Br J Psychiatry 1997 Jun;170:541-8 The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study
Recent Genetic Studies on Various Addictions from a Large Twin Registry in Virginia by Kenneth Kendler, M.D. at the Medical College of Virginia
This is a series of abstracts of studies evaluating the genetics of substance and behavioral addictions, including people addiction, done by Kenneth Kendler,M.D. et. al. using a large twin registry for the first time in the U.S. It clearly dissects out bogus environmental effects in addiction etiology, and as a group presents a tour de force in addiction genetics. Finally, we are getting unbiased and valid science to act as a basis for future delineation of the genetically transmitted neurobiological mechanism causing the entire gamut of addictions. This is groundbreaking and important work. I have two problems with these studies and others like them. (1) The first problem has to do with methodology. For the most part, these studies obtained their data from telephone interviews. This method greatly underreports subject's use, abuse, and dependence of drugs and other stigmatized behaviors. Thus, the data reported below probably underestimates heritable percentages and, thus, the numbers should be viewed as the low end of the real heritabilities, in other words, more heritable than reported. (2) The second problem is that all addiction genetics studies to date look for concordance in twins of a particular addiction, instead of for the underlying addiction producing mechanism. The main reason for this is that no one but me has hypothesized an underlying mechanism. This, I believe, is the reason we donít see 100% concordance in monozygous twins. Hypoism predicts 100% concordance of some addiction (the presence of the hypoic addiction machine - DMA), but not necessarily the same addiction. Although the inheritance of the same addiction will be the most common occurrence due to the same evaluative alleles being inherited, it may not be expressed perfectly in the phenotypes due to environmental effects possibly ruling out one addiction or another through conscious processes. ["I will never take a drink because of what it did to Dad." He/she then goes on and gets addicted to marijuana or sex, etc.] Thus, we need studies similar to those below examining the occurrence of any addiction in twins, not just the presence or absence of the same addiction. This type of study, none of which have been done as far as I know, would show inheritance of the mechanism, Hypoism, rather than that of specific addictions, which clearly is not 100%, and is not what is being inherited. Of course, this is how it should be since specific behaviors are never inherited, just their cognitive mechanisms. I will show the heritability numbers in blue letters. Notice, if you will, the often quoted number of 40% or even "about 40%" is not seen in these studies or in the studies on the next page on the menu. I discuss the 4 major problems with the validity of all Heritability studies and why they are really much higher in my paper entitled Hypoism Hypothesis on this web site.
(substance abuse disorders aggregate in families - see assortive mating study below for the explanation of this)
Br J Psychiatry 1997 Jun;170:541-8
The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. Kendler KS, Davis CG, Kessler RC Virginia Institute for Psychiatric and Behavioural Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0126, USA. BACKGROUND: Most family studies of psychiatric disorders examine one syndrome at a time, and identify probands in clinical rather than epidemiological settings. METHOD: In the National Comorbidity Survey, 5877 respondents were asked about the history of five psychiatric disorders in their parents: major depression (MD), generalised anxiety disorder (GAD), antisocial personality disorder (ASP), alcohol abuse/dependence (AAD) and drug abuse/dependence (DAD). RESULTS: Significant familial aggregation was seen for all disorders. Controlling for other disorders produced only modest reductions in the odds ratios for MD, GAD and AAD and larger reductions for ASP and DAD. The familial transmission of these disorders can be explained by underlying vulnerabilities to internalising and to externalising disorders transmitted across generations with moderate fidelity. CONCLUSIONS: Familial aggregation of common psychiatric and substance use disorders is substantial in epidemiologic samples. The examined environmental adversities account for little of the observed parent-offspring transmission of these conditions.
(genetics - -not environment -- in people addiction)
Br J Psychiatry 1998 Feb;172:154-8
Longitudinal study of interpersonal dependency in female twins. O'Neill FA, Kendler KS Mater Hospital Trust, Alexandra Gardens Day Hospital, Belfast, Northern Ireland. BACKGROUND: Interpersonal dependence is thought to be important in a number of physical and psychological disorders. There are several developmental theories that suggest environmental influences in childhood are important. METHOD: A twin study methodology was used to look at the genetic and environmental influences on interpersonal dependence as measured by a sub-scale of the Interpersonal Dependency Inventory with a population-based sample of 2230 twins. RESULTS: Psychometric analysis revealed that this was a stable measure and that there was a substantial degree of construct validity. Both univariate and longitudinal twin analysis suggested that there was a modest genetic influence and a large, specific environment influence on interpersonal dependency as measured by this scale. The longitudinal analysis revealed that the genetic influence was stable over the time-scale sampled and the environmental influence was moderately stable. CONCLUSIONS: This finding is at odds with theories that suggest shared environment is important in the aetiology of interpersonal dependency.
(genetics of bulimia nervosa)
Br J Psychiatry 1998 Jul;173:75-9
Genetic epidemiology of binging and vomiting. Sullivan PF, Bulik CM, Kendler KS Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond 23298-0126, USA. BACKGROUND: Bulimia nervosa is typically defined as the combination of the behaviours of binging and vomiting. We sought to clarify the relationship of these behaviours from a genetic epidemiological perspective. METHOD: Using data on the lifetime history of binging and vomiting from a personally interviewed population-based sample of female twins (n = 1897), we applied bivariate twin modelling to estimate the sources of variation for these traits. RESULTS: The association between having ever binged (23.6%) and having ever induced vomiting (4.8%) was very strong (odds ratio = 8.78, P << 0.0001). The best-fitting model indicated that lifetime binging and vomiting were both heritable (46% and 72%) and influenced by individual-specific environmental factors (54% and 28%). The overlap between the genetic (ra = 0.74) and individual-specific environmental factors (re = 0.48) for the two traits was substantial. No violations of the equal environmental assumption were evident. CONCLUSIONS: Including binging and vomiting under the rubric of bulimia nervosa appears to be appropriate. Our data are consistent with the identification of binging and vomiting as complex traits resulting from the interplay of multiple genes and individual-specific environmental influences. In contrast to 'environmentalist' theories, our results suggest that genetic influences may be of particular relevance to the aetiology of binging and vomiting.
(genetics of cannabis addiction in females)
Am J Psychiatry 1998 Aug;155(8):1016-22
Cannabis use, abuse, and dependence in a population-based sample of female twins. Kendler KS, Prescott CA Department of Psychiatry, Medical College of Virginia Commonwealth University, and the Virginia Institute for Psychiatric and Behavioral Genetics, Richmond 23298-0126, USA. OBJECTIVE: The rate of cannabis use by women has been increasing in recent decades. This study examined the etiology of cannabis use and abuse among women and the possible role of genetic risk factors. METHOD: Unselected individual twins (N=1,934) from female-female pairs ascertained through a population-based registry, including both members of 485 monozygotic pairs and of 335 dizygotic pairs, were interviewed by telephone to assess lifetime cannabis use, heavy use, abuse, and dependence as defined by DSM-IV criteria. Biometric model fitting was performed with the Mx computer package. RESULTS: The prevalences of lifetime cannabis use, heavy use, abuse, and dependence were 47.9%, 6.7%, 7.2%, and 2.2%, respectively. Model fitting suggested that twins' resemblance for liability to cannabis use was due to both genetic and familial-environmental factors, while twins' resemblance for heavy cannabis use and abuse and symptoms of dependence resulted solely from genetic factors, with heritabilities ranging from 62% to 79%. The frequency of adolescent social contact between co-twins, which was greater among monozygotic than among dizygotic twins, predicted the twins' resemblance in cannabis use. However, further analyses suggested that the heritability of cannabis use was at most modestly inflated by such social factors. CONCLUSIONS: In women, genetic risk factors have a moderate impact on the probability of ever using cannabis and a strong impact on the liability to heavy use, abuse, and, probably, dependence. By contrast, the family and social environment substantially influences risk of ever using cannabis but plays little role in the probability of developing heavy cannabis use or abuse.
(genetics of female cocaine addiction)
Br J Psychiatry 1998 Oct;173:345-50
Cocaine use, abuse and dependence in a population-based sample of female twins. Kendler KS, Prescott CA Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0126, USA. BACKGROUND: Although cocaine use in women has increased substantially over the past half-century, we understand little about the aetiology in women of cocaine use and abuse, and know almost nothing about the role of genetic factors. METHOD: We obtained by telephone interview a history of lifetime cocaine use, abuse and dependence from 1934 individual twins from female-female pairs ascertained through a population-based registry, including both members of 485 monozygotic (MZ) and 335 dizygotic (DZ) pairs. RESULTS: The prevalence of lifetime cocaine use, abuse and dependence were 14.0%, 3.3% and 2.3%. Probandwise concordance rates, in MZ and DZ twins, respectively, were: cocaine use 54% and 42%; cocaine abuse 47% and 8% and cocaine dependence 35% and 0%. In MZ and DZ twins, odds ratios were: cocaine use 14.2 and 6.7 and cocaine abuse 40.8 and 2.7. Biometrical model-fitting suggested that twin resemblance for liability to cocaine use was due to both genetic and familial-environmental factors while twin resemblance for cocaine abuse and symptoms of dependence was due solely to genetic factors. Estimated heritabilities were: cocaine use 0.39, cocaine abuse 0.79 and symptoms of dependence 0.65 (65%). CONCLUSIONS: The vulnerability to cocaine use and particularly cocaine abuse and dependence in women is substantially influenced by genetic factors.
(assortive mating - like marries, mates, and has kids with like - an important principle behind the production of offspring having the same genetic mechanisms)
Psychol Med 1998 Nov;28(6):1389-401
Assortative mating for major psychiatric diagnoses in two population-based samples. Maes HH, Neale MC, Kendler KS, Hewitt JK, Silberg JL, Foley DL, Meyer JM, Rutter M, Simonoff E, Pickles A, Eaves LJ Department of Human Genetics, Virginia Commonwealth University, Richmond 23298-0003, USA. BACKGROUND: Previous studies on assortment for psychiatric disorders have reported discrepant findings. We aimed to test whether there is a significant association for psychiatric diagnoses, including alcoholism, generalized anxiety disorder, major depressive disorder, panic disorder and phobias between husbands and wives in two population-based samples. We further evaluated whether marital resemblance occurs primarily within or across psychiatric disorders and if assortment for psychopathology is primary or secondary to assortment for correlated variables. METHODS: A model for mate selection addressed whether the correlation between mates for psychiatric disorders arises from direct assortment (primary homogamy) or through correlation with other variables for which assortment occurs (secondary homogamy) or through cross-variable assortment. The model accounted for within-person co-morbidity as well as across-spouse data. RESULTS: Findings suggested that a moderate degree of assortment exists both within and across psychiatric diagnoses. Only a small amount of the observed marital resemblance for mental illness could be explained by assortment for correlated variables such as age, religious attendance and education. Similar results were obtained for the two samples separately and confirmed in their joint analysis, revealing that the co-morbidity and assortment findings, except for the marital correlation for age, religious attendance and education, replicate across samples. CONCLUSIONS: Significant but moderate primary assortment exists for psychiatric disorders. The bias in twin studies that have ignored the small amount of assortment is negligible.
(genetics of eating disorders)
Biol Psychiatry 1998 Dec 15;44(12):1210-8
Heritability of binge-eating and broadly defined bulimia nervosa. Bulik CM, Sullivan PF, Kendler KS. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond 23298-0126, USA. BACKGROUND: Using diagnostic information obtained at two different times, we incorporated error of measurement into structural equation twin models to evaluate the contribution of additive genetic, common environmental, and individual-specific environmental factors to the liability to binge-eating and broadly defined bulimia nervosa (BN). We also evaluated the validity of the equal environment assumption (EEA) with reference to these two phenotypes. METHODS: We interviewed 1897 female twins (including both members of 854 twin pairs) from a population-based register about their lifetime history of binge-eating and of broadly defined BN twice, approximately 5 years apart. RESULTS: The reliabilities of a lifetime history of binge-eating (kappa = .34) and of broadly defined BN (kappa = .28) were low. Based on single interviews, the heritability of binge-eating was estimated to be 50% and broad BN 60%, with the remaining variance attributable to individual-specific environment. Common environmental influences had no effect on liability to either trait. By combining information from two interview waves and thereby incorporating error of measurement into a structural equation model, the estimated heritability of the latent vulnerability to binge-eating (82%) and broadly defined BN (83%) increased substantially. Although there were no violations of the EEA detected for binge-eating, cosocialization influenced twin concordance for broadly defined BN. CONCLUSIONS: Lifetime histories of binge-eating and broadly defined BN appear to be highly heritable conditions of low reliability.
(genetics of alcohol addiction in males)
Am J Psychiatry 1999 Jan;156(1):34-40
Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Prescott CA, Kendler KS Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0126, USA. OBJECTIVE: Most twin and adoption studies of alcoholism have ascertained cases through treatment settings or archival data; these subjects may differ from affected subjects identified epidemiologically. The authors studied the importance of genetic influences on risk of alcohol-related disorders in a new population-based twin sample. METHOD: Structured personal interviews were used to assess DSM-III-R-defined and DSM-IV-defined alcohol abuse and dependence among 3,516 twins from male-male pairs born in Virginia between 1940 and 1974. RESULTS: The magnitude of resemblance among twin pairs was similar across several definitions of alcoholism and was substantially higher among 861 identical pairs than among 653 fraternal pairs. On the basis of a liability threshold model, 48%-58% of the variation in liability was attributed to additive genetic factors, with the remainder attributed to environmental influences not shared by family members. When a treatment-based proband concordance model was used, evidence for shared environmental as well as genetic influences emerged. CONCLUSIONS: In this first population-based study of male twins from the United States, it was found that genetic factors played a major role in the development of alcoholism among males, with similar influence for alcohol abuse and alcohol dependence. Prior findings implicating the influence of common environment may be attributable to sampling strategy; in this population-based sample, environmental factors shared by family members appear to have had little influence on the development of alcoholism in males.
(familiar factors in female hallucinogen, opiate, sedative, and stimulant use and addiction)
Acta Psychiatr Scand 1999 May;99(5):368-76
Hallucinogen, opiate, sedative and stimulant use and abuse in a population-based sample of female twins. Kendler KS, Karkowski L, Prescott CA Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA. OBJECTIVE: Rates of illicit psychoactive substance use and abuse in women have increased substantially over the last 50 years. However, we understand little about the aetiology of these behaviors in women, and almost nothing about the role of familial-environmental and genetic factors. METHODS: We obtained, by means of blind telephone interviews with 1934 individual twins from female-female adult pairs ascertained through a population-based registry, including both members of 500 MZ and 326 DZ pairs, a history of lifetime illicit use, abuse and dependence, as defined by DSM-IV, of hallucinogens, opiates, sedatives and non-cocaine stimulants. RESULTS: Lifetime prevalences for substance use ranged from 3.3% for opiates to 10.4% for hallucinogens. Rates of abuse (ranging from 0.7% for opiates to 3.2% for stimulants) and dependence (ranging from 0.2% for hallucinogens to 1.4% for stimulants) were substantially lower. Significant twin resemblance was found for hallucinogen use, opiate use, sedative use and stimulant use, abuse and symptoms of dependence. The results of twin-model fitting suggested that twin resemblance for hallucinogen and stimulant use was due to both genetic and familial environmental factors, while twin resemblance for opiate and sedative use as well as stimulant abuse and symptoms of dependence was solely the result of genetic factors. Heritability of liability ranged from 21% to 72%. Twin resemblance for substance use, abuse and dependence could not be explained by the similarity of the twins' environment in childhood, adolescence or adulthood. CONCLUSION: Although limited by the rarity in women of these forms of substance use and misuse, our results none the less suggest that familial factors, which are at least in part genetic, strongly influence the vulnerability to hallucinogen, opiate, sedative and stimulant use and abuse in women.
(genetics of both male and female alcohol addiction)
Alcohol Clin Exp Res 1999 Jul;23(7):1136-44
Sex differences in the sources of genetic liability to alcohol abuse and dependence in a population-based sample of U.S. twins. Prescott CA, Aggen SH, Kendler KS Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0126, USA. email@example.com BACKGROUND: There are substantial sex differences in all levels of alcohol involvement among U.S. adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women. METHODS: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling. RESULTS: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely. CONCLUSION: In this first population-based study of alcoholism among male and female twins from the U.S., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women.
(genetics of male cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens addiction)
Arch Gen Psychiatry 2000 Mar;57(3):261-9
Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Kendler KS, Karkowski LM, Neale MC, Prescott CA Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0126, USA. BACKGROUND: In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. METHODS: In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. RESULTS: Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the equal environment assumption. CONCLUSIONS: In accord with prior results in studies of women, the family environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.
Ming Tsuang, M.D. found that men (only studied men) addicted to one drug were highly likely to be or get addicted to many other drugs. This finding is consistent with an "underlying disease mechanism" hypothesis such as Hypoism rather than "the addiction is the disease" theory (hijacked brain hypothesis) of the NIDA and others.
Dr. Ming Tsuang, a NIDA-supported researcher at Harvard University in Cambridge, Massachusetts, has found that, in males, genetic influences are stronger for abuse of some drugs than for others. Dr. Tsuang and his colleagues studied drug use in 1,874 identical male twin pairs and 1,498 fraternal male twin pairs recruited from the Vietnam Era Twin Registry, a database compiled from Department of Defense records. The average age of participants was 45.
The researchers found evidence to suggest that genetic influences contribute to a common vulnerability for abusing marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. "There is some characteristic of the individual that imparts vulnerability to the abuse of all categories of drugs. Abusing any category of drugs was associated with a marked increase in the probability of abusing every other category of drugs," Dr. Tsuang says. In addition to this shared vulnerability, the researchers found different vulnerabilities for different drugs. "Each category of drugs we looked at, except psychedelics, had unique genetic influences," Dr. Tsuang says. "The genetic influence for abuse was greater for heroin than for any other drug."
The reference for this work is: Tsuang, M., et al. Co-occurrence of abuse of different drugs in men. Archives of General Psychiatry 55:967-972, 1998.
For some reason this issue is not available on the web page of the journal.
Tracking Twins: Her doctor is Dr. Cynthia Bulik, an eating disorders expert at Virginia Commonwealth University whose research has shown that a woman's risk for bulimia nervosa is largely inherited. After studying nearly 2,000 identical and fraternal twins, Bulik concluded that genes account for 83 percent of female susceptibility to the disorder. Other studies have clearly shown that eating disorders run in families, but until Bulik's research, it wasn't clear if that was because families share the same genes, or the same dysfunctional environment. Her findings appear in the latest issue of Biological Psychiatry. So, what about the conventional wisdom that girls starve themselves nearly to death, or binge and then force themselves to throw up, because of overwhelming societal pressure to be thin? "We're not letting society off the hook," Bulik says. "We like to say that the genes load the gun and environment pulls the trigger." Identical twins have 100 percent identical genes, while fraternal twins have only half in common. So if bulimia in both twins is more common among identical pairs than fraternal pairs, Bulik says, you can deduce that the reason is genetic. Parents Get a Break: And that's exactly what she did. Bulik and colleagues interviewed 1,897 female twins at age 30 and again at age 35 and then used that information to parse out genetic factors, shared environmental conditions like parenting, unique environmental influences (something that one twin experienced but not the other) and socioeconomic factors.