Gene variants associated with antisocial behaviour: a latent variable approach.

OBJECTIVE: The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. METHODS: Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. RESULTS: Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. CONCLUSIONS: This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential 'co-action' of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a 'shared' variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well-characterized research participants.

Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations.

OBJECTIVE: To examine prescribing practices in the use of biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) to treat patients with rheumatoid arthritis (RA), before and after publication of the American College of Rheumatology (ACR) treatment recommendations. METHODS: Biologics-naive RA patients under the care of a rheumatologist in the US were identified from the Consortium of Rheumatology Researchers of North America registry. Patients were included if their visits occurred prior to and/or at least 6 months after publication of the ACR treatment recommendations (time periods of February 2002-June 2008 versus December 2008-December 2009). The population was divided into 2 mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2) multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and nonbiologic DMARDs in response to active disease was assessed cross-sectionally and longitudinally in comparison to the ACR recommendations. The impact of the publication of the ACR recommendations on treatment practices was assessed using logistic regression, stratified by disease activity and adjusted for clustering of physicians and geographic region. RESULTS: After 1 visit, 24-37% of patients receiving MTX monotherapy who had moderate disease activity and a poor prognosis or high disease activity received care consistent with the ACR recommendations; after 2 visits, 34-56% of the MTX monotherapy group received care consistent with the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31-47% of those with moderate or high disease activity received care consistent with the recommendations after 1 visit, and 43-51% received such care after 2 visits. Publication of the recommendations did not significantly change treatment patterns for those with active disease. CONCLUSION: Substantial numbers of RA patients with active disease did not receive care consistent with the current ACR treatment recommendations. Innovative approaches to improve care are necessary.

Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder.

Chronic tic disorders (TD) are consistently found to have high rates of comorbidity with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). The purpose of this study is to compare the severity of TD only to TD with comorbid OCD or ADHD based on severity of tics, measures of psychopathology and additional comorbid diagnoses. Baseline data from 158 youth with a chronic TD who participated in two longitudinal studies were examined. Fifty-three percent (N = 85) of the youth also met criteria for a diagnosis of OCD, 38.6 % (n = 61) met criteria for ADHD and 24.1 % (N = 38) met criteria for both. Measures of interest addressed severity of tics, symptoms of anxiety, depression, ADHD, psychosocial stress, global functioning and the presence of comorbid diagnoses. Youth with comorbid TD and OCD were characterized by more severe tics, increased levels of depressive and anxious symptoms, heightened psychosocial stress and poorer global functioning. Youth with comorbid TD and ADHD did not differ from those with TD alone on measures of tic severity, but experienced greater psychosocial stress and poorer global functioning. Subjects with comorbid TD and OCD had more internalizing disorders than those without OCD, while those with comorbid ADHD were more likely to meet criteria for oppositional defiant disorder. TD with OCD is a more severe subtype of TD than TD without OCD. TD with ADHD is associated with higher psychosocial stress and more externalizing behaviors. Further research is needed into the underlying relationships between these closely associated conditions.

Changes in mental health outcomes with the intensive in-home child and adolescent psychiatric service: a multi-informant, latent consensus approach.

This study investigates the Intensive In-home Child and Adolescent Psychiatric Service (IICAPS), a large-scale home-based intervention that collaboratively engages the family, school, and various other service providers (e.g. health practitioners or judicial systems) to prevent the hospitalization, institutionalization or out-of-home placement of children and adolescents with serious emotional disturbance. Multi-informant data (youth, parents and clinician) on the level of youth problem severity and functioning was gathered from 7169 youth and their families served by the IICAPS network, pre- and post-intervention. A newly developed "Multi-informant Latent Consensus" (MILC) approach was employed to measure mental health "baseline levels" and change, within a Structural Equation Modeling framework. The MILC approach demonstrated promise integrating information from multiple informants involved in the therapeutic process to yield a more accurate and systemic view of a child's level of functioning and problem severity than each report taken individually. Results indicated that the IICAPS family and community based intervention model led to a reduction of problem severity and improved functioning in children and adolescents with severe emotional disturbance.