Publications by authors named "Joseph H Beitchman"

31 Publications

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

J Psychiatr Res 2021 Aug 27;140:522-528. Epub 2021 May 27.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science & Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.062DOI Listing
August 2021

Pharmacogenomic Studies in Intellectual Disabilities and Autism Spectrum Disorder: A Systematic Review: Études Pharmacogénomiques en Déficiences Intellectuelles et Trouble du Spectre de L'autisme: Une Revue Systématique.

Can J Psychiatry 2020 Nov 23:706743720971950. Epub 2020 Nov 23.

Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

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 (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 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 and 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.
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http://dx.doi.org/10.1177/0706743720971950DOI Listing
November 2020

Pharmacogenomic Studies in Intellectual Disabilities and Autism Spectrum Disorder: A Systematic Review: Études Pharmacogénomiques en Déficiences Intellectuelles et Trouble du Spectre de L'autisme: Une Revue Systématique.

Can J Psychiatry 2020 Nov 23:706743720971950. Epub 2020 Nov 23.

Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

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 (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 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 and 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.
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http://dx.doi.org/10.1177/0706743720971950DOI Listing
November 2020

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

Can J Psychiatry 2019 02 21;64(2):116-125. Epub 2018 Jun 21.

1 Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario.

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.
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http://dx.doi.org/10.1177/0706743718784935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405806PMC
February 2019

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

Early Interv Psychiatry 2019 02 26;13(1):110-119. Epub 2017 Jul 26.

Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1111/eip.12458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492445PMC
February 2019

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

J Child Psychol Psychiatry 2017 Oct 13;58(10):1114-1121. Epub 2017 Apr 13.

Child, Youth and Emerging Adult Service, Centre for Addiction and Mental Health, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1111/jcpp.12723DOI Listing
October 2017

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression.

Psychiatry Res 2016 Aug 7;242:277-280. Epub 2016 Jun 7.

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Child, Youth, and Family Services, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Genetic variation in stress response protein FKBP5 is associated with adult psychopathology, but little is known about its role in children's mental health. 5 polymorphisms were genotyped in 170 high aggression cases and 170 age- and sex-matched controls. The rs9470080 polymorphism was associated with physiological anxiety, while rs4713916 polymorphism interacted with maltreatment to influence externalizing traits. These results suggest that genetic variation in FKBP5 has a role in children's vulnerability to stress-related behaviours.
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http://dx.doi.org/10.1016/j.psychres.2015.09.052DOI Listing
August 2016

The Role of the Catechol-o-Methyltransferase (COMT) GeneVal158Met in Aggressive Behavior, a Review of Genetic Studies.

Curr Neuropharmacol 2015 ;13(6):802-14

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8 Canada.

Aggressive behaviors have become a major public health problem, and early-onset aggression can lead to outcomes such as substance abuse, antisocial personality disorder among other issues. In recent years, there has been an increase in research in the molecular and genetic underpinnings of aggressive behavior, and one of the candidate genes codes for the catechol-O-methyltransferase (COMT). COMT is involved in catabolizing catecholamines such as dopamine. These neurotransmitters appear to be involved in regulating mood which can contribute to aggression. The most common gene variant studied in the COMT gene is the Valine (Val) to Methionine (Met) substitution at codon 158. We will be reviewing the current literature on this gene variant in aggressive behavior.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759319PMC
http://dx.doi.org/10.2174/1570159x13666150612225836DOI Listing
September 2016

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

Dev Psychopathol 2016 May 27;28(2):489-504. Epub 2015 Nov 27.

Centre for Addiction and Mental Health.

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.
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http://dx.doi.org/10.1017/S0954579415001054DOI Listing
May 2016

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

BMC Health Serv Res 2015 Sep 18;15:393. Epub 2015 Sep 18.

Child Youth and Family Services, Centre for Addiction and Mental Health, Toronto, Canada.

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.
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http://dx.doi.org/10.1186/s12913-015-1060-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574726PMC
September 2015

Age 31 mental health outcomes of childhood language and speech disorders.

J Am Acad Child Adolesc Psychiatry 2014 Oct 7;53(10):1102-10.e8. Epub 2014 Aug 7.

Centre for Addiction and Mental Health, Toronto, ON, Canada.

Objective: Language disorders are associated with emotional and behavioral problems in childhood and adolescence. Although clinical studies with small samples suggest that psychosocial difficulties continue into adulthood, adult mental health outcomes of childhood language disorders are not well known. The objective of this prospective longitudinal study is to determine whether the age 31 mental health outcomes of individuals who had childhood language disorders differ from the outcomes of typically developing controls.

Method: A 26-year cohort study followed up children with language or speech disorders from age 5 to age 31. The children were selected from a 1-in-3 random sample of 5-year-olds using a 3-stage screening and assessment process. A control group matched by sex, age, and classroom or school was also selected. Diagnoses were assigned with the Composite International Diagnostic Interview with the additional criterion that Global Assessment of Functioning scores indicated at least mild impairment. Dimensional psychosocial self-report measures were also administered.

Results: Rates of diagnosis at age 31 years were equivalent between participants who had childhood language disorders and controls, with and without multiple imputation to estimate missing outcomes. Differences in rates of affective and substance use disorders could not be ruled out because of attrition in the cohort with language disorders, who were less likely to participate at age 31. Psychosocial scores for both cohorts were in the normal range. The cohort with language disorders had poorer self-rated physical health than controls.

Conclusion: Mild/moderate language disorders may not have significant long-term mental health consequences in early adulthood.
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http://dx.doi.org/10.1016/j.jaac.2014.07.006DOI Listing
October 2014

The role of genetic variants in genes regulating the oxytocin-vasopressin neurohumoral system in childhood-onset aggression.

Psychiatr Genet 2014 Oct;24(5):201-10

aDepartment of Psychiatry bInstitute of Medical Science, University of Toronto cChild, Youth and Family Program dNeurogenetics, Centre for Addiction and Mental Health, Toronto eUniversity of Western Ontario (UWO), London, Ontario, Canada.

Objective: The genetic etiology of aggressive behaviors remains elusive, but growing evidence suggests that they are heritable, and certain genetic variants have been implicated as contributing factors. The oxytocin-vasopressin (OXT-AVP) neurohumoral system has recently been implicated in social behaviors. Oxytocin, especially, has been linked to prosocial behaviors such as trust and social bonds. Hence, the aim of this study was to determine whether genes regulating this system were also associated with childhood-onset aggressive behaviors.

Methods: Our sample included 182 White children showing extreme, persistent, and pervasive aggressive behavior. These cases were matched with 182 White controls on the basis of sex and age. We used PCR to determine the genotype for 28 single nucleotide polymorphisms within eight genes regulating the OXT-AVP system, including CD38 polymorphisms. Genotypic analyses were carried out using STATA, whereas differences in haplotypic and allelic frequencies were analyzed using Unphased.

Results: None of the results reached significance after correction for multiple testing. However, nominally significant allelic effects were observed for OXTR rs6770632T (P=0.028) and AVPR1A rs11174811G (P=0.040) in females, and OXTR rs237898A (P=0.006), rs237902C (P=0.007), and AVP rs3761249A (P=0.008) in males.

Conclusion: Genetic variants regulating the OXT-AVP system may be associated with childhood-onset aggression.
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http://dx.doi.org/10.1097/YPG.0000000000000044DOI Listing
October 2014

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

Aggress Behav 2013 Jan 12;39(1):45-51. Epub 2012 Sep 12.

Department of Psychiatry, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1002/ab.21448DOI Listing
January 2013

Possible genetic association between vasopressin receptor 1B and child aggression.

Psychiatry Res 2012 Dec 19;200(2-3):784-8. Epub 2012 Aug 19.

Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.

Background: Studies on animal models have implicated arginine vasopressin signalling pathway in aggressive behaviour. The role of arginine vasopressin in childhood onset aggression is unclear.

Methods: We investigated 11 single-nucleotide polymorphisms in the genes coding for arginine vasopressin and its receptors in our sample of 177 aggressive child cases paired with adult controls matched for sex and ethnicity.

Results: We found the non-synonymous polymorphism AVPR1B_rs35369693 to be associated with child aggression in our sample (P=0.007). We also found two-marker haplotype window containing AVPR1B_rs35369693 and AVPR1B_rs28676508 to be associated (P=0.003). The haplotype findings survived multiple-testing adjusted significance threshold of 0.0063.

Conclusions: This is the first report of a genetic association between vasopressin receptor 1B and child aggression. Replication in independent samples are required to confirm these findings.
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http://dx.doi.org/10.1016/j.psychres.2012.07.031DOI Listing
December 2012

Childhood aggression, callous-unemotional traits and oxytocin genes.

Eur Child Adolesc Psychiatry 2012 Mar 1;21(3):125-32. Epub 2012 Feb 1.

Child, Youth and Family Program, Centre for Addiction and Mental Health, 250 College Street, Room 125, Toronto, Canada.

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 case–control 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 case–control 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.
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http://dx.doi.org/10.1007/s00787-012-0240-6DOI Listing
March 2012

Dopaminergic system genes in childhood aggression: possible role for DRD2.

World J Biol Psychiatry 2012 Jan 19;13(1):65-74. Epub 2011 Jan 19.

Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.

Unlabelled: Excessive or deficient levels of extracellular dopamine have been hypothesized to contribute to a broad spectrum of mood, motor, and thought abnormalities, and dopaminergic system genes have been implicated in aggressive behaviour from animal and human studies. OBJECTIVE. We examined selected members of the dopaminergic system genes for association with child aggression.

Method: We analyzed polymorphisms in the dopamine transporter DAT1/SLC6A3, dopamine receptor DRD2, and DRD4 genes in our sample of pervasive childhood aggression consisting of 144 cases paired with 144 healthy controls, matched for sex and ethnicity.

Results: Aggressive children were significantly more likely to have the at least one copy of the G allele for the DRD2 A-241G polymorphism (genotypic P=0.02; allelic P=0.01). The DRD2 rs1079598 CC genotype was overrepresented in aggressive children compared to controls (genotype P=0.04). The DRD2 TaqIA T allele (P=0.01) and the TT genotype (P=0.01) were also significantly overrepresented in aggressive children.

Conclusions: Our preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression. Future studies are required to replicate the current results and to further explore the relationship between the dopamine system and aggressive behaviour in children.
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http://dx.doi.org/10.3109/15622975.2010.543431DOI Listing
January 2012

Twenty-year follow-up of children with and without speech-language impairments: family, educational, occupational, and quality of life outcomes.

Am J Speech Lang Pathol 2010 Feb 30;19(1):51-65. Epub 2009 Jul 30.

University of Toronto, Ontario, Canada.

Purpose: Parents, professionals, and policy makers need information on the long-term prognosis for children with communication disorders. Our primary purpose in this report was to help fill this gap by profiling the family, educational, occupational, and quality of life outcomes of young adults at 25 years of age (N = 244) from the Ottawa Language Study, a 20-year, prospective, longitudinal study of a community sample of individuals with (n = 112) and without (n = 132) a history of early speech and/or language impairments. A secondary purpose of this report was to use data from earlier phases of the study to predict important, real-life outcomes at age 25.

Method: Participants were initially identified at age 5 and subsequently followed at 12, 19, and 25 years of age. Direct assessments were conducted at all 4 time periods in multiple domains (demographic, communicative, cognitive, academic, behavioral, and psychosocial).

Results: At age 25, young adults with a history of language impairments showed poorer outcomes in multiple objective domains (communication, cognitive/academic, educational attainment, and occupational status) than their peers without early communication impairments and those with early speech-only impairments. However, those with language impairments did not differ in subjective perceptions of their quality of life from those in the other 2 groups. Objective outcomes at age 25 were predicted differentially by various combinations of multiple, interrelated risk factors, including poor language and reading skills, low family socioeconomic status, low performance IQ, and child behavior problems. Subjective well-being, however, was primarily associated with strong social networks of family, friends, and others.

Conclusion: This information on the natural history of communication disorders may be useful in answering parents' questions, anticipating challenges that children with language disorders might encounter, and planning services to address those issues.
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http://dx.doi.org/10.1044/1058-0360(2009/08-0083)DOI Listing
February 2010

Emerging adult outcomes of adolescent psychiatric and substance use disorders.

Addict Behav 2009 Oct 2;34(10):800-5. Epub 2009 Apr 2.

Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada.

This study investigates the age 25 outcomes of late adolescent mental health and substance use disorders. A hierarchical cluster analysis of age 19 DSM-III-R mental health and substance diagnoses placed participants into one of 9 clusters: Anxious, Depressed, Antisocial, Drug Abuser, Problem Drinker, Anxious Drinker, Depressed Drug Abuser and Antisocial Drinker, and No Diagnosis. Diagnoses were generated from the University of Michigan Composite International Diagnostic Interview. Repeated measures multivariate analyses of variance revealed distinct trajectories of improvement and decline among the 9 clusters. Clusters with co-occurring substance and mental health disorders improved over adolescent levels, but continued to have higher levels of depression symptoms, poorer global functioning, and higher levels of substance use than the No Diagnosis cluster. Members of the The Problem Drinkers cluster, who tended to have alcohol use disorders only at age 19, did not differ from their peers with no diagnoses. Drug use disorders in adolescence, with or without a co-occurring mental health disorders, were associated with a poor prognosis in emerging adulthood. Clinical interventions should distinguish among these diverse clinical presentations.
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http://dx.doi.org/10.1016/j.addbeh.2009.03.035DOI Listing
October 2009

Models and determinants of vocabulary growth from kindergarten to adulthood.

J Child Psychol Psychiatry 2008 Jun 10;49(6):626-34. Epub 2008 Mar 10.

Centre for Addiction and Mental Health, Toronto, Canada.

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.
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http://dx.doi.org/10.1111/j.1469-7610.2008.01878.xDOI Listing
June 2008

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

Psychoanal Study Child 2006 ;61:56-81

University of California, San Francisco, USA.

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.
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http://dx.doi.org/10.1080/00797308.2006.11800761DOI Listing
May 2007

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

Arch Gen Psychiatry 2006 Dec;63(12):1410-6

Department of Psychology, and Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1001/archpsyc.63.12.1410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283582PMC
December 2006

Serotonin transporter polymorphisms and persistent, pervasive childhood aggression.

Am J Psychiatry 2006 Jun;163(6):1103-5

Division of Child and Adolescent Psychiatry, University of Toronto, and the Centre for Addiction and Mental Health, 250 College St., Toronto, Ont. Canada, M5T 1R8.

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.
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http://dx.doi.org/10.1176/ajp.2006.163.6.1103DOI Listing
June 2006

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

J Anxiety Disord 2006 28;20(7):915-30. Epub 2006 Feb 28.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1016/j.janxdis.2006.01.007DOI Listing
December 2006

Psychiatric and substance use disorders in late adolescence: the role of risk and perceived social support.

Am J Addict 2005 Mar-Apr;14(2):124-38

Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.

This article explores how measures of risk and perceived social support relate to different configurations of adolescent psychopathology using data from a community-based, longitudinal investigation of 284 individuals interviewed in 1982 at age 5 and again at age 19. Discriminant analysis was used to assess differences in risk and social support variables among eight clusters of youth: anxious, anxious drinkers, depressed, depressed drug abusers, antisocial, antisocial drinkers, drug abusers, problem drinkers, and a ninth group representing those participants without a diagnosis. The results indicated that one function, defined by loadings for (low) family support and (high) early cumulative risk, accounted for the majority of between-group associations. Two groups of drug-abusing youth with multiple adjustment problems were highest on this function, while non-disordered youth and a group of participants with substance abuse alone were lowest. Findings are discussed in terms of the need to consider comorbidity when examining risk factors for later disorder.
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http://dx.doi.org/10.1080/10550490590924755DOI Listing
October 2005

Association of the serotonin transporter and 5HT1Dbeta receptor genes with extreme, persistent and pervasive aggressive behaviour in children.

Psychiatr Genet 2004 Sep;14(3):143-6

Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.

There is an inverse correlation between central nervous system serotonergic activity and human aggression, and aggressive traits are at least partially heritable. The present study sought to investigate the relationship between childhood aggression and polymorphisms of two serotonin system genes: the 5HT1Dbeta receptor gene and the serotonin transporter (5HTT) gene. Fifty children with a minimum 2-year history of aggression and scores above the 90th percentile on the Aggression subscales of both the Child Behaviour Checklist and the Teacher's Report Form were included in the study. All probands and locally recruited ethnically matched controls were genotyped for the 5HT1Dbeta G861C, 5HTTLPR (promoter) and 5HTT variable number of tandem repeats (VNTR) polymorphisms. Chi-square tests revealed a significantly reduced frequency of the 5HTT VNTR 10R allele in children displaying the high-aggression phenotype compared with normal controls (P=0.039). After correction for multiple comparisons, this association reached the level of a trend but was no longer significant. Probands also demonstrated an increased 5HT1Dbeta 861C allele frequency, but this was not statistically significant (P=0.156). 5HTTLPR was not found to be significantly associated with aggression, but our data support previous findings of an association between this polymorphism and attention deficit hyperactivity disorder (P=0.025). While these preliminary findings should be interpreted cautiously, our data suggest that the 5HTT VNTR polymorphism is associated with measures of aggressive behaviour in a sample of children displaying extreme, persistent and pervasive aggression.
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http://dx.doi.org/10.1097/00041444-200409000-00004DOI Listing
September 2004

Early language impairment and young adult delinquent and aggressive behavior.

J Abnorm Child Psychol 2004 Aug;32(4):453-67

Psychology Department, Simon Fraser University, Burnaby, British Columbia, Canada.

Clinic and forensic studies have reported high rates of language impairments in conduct disordered and incarcerated youth. In community samples followed to early adolescence, speech and language impairments have been linked to attention deficits and internalizing problems, rather than conduct problems, delinquency, or aggression. This study examines the young adult antisocial outcomes of speech or language impaired children. Language impaired boys had higher levels of parent-rated delinquency symptoms by age 19 than boys without language impairment, controlled for verbal IQ and for demographic and family variables. Language impaired boys did not differ from controls in self-reported delinquency or aggression symptoms on a standardized checklist; however, language impaired boys reported higher rates of arrests and convictions than controls. Language impairment was not related to aggression or delinquency in girls. We examine alternate models of the interrelationships between language, academics, and behavior, at ages 5, 12, and 19.
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http://dx.doi.org/10.1023/b:jacp.0000030297.91759.74DOI Listing
August 2004

The serotonin transporter gene in aggressive children with and without ADHD and nonaggressive matched controls.

Ann N Y Acad Sci 2003 Dec;1008:248-51

Department of Psychiatry, Hospital for Sick Children, Toronto, Ontario, Canada.

Using an ethnically homogeneous sample of highly aggressive Caucasian children and their matched controls, we report differential associations of the 5HTTLPR and VNTR polymorphisms with ADHD and aggression, respectively. Given the small sample size and the preliminary nature of our findings, replication is necessary.
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http://dx.doi.org/10.1196/annals.1301.025DOI Listing
December 2003

Single-word and conversational measures of word-finding proficiency.

Am J Speech Lang Pathol 2003 Aug;12(3):359-68

University of Toronto, Ontario, Canada.

Two studies with young adults as participants evaluated the relationship, presumed in the word-finding literature to exist, between slow, inaccurate performances in single-word-naming and semantic-retrieval tasks and disruptions to conversational fluency. The measures evaluated were the frequency of conversational disruptions and the scores from 3 single-word tasks: total time from the Rapid Automatized Naming task (RAN; M. B. Denckla and R. G. Rudel, 1976), standard score from the Brief Test of the Test of Adolescent/Adult Word Finding (TAWF; D. J. German, 1990), and total unique words from the Controlled Oral Word Association task (FAS; A. L. Benton and K. Hamsher, 1978). RAN time was the only significant predictor of the frequency of conversational disruptions, although this relationship was weak (R(2) =.11). In addition, single-word performances did not discriminate between groups of participants with differing levels of conversational fluency. Clinicians are cautioned against identifying word-finding deficits using single-word measures alone. Moreover, the theoretical construct of word-finding difficulties requires additional validation.
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http://dx.doi.org/10.1044/1058-0360(2003/081)DOI Listing
August 2003
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