The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women

BACKGROUND: Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. METHODS: Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. RESULTS: We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.     

Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis,cocaine, hallucinogens,sedatives, stimulants,and opiates in male twins

OBJECTIVE: Data on use and misuse of six classes of illicit substances by male twin pairs were used to examine whether genetic and shared environmental risk factors for substance use disorders are substance-specific or -nonspecific in their effect. METHOD: Lifetime history of use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates was assessed at personal interview in both members of 1,196 male-male twin pairs ascertained by the Virginia Twin Registry. Multivariate twin modeling of substance-nonspecific (common) and substance-specific genetic, shared environmental, and unique environmental risk factors was performed by using the program Mx. RESULTS: High levels of comorbidity involving the different substance categories were observed for both use and abuse/dependence. One common genetic factor was found to have a strong influence on risk for illicit use and abuse/dependence for all six substance classes. A modest influence of substance-specific genetic factors was seen for use but not for abuse/dependence. Shared environmental factors were more important for use than for abuse/dependence and were mediated entirely through a single common factor. CONCLUSIONS: In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.     

Twin closeness and co-twin risk for substance use disorders: assessing the impact of the equal environment assumption

Various environmental variables are hypothesized to operate differentially within identical and fraternal twin pairs. To the extent that these factors are correlated with behavioral outcomes, such as alcohol or drug abuse, traditional twin studies of concordance may be biased. Self-ratings of within-pair emotional closeness, assessed in 169 same-sex twin pairs ascertained through alcohol and drug treatment centers, were used to determine the impact of the twin relationship on concordance for alcohol dependence (N=130 twin pairs) and other drug abuse and/or dependence (N=85 twin pairs). In general, identical twin pairs reported significantly closer relationships than fraternal twin pairs, and female twin pairs reported significantly closer relationships than male twin pairs. The data did not indicate an overall effect of closeness on co-twin risk for alcohol dependence. In contrast, closeness was significantly related to co-twin risk for other drug abuse and/or dependence. However, the MZ/DZ concordance difference for other drug abuse and/or dependence remained significant when the effects of within-pair closeness were controlled. Thus, the initial zygosity and sex differences in concordance for substance use disorders cannot be explained solely by differences in twin relationship due to closeness as assessed in this study. © 1997 Elsevier Science Ireland Ltd.     

Specificity of familial vulnerability for alcoholism versus major depression in men

There are various hypotheses regarding comorbidity between alcohol dependence (AD) and major depression (MD). We interviewed 3372 pairs of male twins assessing DSM-III-R MD and AD. Individuals with comorbid MD and AD exhibited greater severity of each disorder than individuals with only one. MD in one twin was associated with risk of MD alone and MD plus AD, but not AD alone in the cotwin. AD in one twin was associated with risk of AD alone and AD plus MD, but not MD alone in the cotwin. The best fitting biometrical comorbidity model was the reciprocal causation model in which AD can cause MD and vice versa. However, a model in which genetic and environmental influences on each disorder were correlated could not be definitively rejected. Our data are most consistent with a mechanism of reciprocal causation, whereby MD increases risk for AD and AD increases risk of MD.     

Shared genetic risk of major depression,alcohol dependence,and marijuana dependence: contribution of antisocial personality disorder in men

BACKGROUND: Little is known about genetic factors that underlie the interrelationships among antisocial personality disorder (ASPD), major depression (MD), alcohol dependence (AD), and marijuana dependence (MJD). We examined the contribution of genetic effects associated with ASPD to the comorbidity of MD and substance use disorders. METHODS: The Vietnam Era Twin Registry is a general population registry of male veteran twins constructed from computerized Department of Defense files and other sources. A telephone diagnostic interview was administered to eligible twins from the Registry in 1992. Of 5150 twin pairs who served on active military duty during the Vietnam era, 3360 pairs (1868 monozygotic and 1492 dizygotic) in which both members completed the pertinent diagnostic interview sections were included. The main outcome measures were lifetime DSM-III-R ASPD, MD, AD, and MJD. RESULTS: Structural equation modeling was performed to estimate additive genetic, shared environmental, and nonshared environmental effects common and specific to each disorder. The heritability estimates for lifetime ASPD, MD, AD, and MJD were 69%, 40%, 56%, and 50%, respectively. Genetic effects on ASPD accounted for 38%, 50%, and 58% of the total genetic variance in risk for MD, AD, and MJD, respectively. After controlling for genetic effects on ASPD, the partial genetic correlations of MD with AD and with MJD were no longer statistically significant. Genetic effects specific to MD and AD and familial effects specific to MJD remained statistically significant. Nonshared environmental contributions to the comorbidity in these disorders were small. CONCLUSIONS: In this sample, the shared genetic risk between MD and both AD and MJD was largely explained by genetic effects on ASPD, which in turn was associated with increased risk of each of the other disorders.     

Personality and major depression: a Swedish longitudinal, population-based twin study

CONTEXT: Prior studies suggest that the personality traits of neuroticism and extroversion may be related to the liability to major depression (MD). OBJECTIVE: To clarify the magnitude and nature of the association between neuroticism and extroversion and the risk for MD. DESIGN: Longitudinal population-based twin cohort. SETTING: General community. PARTICIPANTS: A total of 20 692 members of same-sex twin pairs from the population-based Swedish Twin Registry who completed a self-report questionnaire assessing neuroticism and extroversion in 1972 and 1973 and were personally interviewed for lifetime history of MD more than 25 years later.Main Outcome Measure Lifetime history of modified DSM-IV MD. RESULTS: Levels of neuroticism strongly predicted the risks for both lifetime and new-onset MD. Twin modeling indicated that the association between neuroticism and MD resulted largely from shared genetic risk factors, with a genetic correlation of +0.46 to +0.47. Levels of extroversion were weakly and inversely related to the risks for lifetime and new-onset MD. This effect disappeared when we controlled for the level of neuroticism. Twin modeling produced similar results. CONCLUSIONS: Results from both longitudinal and genetic analyses support the hypothesis that neuroticism strongly reflects the liability to MD. This association arises largely because neuroticism indexes the genetic risk for depressive illness. However, substantial proportions of the genetic vulnerability to MD are not reflected in neuroticism. By contrast, extroversion is only weakly related to risk for MD.     

Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins

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.     

Sex influences on shared risk factors for bulimia nervosa and other psychiatric disorders

BACKGROUND: The examination of opposite-sex and same-sex dizygotic twins allows us to explore the sex-specific comorbidity of psychiatric disorders. To date, this question has not been explored in eating disorders. OBJECTIVE: To determine whether sex influences shared risk factors between bulimia nervosa (BN) and other forms of psychopathology. DESIGN: The study examines associations between BN and other forms of psychopathology in twin pairs using interview and survey reports. SETTING: Twins from the Virginia population-based twin registry. PARTICIPANTS: Male-female dizygotic twins (N = 1192 pairs), mean (SD) age 36.6 (8.9) years, and female-female dizygotic twins (N = 467 pairs), mean (SD) age 36.0 (7.6) years. MAIN OUTCOME MEASURES: Lifetime psychiatric disorders as diagnosed by a structured psychiatric interview, including major depression, anxiety disorders, and substance abuse and dependence. Also, continuous measures of body mass index and personality, including neuroticism and novelty seeking. RESULTS: Significant within-person associations existed for women between BN and higher body mass index, neuroticism, novelty seeking, and all lifetime psychopathology. Results from this study suggest the presence of either familial or nonfamilial shared risk factors between BN and generalized anxiety disorder, neuroticism, psychoactive substance use, novelty seeking, major depression, and panic disorder. The shared risk factors between BN and generalized anxiety disorder and BN and novelty seeking were only present in men. CONCLUSION: Evidence supports the existence of a sex-specific manifestation of familial liability with respect to BN and generalized anxiety disorder and BN and novelty seeking.     

Major depression and immunity in alcohol-dependent persons

Altered immunity has been associated with both alcoholism and major depression (MD). We investigated the contribution of MD, as well as alcoholism, to in vitro measures of immunity in inner-city alcohol-dependent (SCID-DSM-III-R) persons and community nonabusers, all otherwise in good health. METHODS: Alcohol-dependent persons at an ambulatory alcohol treatment center who did not abuse other substances were studied along with the comparison sample (total n=122). Enumerative and functional immune measures included leukocyte and lymphocyte subsets, mitogen response, natural killer cell activity (NKCA), and granulocytic phagocytosis. RESULTS: Controlling for alcohol dependence, age, gender, racial background, and medical status, MD was associated with decreased phytohemagglutinin (PHA) responses (p<.03), possibly decreased NKCA (p<.08), and increased circulating monocytes (p<.04). Controlling for MD, age, gender, racial background, and medical status, alcohol dependence was associated with decreased circulating B lymphocytes (p<.02), possibly decreased CD56+ (NK) cells (p<.06), and increased monocytes (p<.04). Responses to concanavalin A and pokeweed mitogen, granulocyte functions, and the composition of other leukocyte and lymphocyte subsets showed no evidence of being associated with MD or with alcoholism (p>.1). Secondary analyses exploring factors such as recent alcohol use, cigarette use, and nutrition suggested that these factors accounted for the altered lymphocyte subsets associated with alcoholism and the possibly decreased NKCA with MD. They did not account for the association of MD with increased monocytes and decreased PHA. DISCUSSION: MD-associated immune changes in alcoholics are modest and consistent with those seen in MD without alcoholism. Some MD- and many alcoholism-associated immune effects appear related to factors such as cigarette use and recent alcohol exposure.     

P3 event-related potential amplitude and the risk for disinhibitory disorders in adolescent boys

BACKGROUND: The children of parents who abuse alcohol typically show reduced amplitude of the P3 event-related potential wave. We determined if this effect was present in a population-based sample of older adolescent boys, whether it was associated with paternal antisocial personality and drug use, and whether it appeared in youth with childhood externalizing and substance use disorders. METHODS: A statewide sample of 502 male youth, identified from Minnesota birth records as members of twin pairs, had their P3 amplitude measured, using a visual oddball paradigm when they were approximately 17 years old. Structured clinical interviews covering attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder, antisocial personality disorder, and substance use disorders were administered in person to the youth and his parents at the time of the P3 assessment and again to the youth 3 years later. RESULTS: Reduced P3 was associated with disorders and paternal risk for disorders, reflecting a behavioral disinhibition spectrum that included attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, antisocial personality disorder, alcoholism, nicotine dependence, and illicit drug abuse and dependence. Reduced P3 at age 17 predicted the development of substance use disorders at age 20. Most effect sizes associated with these group differences exceeded 0.70, indicating medium to moderately large group differences. Maternal alcoholism and substance use during pregnancy were unrelated to P3 amplitude in offspring. CONCLUSION: Small amplitude P3 may indicate genetic risk for a dimension of disinhibiting psychiatric disorders, including childhood externalizing, adult antisocial personality disorder, and substance use disorders.     

Genetic and environmental effects on offspring alcoholism: new insights using an offspring-of-twins design

CONTEXT: Although there is now considerable evidence that genetic effects play a critical role in the development of alcohol dependence (AD), theoretical and methodological limitations of this literature require caution in describing the etiology and development of this disorder. OBJECTIVE: To disentangle genetic and environmental effects on AD by means of the infrequently used, yet potentially powerful, offspring-of-twins design. DESIGN: Offspring of twins. PARTICIPANTS: Male monozygotic and dizygotic twins concordant or discordant for AD and control pairs from the Vietnam Era Twin Registry were assessed, as were the offspring of these twins and the mothers of these offspring. INTERVENTIONS: Structured psychiatric interviews. MAIN OUTCOME MEASURES: Participants' psychiatric, alcohol abuse (AA), and AD histories (DSM-IV). RESULTS: Offspring of monozygotic and dizygotic twins with a history of AD were significantly more likely to exhibit AA or AD than were offspring of nonalcoholic fathers. Offspring of an alcohol-abusing monozygotic twin whose co-twin was AD were also more likely to exhibit AD than were offspring of nonalcoholic twins. In contrast, offspring of an unaffected (ie, no history of abuse or dependence) monozygotic twin whose co-twin was AD were no more likely to exhibit AA or AD than were offspring of nonalcoholic twins. CONCLUSIONS: These findings support the hypothesis that family environmental effects do make a difference in accounting for offspring outcomes, in particular, that a low-risk environment (ie, the absence of parental alcoholism) can moderate the impact of high genetic risk regarding offspring for the development of alcohol-use disorders.     

Hallucinogen, opiate, sedative and stimulant use and abuse in a population-based sample of female twins.

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.     

Suspiciousness and alcohol use disorders in schizophrenia

Problems with alcohol are a common and important comorbidity in patients with schizophrenia. Previous studies showed an association between depression and alcohol abuse in patients with schizophrenia. Suspiciousness has been shown to be associated with depression. In a population-based study, the authors tested the hypothesis that suspiciousness is associated with alcohol problems in patients with schizophrenia. Data came from the first wave of the five-site Epidemiological Catchment Area study. Baseline clinical and demographic data were analyzed to assess associations between symptoms and an alcohol abuse or dependence diagnosis in patients with a Diagnostic Interview Schedule (DIS) diagnosis of schizophrenia. Suspiciousness was associated with an alcohol dependence or abuse diagnosis in male DIS-DSM-III schizophrenia patients, after accounting for demographic and other clinical variables. There were no associations between alcohol problems and either conceptual disorganization or hallucinations and nonsuspicious delusions. Suspiciousness appears to be associated with alcohol abuse and dependence in men with schizophrenia. Further studies should attempt to investigate the temporal relationship between suspiciousness and alcohol problems. Interventions that address suspiciousness may decrease the risk of alcohol problems in this population.     

Genetic variation and shared biological susceptibility underlying comorbidity in neuropsychiatry

Genetic factors underlying alcoholism, substance abuse, antisocial and violent behaviour, psychosis, schizophrenia and psychopathy are emerging to implicate dopaminergic and cannabinoid, but also monoaminergic and glutamatergic systems through the maze of promoter genes and polymorphisms. Candidate gene association studies suggest the involvement of a range of genes in different disorders of CNS structure and function. Indices of comorbidity both complicate the array of gene-involvement and provide a substrate of hazardous interactivity. The putative role of the serotonin transporter gene in affective-dissociative spectrum disorders presents both plausible genetic variation and complication of comorbidity The position of genetic variation is further complicated through ethnic, contextual and social factors that provide geometric progressions in the comordity already underlying diagnostic obstacles. The concept of shared biological susceptibility to two or more disorder conditions of comorbidity seems a recurring observation, e.g., bipolar disorder with alcoholism or schizophrenia with alcohol/substance abuse or diabetes with schizopsychotic disorder. Several lines of evidence seem to suggest that the factors influencing variation in one set of symptoms and those affecting one or more disorders are observed to a marked extent which ought to facilitate the search for susceptibility genes in comorbid brain disorders. Identification of regional genetic factors is awaited for a more compelling outline that ought eventually to lead to greater efficacy of symptom-disorder arrangements and an augmentation of current pharmacological treatment therapies.     

Co-occurrence patterns of anxiety,depression and alcohol use disorders

Co-occurrence of anxiety and depressive symptoms with alcohol consumption/abuse was analyzed in a sample of 2,302 adults in Bahia, Brazil. A cross-sectional household survey collected self-reported information on social and personal health, as well as individual psychological status, with standardized techniques and trained examiners. Twelve-month prevalence was 15% for anxiety, 12% for depressive disorders and 7% for alcohol abuse/ dependence. Symptom co-occurrence was more frequent for depression (94% of cases co-occurring with other diagnoses), followed by anxiety disorders (82%), and alcoholism (only 20%). There was a 74% proportion of anxiety symptoms among depressed, and a 61% proportion of depressed among anxiety sufferers. The combination of depression plus anxiety was the most prevalent in both gender groups, ranging from 17% for women to 5% for men. Comorbid combinations of alcoholism yielded low prevalences, the smallest (around 1%) being the triple combo alcoholism+anxiety+depression. Gender ratios increased substantially in the absence of comorbidity, reaching peaks in depression (F:M ratio = 13.8) and alcoholism (M:F ratio = 11.8). Set component analyses indicate strong overlapping of anxiety and depression and complementarity between depression and alcoholism, modulated by gender (women depressed, men alcoholic).     

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.     

Lifetime and 6-month prevalence of abuse and dependence of alcohol in the Munich follow-up study

Summary This paper reports lifetime and 6-month prevalence rates of alcohol abuse and dependence in West Germany. Assessment instruments are a modified German version of the Diagnostic Interview Schedule (DIS), a fully standardized interview for the assessment of selected DSM-III diagnoses and the Munich Alcoholism Test (MALT). According to the DIS/DSM-III criteria, 13.0% of the adult general population (aged 25–64 years) were found to fulfill the lifetime criteria for alcohol abuse, alcohol dependence, or both; however, only 1.3% of all men and 0.9% of the women interviewed received a current DSM-III diagnosis of alcohol abuse or dependence. There was good consensus between current DSM-III diagnoses with current clinical ICD-diagnoses, but poor concordance with lifetime diagnoses. Symptoms of alcoholism, onset and severity, comorbidity with other DIS/DSM-III disorders as well as some selected risk factors are reported. The results are primarily compared with the results of the US-Epidemiological Catchment Area Program (ECA).     

Familial influences on the clinical characteristics of major depression: a twin study.

We sought in this study to clarify the role that familial factors play in influencing the clinical presentation of major depression (MD). We examined the similarity of the historical and symptomatic features of MD in 176 pairs of female-female monozygotic (MZ) and dizygotic (DZ) twins from a population-based registry, where both members reported a history of MD defined by DSM-III-R criteria. The age at onset and treatment-seeking were significantly correlated in all twin pairs and the correlation in concordant DZ pairs was actually somewhat higher than in concordant MZ twins. The degree of impairment was modestly correlated in all twin pairs with substantially higher correlations in MZ vs DZ twins. No twin resemblance was observed for number of episodes or longest duration of an episode. Twin resemblance for the clinical features of MD was modest, but so was their consistency for the same individual over successive 1-year periods. However, in 5 of the 6 neurovegetative symptoms involving changes in appetite, weight and sleep, MZ twins were significantly correlated and correlations were significantly greater in concordant MZ vs DZ twins. Although the familial factors that cause twin resemblance for the age at onset and treatment seeking appear to be largely environmental, twin resemblance for the degree of impairment and neurovegetative symptoms are probably due largely to genetic factors. Our results suggest that familial factors influence the predisposition to some clinical features of MD.     

The relationship between social support and major depression: cross-sectional, longitudinal, and genetic perspectives

Although social support (SS) is associated with risk for major depression (MD), we are uncertain of the extent to which a) low SS increases risk for MD, b) MD lowers SS, or c) both variables reflect a common genetic liability. Using two waves of interview data on female twin pairs from a population-based registry, we examine the cross-sectional and longitudinal association of eight dimensions of perceived SS and MD. Risk for MD in the last year was inversely associated with supportive spouse and relative relationships, and directly associated with problems in these relationships (e.g., too many demands, criticism, tension, and disagreements). Significant cross-time associations were seen only for spousal variables. The history of MD in one twin significantly predicted low relative and spouse support, and relative and friend problems, in her co-twin (MZ > DZ pairs). The relationship between SS and MD in women is complex and due to at least the three separate mechanisms outlined above that operate to varying degrees in different dimensions of SS.     

The structure of genetic and environmental risk factors for anxiety disorders in men and women

BACKGROUND: The anxiety disorders exhibit high levels of lifetime comorbidity with one another. Understanding the underlying causes of this comorbidity can provide insight into the etiology of the disorders and inform classification and treatment. OBJECTIVE: To explain anxiety disorder comorbidity by examining the structure of the underlying genetic and environmental risk factors. DESIGN: Lifetime diagnoses for 6 anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, and situational phobia) were obtained during personal interviews from a population-based twin registry. Multivariate structural equation modeling that allowed for sex differences was performed. SETTING: General community sample. PARTICIPANTS: More than 5000 members of male-male and female-female twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. MAIN OUTCOME MEASURES: Parameter estimates for best-fitting model. RESULTS: The full model, which contained 2 common genetic, shared environmental, and unique environmental factors plus disorder-specific factors, could be constrained to equality across male and female study participants. In the best-fitting model, the genetic influences on anxiety were best explained by 2 additive genetic factors common across the disorders. The first loaded most strongly in generalized anxiety disorder, panic disorder, and agoraphobia, whereas the second loaded primarily in the 2 specific phobias. Social phobia was intermediate in that it was influenced by both genetic factors. A small role for shared environmental influences was observed owing to a single common factor that accounted for less than 12% of the total variance for any disorder. Unique environmental influences could be explained by a single common factor plus disorder-specific effects. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the anxiety disorders is similar between men and women. Genes predispose to 2 broad groups of disorders dichotomized as panic-generalized-agoraphobic anxiety vs the specific phobias. The remaining associations between the disorders are largely explained by a unique environmental factor shared across the disorders and, to a lesser extent, a common shared environmental factor.