Abstract Purpose Recent results suggests the risk of a new onset of depression increases with longer duration of opioid analgesic use. It is unclear whether new-onset depression related to opioid ...analgesic use is a function of the dose prescribed or the duration of use or both. Methods Using a retrospective cohort design, we collected patient data from 2000 to 2012 from the Veterans Health Administration (VHA), and from 2003 to 2012 from both Baylor Scott & White Health (BSWH) and the Henry Ford Health System (HFHS). Patients (70,997 VHA patients, 13,777 BSWH patients, and 22,981 HFHS patients) were new opioid users, aged 18 to 80 years, without a diagnosis of depression at baseline. Opioid analgesic use duration was defined as 1 to 30, 31 to 90, and more than 90 days, and morphine equivalent dose (MED) was defined as 1 to 50 mg/d, 51 to 100 mg/d, and greater than 100 mg/d of analgesic. Pain and other potential confounders were controlled for by inverse probability of treatment–weighted propensity scores. Results New-onset depression after opioid analgesic use occurred in 12% of the VHA sample, 9% of the BSWH sample, and 11% of the HFHS sample. Compared with 1- to 30-day users, new-onset depression increased in those with longer opioid analgesic use. Risk of new-onset depression with 31 to 90 days of opioid analgesic use ranged from hazard ratio HR = 1.18 (95% CI, 1.10–1.25) in VHA to HR = 1.33 (95% CI, 1.16–1.52) in HFHS; in opioid analgesic use of more than 90 days, it ranged from HR = 1.35 (95% CI, 1.26–1.44) in VHA to HR = 2.05 (95% CI, 1.75–2.40) in HFHS. Dose was not significantly associated with a new onset of depression. Conclusions Opioid-related new onset of depression is associated with longer duration of use but not dose. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Opioid analgesic use, not just pain, should be considered a potential source when patients report depressed mood.
Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have ...shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates.
Stressful life events, perceived stress, and social support relationships with consumption, at-risk drinking, and alcohol use disorder (AUD) were studied in a population-based sample of current ...drinkers age 60+ in the National Epidemiologic Survey of Alcohol and Related Conditions (Wave 2; 2004-2005; n = 4,360). Stressful life events were associated with AUD among men and women, and crime victimization among men only. However, greater perceived stress was associated with lower consumption among women and greater odds of AUD in men, highlighting differences in the relationship between stress and alcohol use by gender that may be the result of the stress alcohol link.
genome-wide association study of alcohol dependence Bierut, Laura J; Agrawal, Arpana; Bucholz, Kathleen K ...
Proceedings of the National Academy of Sciences - PNAS,
03/2010, Letnik:
107, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol ...dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10⁻⁵, but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
The current study examines the association of perceived racial and social class discrimination with cannabis involvement among Black youth and young adults.
This secondary analysis used data from the ...Missouri Family Study (MOFAM), a high-risk longitudinal family study of alcohol use disorder, oversampled for Black families. Offspring (n = 806) and their mothers were interviewed by telephone. Cox proportional hazards regression analyzes were used to examine associations of racial and social class discrimination (experienced by offspring and their mothers) with offspring cannabis involvement. Two stages of cannabis involvement were analyzed: timing of 1) initiation and 2) transition from initiation to first cannabis use disorder (CUD) symptom.
The study found that offspring report of experiencing racial (HR: 1.28, CI: 1.01–1.62) and social class discrimination (HR: 1.45, CI: 1.14–1.84) were associated with cannabis initiation in our fully adjusted model. Mothers’ report of discrimination predicted a lower hazard of cannabis initiation among offspring (HR: 0.79, CI: 0.64–0.98). Offspring social class discrimination (HR: 2.45, CI: 1.71–3.51) predicted an increased hazard of transition from initiation to first CUD symptom, while offspring racial discrimination (HR: 0.57, CI: 0.39–0.85) was associated with lower hazard of transition in our fully adjusted model.
As rates for cannabis use among Black youth are disproportionately rising, there is a critical need to identify pathways to its use among Black youth. These findings suggest racial and social class discrimination may be important targets in efforts to prevent cannabis involvement among Black youth and emerging adults.
•Discrimination was examined in relation to two stages of cannabis use among African Americans.•The association between offspring and maternal discrimination with offspring cannabis initiation was explored.•Offspring endorsement of racial and social class discrimination were associated with cannabis initiation.•Offspring endorsement of social class discrimination was associated with a higher risk of transition from iniiation to first CUD symptom.•Maternal experiences of discrimination was a protective factor for cannabis initiation.
Abstract Long-term prescription opioid use is associated both with new-onset and recurrence of depression. Whether chronic opioid use interferes with depression management has not been reported, ...therefore we determined whether patients' longer duration of opioid use and higher opioid dose are associated with new-onset treatment resistant depression (TRD) after controlling for confounding from pain and other variables. Data was obtained from Veteran Health Administration (VHA) de-identified patient medical records. We used a retrospective cohort design from 2000-2012. Eligible subjects (n = 6,169) were 18-80 years of age, free of cancer and HIV, diagnosed with depression and opioid-free for the 24-month interval prior to the observation period. Duration of a new prescription for opioid analgesic was categorized as 1-30 days, 31-90 days and > 90 days. Morphine-equivalent dose (MED) during follow-up categorized as ≤ 50 mg versus > 50 mg per day. Pain and other sources of confounding were controlled by propensity scores and inverse probability of treatment weighting. Cox proportional hazard models were computed to estimate the association between duration and dose of opioid and onset of TRD. After removing confounding by weighting data, opioid use for 31-90 days and for > 90 days, compared to 1-30 days, was significantly associated with new onset TRD (HR = 1.25; 95%CI: 1.09-1.45 and HR = 1.52; 95%CI: 1.32-1.74, respectively). MED was not associated with new onset TRD. The risk of developing TRD increased as time spent on opioid analgesics increased. Long-term opioid treatment of chronic pain may interfere with treatment of depression.
ABSTRACT
BACKGROUND
Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring ...substance use and major depression. Little is known about depressogenic effects of opioid use in other populations.
OBJECTIVE
The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression.
DESIGN
Retrospective cohort study, new user design.
PATIENTS
Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000.
MAIN MEASURES
Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007.
KEY RESULTS
Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90–180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05–1.46 for 90–180 days, and HR = 1.51; 95 % CI:1.31–1.74 for > 180 days).
CONCLUSIONS
In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.
Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. ...In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium's Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)-and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p < 0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: (A) MDD PRS and non-problem cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.
Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a ...portion of the risk.
Methods: We carried out a genome‐wide association study (GWAS) on a case–control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p ≤ 2.1 × 10−4) in a sample of alcohol‐dependent families and performed pedigree‐based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells.
Results: Although no single SNP met genome‐wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case–control study, the follow‐up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3.
Conclusions: We have identified several promising associations that warrant further examination in independent samples.
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