Jeffrey F. Scherrer

Adolescent alcohol use is a risk factor for adult alcohol and drug dependence: evidence from a twin design

BACKGROUNDnEarly alcohol use is associated with abuse and dependence of licit and illicit substances later in life. The role of genetic and environmental factors in this association is not conclusive.nnnMETHODnIn 1992, data on substance use, abuse/dependence and psychiatric disorders were collected from 8169 male twin members of the Vietnam Era Twin Registry. The interview obtained age of onset of regular drinking (one drink/month for 6 or more months). Regression analyses of twin pairs discordant for early alcohol use tested whether the association between early drinking (before age 17) and adult substance use and abuse/dependence remained after controlling for genetic factors, family environment and covariates. Twin models tested for common genetic and/or environmental influences on early drinking and adult alcohol dependence and ever use and abuse/dependence on marijuana and other drugs.nnnRESULTSnCo-twin analyses suggested the association between early regular alcohol use and adult alcohol dependence, marijuana and other drug use, and marijuana and other drug abuse/dependence could not be entirely explained by common genetic and shared family environmental factors. Genetic contributions to early regular drinking were significantly correlated with those on use of marijuana (rA=0.59), use of other drugs (rA=0.64), alcohol dependence (rA=0.54) and abuse/dependence of marijuana and other drugs (rA=0.63 and 0.66). Small but significant unique environmental correlations (rE range 0.11-0.22) indicated that familial factors could not entirely explain the association between early alcohol use and later substance use, abuse and dependence.nnnCONCLUSIONSnEarly regular drinking is associated with later alcohol dependence and use, abuse/dependence on drugs. The association is not entirely explained by genetic or shared family environmental factors. This suggests unique environmental factors contribute to transitions from early regular alcohol drinking to use, abuse and dependence on alcohol and other substances.

The effects of maternal smoking during pregnancy on offspring outcomes

OBJECTIVEnTo evaluate the possible association between maternal smoking during pregnancy and offspring outcomes of birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct problems while controlling for similar behaviors in parents.nnnMETHODSnUsing telephone interviews, data were collected, in 2001 and 2004, as a part of two United States offspring-of-twins projects. Fathers, who were twins participating in the Vietnam Era Twin Registry, their female spouse and their offspring were interviewed - information on 1,342 unique pregnancies in mothers with a history of regular smoking was utilized for these analyses. The association between maternal smoking during pregnancy and birth weight, pre-term birth, remediation, low scholastic achievement, regular smoking, attention deficit hyperactivity disorder and conduct disorder while controlling for similar behaviors in parents, was examined using regression.nnnRESULTSnMaternal smoking during pregnancy was associated with decreased birth weight, low scholastic achievement, regular smoking and attention deficit hyperactivity disorder. However, the association between maternal smoking during pregnancy and offspring attention deficit hyperactivity disorder was explained by maternal attention deficit hyperactivity disorder. Maternal smoking during pregnancy was also associated with earlier age of offspring initiation of smoking and onset of regular smoking.nnnCONCLUSIONSnMaternal smoking during pregnancy may influence certain offspring outcomes via mechanisms that are independent from genetic risk attributable to comorbid conditions. Assisting expecting mothers with their smoking cessation efforts will likely provide widespread health benefits to both mother and offspring.

Anxiety disorders increase risk for incident myocardial infarction in depressed and nondepressed Veterans Administration patients.

BACKGROUNDnDepression is a risk factor for incident myocardial infarction (MI), but little is known about the independent or additive risk from anxiety disorders.nnnMETHODSnIn a 7-year retrospective cohort design, we identified a cohort free of cardiovascular disease in fiscal years 1999 and 2000 that contained 96,612 patients between 25 and 80 years of age who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating a diagnosis of depression in 2000 (baseline) and 259,387 patients without depression. Cox proportional hazards models stratified by depression were computed to test for a main effect of anxiety disorder unspecified, generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder (PTSD) on risk of incident MI. The models were adjusted for multiple MI risk factors and sociodemographics.nnnRESULTSnDepressed as compared to nondepressed Veterans Administration patients were at increased risk for incident MI (HR 1.39; 95% CI 1.34-1.45). In nondepressed patients those with anxiety disorder unspecified (HR 1.34; 95% CI 1.21-1.47), panic disorder (HR 1.43; 95% CI 1.11-1.83), and PTSD (HR 1.25; 95% CI 1.16-1.36) were at increased risk for incident MI. The independent risk associated with anxiety disorders was reduced in patients comorbid for depression.nnnCONCLUSIONSnIn Veterans Administration patients free of heart disease in 1999 and 2000, those with depression, anxiety disorder unspecified, panic disorder, and PTSD were at increased risk of incident MI. Anxiety disorders are independent risk factors for MI. Depression partially accounts for the effect of anxiety disorders on risk of MI in patients with both conditions.

Posttraumatic stress disorder; combat exposure; and nicotine dependence, alcohol dependence, and major depression in male twins

Combat exposure is associated with increased risk of psychiatric and substance use disorders in veterans. However, it is not known whether combat exposure independently increases risk for these disorders or whether this association is accounted for by genetic vulnerability common to posttraumatic stress disorder (PTSD). This article tests competing explanations for the association of combat exposure and PTSD with nicotine dependence (ND), alcohol dependence (AD), and major depression (MD). Data were obtained from 6099 members of the Vietnam Era Twin Registry, a national registry of male-male twin pairs who served in the military during the Vietnam era. Twin models were fit to estimate the genetic and environmental variance common and specific to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, lifetime diagnoses of PTSD, combat trauma, and 3 comorbid conditions: ND, AD, and MD. Variance specific to ND, AD, and MD was due to genetic factors (48%, 36%, and 12%, respectively) and unique environmental factors (36%, 42%, and 58%, respectively). After accounting for variance common to PTSD, no residual genetic and environmental variance overlapped between combat and ND, combat and AD, and combat and MD. Combat exposure is not independently associated with lifetime ND, AD, and MD. The association of combat exposure with these 3 disorders is due to genetic and unique environmental contributions in common with PTSD. These findings suggest comorbid PTSD may represent a genetically mediated vulnerability to psychopathology after trauma.

Prescription opioid analgesics increase the risk of depression.

ABSTRACTBACKGROUNDPrescription 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.OBJECTIVEThe purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression.DESIGNRetrospective cohort study, new user design.PATIENTSMedical 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 MEASURESPropensity 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 RESULTSOf 49,770 patients who were prescribed an opioid analgesic, 91xa0% had a prescription for < 90xa0days, 4xa0% for 90–180xa0days, and 5xa0% for > 180xa0days. Compared to patients whose prescription was for < 90xa0days, the risk of depression increased significantly as the duration of opioid prescription increased (HRu2009=u20091.25; 95xa0% CI: 1.05–1.46 for 90–180xa0days, and HRu2009=u20091.51; 95 xa0% CI:1.31–1.74 for > 180xa0days).CONCLUSIONSIn 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.

Lifetime and 12-Month Prevalence of Psychiatric Disorders in 8,169 Male Vietnam War Era Veterans

OBJECTIVEnThis study reports the prevalence of psychiatric disorders among a nationally distributed sample of Vietnam Era veterans assessed using standardized psychiatric interviewing methods.nnnMETHODSnIn 1992, the National Institute of Mental Health Diagnostic Interview Schedule was administered by telephone to 8,169 middle-aged males who served in the military during the Vietnam era (1965-1975).nnnRESULTSnApproximately 72% of respondents reported a lifetime history and 36% reported a 12-month history of at least one psychiatric disorder. The most prevalent psychiatric disorders included alcohol abuse and/or dependence (54% lifetime, 17% 12 month), nicotine dependence (48% lifetime, 22% 12 month), and posttraumatic stress disorder (10% lifetime, 4.5% 12 month).nnnCONCLUSIONSnBecause of possible participation bias, these results likely represent conservative estimates of psychiatric disorder prevalences among the more than eight million Vietnam Era veterans and reinforces the major public health challenge of preventing, identifying, and treating psychiatric illness in American veterans.

Genetic and environmental contributions to nicotine, alcohol and cannabis dependence in male twins.

AIMSnTo compute the common and specific genetic and environmental contributions to nicotine dependence (ND) alcohol dependence (AD) and cannabis dependence (CD).nnnDESIGNnTwin model.nnnPARTICIPANTSnData from 1874 monozygotic and 1498 dizygotic twin pair members of the Vietnam Era Twin Registry were obtained via telephone administration of a structured psychiatric interview in 1992.nnnMEASUREMENTSnData to derive life-time diagnoses of DSM-III-R ND, AD and CD were obtained via telephone administration of the Diagnostic Interview Schedule.nnnFINDINGSnThe best-fitting model allowed for additive genetic contributions and unique environmental influences that were common to all three phenotypes. Risks for ND and AD were also due to genetic and unique environmental influences specific to each drug. A specific shared environmental factor contributed to CD.nnnCONCLUSIONSnThese results suggest that the life-time co-occurrence of ND, AD and CD is due to common and specific genetic factors as well as unique environmental influences, and vulnerability for CD is also due to shared environmental factors that do not contribute to ND and AD. The majority of genetic variance is shared across drugs and the majority of unique environmental influences are drug-specific in these middle-aged men. Because differences between models allowing for specific genetic versus shared environment were small, we are most confident in concluding that there are specific familial contributions-either additive genetic or shared environment-to CD.

Antidepressant Drug Compliance: Reduced Risk of MI and Mortality in Depressed Patients

BACKGROUNDnThe long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for nontricyclic antidepressants. The present study uses a national Veterans Affairs cohort to test whether antidepressants increase or decrease risk of MI and all-cause mortality.nnnMETHODSnUS Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25-80 years, who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating an episode of depression (n=93,653). Incident MI and all-cause mortality were modeled in patients who received 12 weeks or more of antidepressant pharmacotherapy as compared with 0-11 weeks during follow-up. Age-adjusted Cox proportional hazard models were computed before and after adjusting for baseline sociodemographics and time-dependent covariates.nnnRESULTSnReceipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants: selective serotonin reuptake inhibitor (SSRIs) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.44-0.52), serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR 0.35; 95% CI, 0.32-0.40), tricyclic antidepressants (TCAs) (HR 0.39; 95% CI, 0.34-0.44), and Other (HR 0.41; 95% CI, 0.37-0.45). Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66.nnnCONCLUSIONSnAcross classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of MI risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients.

Depression increases risk of incident myocardial infarction among Veterans Administration patients with rheumatoid arthritis

OBJECTIVEnThis study evaluates whether depression is a risk factor for incident myocardial infarction (MI) in Department of Veterans Affairs (VA) patients with rheumatoid arthritis (RA) between 30 and 79 years of age.nnnMETHODSnWe used a retrospective cohort study of 15,634 patients with RA. Diagnoses and sociodemographic data were obtained from VA administrative and pharmacy databases between fiscal years 1999 and 2006. Entry into the cohort required 2 years of patient time with no evidence of cardiovascular disease. Cox proportional hazard models with time-dependent covariates were computed to determine whether RA patients with depression as compared to RA patients without depression were at increased risk for MI during the maximum 6-year follow-up period.nnnRESULTSnUnadjusted analyses indicated depressed RA patients were 1.4 times more likely than nondepressed RA patients to have an MI during follow-up. These results remained significant (HR=1.4; 95% CI: 1.1-1.8) in the adjusted Cox proportional hazards model which included the effects of sociodemographics and known physical risks (e.g., diabetes) for MI.nnnCONCLUSIONSnDepressed RA patients, without a history of cardiovascular disease, are 40% more likely to have a heart attack as compared to those without depression. These data demonstrate a rapid (within 6 years) transition to MI following onset of depression in RA patients. Increased monitoring of depression and heart disease status in this patient population may be warranted which in turn may result in longer duration of life.

Association of cognitive distortions with problem and pathological gambling in adult male twins

Treatment studies suggest that gambling-related irrational beliefs and attitudes (i.e., cognitive distortions (CDs)) contribute to the risk for problem gambling behavior. In a community sample of men, we investigated the associations among lifetime gambling-related CDs, psychiatric disorders other than pathological gambling , and problem gambling severity. Subjects were 1354 members of the Vietnam Era Twin Registry. Problem gambling and gambling-related CDs were derived from a 2002 interview using the National Opinion Research Center DSM-IV Screen for Gambling Problems (NODS). Exploratory factor analysis was performed with the 12 CD items to identify an underlying construct. Generalized linear models were computed to test for associations among CDs, psychiatric disorders other than pathological gambling, and gambling problem severity. Co-twin control analyses of monozygotic twin pairs discordant for problem gambling severity adjusted for genetic and shared environmental influences. Twelve CD items related to one underlying CD construct. After adjustment for lifetime psychiatric disorders, pathological gambling symptoms were positively associated with higher CD scores. Pathological gambling symptoms remained significantly associated with CD scores after controlling for genetic and shared environmental influence. These results provide empirical support for an association between gambling-related CDs and gambling problem severity, even after controlling for genetic and shared environmental influences and non-pathological gambling psychiatric disorders. Public health messages and therapeutic interventions that reinforce the randomness of gambling and draw attention to distorted thinking may prevent the development of problem gambling and improve treatment outcomes.