A common genetic network underlies substance use disorders and disruptive or externalizing disorders

Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

Systematic review on quality control for drug management programs: Is quality reported in the literature?

<p>Abstract</p> <p>Background</p> <p>Maintaining quality of care while managing limited healthcare resources is an ongoing challenge in healthcare. The objective of this study was to evaluate how the impact of drug management programs is reported in the literature and to identify potentially existing quality standards.</p> <p>Methods</p> <p>This analysis relates to the published research on the impact of drug management on economic, clinical, or humanistic outcomes in managed care, indemnity insurance, VA, or Medicaid in the USA published between 1996 and 2007. Included articles were systematically analyzed for study objective, study endpoints, and drug management type. They were further categorized by drug management tool, primary objective, and study endpoints.</p> <p>Results</p> <p>None of the 76 included publications assessed the overall quality of drug management tools. The impact of 9 different drug management tools used alone or in combination was studied in pharmacy claims, medical claims, electronic medical records or survey data from either patient, plan or provider perspective using an average of 2.1 of 11 possible endpoints. A total of 68% of the studies reported the impact on plan focused endpoints, while the clinical, the patient or the provider perspective were studied to a much lower degree (45%, 42% and 12% of the studies). Health outcomes were only accounted for in 9.2% of the studies.</p> <p>Conclusion</p> <p>Comprehensive assessment of quality considering plan, patient and clinical outcomes is not yet applied. There is no defined quality standard. Benchmarks including health outcomes should be determined and used to improve the overall clinical and economic effectiveness of drug management programs.</p

Treatment development and feasibility study of family-focused treatment for adolescents with bipolar disorder and comorbid substance use disorders.

BACKGROUND: Comorbid substance use disorders (SUD) are associated with increased illness severity and functional impairment among adolescents with bipolar disorder (BD). Previous psychosocial treatment studies have excluded adolescents with both BD and SUD. Studies suggest that integrated interventions are optimal for adults with BD and SUD. METHODS: We modified family-focused treatment for adolescents with BD (FFT-A) in order to explicitly target comorbid SUD (FFT-SUD). Ten adolescents with BD who had both SUD and an exacerbation of manic, depressed, or mixed symptoms within the last 3 months were enrolled. FFT-SUD was offered as an adjunct to pharmacotherapy, with a target of 21 sessions over 12 months of treatment. The FFT- SUD manual was iteratively modified to integrate a concurrent focus on SUD. RESULTS: Six subjects completed a mid-treatment 6-month assessment (after a mean of 16 sessions was completed). Of the 10 subjects, 3 dropped out early (after ≤1 session); in the case of each of these subjects, the participating parent had active SUD. No other subjects in the study had a parent with active SUD. Preliminary findings suggested significant reductions in manic symptoms and depressive symptoms and improved global functioning in the subjects who completed 6 months of treatment. Reduction in cannabis use was modest and did not reach significance. Limitations. Limitations included a small sample, open treatment, concurrent medications, and no control group. CONCLUSIONS: These preliminary findings suggest that FFT-SUD is a feasible intervention, particularly for youth without parental SUD. FFT-SUD may be effective in treating mood symptoms, particularly depression, despite modest reductions in substance use. Integrating motivation enhancing strategies may augment the effect of this intervention on substance use. Additional strategies, such as targeting parental substance use, may prevent early attrition

Treatment development and feasibility study of family-focused treatment for adolescents with bipolar disorder and comorbid substance use disorders.

BACKGROUND: Comorbid substance use disorders (SUD) are associated with increased illness severity and functional impairment among adolescents with bipolar disorder (BD). Previous psychosocial treatment studies have excluded adolescents with both BD and SUD. Studies suggest that integrated interventions are optimal for adults with BD and SUD. METHODS: We modified family-focused treatment for adolescents with BD (FFT-A) in order to explicitly target comorbid SUD (FFT-SUD). Ten adolescents with BD who had both SUD and an exacerbation of manic, depressed, or mixed symptoms within the last 3 months were enrolled. FFT-SUD was offered as an adjunct to pharmacotherapy, with a target of 21 sessions over 12 months of treatment. The FFT- SUD manual was iteratively modified to integrate a concurrent focus on SUD. RESULTS: Six subjects completed a mid-treatment 6-month assessment (after a mean of 16 sessions was completed). Of the 10 subjects, 3 dropped out early (after ≤1 session); in the case of each of these subjects, the participating parent had active SUD. No other subjects in the study had a parent with active SUD. Preliminary findings suggested significant reductions in manic symptoms and depressive symptoms and improved global functioning in the subjects who completed 6 months of treatment. Reduction in cannabis use was modest and did not reach significance. Limitations. Limitations included a small sample, open treatment, concurrent medications, and no control group. CONCLUSIONS: These preliminary findings suggest that FFT-SUD is a feasible intervention, particularly for youth without parental SUD. FFT-SUD may be effective in treating mood symptoms, particularly depression, despite modest reductions in substance use. Integrating motivation enhancing strategies may augment the effect of this intervention on substance use. Additional strategies, such as targeting parental substance use, may prevent early attrition

Population-Based Assessment of Asthma Symptom Burden in Children

The Minneapolis and St. Paul Controlling Asthma in American Cities Project (CAACP) used a school-based symptom survey to inform community-based programming and provide an intermediate outcome measure of progress toward reducing the burden of asthma. In collaboration with the two school districts, the project mailed the Child Asthma Short Form, a validated health-related quality of life instrument to parents of children in grades K–8 every other school year from 2003 to 2007. The survey was mailed to a randomly selected sample in four languages (English, Spanish, Hmong, and Somali). The overall response rate was 47%, 41%, and 32% for years 1, 3, and 5, respectively. Two out of three children for whom surveys were completed were children of minority populations; more than 50% were eligible for free or reduced-price meals. The changes in scores from the first round (2003–2004) to the third round (2007–2008) were statistically significant for daytime symptom burden (p < 0.05). Improvements were noted, but not statistically significant, for nighttime symptoms and functional limitations. Children of some racial/ethnic minority groups and children eligible for free or reduced-price meals had the highest symptom burden. Findings were used to guide CAACP’s program development and delivery to populations in greatest need. CAACP’s experience in Minneapolis and St. Paul demonstrates the feasibility of administering a symptom burden survey at low cost and in compliance with school system and institutional review board requirements to maintain confidentiality. The symptom-based survey may be a useful tool to track trends and changes in health disparities at a community and population level