Seth A. Eisen

Major Depression and Medication Adherence in Elderly Patients With Coronary Artery Disease

Little is known about the effects of depression on adherence to medical treatment regimens in older patients with chronic medical illnesses. Poor adherence may explain the increased risk of medical morbidity and mortality found in depressed medical patients. Ten of 55 patients over the age of 64 with coronary artery disease met the criteria for major depression from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987). All patients were prescribed a twice-per-day regimen of low dose aspirin to reduce their risk for myocardial infarction. Medication adherence was assessed for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p < .02). Thus, major depression is associated with poor adherence to a regimen of prophylactic aspirin after the diagnosis of coronary artery disease.

Genetic influences on DSM‐III‐R drug abuse and dependence: A study of 3,372 twin pairs

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individuals risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.

Objective Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment. This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome. Method: Sixty-eight diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, placebo-controlled, double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was determined with the Beck Depression Inventory; glucose control was measured by glycated hemoglobin levels. Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory. Results: The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8, p =.03). Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects (p =.5). However, path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin. These findings were not explained by the relationships of nortriptyline treatment to weight change (r = -0.21, p =.31) or depression improvement to compliance with the protocol for self-monitoring of blood glucose (r = 0.01, p =.97). Conclusions: Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect. Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control, suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome.

Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires

The Vietnam Era Twin Registry (VETR) is a registry of 7375 American male veteran twin pairs born between 1939 and 1955 who served in the armed forces of the United States between 1964 and 1975. Optimal use of registry data requires the determination of zygosity. Two approaches are available: analysis of blood genetic marker systems and responses of twins to questions about sibling similarity. Zygosity for the VETR was determined using the questionnaire technique supplemented with blood group typing data abstracted from military records. After comparing four alternative zygosity assignment methods, a logistic regression technique which uses discriminating variables based on race was selected. The approach is similar to that described by Magnus et al. (1983) in their study of Norwegian twins, suggesting that questionnaire responses are independent of nationality and reinforcing the reliability of the questionnaire method for zygosity ascertainment.

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

BACKGROUND Early 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. METHOD In 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. RESULTS Co-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. CONCLUSIONS Early 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.

A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder

This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.

A twin study of the association between pathological gambling and antisocial personality disorder.

Many individuals with a history of pathological gambling (PG) also have a history of engaging in antisocial behaviors, and this has often been interpreted as a result of the former causing the latter. In a sample of 7,869 men in 4,497 twin pairs from the Vietnam Era Twin Registry, the authors examined (a) the association between PG and antisocial personality disorder (ASPD), (b) the extent to which PG might be differentially associated with childhood conduct disorder (CD) and adult antisocial behavior (AAB), and (c) the contribution of genetic and environmental factors to the association of PG with ASPD, CD, and AAB. PG was significantly associated with all 3 antisocial behavior disorders, and the association of PG with ASPD, CD, and AAB was predominantly explained by genetic factors. The results of this study suggest that the greater-than-chance co-occurrence of PG and antisocial behavior disorders is partially due to their sharing a common genetic vulnerability. The antisocial behavior observed among many individuals with PG probably cannot be interpreted as being simply a consequence of the PG.

Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs

We investigated whether and to what degree genetic and environmental contributions overlap among posttraumatic stress disorder (PTSD), alcohol dependence (AD) and drug dependence (DD). Subjects were 3304 monozygotic and dizygotic male-male twin pair members of the Vietnam Era Twin Registry who participated in 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS-3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of DSM-III-R PTSD, AD and DD. The liability for PTSD was partially due to a 15.3% genetic contribution common to AD and DD and 20.0% genetic contribution specific to PTSD. Risk for AD was partially due to a 55.7% genetic contribution common to PTSD and DD. Genetic influences common to PTSD and AD accounted for 25.2% of the total risk for DD. Specific family environmental influence accounted for 33.9% of the total variance in risk for DD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that PTSD, AD and DD each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.

Genetic and environmental influences on the size of specific brain regions in midlife: The VETSA MRI study

The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.

A twin study of depression symptoms, hypertension, and heart disease in middle-aged men

Objective: Epidemiological and clinical studies have established an association between major depression and cardiovascular disease. We utilized a twin design to test whether there are common genetic and environmental risk factors underlying depression symptoms, hypertension and heart disease. Methods: Association studies were conducted with 6,903 male‐male twins from the Vietnam Era Twin Registry who responded to both a 1990 health questionnaire and a 1992 telephone administration of a structured psychiatric interview. Data from 2,731 complete twin pairs were used to fit genetic models which determined the extent to which lifetime depression symptoms, heart disease and hypertension shared genetic and/or environmental factors. Results: Heart disease was significantly associated with 1‐4 symptoms and 5 or more symptoms of depression (odds ratio [OR] = 2.62; 95% confidence interval [CI]: 1.54‐4.46 and OR = 4.02; 95% CI: 2.16‐7.46). Hypertension was significantly associated with 1 to 4 symptoms and 5 or more symptoms of depression (OR = 1.29; 95% CI: 1.11‐1.50 and OR = 1.49; 95% CI: 1.21‐1.83). The genetic correlations were significant between depression symptoms and hypertension (r = .19), and between depression symptoms and heart disease (r = .42). Of the total variance in depression, 8% was common to hypertension and heart disease, 7% of the variance in hypertension was common with depression symptoms and heart disease, and 64% of the variance in heart disease was common with depression symptoms and hypertension. Conclusions: Men who reported cardiovascular disease were significantly more likely to have depression symptoms. The lifetime co‐occurrence of these phenotypes is partly explained by common genetic risk factors.