Association of the MAOA-uVNTR polymorphism with psychopathic traits may change from childhood to adolescence.

Psychopathic traits can lead to violence, making it a serious public health concern. Genetic factors contribute to the aetiology of psychopathy. We examined whether monoamine oxidase A (MAOA-uVNTR) was associated with psychopathic traits measured quantitatively from controls through clinically aggressive youth (n = 336). Subjects were sub-categorized into at or above, and below age 13 years. Results reveal that males below age 13 were more likely to display psychopathic traits with the MAOA long variant, whereas males above age 13 years were more likely to display with the short variant. This suggests that developmental factors may be crucial for understanding the role of the MAOA polymorphism in psychopathic traits in males.

COMT Val/Met and Psychopathic Traits in Children and Adolescents: A Systematic Review and New Evidence of a Developmental Trajectory toward Psychopathy.

Psychopathic traits in youth may lead to adult criminal behaviors/psychopathy. The Val158Met polymorphism of catechol-O-methyltransferase (COMT) may influence the risk for psychopathy-related behaviors, while acting as a biomarker for predicting treatment response to dopaminergic medications. The literature shows inconsistent findings, making the interpretation of COMT's role difficult. The aims of this article are (i) to conduct a systematic review to analyze the effects of COMT Val158Met on psychopathic traits in children and adolescents, and (ii) to present new evidence on the developmental trajectory of the association of Val158Met and youth psychopathic traits. For the systematic review, a literature search was conducted using PubMed, EMBASE, OVID Medline and PsychINFO with the search terms for psychopathic traits, Val158Met and age of interest. In our genotype study, the COMT Val158Met genotype of 293 youth with European ancestry was analyzed in association with the psychopathy-related behavior scores from the Child Behavior Checklist and the Psychopathy Screening Device. To examine the potential influence of developmental changes, the sample was split into at or above and below age 13, and analyses were performed in males and females separately. The literature search yielded twenty-eight articles to be included in the systematic review, which demonstrated mixed results on the association depending on environmental factors, sex ratios, age groups and behavioral disorder diagnoses. The results from our genotype study revealed that Met homozygous youth in the below age 13 group and conversely Val carrier youth in the above age 13 group were more likely to display psychopathic traits. To our knowledge, this is the first study to systematically review the effects of COMT Val158Met on psychopathic traits in childhood and adolescence, and to provide new evidence on the changing effects of Val158Met on psychopathy-related behaviors with development. Elucidating the role of the COMT genotype in conjunction with the child versus adolescent stage of development for psychopathic traits may help predict treatment response, and may lead to early intervention and prevention strategies.

Pharmacogenomic Studies in Intellectual Disabilities and Autism Spectrum Disorder: A Systematic Review.

BACKGROUND: Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to treat aberrant behaviors and mood symptoms, frequently resulting in polypharmacy and drug-related adverse effects. Pharmacogenomic (PGx) studies with ASD and/or ID (ASD/ID) have been scarce despite the promise of optimizing treatment outcomes. We reviewed the literature on PGx studies with antipsychotics and antidepressants (e.g., treatment response and adverse effects) in ASD/ID. METHODS: We performed a systematic review using MEDLINE, Embase, and PsycINFO, including peer-reviewed original articles in English referring to PGx in the treatment of ASD/ID in any age groups (e.g., treatment response and adverse effects). RESULTS: A total of 28 PGx studies using mostly candidate gene approaches were identified across age groups. Notably, only 3 studies included adults with ASD/ID while the other 25 studies focused specifically on children/adolescents with ASD/ID. Twelve studies primarily investigated treatment response, of which 5 and 6 studies included patients treated with antipsychotics and antidepressants, respectively. Most interesting results for response were reported for 2 sets of candidate gene studies, namely: (1) The DRD3 Ser9Gly (rs6280) polymorphism was examined in patients treated with risperidone in 3 studies, 2 of which reported an association with risperidone treatment response and (2) the SLC6A4 5-HTTLPR polymorphism and treatment response to antidepressants which was investigated in 4 studies, 3 of which reported significant associations. In regard to side effects, 9 of 15 studies focused on hyperprolactinemia in patients treated with risperidone. Among them, 7 and 5 studies examined the impact of CYP2D6 and DRD2 Taq1A polymorphisms, respectively, yielding mostly negative study findings. CONCLUSIONS: There is limited data available on PGx in individuals with ASD/ID and in particular in adults. Given the potential for PGx testing in improving treatment outcomes, additional PGx studies for psychotropic treatment in ASD/ID across age groups are warranted.

Early Adolescent Substance Use and Mental Health Problems and Service Utilisation in a School-based Sample.

OBJECTIVE: This paper reports on substance use, mental health problems, and mental health service utilisation in an early adolescent school-based sample. METHOD: Participants were 1,360 grade 7 and 8 students from 4 regions of Ontario, Canada. Students completed an in-class survey on mental health and substance use. The sampling strategy and survey items on demographics, substance use, service utilisation, and distress were adapted from the Ontario Student Drug Use and Health Survey. Internalising and externalising mental health problems were assessed using the Global Assessment of Individual Needs - Short Screener. Distress was defined as fair or poor self-rated mental health. RESULTS: Rates of internalising and/or externalising problems above the threshold exceeded 30%; yet, fewer than half had received mental health services in the past 12 mo. Substance use was associated with increased odds of internalising and externalising problems above the threshold and distress. Youth using cannabis had 10-times the odds of exceeding the threshold for internalising or externalising problems. The use of substances other than alcohol or cannabis was associated with increased odds of fair or poor self-rated mental health among grade 8 students. Of the youth who confirmed at least a substance use problem, most also reported mental health problems; this association was stronger among girls than boys. CONCLUSIONS: Early adolescent substance use was associated with concurrent self-reported mental health problems in a non-clinical sample. The low levels of service utilisation reported highlight the need for improved access to early identification and intervention to prevent the development of concurrent disorders.

Language disorder and retrospectively reported sexual abuse of girls: severity and disclosure.

BACKGROUND: Despite emerging evidence for an association between communication disorders and maltreatment, little research has examined sexual abuse characteristics or disclosure experiences among individuals with language disorder (LD). Given that communication difficulties may constitute a barrier to disclosure, the disclosure experiences among individuals with and without communication difficulties may also differ. METHODS: Five-year-old children identified with a language and/or speech disorder from a nonclinical community sample and a control group were followed to adulthood in a prospective longitudinal study. At age 31, participants completed a behaviorally specific questionnaire on experiences of sexual abuse and questionnaires on disclosure experiences and social reactions to disclosure. Due to low endorsement of sexual victimization among male participants and low sample size, results are reported for women only and exclude nine participants with speech disorder without LD. Participation rates were 28 of 40 in the LD cohort and 45 of 51 controls. Sexual victimization severity was defined using an index combining five indicators (duration, invasiveness, relationship to perpetrator, coercive tactics used, and number of perpetrators). Subthreshold sexual victimization was defined as a single, noncontact incident with a perpetrator unknown to the child; experiences with greater severity were classified as child sexual abuse. RESULTS: Among women who reported sexual victimization by age 18, invasiveness and overall severity were greater in the LD cohort than in the control cohort. Women in the LD cohort (43%) were more likely than controls (16%) to report child sexual abuse, excluding subthreshold experiences. There were no differences between cohorts in probability of disclosure, latency to disclosure, or social reactions. CONCLUSIONS: Women with a history of child LD in a nonclinical sample reported substantial child sexual abuse experiences. Implications for understanding associations between LD and mental health and for prevention and early intervention are discussed.

Mental health trajectories from adolescence to adulthood: Language disorder and other childhood and adolescent risk factors.

Longitudinal research on mental health development beyond adolescence among nonclinical populations is lacking. This study reports on psychiatric disorder trajectories from late adolescence to young adulthood in relation to childhood and adolescent risk factors. Participants were recruited for a prospective longitudinal study tracing a community sample of 5-year-old children with communication disorders and a matched control cohort to age 31. Psychiatric disorders were measured at ages 19, 25, and 31. Known predictors of psychopathology and two school-related factors specifically associated with language disorder (LD) were measured by self-reports and semistructured interviews. The LD cohort was uniquely characterized by a significantly decreasing disorder trajectory in early adulthood. Special education was associated with differential disorder trajectories between LD and control cohorts, whereas maltreatment history, specific learning disorder, family structure, and maternal psychological distress were associated with consistent trajectories between cohorts. From late adolescence to young adulthood, childhood LD was characterized by a developmentally limited course of psychiatric disorder; maltreatment was consistently characterized by an elevated risk of psychiatric disorder regardless of LD history, whereas special education was associated with significantly decreasing risk of psychiatric disorder only in the presence of LD.

Program manager perspectives on the service system to meet the needs of youth with concurrent disorders: findings from a Canadian national survey.

BACKGROUND: Concurrent mental health and substance use issues are a serious problem for adolescents and transition-aged youth. Service providers across sectors must be involved in informing system change to meet youth needs. This study examines stakeholder perspectives on services for youth with concurrent disorders including 1) clinical issues in youth services; 2) priority system issues; and 3) optimal knowledge translation strategies to enhance researcher-stakeholder communication. METHODS: A database of youth clinical services across Canada was developed. Program managers (n = 481) at cross-sectoral (mental health, addictions, justice, child welfare, advocacy, and outreach) youth-serving (aged 12-24) programs were invited to complete an online survey; 232 responded. Survey questions concerned youth needs, program characteristics, priorities for service system enhancement; and usual and preferred knowledge translation methods. RESULTS: Across service sectors, the mean estimated proportion of youth using services with concurrent mental health and substance use problems was 55%. Program managers reported routine screening for mental health and substance use concerns (66%), referring to other agencies to meet the concurrent disorder needs of youth (54%), offering specific programming for concurrent disorders (42%), and program evaluation (48%). Notably, mental health programs were significantly less likely to offer concurrent disorders services than addictions programs. Where services do exist, most are targeted at youth aged 12-18 years, with fewer services available for transition-aged youth. Endorsement of various system change goals exceeded 80%, with a particular emphasis on improving access to services (49%), ensuring a continuum of services for varying levels of severity (37%), and improved integration across sectors (36%). Preferred knowledge exchange methods were workshops and websites for receiving information; and focus groups or surveys, rather than intensive participation on research teams, to inform research. CONCLUSIONS: There is a high need to build capacity across most sectors for meeting the needs of youth with co-occurring mental health and substance use problems, especially for transition-aged youth. In addition, limits in program evaluation should be addressed. Innovative knowledge exchange strategies are needed to better meet the needs of youth with concurrent disorders. Although service providers expressed readiness to participate in service enhancement and knowledge translation activities, effective, feasible approaches must integrate strategies likely to result in desired clinical outcomes, given clinical workload challenges.

Study of the catechol-o-methyltransferase (COMT) gene with high aggression in children.

The etiology of childhood-onset aggression (COA) is poorly understood, but early COA can be considered as a strong risk factor for adult delinquency and criminal behavior. Callous-unemotional (CU) traits have been proposed as a developmental model of antisocial behavior. Catechol O-methyltransferase (COMT) has been associated with aggression, attention deficit/hyperactivity disorder (ADHD), and other psychiatric disorders. We report an association study between COMT single-nucleotide polymorphisms (SNPs), childhood aggression, and the CU trait in our sample of 144 children with scores at or exceeding the 90th percentile on the aggression subscale of the parent-reported Child Behavior Checklist and the Teacher's Report Form. The genotype analysis of rs6269 showed nominally significant association (P = .019) and rs4818 showed a trend (P = .064) with COA. Trends were observed for rs6269 and rs4818 with CU scores (P < .10) as well. The analyses stratified by ADHD, or gender showed no significant results. This is the first report to our knowledge evaluating COMT SNPs with the phenotype of high aggression in children with a possible role for the COMT marker in CU traits. Given the importance of CU traits in antisocial behavior, further investigation of COMT is warranted.

COMT Val/Met, stressful life events and externalizing behaviors in youth: A longitudinal study from the ABCD sample.

Early adolescence is a crucial time for understanding and detecting the risk factors that may influence youth externalizing/disruptive behaviors and disorders. Previous literature reported evidence that risk factors for disruptive behaviors include catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism and environmental influences. An unanswered question is whether there is a change in these risk factors over stages of youth development. This longitudinal study examines the interaction effect of Val158Met and stressful life events (SLE) on youth externalizing behaviors from ages 9-11. Participants were 2363 children of European ancestry recruited as part of the Adolescent Brain Cognitive Development study. Repeated measures linear mixed models were used to examine the effect of the interaction between Val158Met and SLE (G × E) on disruptive behaviors over development. Externalizing behaviors were analyzed at both baseline and two-year follow-up. Both Val158Met genotype and SLE scores demonstrated significant main effects on disruptive behaviors in youth, and those effects were consistent at both time points. G × E was not associated with externalizing behaviors. Youth who carried the Val allele and/or were exposed to higher SLE consistently had increased externalizing behavior scores. To our knowledge, this is the first study to longitudinally examine the interaction effects of Val158Met and SLE on externalizing behaviors in youth. The results highlight the importance of understanding the genetic and environmental factors underlying externalizing behaviors for better detection of at-risk youth, helping further with early prevention efforts. The findings propose that COMT Val158Met genotype may act as a biomarker for development of novel treatment strategies for disruptive behaviors.

Childhood aggression, callous-unemotional traits and oxytocin genes.

Given the known behavior effects of oxytocin,and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case­control study design as well as with callous-unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case­control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous-unemotionals cores than other haplotypes. This is the first known study to show a significant association between callous unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required.

Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents.

BACKGROUND: There is growing evidence that inflammation influences mental health. Blood interleukin levels, which regulate inflammation, have been linked to aggression and internalizing behaviors. We performed a hypothesis-driven genetic study to (1) evaluate the association of IL1B, IL2, and IL6 gene variants with aggression and internalizing behaviors and (2) explore gene-environment interactions with childhood adversity in a deeply phenotyped childhood-onset aggression sample including 255 cases and 226 controls of European ancestry. METHODS: We evaluated the association of putative functional and tag SNPs within IL1B, IL2, and IL6 with aggression case status, parent-reported internalizing problems, self-reported anxiety symptoms, and self-reported depressive symptoms in our sample. We also performed exploratory GxE analyses within cases, testing for statistical interaction between interleukin SNP genotype and childhood adversity for depressive symptoms. RESULTS: No significant association was observed between any of the interleukin SNPs and childhood-onset aggression. We observed association of IL6 variant rs2069827 with depressive symptoms (p = 7.15×10-4 ), and trends for an interaction between severe childhood adversity and SNPs in IL1B and IL2 for depressive symptoms. CONCLUSIONS: Our findings provide preliminary evidence that common variation in IL6 may be associated with depressive symptoms in children and adolescents, and that common variation in interleukin genes may sensitize individuals to the depressogenic effects of traumatic life experiences. Replication in independent samples is needed.

Evidence for association of vasopressin receptor 1A promoter region repeat with childhood onset aggression.

OBJECTIVE: Childhood onset aggression can cause major suffering to affected families and is associated with many negative outcomes in the child's later life, including poor academic performance, adolescent delinquency, drug abuse, depression and antisocial personality disorder. Currently available prevention and intervention strategies have limited efficacy, but a better understanding of underlying genetic and neurobiological factors can lead to more effective prevention and treatment strategies, through genetic screening programs and novel therapies. METHOD: This study examined the RS1 (n = 299 aggression, n = 192 controls) and RS3 (n = 291 aggression, n = 189 controls) microsatellite repeats within the promoter region of the vasopressin receptor 1A gene (AVPR1A) and their association with extreme childhood aggression, as assessed by the Child Behavior Checklist (CBCL), as well as the Teacher Report Form (TRF) and Youth Self Report (YSR). Binary logistic regression was used to model the relationship between microsatellite length and childhood aggression. Age and sex were used as covariates. RESULTS: Logistic regression revealed a nominally significant association between one specific RS3 repeat and non-aggressive status. No association was found for any of the RS1 repeats. In a separate model, grouping repeats into short and long, carriers of long RS3 repeats were nominally significantly associated with non-aggressive status. CONCLUSIONS: These findings suggest a role for AVPR1A and its RS3 microsatellite in extreme childhood aggression and could lead to a better understanding of the biological pathways of aggressive behavior. However, independent replication and further research into the functionality of studied genetic variants is required.

Longitudinal Emergence of Concurrent Mental Health and Substance Use Concerns in an Ontario School-Based Sample: The Research and Action for Teens Study.

OBJECTIVES: This study characterizes patterns of mental health, substance use and their co-occurrence, and identifies developmental trajectories associated with progression from single to concurrent mental health and substance use concerns in an Ontario school-based population. It is a longitudinal extension of the Ontario Student Drug Use and Mental Health Survey, as part of the RAFT collaborative project. METHODS: In this study, an Ontario-wide survey was administered to students across three biennial waves starting in grades 7-8 (ages 12-14). We explored how developmental patterns of externalizing, internalizing and co-occurring symptoms were differentially associated with late-adolescent (ages 17-19) problematic substance use. RESULTS: On average, students exhibited early (ages 12-14) moderate risk of an internalizing and/or externalizing disorder and approached the low threshold for a diagnostic concern for substance use disorder at age 17-19. The pattern confirmed a potential pathway from early mental health concerns to later adolescent problematic substance use, with rates of co-occurrence increasing with age. Youth with early moderate-to high externalizing and co-occurring internalizing and externalizing symptomology had the highest levels of problematic substance use, with scores indicating high likelihood of a substance use disorder diagnosis. CONCLUSIONS: Given the overall pattern of progression, early identification and referral of at-risk youth, especially youth with co-occurring mental health concerns, is of critical importance. Findings support the importance of integrated and co-located mental health and substance use services for youth to more effectively serve a diverse population of youth with varying levels of need.

OBJECTIFS: La présente étude caractérise les modèles de santé mentale, l'utilisation de substances et leur cooccurrence, et identifie les trajectoires développementales associées à la progression des problèmes isolés à concurrents de santé mentale et d'utilisation de substances dans une population scolaire de l'Ontario. Il s'agit d'une extension longitudinale du Sondage sur la consommation de drogues et la santé des élèves de l'Ontario, dans le cadre d'un projet RAFT de collaboration. MÉTHODES: Dans la présente étude, un sondage a été administré à l'échelle de l'Ontario à des élèves de trois vagues biennales commençant en 7e et 8e année (de 12 à 14 ans). Nous avons exploré comment les modèles développementaux d'externalisation, d'internalisation et les symptômes co-occurrents étaient différemment associés au début tardif (de 17 à 19 ans) d'une utilisation de substances problématique. RÉSULTATS: En moyenne, les élèves montraient un risque modéré précoce (de 12 à 14 ans) d'un trouble d'internalisation et/ou d'externalisation et s'approchaient du seuil bas d'un problème diagnostique d'utilisation de substances entre 17 et 19 ans. Le modèle confirmait une trajectoire potentielle allant de problèmes précoces de santé mentale à l'apparition ultérieure d'une utilisation de substances problématique, avec des taux de cooccurrence augmentant avec l'âge. Les jeunes ayant une externalisation modérée à élevée et une symptomatologie d'internalisation et d'externalisation co-occurrentes avaient les taux les plus élevés d'utilisation de substances problématique, leurs scores indiquant une probabilité élevée d'un diagnostic de trouble d'utilisation de substances. CONCLUSIONS: Étant donné le modèle de progression général, l'identification précoce et l'aiguillage d'un jeune à risque, surtout les jeunes présentant des problèmes de santé mentale co-occurrents, sont d'une importance vitale. Les résultats appuient l'importance des services intégrés et en colocation de santé mentale et d'utilisation de substances pour les jeunes afin de servir plus efficacement une population de jeunes diversifiée dont les besoins sont de niveaux variés.

Predicting risk of suicidal ideation in youth using a multigene panel for impulsive aggression.

Childhood traumatic experiences and impulsive aggression are strong predictors of suicide ideation in youth.  This study examines whether a gene panel previously associated with impulsive aggression, together with a measure of traumatic experience, will predict suicidal ideation in youth. The sample consisted of 158 youth (ages 9-17 years) of European ancestry that participated in a case-control study for childhood aggression.  The Massachusetts Youth Screening Instrument (MAYSI-2) was used to examine suicide ideation and traumatic experiences. The impulsive aggression gene panel consists of 5 markers across 5 susceptibility genes (CRH, CRHR2, MC2R, OXTR, BDNF). A multi-gene risk score (MRS) for each individual was calculated by taking the total number of risk genotypes for that person. The covariates for the multiple regression model included sex, age, symptoms of anxiety/depression, MRS, traumatic experiences, and MRS x traumatic experience interaction. Results show the MRS x traumatic experience interaction term and the anxious/depressed symptoms to be significant predictors of suicide ideation in the full model. Importantly, genetic susceptibility to impulsive aggression and traumatic experiences remained a significant predictor for suicide ideation over and above the youth's level of anxiety and depression. This finding may have important implications for early intervention for youth suicide-related behaviors.

Enhancing prevention and intervention for youth concurrent mental health and substance use disorders: The Research and Action for Teens study.

BACKGROUND: Concurrent mental health and substance use disorders among youth are associated with functional impairment in developmentally salient domains, yet research on prevention and intervention for this vulnerable population is sparse. This paper describes the rationale and design of the Research and Action for Teens study, an initiative designed to strengthen the evidence base for prevention, screening, treatment and service delivery for youth concurrent mental health and substance use concerns. METHODS: Four sub-studies were developed: (1) a cohort study examining the emergence of mental health and substance use concerns from early to mid-adolescence; (2) a screening and diagnosis study validating screening tools with a diagnostic interview; (3) a treatment study examining the feasibility and effectiveness of dialectical behaviour therapy skills training interventions for youth and family members; and (4) a systems study implementing cross-sectoral collaborative networks of youth-serving agencies using a common screening tool. RESULTS: Multiple stakeholders, including service providers from youth-serving agencies across sectors, consumer groups and family members participated in an initial consultation, and in the implementation of 4 sub-studies. CONCLUSIONS: Collaboration with community stakeholders across sectors and disciplines throughout the research process is challenging but feasible, and is important for the production of applicable knowledge across the continuum of care.

Models and determinants of vocabulary growth from kindergarten to adulthood.

BACKGROUND: Increasing evidence suggests that childhood language problems persist into early adulthood. Nevertheless, little is known about how individual and environmental characteristics influence the language growth of individuals identified with speech/language problems. METHOD: Individual growth curve models were utilised to examine how speech/language impairment and environmental variables (socioeconomic status, family separation, and maternal factors) influence vocabulary development from age 5 to 25. Participants were taken from a community sample of children initially diagnosed with speech/language problems at age 5 and their sex- and age-matched controls. RESULTS: The language impaired group had significantly poorer receptive vocabulary than the speech impaired and control groups throughout the 20-year period. Family income was a significant predictor of vocabulary growth when considered separately, but ceased to be a predictor when language impairment status was taken into account. Maternal education and family separation were determinants of vocabulary at age 5, over and above language impairment status. CONCLUSION: Language impairment is a significant risk factor for vocabulary development from childhood to adulthood. Individuals with speech impairment were less impaired on receptive vocabulary than individuals with language impairment. Further investigation into maternal and familial risk factors may provide targets for early intervention with children at risk for language impairment.

The dopamine D4 receptor gene and moderation of the association between externalizing behavior and IQ.

BACKGROUND: Dopaminergic neurotransmission is implicated in externalizing behavior problems, such as aggression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive ability. Activation of dopamine D4 receptors appears to inhibit the functioning of the prefrontal cortex, a brain region implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less efficient receptors, relative to other alleles, and this may alter the effects of dopamine on cognitive function. OBJECTIVE: To examine the influence of a polymorphism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ. DESIGN: In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was examined as a moderator of the association between externalizing behavior and IQ; the strength of this effect across samples was estimated meta-analytically. PATIENTS: Eighty-seven boys from a longitudinal community study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/hyperactivity disorder. MAIN OUTCOME MEASURES: IQ scores and observer ratings of externalizing behavior were taken from existing data sets. RESULTS: Among individuals lacking the 7-repeat allele, externalizing behavior was negatively correlated with IQ (mean r = -0.43; P<.001). Among individuals having at least 1 copy of the 7-repeat allele, externalizing behavior and IQ were uncorrelated (mean r = 0.02; P = .45). The difference between these correlations was significant (z = -2.99; P<.01). CONCLUSIONS: Allelic variation of the dopamine D4 receptor gene appears to be a genetic factor moderating the association between externalizing behavior and cognitive ability. This finding may help to elucidate the adaptive value of the 7-repeat allele.

Serotonin transporter polymorphisms and persistent, pervasive childhood aggression.

OBJECTIVE: The purpose of this study was to examine the potential association of the serotonin transporter (5-HTT) gene and childhood aggression by testing the 5-HTT variable-number-tandem-repeat and serotonin transporter promoter polymorphism (5-HTTLPR), including the recently discovered Lg allelic variant of 5-HTTLPR. METHOD: Clinically referred children displaying extreme aggression, with a minimum 2-year history, were genotyped for 5-HTTLPR (N=77) and 5-HTT variable-number-tandem-repeat (N=78). Analyses compared genotype frequencies of the aggressive children with healthy comparison subjects. RESULTS: The "low expressing" genotypic variants of the 5-HTTLPR polymorphism (S/S, Lg/S, Lg/Lg) were significantly associated with childhood aggression. CONCLUSIONS: This is the first study to report a significant association between the 5-HTTLPR gene and childhood aggression.

Social anxiety in late adolescence: the importance of early childhood language impairment.

Social phobia is a common, highly comorbid, poorly understood and relatively understudied condition. The origins of social phobia share familial and biological features common with those of other anxiety disorders, but seldom have precursors of the fear of social communication been examined as a possible pathway to social phobia. Here we examine the role of early childhood language impairment as an antecedent to social phobia in late adolescence. Participants in a prospective longitudinal community study identified as having language impairment at age 5 and matched controls were followed up at age 19. Compared to normal language controls, individuals with a history of early language impairment had 2.7 times the odds of having a social phobia by age 19. Results suggest that early language impairment represents a distinct pathway to late adolescent social phobia.

Children's turn-arounds in psychotherapy: the doctor's gesture.

UNLABELLED: Over the past year, a number of us have been examining the organizing principles behind dramatic turning points in the psychotherapies of children. We wondered whether any particular techniques or occurrences in therapy promoted childhood change. METHOD: One of us (L. T) asked the health care professionals on the UCSF child psychiatry grand rounds email list and 50 colleagues across the United States and Canada to select key "moments," or turning points, in their treatments of young people. No organizing principles were suggested in the request letters. Over 3 months, 21 vignettes telling of major changes in children and adolescents arrived in San Francisco. Some of them came from psychotherapies-others, from consultations or very brief therapies. Eleven are included in this paper. RESULTS: Gestures from the psychotherapist were shown to effect dramatic turn-arounds in some young people. These shifts in the doctor's emphasis or behavior included: (1) making an entirely unexpected statement; (2) advocating strongly for the youngster; (3) confessing personal flaws and/or frustrations to the patient; (4) feeding or rewarding the young patient; and (5) inquiring deeply into something personal with the child. A gesture never given--in this instance, an undelivered inquiry into incest--is shown to have left an adolescent patient unchanged. The young people described in this report suffered from anxiety, trauma, neglect, cancer; anorexia, bulimia, and personality disorders. Two were institutionalized at the time of their dramatic changes. One had been previously hospitalized 4 times. Another small child had suffered a double amputation. These children came with a far broader spectrum of problems than the relatively mild disorders for which child-psychodynamic psychotherapy was originally tailored. Although we were not primarily concerned with the "ground" on which the doctor's gesture fell, in 5 of our cases there had been little to no therapeutic relationship prior to the gesture; in 4, the relationship had been primarily positive; and, in 2, it had been negative. CONCLUSIONS: Doctors' gestures are usually given on impulse and unexpectedly during psychotherapy. To the child, these gestures appear counter-intuitive and surprising. From the therapist's perspective, they first generate a brief sense of confusion in the patient, and then a strong sense of connection between the young person and the adult. In the cases we report, the physicians'gestures created a new alliance. The tone of the therapy switched, leading to a noticeable psychic shift in the child. SUMMARY: A doctor's gesture may elicit a dramatic turn-around in a young patient. This therapeutic climax is implicitly understood between the two parties and then may be converted to consciousness and worked with explicitly. Therapeutic "moments" occur in a broad range of disorders, that in many cases are also being treated simultaneously with medications, and with family or institutional counseling.