Community energies under-evaluated: Drug initiatives on the margins

This article draws together an effectiveness review of community responses to drug concerns and supplementary interviews with key informants. Despite accessing nearly 300 publications relating to initiatives, there is a paucity of published evaluative evidence. The literature does provide a greater amount of information about initiatives that are delivered into the community as opposed to initiated by the community. Community-led responses have taken a number of approaches. To assess the current evidence on ‘what works?’, we have defined community responses to drug problems under five banners - self-help groups, parents’ groups, residents’ groups, community development groups and diversionary activity groups - for ease of discussion. There are a number of commonly identified elements that exist in successful and sustainable initiatives which are discussed

Evaluation of the Airdrie and Hamilton Youth Court Pilots

Pilot Youth Courts were introduced at Hamilton Sheriff Court in June 2003 and at Airdrie Sheriff Court in June 2004. Although introduced as one of a number of measures aimed at responding more effectively to youth crime (including young people dealt with through the Children’s Hearings System), the Youth Courts were intended for young people who would otherwise have been dealt with in the adult Sheriff Summary Court. The objectives of the pilot Youth Courts were to: • reduce the frequency and seriousness of re-offending by 16 and 17 year old offenders, particularly persistent offenders (and some 15 year olds who are referred to the court); • promote the social inclusion, citizenship and personal responsibility of these young offenders while maximising their potential; • establish fast track procedures for those young persons appearing before the Youth Court; • enhance community safety, by reducing the harm caused to individual victims of crime and providing respite to those communities which are experiencing high levels of crime; and • test the viability and usefulness of a Youth Court using existing legislation and to demonstrate whether legislative and practical improvements might be appropriate. Evaluation of the Hamilton and Airdrie Sheriff Youth Court pilots suggested that they had been successful in meeting the objectives set for them by the Youth Court Feasibility Group. Both were tightly run courts that dealt with a heavy volume of business. The particular strengths of the Youth Court model over previous arrangements included the fast-tracking of young people to and through the court, the reduction in trials, the availability of a wider range of resources and services for young people and ongoing judicial review. The successful operation of the pilot Youth Courts was dependent upon effective teamwork among the relevant agencies and professionals concerned. Good information sharing, liaison and communication appeared to exist across agencies and the procedures that were in place to facilitate the sharing of information seemed to be working well. This was also facilitated by the presence of dedicated staff within agencies, resulting in clear channels of communication, and in the opportunity provided by the multi-agency Implementation Groups to identify and address operational issues on an ongoing basis. However, whether Youth Courts are required in Scotland or whether procedural improvement were possible in the absence of dedicated resources and personnel was more difficult to assess. Two issues in particular required further attention. First, consideration needed to be given to whether the Youth Courts should be more explicitly youth focused and what this might entail. Second, greater clarity was required regarding for whom the Youth Courts were intended. This suggested the need for further discussion of Youth Court targeting and its potential consequences among the various agencies concerned

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts

Clinical predictors of response to cognitive-behavioral therapy in pediatric anxiety disorders: the genes for treatment (GxT) study.

OBJECTIVE The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child's gender, type of anxiety disorder, initial severity and comorbidity, and parents' psychopathology would significantly predict outcome. METHOD A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points. RESULTS Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up. CONCLUSION SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

Race and Ethnicity and Breast Cancer Outcomes in an Underinsured Population

BACKGROUND: The disparity in breast cancer mortality between African American women and non-Hispanic white women has been the subject of increased scrutiny. Few studies have addressed these differences in the setting of equal access to health care. We compared the breast cancer outcomes of underinsured African American and non-Hispanic white patients who were treated at a single institution. METHODS: We conducted a retrospective review of medical records for breast cancer patients who were treated at Wishard Memorial Hospital from January 1, 1997, to February 28, 2006. A total of 574 patients (259 non-Hispanic whites and 315 African Americans) were evaluated. A Cox proportional hazards regression analysis for competing risks was performed. All statistical tests were two-sided. RESULTS: Sociodemographic characteristics were similar in the two groups, and both racial groups were equally unlikely to have undergone screening mammography during the 2 years before diagnosis. Most (84%) of the patients were underinsured. The median time from diagnosis to operation, receipt of adequate surgery, and use of all types of adjuvant therapy were similar in the two groups. Median follow-up was 80.3 months for non-Hispanic whites and 77.9 months for African Americans. After accounting for the effect of comorbidities, African American race was statistically significantly associated with breast cancer-specific mortality (African Americans vs non-Hispanic whites: 26.0% vs 17.5%, P = .028; hazard ratio [HR] of death = 1.64, 95% confidence interval [CI] = 1.06 to 2.55). Adjustment for age at diagnosis, clinical stage, and hormone receptor status attenuated the effect, and the effect of race on breast cancer-specific survival was no longer statistically significant (HR of death from breast cancer = 1.43, 95% CI = 0.89 to 2.30). After adjustment for sociodemographic factors, the hazard ratio for race was further attenuated (HR = 1.26; 95% CI = 0.79 to 2.00). CONCLUSIONS: In this underinsured population, African American patients had poorer breast cancer-specific survival than non-Hispanic white patients. After adjustment for clinical and sociodemographic factors, the effect of race on survival was no longer statistically significant