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Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Background: Adolescent cannabis use is an established risk factor for the development of psychosis, but the premorbid vulnerability factors and specificity versus generality of the psychotic sympto...

Adults with hepatocellular carcinoma (HCC) have a high symptom burden. Their quality of life (QOL) has been shown to be significantly impacted by both the disease and its treatment, adding to the high symptom burden that these patients experience. The primary aims of this paper are as follows: (1) to identify how QOL is being defined in HCC literature and (2) to identify how QOL is being measured in the HCC literature using Ferrell’s model of QOL. A systematic review was completed of relevant studies published after 2014, using PubMed, CINHAL, and PsycInfo. Relevant studies were reviewed by 2 reviewers using PRISMA guidelines. From a total of 1312 papers obtained in the initial database search, 30 met inclusion criteria and are included in this review. From the included articles, 10% included a definition of QOL and 3% addressed the spiritual domain of QOL. Majority of study participants were in the early stage of HCC, though the majority of adults with HCC are diagnosed in the advanced stage. Only 3% of included studies included greater than 22% population of advanced stage of HCC. The results of this systematic review demonstrate the need for future research into QOL in the advanced stage of QOL. It also identified gap in the literature concerning the definition of QOL in HCC and the spiritual domain of QOL in HCC.

Objective Individuals with systemic lupus erythematosus (SLE) are at high risk for infections and SLE- and medication-related complications. The present study was undertaken to define a set of SLE-specific adverse outcomes that could be prevented, or their complications minimized, if timely, effective ambulatory care had been received. Methods We used a modified Delphi process beginning with a literature review and key informant interviews to select initial SLE-specific potentially preventable conditions. We assembled a panel of 16 nationally recognized US-based experts from 8 subspecialties. Guided by the RAND-UCLA Appropriateness Method, we held 2 survey rounds with controlled feedback and an interactive webinar to reach consensus regarding preventability and importance on a population level for a set of SLE-specific adverse conditions. In a final round, the panelists endorsed the potentially preventable conditions. Results Thirty-five potential conditions were initially proposed; 62 conditions were ultimately considered during the Delphi process. The response rate was 100% for both survey rounds, 88% for the webinar, and 94% for final approval. The 25 SLE-specific conditions meeting consensus as potentially preventable and important on a population level fell into 4 categories: vaccine-preventable illnesses (6 conditions), medication-related complications (8 conditions), reproductive health-related complications (6 conditions), and SLE-related complications (5 conditions). Conclusion We reached consensus on a diverse set of adverse outcomes relevant to SLE patients that may be preventable if patients receive high-quality ambulatory care. This set of outcomes may be studied at the health system level to determine how to best allocate resources and improve quality to reduce avoidable outcomes and disparities among those at highest risk.

Objective To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). Methods We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. Results This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. Conclusion This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

The incidence of early onset colorectal cancer, or colorectal cancer (CRC) diagnosed before age 50, is increasing.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs

Background: Severity of substance use disorder (SUD) is typically evaluated by tabulating the number of symptoms. The resulting estimate of disorder severity is, however, biased due to intercorrelations among symptoms and their unequal salience. Objective. Employing item response theory (IRT) methodology, opioid use disorder symptoms were calibrated to derive the Opioid Use Disorder Severity Scale (OUDSS) and assess its predictive ability in men and women separately. Methods: A two-parameter IRT model was utilized to derive the OUDSS from DSM-IV symptoms recorded on the Structured Clinical Interview for DSM-IV (SCID) in 438 men and 429 women who reported at least one lifetime opioid consumption event. The predictive ability of the OUDSS was evaluated using the 10 health, psychological, and social adjustment domains of the revised Drug Use Screening Inventory (DUSI-R) assessed 2 years later. Results: The OUDSS score predicted the severity of problems in all 10 DUSI-R domains in men and women. The OUDSS also predicted the DUSI-R diagnostic cutoff score of overall problem density score in men and women (OR = 2.21 and OR = 4.83, respectively). Withdrawal was the most frequently endorsed symptom in this sample of opioid users. The other symptoms' frequencies, while somewhat lower than withdrawal's, did not differ from it substantially, indicating a similar severity threshold. Conclusions: OUDSS enables dimensional measurement of opioid use severity on an interval scale. The OUDSS and DUSI-R together can identify problem areas requiring prevention or treatment.

Use of urban trails and other green space during the early stages of the COVID-19 pandemic reached record highs around the world. Although the use of these resource amenities has been documented to have several physical and mental health benefits, the density of their use during the pandemic required managers to issue guidance and/or use-requirements to mitigate the spread of the virus. Hence, this investigation sought to document adherence to commonly suggested physical distancing guidelines at 14 trails across six states in the United States. Trained research team members unobtrusively observed over 10,000 encounters between trail visitors. Results indicated that over half of visitor groups failed to allow for enough physical distancing between themselves and another party, suggesting a need for trail and green space managers to consider additional messaging and trail design changes to encourage greater adherence to future public health guidelines.Subscribe to JPRA

Gallium-68 DOTATATE provides physiologic imaging and assists in disease localization for somatostatin receptor (SSTR) positive neuroendocrine tumor (NET) patients. However, questions regarding usefulness of gallium- 68 DOTATATE imaging in identifying the primary site in neuroendocrine tumors (NETS) of unknown primary, correlation of NET grade with median Standardized Uptake Value (SUV) and effects of long acting somatostatin analog on gallium-68 DOTATATE imaging quality needs to be evaluated. A single institution retrospective review of the first 200 NET patients with gallium-68 DOTATATE imaging from Dec 2016 to Dec 2017 was conducted. Questions related to NETs of unknown primary, correlation of Standardized Uptake Value (SUV) to Ki-67 (which signifies proliferation rate), the effects of long-acting systemic somatostatin analog (SSA) on SUV were part of our data analysis. From these 200 patients, 59.5% (119) were females, 40.5% (81) were males; the median age was 62 years. The following primary tumor sites were identified: small bowel-37.5%; pancreas-18.5%; bronchial-14%; colon-3.5%; rectum-2%; appendix-1.5%; adrenal-0.5%; prostate-0.5%; others-3% and unknown primary-19%. Mean hepatic SUV of the lesion with the greatest radiolabeled uptake in 96 patients was similar irrespective to exposure to long acting SSA. Patients exposed to long acting SSA had mean SUV of 31.3 vs 27.8 for SSA naïve patients. The difference was not statistically significant. Gallium-68 DOTATATE imaging seems to distinguished G3 NET from G1/G2 based on mean SUV, and also identified the primary tumor site in 17 of 38 (45%) patients with unknown primary. Systemic exposure to long acting SSA does not appear to influence mean SUV of gallium-68 DOTATATE scan.

Background: With increases in marijuana use and legalization efforts, it is imperative to establish its impact on the developing brain. Therefore, we investigated whether exposure to marijuana alters brain derived neurotropic-factor (BDNF), given its critical role in brain development and plasticity. We then examined whether onset age of cannabis use was associated with more severe changes. A single site, cohort study following 500 urban healthy American adolescents. Changes in plasma m-BDNF levels were longitudinally assessed, and a multi-method approach was implemented to ascertain marijuana use. Multivariate and general linear model (GLM) regression modeling were utilized to test the main hypothesis, controlling for confounders. Results: Group-based trajectory modeling identified four distinct groups, characterized by naive (60% control), starters (14%), chronic users (20%), and experimenting/quitters (6%). Compared to controls, those initiating marijuana use had similar pre-existent m-BDNF (1939.2 ± 221 vs. 2640.7 ± 1309 ng/ml, p=0.4) After adjusting for confounding factors, GLM analyses revealed that, compared to controls, younger adolescents increased BDNF levels when experimenting and during moderate marijuana use. Older adolescents had a steeper increase in endogenous BDNF levels, particularly when escalating use. Multivariate analyses confirmed marijuana use as a predictor of m-BDNF (p = 0.001). Conclusions: This is the first study demonstrating BDNF alterations were not a precondition. Rather, BDNF alteration was secondary to marijuana use, serving as cautionary evidence of marijuana’s deleterious effects. Findings suggest that when marijuana use escalates, the BDNF pathway becomes more deregulated. Analyses confirm that age of marijuana use onset influences the magnitude of these changes.

Objectives Community pharmacy continues to play a crucial role in the national response to the opioid epidemic. The purpose of this article is to describe the protocol for a pilot study that is examining the feasibility and acceptability of the Motivational Intervention–Medication Therapy Management (MI-MTM) model. This study also examines the preliminary clinical effect of MI-MTM for improving opioid medication misuse and patient activation in self-management of health conditions that increase risk for misuse. Design MI-MTM is a pharmacy-based integrated care model made up of 4 evidence-based practices: medication therapy management; brief motivational intervention; patient navigation; and naloxone training and referral. To test MI-MTM compared with Standard Medication Counseling (SMC), we are conducting a 2-group randomized single-blinded controlled trial with assessments at 3 time points. Setting and participants The study is being conducted within a western Pennsylvania university-based community pharmacy with 46 patients with opioid misuse (MI-MTM = 23; SMC = 23). Main outcome measures Feasibility will be measured by capturing patient completion rate of MI-MTM sessions. Acceptability will be measured by administering satisfaction surveys regarding pharmacist and patient navigator services. Acceptability will also be captured by conducting intensive qualitative interviews. Preliminary effect of the intervention on misuse will be measured with the use of the Prescription Opioid Misuse Index and the Opioid Compliance Checklist. Activation in self-management will be measured with the use of the Patient Activation Measure. Results This project is currently recruiting, and results are to come. Conclusion This study is the first in the United States to implement an evidence-based integrated behavioral intervention into the community pharmacy setting to address opioid medication misuse among pharmacy patients. The results of this study will provide necessary foundational data that allow further testing of this intervention model in a larger trial.

Objectives The public health burden of opioid use disorder (OUD) among pregnant women has significantly increased in recent years. The Optimizing Pregnancy Treatment Interventions for Moms study was a pilot project that examined the feasibility of a patient navigation (PN) intervention model to reduce substance use and improve mental health, quality of life, and to increase engagement with treatment services among pregnant women with OUD. Methods A 1-group repeated-measures pilot study was conducted with treatment-seeking pregnant women with opioid dependence initiating buprenorphine maintenance treatment. Participants received the PN intervention delivered as 10 sessions before delivery and 4 sessions postpartum. Participants completed assessments at baseline and after the prenatal and postnatal portions of the intervention. Demographics were assessed using descriptive statistics, and general estimating equation analyses were employed to examine changes in health and service engagement across time. Results in all, 21 women were enrolled and completed the PN intervention and follow-up assessments. Participants reported improvements in abstinence from illicit opioids (B = 0.15, 95% confidence interval [CI] 0.1-0.2), drug use (odds ratio [OR] 5.25, 95% CI 2.1-13.0), and depression (OR 7.70, 95% CI 2.4-25.1). Results also showed nonsignificant trends suggesting enhancements in general health (B = 0.17, 95% CI 0.0-0.3, P = 0.06) and increases in substance use treatment attendance (B = 2.15, 95% CI -0.2 to 4.5, P = 0.07). Most study participants achieved adequate or better prenatal care. Conclusions These findings provide support that PN is a feasible adjunctive intervention that shows promise for health improvements and service engagement among treatment-seeking pregnant women with opioid dependence initiating buprenorphine.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Background Community pharmacists are well-positioned to address the US opioid medication crisis, which has created a need to detect misuse risk in order to provide optimal patient care. Objectives This study sought to identify community pharmacy patient subgroups at risk for opioid medication misuse. Methods This study was a cross-sectional survey that examined behavioral, mental, and physical health characteristics among patients filling opioid pain medications. A convenience sample of adult patients filling opioid pain medications who were not receiving cancer treatment were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. Patient subgroups were identified using latent class analysis. Latent class regression analysis was used to examine the association between subgroup membership and misuse. Results A total of 333 patients completed the survey (response rate 71.4%). Latent class analysis results showed that a 3-class solution best fit the data, which were labeled: mental health (8.4%, n = 28), poor health (79.6%, n = 265), and hazardous alcohol use (12%, n = 40). Individuals within the mental health subgroup had an increased risk for opioid medication misuse (Odds Ratio = 6.23, 95% CI = 5.13–7.33). Conclusion These findings demonstrate heterogeneity of this population receiving prescribed opioids and the potential to identify subgroups with high misuse risk. These findings also support routine screening of patients filling opioid medications and suggest the need for evidence-based patient-centered intervention development.

Background Combining opioid medications and alcohol has serious implications for patient health, including overdose. Information regarding those who use/misuse opioid medications and engage in unhealthy alcohol use is limited to pharmacological and epidemiological descriptions. This study presents opioid medication misuse and behavioral, mental, and physical health characteristics of persons filling opioid medications that are engaged in unhealthy alcohol use. Methods We conducted a cross-sectional survey at 5 community pharmacies in Southwestern, Pennsylvania among patients filling opioid medications. Respondents completed validated opioid medication misuse, alcohol use, illicit drug use, depression, posttraumatic stress disorder (PTSD), and physical health functioning assessments. We present univariate and multivariate statistics describing opioid medication misuse and health risks among those positive for unhealthy alcohol use. Results A total of 344 patients completed the survey (75.8% response). A total of 15.9% of respondents screened positive for opioid medication misuse, of whom 20.3% reported unhealthy alcohol use. Taking opioid medications too often was reported among a larger proportion of the sample with unhealthy alcohol use (34.3%) compared to those without (22.1%, p = 0.04). Further, among respondents with unhealthy alcohol use, illicit drug use (Adjusted odds ratio [AOR] = 12.14, 95% Confidence Interval [CI] = 1.64-89.72) and PTSD (AOR = 9.77, 95% CI = 1.70-56.11) were associated with increased odds for opioid medication misuse. Conclusion Results suggest respondents with unhealthy alcohol use had distinct health profiles, which may place them at risk for opioid misuse and adverse events, such as overdose. Continued research must work to further understand these relationships and identify intervention and treatment strategies.

Vector surveillance is an essential component of vector-borne disease prevention, but many communities lack resources to support extensive surveillance. The Great Arizona Mosquito Hunt (GAMH) was a collaborative citizen science project conducted during 2015–17 to enhance surveillance for Aedes aegypti in Arizona. Citizen science projects engage the public in scientific research in order to further scientific knowledge while improving community understanding of a specific field of science and the scientific process. Participating schools and youth organizations across the state conducted oviposition trapping for 1–4 wk during peak Ae. aegypti season in Arizona and returned the egg sheets to collaborating entomologists for identification. During the 3-year program, 120 different schools and youth organizations participated. Few participants actually collected Aedes eggs in their traps in 2015 or 2017, but about one-third of participants collected eggs during 2016, including 3 areas that were not previously reported to have Ae. aegypti. While relatively few new areas of Ae. aegypti activity were identified, GAMH was found to be a successful method of engaging citizen scientists. Future citizen science mosquito surveillance projects might be useful to further define the ecology and risk for vector-borne diseases in Arizona.

BACKGROUND: This longitudinal study explored the utility of machine learning (ML) methodology in predicting the trajectory of severity of substance use from childhood to thirty years of age using a set of psychological and health characteristics. DESIGN: Boys (N=494) and girls (N=206) were recruited using a high-risk paradigm at 10–12 years of age and followed up at 12–14, 16, 19, 22, 25 and 30 years of age. MEASUREMENTS: At each visit, the subjects were administered a comprehensive battery to measure psychological makeup, health status, substance use and psychiatric disorder, and their overall harmfulness of substance consumption was quantified according to the multidimensional criteria (physical, dependence, and social) developed by Nutt et al. (2007). Next, high- and low- substance use severity trajectories were derived differentially associated with probability of segueing to substance use disorder (SUD). ML methodology was employed to predict trajectory membership. FINDINGS: The high-severity trajectory group had a higher probability of leading to SUD than the low-severity trajectory (89.0% vs 32.4%; odds ratio=16.88, p

Background: Opioid misuse imposes a disproportionately heavy burden on individuals living in rural areas. Community pharmacy has the potential to expand and coordinate with health professionals to identify and intervene with those who misuse opioids. Objective: Rural and urban community pharmacy patients were recruited in this pilot project to describe and compare patterns of opioid misuse. Methods: We administered a health screening survey in 4 community pharmacies among patients filling opioid medications. Univariate statistics were used to assess differences in health characteristics and opioid medication misuse behaviors between rural and urban respondents. Multivariable statistics were used to identify risk factors associated with rural and urban opioid misuse. Results: A total of 333 participants completed the survey. Participants in rural settings had poorer overall health, higher pain levels, lower education, and a higher rate of unemployment compared to patients in urban pharmacies. Rural respondents with illicit drug use (adjustable odds ratio [aOR]: 14.34, 95% confidence interval [CI] = 2.16-95.38), posttraumatic stress disorder (aOR: 5.44, 95% CI = 1.52-19.50), and ≤high school education (aOR: 6.68, 95% CI = 1.06-42.21) had increased risk for opioid misuse. Conclusions: Community pharmacy represents a promising resource for potential identification of opioid misuse, particularly in rural communities. Continued research must extend these findings and work to establish collaborative services in rural settings.

Many burdens come with caring for someone with dementia, but telehealth interventions can provide information and support and reduce barriers to access. In this review we describe current telehealth interventions for family care partners of people diagnosed with Alzheimer’s disease or related dementias (ADRDs). We conducted a systematic literature search using PubMed. Inclusion criteria were peer-reviewed, data-based research articles focusing on technological clinical interventions, published within the past two years, with participants providing unpaid care to persons with a diagnosis of ADRDs. We identified 53 relevant articles, of which 13 met our criteria. Included studies fell into three categories: peer support groups facilitated by gerontological social workers and psychologists, psychoeducation and behavior modification interventions delivered by nursing professionals, and symptom management advising overseen by physicians. Different technologies were used including computers, iPads, smartphones, and smartwatches. The duration of interventions also ranged from four weeks to three months, representing varying approached to participant engagement. The majority of caregivers were women, non-Hispanic white, spouses. Based on our findings of a lack of diversity in the samples of extant studies, and the need for interventions tailored to specific stages of ADRDs, future researchers can design studies to address these gaps. Overall, the interventions’ effectiveness and participant satisfaction were high, resulting in improvements in burden, competence, and coping skills. Although every approach has its own strengths and weaknesses, we believe that the continued expansion of telehealth interventions will not only offer many benefits, but also transform the delivery of health care.

Objective To evaluate the accuracy of detecting 16-year-old male (n = 465) and female (n = 162) youths who subsequently manifest opioid use disorder (OUD) at 25 years of age. We hypothesized that the combined measures of 2 components of etiology, heritable risk, and substance use, accurately detect youths who develop OUD. Study design Heritable risk was measured by the transmissible liability index (TLI). Severity of the prodrome presaging OUD was quantified by the revised Drug Use Screening Inventory containing the consumption frequency index (CFI) documenting substance use events during the past month and the overall problem density (OPD) score indicating co-occurring biopsychosocial problems. Diagnosis of OUD was formulated by a clinical committee based on results of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition in conjunction with medical and social history records. Results Bivariate analysis shows that the TLI, CFI, and OPD scores at 16 years of age predict OUD at 25 years. Multivariate modeling indicates that the TLI combined with the CFI predict OUD with 86% accuracy (sensitivity = 87%; specificity = 62%). The TLI and CFI at 16 years of age mediate the association between parental substance use disorder and OUD in offspring at 25 years of age, indicating that these measures respectively evaluate risk and prodrome. Conclusions These results demonstrate the feasibility of identifying youths requiring intervention to prevent OUD.

Caught in a Flare This interactive case features a 24-year-old woman with systemic lupus erythematosus who presents with a 1-month history of worsening fatigue, diffuse arthralgias, a rash on her f...

e24107 Background: Gastrointestinal toxicity is a common side effect of cancer therapy. Pre-clinical studies using a proprietary mixture of amino acids, demonstrated a reduction in mucositis and gastrointestinal toxicity following irradiation via tightening of the mucosal barrier, increasing proliferation of crypt cells, increasing villous height and increasing absorption of fluid, electrolytes and nutrients. A novel 5-amino acid mixture “enterade” was previously evaluated in a Phase II clinical trial for anti-diarrheal effects in post bone marrow transplant patients at Dana Farber Cancer Institute (NCT02919670). Signs of anti-diarrheal efficacy were found in treatment-compliant patients.Enterade is currently being tested in two prospective Phase II studies (NCT03722511 and NCT04073017) in neuroendocrine tumor patients with quality of life limiting diarrhea. We conducted a pilot study to evaluate early antidiarrheal signals in oncologic treatment-induced diarrhea. Methods: An IRB-approved retrospective chart review was conducted at Markey Cancer Center between Sept 2019 and Dec 2019. Medical records were retrospectively reviewed for all solid tumor patients who received enterade for chemotherapy or immunotherapy-induced diarrhea. Patients were instructed to consume one 8-oz bottle of enterade twice a day for at least one week in addition to standard of care antidiarrheal medications. Results: A total of 46 patients were offered enterade. Antidiarrheal efficacy data was available on 17 patients. 11 were female and the mean age of the cohort was 64 years. Six out of 17 patients had a previous history of bowel resection. Four patients had immune checkpoint induced colitis. Three patients developed diarrhea from TKI use and rest were on cytotoxic chemotherapy at the time of the diarrheal episode. Eighty-eight percent (15/17) of patients reported a reduction in diarrhea frequency after consuming enterade. On average, patients noticed an improvement in diarrhea frequency after 3.6 days of enterade consumption, with 86% (13/15) of responders reporting at least 50% reduction in diarrhea frequency. Conclusions: Patient-reported diarrheal improvement after enterade consumption is consistent with pre-clinical data. Results suggest the amino acid mixture may alleviate symptoms of cancer therapy-induced gastrointestinal toxicity (i.e. diarrhea). A prospective clinical trial is warranted to substantiate the observed improvement in chemotherapy and immunotherapy induced diarrhea.

Introduction: Hispanic adolescents domiciling in Florida rank second in the U.S. with respect to HIV/AIDS incidence and prevalence. Extending studies showing that risky sexual behavior is associated with limited access to information, this project surveyed knowledge about HIV etiology, prevention and treatment. Methods: The sample consisted of 400 Hispanic youth between 11-18 years of age living in Miami, Florida. The sample is enrolled in an ongoing project Role of Brain Derived Neurotrophic Factor in Decision Making (ROBIM). The HIV Knowledge Questionnaire (HIV-KQ-18), an 18 item self-administered questionnaire was used to measure HIV knowledge, particularly transmission and prevention. Results: Less than 10% of the sample had comprehensive knowledge about HIV/AIDS. Approximately 25% incorrectly answered all of the questions. Questions pertaining to transmission were incorrectly answered by more than half of the sample. The most frequent topics reflecting absence of knowledge are related to high-risk sexual behaviors (sex during the menses) and infection prevention methods (e.g. condoms). A majority of youth believed incorrectly that HIV could be cured (61%), an effective vaccine is available (61%), and antibiotics protect against HIV infection (76%). School (28%) and parents (26%) were the most frequent sources of knowledge about HIV/AIDS. However, youth receiving information from parents had significantly higher knowledge scores than peers receiving education in school (7.4 ± 4.15 vs. 6.1 ± 4.5 scores, p = 0.037). Yet, 68% of the sample had never discussed condom use with their parents. Conclusions: These findings indicate Hispanic youths, although at very high risk, are poorly informed about prevention of HIV/AIDS. Moreover, the most frequent source of information, namely schools, inculcates less knowledge than parents. Lastly, youths who discuss sex with parents do not typically dialog about condoms, the most readily available protection from HIV/AIDS. These findings identify gaps that need to be addressed for lowering the high rate of HIV infection in Hispanic youths.

Ameliorating the factors that cause and sustain opioid addiction is essential for effective prevention. Accordingly, this discussion begins with a brief review of the etiological components, developmental pathways, and phases of addiction across the lifespan. Next, assessment of risk for addiction is discussed as to the basis of objective determination of prevention tactics. The main prevention tactics are succinctly noted. Lastly, the challenges that need to be surmounted to increase access to and success of prevention interventions are considered. Recommendations that may improve effectiveness of prevention of opioid addiction conclude this article. In particular, it is argued that successful prevention is contingent on shifting resources from the criminal justice system to the health care system.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnosed AD. Genome - wide data on 14,904 individuals with AD and 37,944 controls from 28 case / control and family - based studies were meta - analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome - wide significant effects of different ADH1B variants were identified in European (rs1229984; p = 9.8E - 13) and African ancestries (rs2066702; p = 2.2E - 9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non - pathological drinking behaviors.

Abnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naive 10-14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naive youths.

Risk for a disorder and the mechanisms that determine its elevation, risk factors, are the focus of medical research. Targeting risk factors should serve the goal of prevention and treatment intervention. Risk, however, is but one of the aspects of liability to a disorder, a latent trait that encompasses effects of all factors leading to or from the diagnostic threshold. The coequal but opposite aspect of liability is resistance to a disorder. The factors that increase resistance and thus enable prevention or recovery may differ from those that elevate risk. Accordingly, there are nontrivial differences between research perspectives that focus on risk and on resistance. This article shows how this distinction translates into goals and methods of research and practice, from the choice of potential mechanisms tested to the results sought in intervention. The resistance concept also differs from those of “resilience” and “protective factors,” subsuming but not limited to them. The implications of the concept are discussed using substance use disorder as an example and substantiate the need for biomedical research and its translation to shift to the resistance perspective.

OBJECTIVES This study tested screening feasibility and described the behavioral, mental, and physical health of patients filling prescriptions for opioid medications in the community pharmacy setting. METHODS We conducted a cross-sectional survey in rural/urban community pharmacies with adult noncancer patients. The survey included validated measures for opioid medication misuse risk, drug and alcohol use, and physical and mental health problems. Descriptive statistics were calculated, and bivariate and multivariable logistic regression evaluated relationships between opioid medication misuse risk and patient demographics, behavioral, mental, and physical health. RESULTS A total of 164 patients completed the survey (87% response rate), revealing positive screens for prescription opioid misuse risk (14.3%), illicit drug use (7.3%), hazardous alcohol use (21.4%), depression (25.8%), and posttraumatic stress disorder (PTSD; 17.1%). Bivariate analyses revealed increased odds of a positive opioid medication misuse risk score with a positive screen for illicit drug use in the previous year (odds ratio = 3.91; 95% confidence interval [CI], 1.05-14.63) and PTSD (odds ratio = 6.7; 95% CI, 2.54-17.69). In adjusted multivariable analyses, these relationships strengthened such that a positive screen for illicit drug use (adjusted odds ratio = 12.96; 95% CI, 2.18-76.9) and PTSD (adjusted odds ratio = 13.3; 95% CI, 3.48-50.66) increased odds for a positive opioid medication misuse risk score. CONCLUSIONS Findings confirmed the feasibility of screening risk factors and positive opioid medication misuse risk among community pharmacy patients. Future research should validate these findings as a foundation to intervention development.

About 30% of college students have smoked hookah tobacco. Although most students perceive this product to be innocuous and non-addictive, hookah tobacco increases the risk for disease and nicotine dependence. Currently, the US Food and Drug Administration (FDA) does not regulate the manufacture, distribution, or sale of hookah tobacco.Empirical literature pertaining to hookah tobacco smoking is reviewed with a focus on the implications for regulatory policy.PubMed, PsycINFO, and Scopus databases were searched to locate articles published in English. The literature search combined several key words including "hookahs", "college", "advertising", "health effects", and "health policy".Smoking hookah tobacco may play a role in the initiation of smoking among tobacco-naïve college students and may portend persistent smoking among those who have smoked cigarettes. College students are typically nondaily, social smokers. They do not perceive that their heightened risk for tobacco diseases and nicotine dependence relates to their smoking behavior. However, few public health messages target college-age adults to counter media messages that endorse hookah tobacco smoking.Given that the FDA is not authorized to ban specific tobacco products, policy actions should focus on the development of effective risk communication strategies that target college-age adults and on limiting the accessibility of hookah tobacco products to these adults. Accordingly, a research agenda that would inform these policy actions is proposed.

Background Psychological items discriminating children of fathers diagnosed with an illicit drug-related substance use disorder and normal controls are indicators of a unidimensional construct termed transmissible liability index (TLI) (Vanyukov et al., 2009). TLI is a highly heritable (Vanyukov et al., 2009; Hicks, Iacono, McGue, 2012) and valid (Vanyukov et al., 2009; Hicks et al., 2009; Kirisci et al., 2013a) measure of childhood liability to substance use disorders (SUDs). Aims This longitudinal study determined whether TLI has incremental validity for predicting SUD beyond commonly measured psychological indicators of risk. Methods TLI and measures of executive cognitive capacity, emotion dysregulation and externalizing disturbance were administered to boys at ages 10–12 and 16. SUD outcome determined at age 22 was assessed as (1) any SUD, (2) the number of drug-specific SUDs, and (3) SUD severity. Results TLI predicted SUD beyond the contribution of measures of emotion dysregulation, executive cognitive capacity and externalizing disturbance. The association of emotion dysregulation and externalizing behavior at ages 10–12 and 16 with SUD at age 22 was also reduced to non-significance after controlling for transmissible risk measured by TLI. Conclusions TLI's incremental validity beyond these latter indicators of risk points to its utility for identifying vulnerable youths requiring intervention.

Liability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1 (HSV-1), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) as well as Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174 daughters of fathers with or without SUD. Its relationships with a cognitive characteristic (IQ) in childhood and with risk for SUD in adulthood were examined using correlation, regression, survival, and path analyses. Exposure to HSV-1, EBV, and T. gondii in males and females, and CMV in males, was associated with lower IQ. Independent of that relationship, EBV in females and possibly in males, and CMV and possibly HSV-1 in females were associated with elevated risk for SUD. Therefore, childhood neurotropic infections may influence cognitive development and risk for behavior disorders such as SUD. The results may point to new avenues for alleviating cognitive impairment and SUD risk.

Background. Item response theory (IRT) based studies conducted on diverse samples showed a single dominant factor for DSM-III-R and DSM-IV substance use disorder (SUD) abuse and dependence symptoms of alcohol, cannabis, sedative, cocaine, stimulants, and opiates use disorders. IRT provides the opportunity, within a person-centered framework, to accurately gauge each person’s severity of disorder that, in turn, informs required intensiveness of treatment. Objectives. The aim of this study was to determine whether the SUD symptoms indicate a unidimensional trait or instead need to be conceptualized and quantified as a multidimensional scale. Methods. The sample was composed of families of adult SUD+ men (n=349), and SUD+ women (n=173), who qualified for DSM-III-R diagnosis of substance use disorder (abuse or dependence) and families of adult men and women who did not qualify for a SUD diagnosis (SUD- men: n=190, SUD- women: n=133). An expanded version of the Structured Clinical Interview for DSM-III-R (SCID) was administered to characterize lifetime and current substance use disorders. Item response theory methodology was used to assess the dimensionality of DSM-III-R SUD abuse and dependence symptoms.Results. A bi-factor model provided the optimal representation of the factor structure of SUD symptoms in males and females. SUD symptoms are scalable as indicators of a single common factor, corresponding to general (non-drug-specific, common) liability to addiction, combined with drug-specific liabilities. Conclusions. IRT methodology used to quantify the continuous general liability to addiction (GLA) latent trait in individuals having SUD symptoms was found effective for accurately measuring SUD severity in men and women. This may be helpful for person-centered medicine approaches to effectively address intensity of treatment.

Background Substance use disorder (SUD) exacts enormous societal costs in the United States, and it is important to detect high-risk youths for prevention. Machine learning (ML) is the method to find patterns and make prediction from data. We hypothesized that ML identifies the health, psychological, psychiatric, and contextual features to predict SUD, and the identified features predict high-risk individuals to develop SUD. Method Male (N = 494) and female (N = 206) participants and their informant parents were administered a battery of questionnaires across five waves of assessment conducted at 10–12, 12–14, 16, 19, and 22 years of age. Characteristics most strongly associated with SUD were identified using the random forest (RF)algorithm from approximately 1000 variables measured at each assessment. Next, the complement of features was validated, and the best models were selected for predicting SUD using seven ML algorithms. Lastly, area under the receiver operating characteristic curve (AUROC) evaluated accuracy of detecting individuals who develop SUD+/- up to thirty years of age. Results Approximately thirty variables strongly predict SUD. The predictors shift from psychological dysregulation and poor health behavior in late childhood to non-normative socialization in mid to late adolescence. In 10–12-year-old youths, the features predict SUD+/- with 74% accuracy, increasing to 86% at 22 years of age. The RF algorithm optimally detects individuals between 10–22 years of age who develop SUD compared to other ML algorithms. Conclusion These findings inform the items required for inclusion in instruments to accurately identify high risk youths and young adults requiring SUD prevention.

Background. Prevention of substance use disorder (SUD) is impeded by the large number, complexity and idiosyncratic configuration of etiological factors. Effective prevention of SUD is feasible however when intervention resources are prioritized to individuals who are objectively determined high risk and tailored to their specific characteristics and circumstances.Objective. This study had the aim of developing a rapid accurate screening instrument for determining current presence of and future risk for SUD. Methods. The sample consisted of 182 girls recruited when they were 10-12 years of age and tracked to 22 years of age. From a large item pool the Drug Use Screening Inventory Quick Screen for Females (DQS-F) was derived consisting of the Substance Involvement Index and the Problem Severity Index.Results. The DQS for Females (DQS-F) has high sensitivity for identifying girls who currently qualify for SUD diagnosis. Furthermore, accuracy of predicting future SUD with the DQS-F is in the good range at age 16 and in the very good range at age 19.Conclusions. Requiring only three minutes for administration on the Web the DQS-F is an efficient method for identifying girls requiring thorough assessment prior to implementing individualized intervention.

Studies are needed that examine neurobiological characteristics in high risk individuals prior to substance use disorder (SUD) development. In this pilot study, 4 adolescent subjects at high risk (having at least 1 parent with a SUD) for SUD were compared with 4 adolescent reference subjects on a corticolimbic reactivity paradigm, where they were presented with affect-laden faces or geometric shapes. FMRI was used to measure cortical activation in response to these stimuli. High risk subjects, compared to low risk, exhibited greater left amygdala activation (t=3.60, df=6, p=0.01), suggesting they may exhibit hyper-responsivity of the amygdala in response to emotional stimuli.

The opioid crisis continues to affect pregnant and postpartum women the United States, with the number of pregnant women diagnosed with opioid use disorder (OUD) quadrupling over the last decade. The associated increase in morbidity and mortality among mother and baby warrants prompt, targeted intervention efforts that improve engagement, linkage of care, and treatment retention. Patient navigation (PN) is a chronic care intervention that can directly address this need by helping women identify medical, behavioral, and psychosocial care goals. Moreover, PN can assist women in preparing for, engaging in, and maintaining patient participation in necessary services. Specifically, PN includes strengths-based case management, 1–1 clinical support, motivational interviewing, and addiction-relapse prevention programming. The objective of this article is to present the study protocol of a pilot multisite randomized clinical trial, entitled: Optimizing Pregnancy and Treatment Interventions for Moms 2.0 (OPTI-Mom 2.0; NCT03833245). In this study, we build upon a proof-of-concept study, employing evidence-informed frameworks for protocol and intervention expansion in order to construct a PN intervention tailored for pregnant women with OUD in central Utah and southwestern Pennsylvania. Our protocol provides an initial framework of a potentially impactful intervention and may guide development of future programs. Importantly, this study further establishes the evidence-base—with potential to ameliorate serious adverse opioid-related outcomes and improve health for women and their children.

BACKGROUND: Stemming the opioid epidemic requires testing novel interventions. Toward this goal, feasibility and acceptability of a Brief Motivational Intervention-Medication Therapy Management (BMI-MTM) intervention was examined along with its impact on medication misuse and concomitant health conditions. METHODS: We conducted a two-group randomized trial in 2 community pharmacies. We screened patients for prescription opioid misuse at point-of-service using the Prescription Opioid Misuse Index. Participants were assigned to standard medication counseling (SMC) or SMC+BMI-MTM (referred to as BMI-MTM herein). BMI-MTM consists of a pharmacist-led medication counseling/brief motivational session and 8-weekly patient navigation sessions. Assessments were at baseline, 2-, and 3-months. Primary outcomes included feasibility, acceptability, and mitigation of opioid medication misuse. Secondary outcomes included pain and depression. Outcomes were analyzed with descriptive and multivariable statistics (intent-to-treat [ITT] and adjusted for number of sessions completed [NUMSESS]). RESULTS: Thirty-two participants provided informed consent (74.4% consent rate; SMC n=17, BMI-MTM n=15; 3-month assessment retention ≥93%). Feasibility was demonstrated by all BMI-MTM recipients completing the pharmacist session and an average of 7 navigation sessions. BMI-MTM recipients indicated ≥4.2 (5 maximum) level of satisfaction with the pharmacist-led session, and 92.4% were satisfied with navigation sessions. Compared to SMC at 3-months, BMI-MTM recipients reported greater improvements in misuse (ITT: Adjusted Odds Ratio [AOR]=0.13; 95% CI=0.05, 0.35, p

This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22).The Youth Attachment to Parents Scale (YAPS) was developed in 10-12-year-old boys and girls (N = 694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10-12, 12-14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use.Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use.Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship.

This research examined the combined impact of alcohol and previous experience growing up in a disadvantaged neighborhood on aggression in a laboratory setting. Participants were 505 young adult social drinkers between 21 and 35 years of age who completed a retrospective measure of neighborhood disadvantage and then participated in an experimental procedure, where they either consumed an alcohol or placebo beverage. They were subsequently tested on a laboratory aggression task in which they were provoked by receiving electric shocks from a fictitious opponent under the guise of a competitive reaction-time task. Aggression was operationalized as shock intensities and durations administered, in retaliation, by the participants to their fictitious opponent. Acute alcohol intoxication significantly increased aggression for those who grew up in disadvantaged neighborhoods. Thus, our investigation supports Sampson’s notions of “legacies of neighborhood inequality” with important implications for the etiology and prevention of violence in real-world settings.

Background This prospective study investigated pubertal timing and transmissible risk in relation to affiliation with deviant peers on the development of substance use disorder (SUD). Method Participants were boys (N = 500) ascertained through proband fathers with (N = 250), and without (N = 250) DSM-III-R lifetime diagnosis of SUD who were prospectively tracked from age 10–12 to 22. Transmissible liability index (TLI), Tanner stage, peer delinquency, and substance use were measured at ages 10–12 and 16. SUD diagnosis during early adulthood was determined. Results Structural equation modeling revealed two pathways in which transmissible risk and sexual maturation influenced development of SUD. In the first pathway, transmissible risk was correlated with and prospectively predicted affiliation with deviant peers and substance use presaging SUD. In the second pathway, advanced sexual maturation positively predicted affiliation with deviant peers and substance use, which in turn predicted SUD. However, transmissible risk was not associated with pubertal development. Conclusion These findings indicate that advanced sexual maturation and transmissible risk constitute unrelated facets of SUD liability; however, both factors bias development toward SUD via affiliation with deviant peers. Scientific Significance Youth with advanced sexual maturation and/or transmissible risk for SUD are at higher risk for developing SUD. Additional research is needed to determine if addressing these risk factors will contribute to advancements in SUD prevention. (Am J Addict 2013;22:474–480)

Risk for substance use disorder is frequently transmitted across generations due to significant heritability.This longitudinal study tests the hypothesis that initial exposure to cannabis in youths having high transmissible risk is a signal event promoting development of cannabis use disorder (CUD).At age 22, 412 men were classified into three groups: (1) lifetime CUD, (2) cannabis use without CUD, and (3) no lifetime cannabis use. Transmissible risk, quantified on a continuous scale using the previously validated transmissible liability index (TLI), along with cannabis use and CUD were documented at 10-12, 12-14, 16, 19, and 22 years of age.The CUD group scored higher on the TLI before they began cannabis use compared to the other two groups. In addition, a progressive increase in TLI severity was evinced by the CUD group beginning at the time of initiation of cannabis use whereas cannabis users who did not subsequently develop CUD exhibited a decline in transmissible risk following first exposure.Initial use of cannabis potentiates development of CUD in youths who are at high transmissible risk but is inconsequential in youths having low risk. The practical ramifications of these results for prevention are discussed.

A 22-year-old woman presented to the emergency department with a history of cough, progressive shortness of breath, subjective fevers, and malaise. On the day of admission, she was unable to walk more than one city block without rest. She noted new swelling in both legs.

Initiating alcohol consumption at a young age is related to amplified risk for alcohol use disorder (AUD; Hingson, Heeren, & Winter, 2006; Pitkanen, Lyyra, & Pulkkinen, 2005). Most alcohol consumers do not, however, develop AUD. For example, 30-day prevalence of alcohol consumption is 52.1% among tenth-grade students (Johnston, O’Malley, Bachman, & Schulenberg, 2012), whereas only about 16% of the population qualifies for lifetime AUD by 65 years of age (Lin et al., 2011). One factor that may distinguish youths who develop AUD from other alcohol users pertains to transmissible (intergenerational) risk. It has been shown, in this regard, that risk for AUD, manifest by age 22, is highly heritable (Chen et al., 2011; Cloninger, Bohman, & Sigvardsson, 1981). However, strong genetic correlations have also been documented between AUD and liabilities to other substance use disorders (SUDs; Kendler, Myers, & Prescott, 2007), reflective of general liability to addiction (GLA; Vanyukov et al., 2012). Consequently, GLA manifest in consumption initiated with one type of substance may culminate in SUD resulting from consumption of other compounds. For example, frequent consumers of hypercaffeinated (“energy”) beverages are 3.5 times more likely than infrequent consumers to develop dependence on alcohol (Arria et al., 2011) and are more likely to subsequently use illicit drugs and prescription drugs without medical supervision (Arria et al., 2010). The present study had the overarching goal of determining whether transmissible risk for SUD in childhood covaries with age of onset of alcohol and cannabis use, leading to AUD and CUD. Notably, Kirisci, Tarter, Ridenour, Reynolds, and Vanyukov (2012) report that boys who progress to CUD obtain a high score on a quantitative measure of transmissible risk (Vanyukov et al., 2012) before consumption onset that remains stable with increasing age. Cannabis-using boys who do not develop CUD, in contrast, exhibit a lower score before cannabis initiation that further declines with age. Based on these findings, it is hypothesized that age at the time of first use of alcohol and cannabis mediates transmissible risk in childhood and AUD and CUD manifest by young adulthood. As shown in Figure 1, the theoretical model guiding this investigation, transmissible risk for SUD is posited to covary negatively with age at the time of first exposure to both compounds, presaging diagnosis of AUD and CUD. Figure 1 Theoretical model of age of alcohol and cannabis use onset mediates the association of transmissible risk in childhood and development of alcohol and cannabis disorders. Furthermore, whereas youths often begin consuming alcohol before initiating cannabis use, the factors underlying this order remain controversial. Within the framework of the gateway hypothesis, a gateway drug is thought to promote the initiation of consumption of other substances, which, in aggregate, results in a sequence of drugs theorized to reflect a developmental process (Kandel & Yamaguchi, 1999). An alternative competing model asserts that the same general liability to addiction, albeit varying in magnitude, underlies consumption of all abusable compounds (Vanyukov, Kirisci, et al., 2003; Vanyukov, Tarter, et al., 2003; Vanyukov et al., 2012). Because youths who begin consumption with cannabis bypass alcohol, which is often more available, legal (for adults), and less severely sanctioned, it is also hypothesized that violation (cannabis use before alcohol) of the putative gateway sequence is associated with more severe transmissible risk in childhood. In view of recent research showing that deviant socialization mediates the association between transmissible risk in childhood and CUD in adulthood (Tarter et al., 2011), the hypothesis is therefore advanced that more severe transmissible liability increases the likelihood of skipping typical or “normative” experimentation with legal substances. Confirmation of the two hypotheses advanced in this study informs etiology and potentially can improve prevention practice and effectiveness. Demonstrating that age at the time of onset of consumption of the most frequently used legal and illegal compounds is an indicator of their congenerous transmissible risk, leading to both types of SUD, underscores the importance of implementing intervention prior to first exposure to psychoactive compounds having abuse potential, including hypercaffeinated beverages, which are legally purchased and consumed by youths. In addition, showing that transmissible risk covaries negatively with age at the time of first use illustrates the need to temporally monitor risk magnitude in children for timely prevention. Furthermore, demonstrating greater transmissible risk in youths who initiate substance consumption with an illegal drug emphasizes the importance of aligning intervention intensity (“dose”) with severity of predisposing liability. Detecting vulnerable youth for timely prevention is an important public health concern, considering that habitual cannabis use impairs cognitive functioning, which does not fully recover with abstinence (Meier et al., 2012), and epidemiological data indicating that almost half the population of high school seniors have had lifetime exposure to this drug (Johnston et al., 2012).

Background Research has shown involvement of hormones of the hypothalamic pituitary adrenal (HPA) axis and hypothalamic pituitary gonadal (HPG) axis in the regulation of behaviors that contribute to SUD risk and its intergenerational transmission. Neighborhood environment has also been shown to relate to hormones of these two neuroendocrine systems and behaviors associated with SUD liability. Accordingly, it was hypothesized that (1) parental SUD severity and neighborhood quality correlate with activity of the HPG axis (testosterone level) and HPA axis (cortisol stability), and (2) transmissible risk during childhood mediates these hormone variables on development of SUD measured in adulthood. Methods Transmissible risk for SUD measured by the transmissible liability index (TLI; Vanyukov et al., 2009 ) along with saliva cortisol and plasma testosterone were prospectively measured in boys at ages 10–12 and 16. Neighborhood quality was measured using a composite score encompassing indicators of residential instability and economic disadvantage. SUD was assessed at age 22. Results Neither hormone variable cross-sectionally correlated with transmissible risk measured at ages 10–12 and 16. However, the TLI at age 10–12 predicted testosterone level and cortisol stability at age 16. Moreover, testosterone level, correlated with cortisol stability at age 16, predicted SUD at age 22. Conclusion HPA and HPG axes activity do not underlie variation in TLI, however, high transmissible risk in childhood predicts neuroendocrine system activity presaging development of SUD.