared environment was only a quarter as important for the language-delayed sample (18%) as for the entire sample (69%).

Exploring the Covariation between Anxiety and Depression Symptoms: A Genetic Analysis of the Effects of Age and Sex

Self-reported anxiety and depression symptoms in children and adolescents have been shown to be heritable, and are also highly correlated. Furthermore, there have been indications in the literature of sex and age differences in the aetiologies of these two types of symptoms. This study set out to ascertain to what extent the genetic and environmental factors that influence anxiety symptoms also influence depression symptoms, and whether these are the same in children and adolescents, and males and females. Four hundred and ninety pairs of twins aged 8 to 16 years completed the Childrens Depression Inventory and the Trait scale of the State-Trait Anxiety Inventory for Children. There were significant effects of age and sex on the variance in and covariance between these two types of symptom. Bivariate genetic analyses of the measures indicated that the genetic influences on anxiety and depression were shared for all four groups, a finding that has been consistently demonstrated for adults.

The serotonin transporter gene and peer-rated neuroticism

POLYMORPHISMS in the serotonin transporter gene (5HTT) have been reported to be associated with neuroticism (emotionality) and with depression. A recent report of an association between 5HTT and neuroticism involved unselected samples and self-report questionnaires.1 We attempted to extend these findings using a selected extremes design and peer ratings. From a sample of 2085 individuals, each assessed on neuroticism by two independent peers, we selected 52 individuals from the top 5% and 54 individuals from the bottom 5%. No association was found for either a functional 44 bp insertion/deletion polymorphism in 5HTT regulatory sequence (5HTTLPR) or for a non-functional variable number tandem repeat 5HTT polymorphism.

Therapygenetics: the 5HTTLPR and response to psychological therapy

Whilst pharmacogenetic research thrives 1 , genetic determinants of response to purely psychotherapeutic treatments remain unexplored. In a sample of children undergoing Cognitive Behavior Therapy (CBT) for an anxiety disorder, we tested whether treatment response is associated with the serotonin transporter gene promoter region (5HTTLPR), previously shown to moderate environmental influences on depression. Children with the short-short genotype were significantly more likely to respond to CBT than those carrying a long allele.

Association analysis of MAOA and COMT with neuroticism assessed by peers.

There are several reported associations between depressive disorders, panic disorder, and obsessive–compulsive disorder (OCD) and a variety of polymorphisms in the monoamine oxidase A (MAOA) gene. Associations have also been reported between the catechol‐O‐methyltransferase (COMT) gene and both OCD and bipolar depression. However, the role of these markers has not been explored for the personality trait of neuroticism (N), a normally distributed quantitative trait, which is highly genetically correlated with anxiety and depression and may be a vulnerability to either type of disorder. We explored the possible role of MAOA, COMT, and their interaction on N using a selected extremes design. From a sample of 2,085 individuals, each assessed for N by two independent peers rather than using self‐report questionnaires, we selected 57 individuals from the top 10% of scores, and 62 individuals from the bottom 10%. Using selected extreme low subjects as the controls, rather than an unselected control group gives roughly twice the power of a standard case‐control design. We typed a functional variable number tandem repeat (VNTR) in the MAOA gene promoter, and a functional polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA VNTR were identified on the basis of their size, and their structure examined by sequencing analysis. We found weak evidence for association with COMT genotype, when the females and males were considered separately, and for MAOA genotype in males only. There was no significant interaction between COMT and MAOA.

A Quantitative Trait Locus Associated With Cognitive Ability in Children

Quantitative trait loci (QTLs) associated with general cognitive ability (g) were investigated for several groups of children selected for very high or for average cognitive functioning. A DNA marker in the gene for insulin-like growth factor-2 receptor (IGF2R) on Chromosome 6 yielded a significantly greater frequency of a particular form of the gene (allele) in a high-g group (.303; average IQ = 136, N = 51) than in a control group (.156; average IQ = 103, N = 51). This association was replicated in an extremely-high-g group (all estimated IQs > 160, N = 52) as compared with an independent control group (average IQ = 101, N = 50), with allelic frequencies of .340 and .169, respectively. Moreover, a high-mathematics-ability group (N = 62) and a high-verbal-ability group (N = 51) yielded results that were in the same direction but only marginally significant (p = .06 and .08, respectively).

Specific life events and chronic experiences differentially associated with depression and anxiety in young twins.

Behavioral genetic analyses indicate that environmental influences associated with depression and anxiety are specific to each symptom type; however, this has not been tested specifically in children. Sixty-one (61) child twin pairs in which at least one twin had a very high anxiety or depression score, and 29 nonanxious, nondepressed pairs were interviewed about life events and chronic stressors in the previous 12 months. Loss events, schoolwork stressors, family relationship problems, and friendship problems were all significantly associated with depression but not anxiety. Threat events were significantly associated with anxiety but not depression. Loss events and schoolwork stressors appeared to act as shared environment influences in that they made twin pairs resemble one another. Threat events, friendship problems, and family relationship problems were individual specific and accounted for differences within the pairs. These results clarify the associations between life events and depressive and anxious symptoms in children and adolescents and reveal specific associations previously unidentified in this age range.