The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring

Background: Few population‐based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). Methods: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. Results: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. Conclusions: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.     

Psychiatric Disorders Among Relatives of Cocaine-Abusing Individuals

Familial risk for psychiatric disorders was assessed among 673 siblings of cocaine-abusing individuals. Various indices of familial risk were examined, including those based on the presence/absence of disorders in parents and those reflecting severity (assessed by age at onset) of disorders. Across risk indices, the findings indicated high vulnerability among siblings (1) to substance abuse in relation to paternal alcoholism and (2) to depression and substance abuse in relation to maternal depression. The validity of the Type I/Type II distinction was upheld in the context of alcoholism only among fathers. In the context of affective disorders, risk to offspring was greatest if exposure to parental psychopathology occurred during the early childhood years.     

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders,substance use,and substance use disorders in preadolescent and adolescent offspring

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.     

Co-Morbidity of Lifetime Psychiatric Disorder Among Male Alcoholic Patients

The lifetime co-morbidity of major psychiatric disorders among male alcoholics was examined with the structured Psychiatric Diagnostic Interview (PDI), which was administered to 928 patients undergoing alcoholism treatment at six Veterans Administration Medical Centers. Thirty-eight percent were positive for alcoholism only; 62% fulfilled inclusive lifetime diagnostic criteria for at least one other additional psychiatric syndrome. Thirty percent satisfied criteria for one additional syndrome; 16% for two additional syndromes; 12% for three; and 4% for four or more disorders in addition to alcoholism. Depression and antisocial personality were the most frequently identified co-occurring syndromes (36% and 24%, respectively) followed by drug abuse and mania (17% each). The additional psychiatric syndromes in this sample were clearly not randomly distributed; instead, certain disorders tended to cluster together such as: drug abuse and antisocial personality; mania and depression; depression and anxiety disorder; and schizophrenia and affective disorder. Implications for classification and treatment are discussed.     

The role of childhood risk factors in initiation of alcohol use and progression to alcohol dependence

AIMS: To identify childhood risk factors that predict (a) age of first drink and (b) time from first use to alcohol dependence (AD) onset, using survival analysis. PARTICIPANTS: The sample consisted of 1269 offspring (mean age = 20.1 years) of male twins from the Vietnam Era Twin Registry; 46.2% were offspring of alcohol-dependent fathers. MEASUREMENTS: DSM-IV psychiatric diagnoses and substance use behaviors were assessed by structured telephone interview. FINDINGS: First drink occurred on average at 15.7 years; AD onset at 19.1 years. A Cox proportional hazard regression analysis revealed conduct disorder (CD) as the most potent predictor of early alcohol initiation (HR 2.48; CI 1.85-3.32). Attention deficit hyperactivity disorder (ADHD), maternal AD, paternal AD, male gender and parental divorce were also associated with early first use (HR 1.20-1.52; CI 1.04-1.39-1.18-1.96). A Cox proportional hazard regression analysis modeling first drink to AD identified nicotine dependence (HR 3.91; CI 2.48-6.17) and generalized anxiety disorder (GAD) (HR 3.45; CI 2.08-5.72) as robust predictors of progression to AD. CD (HR 1.75; CI 1.10-2.77) and cannabis abuse (HR 1.88; CI 1.22-2.90) were also associated with rapid transition to AD. CONCLUSIONS: Results highlight the role of psychiatric and substance use disorders in progression from first drink to AD, underscore the continuity of risk associated with CD and indicate that (with the exception of CD) different factors play a role in transition to AD than in initiation of alcohol use. Distinctions between stages are interpreted in a developmental framework.     

Environmental transmission of DSM-IV substance use disdorders in adoptive and step families

BACKGROUND: One factor contributing to the 3- to 5-fold increase in risk for substance use disorders (SUDs) among children of alcoholics may be the rearing environment. These influences may include availability of substances, modeling of SUDs, inadequate parenting, or other factors. The contribution of parental environmental influences on offspring with SUDs may be estimated independently of genetic influences through assessment of adoptees raised by nonbiological parents. METHODS: Relative risk of SUDs was assessed in adult adoptees (N = 442) of alcoholic and nonalcoholic adoptive parents as well as in stepchildren (N = 1859) with alcoholic or nonalcoholic stepfathers who participated in the community-based National Longitudinal Alcohol Epidemiologic Survey (NLAES). RESULTS: Rearing by an alcoholic adoptive mother was associated with increased DSM-IV alcohol abuse. Rearing by an alcoholic adoptive father was predictive of adoptees' illicit drug use, as well as DSM-IV drug dependence. Rearing by an alcoholic stepfather was predictive of stepchild DSM-IV alcohol abuse, illicit drug use, and drug dependence, whereas an alcoholic stepmother was associated with increased illicit drug use in the stepchild. Alcoholism in adoptive parents or step parents did not increase risk for offspring DSM-IV alcohol dependence. In both adoptive and biological families, there was a subadditive interaction of mother by father alcoholism such that the rate of substance abuse when both parents were alcoholic was less than that expected based on the additive effects of each alcoholic parent. CONCLUSIONS: Rearing by an alcoholic parent had a greater influence on alcohol abuse by offspring than on alcohol dependence. The increased risk of proband illicit drug use and drug dependence associated with paternal alcoholism suggested nonspecificity of environmental transmission. Both maternal and paternal cultural transmission effects influenced offspring SUDs.     

Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism

Background: Gender differences are known to exist in the prevalence, characteristics, and course of alcohol dependence. Elucidating gender differences in the characteristics of alcohol dependence is important in gender‐based medicine and may improve treatment outcomes. Many studies have shown that genetic factors are associated with the risk of alcohol dependence in both genders. Polymorphisms of alcohol dehydrogenase‐1B (ADH1B) and aldehyde dehydrogenase‐2 (ALDH2) are strong genetic determinants of alcohol dependence. This study aimed to clarify gender differences in the effects of ADH1B and ALDH2 polymorphism on the development of alcohol dependence. Methods: Subjects were 200 female alcoholics and 415 male alcoholics hospitalized in Kurihama Alcoholism Center. Clinical information and background data were obtained by chart review. ALDH2 and ADH1B genotyping was performed by the polymerase chain reaction–restriction fragment length polymorphism method. Results: The onset age of female alcoholics with inactive ALDH2 genotype was significantly lower than those with active ALDH2 genotype, but the onset age did not differ between the inactive and active ALDH2 group in male alcoholics. The difference in onset age between the ADH1B genotype groups did not reach significant levels. The prevalence of comorbid psychiatric disorders, including major depression, eating disorder, panic disorder, and borderline personality disorder, was significantly higher in female alcoholics with inactive ALDH2 or superactive ADH1B than in those with active ALDH2 or normal ADH1B. Conclusions: ALDH2 polymorphism appears to have contrasting effects on the development of alcoholism in women and men. One possible reason for this gender difference may be the high prevalence of psychiatric comorbidities in female alcoholics with inactive ALDH2.     

Alcoholism,antisocial behavior and family history*

Previous investigations in selected and clinical samples have demonstrated a close association between alcoholism and both antisocial behavior and a family history of problem drinking. This study uses the National Institute of Mental Health (NIMH) Epidemiological Catchment Area (EGA) data to assess this relationship in the general population in St. Louis, Missouri (U.S.A.). The results showed that serious antisocial behavior (both conduct disorder and antisocial personality disorder), gender, and a family history of problem drinking were all significantly associated with alcoholism (DSM-III alcohol abuse or dependence). Having either conduct disorder, antisocial personality, or a first-degree relative (parent, sibling, or child) with problem drinking increased the probability of alcoholism; being male also increased its probability. Antisocial behavior and gender interacted in that antisocial behavior was a more potent risk factor for women than for men. However, despite their close association with alcoholism, having either antisocial personality or a positive family history of problem drinking identified only 49% of male alcoholics and 14% of female alcoholics. Thus, these two important predictors of alcoholism would be somewhat inefficient screeners for primary prevention. More investigation is needed to understand the development of alcoholism in those without these major risk factors and the lack of alcoholism in those with them.     

Paternal skeletal size predicts intrauterine bone mineral accrual

BACKGROUND: We have previously demonstrated that maternal body build and lifestyle factors predict neonatal bone mineral accrual. However, the paternal determinants of neonatal bone mass are not known. In this study we explored the relationship between a father's bone mass and that of his offspring. METHODS: A total of 278 pregnancies (142 male and 136 female neonates) were recruited from the Southampton Women's Survey, a unique, well-established cohort of women, aged 20-34 yr, who had been assessed before and during pregnancy. The neonates and their fathers underwent whole body dual-x-ray absorptiometry (DXA) within 2 wk of birth using a Lunar DPX (General Electric Corp., Madison, WI) and Hologic Discovery instrument (Hologic Inc., Bedford, MA), respectively; correlation and regression methods were used to explore the parental determinants of neonatal bone mass. RESULTS: After adjusting the paternal DXA indices for father's age and the neonatal for baby's gestational age and age at DXA scan, there were highly significant positive associations between baby's whole body bone area, bone mineral content, and bone mineral density and the corresponding indices in the father (P = 0.003, 0.0002, 0.046, respectively) among female infants. These relationships were independent of maternal height and fat stores. The associations for male infants with paternal DXA indices did not achieve statistical significance. CONCLUSIONS: The father's skeletal size predicts skeletal size more strongly in female than male offspring, independently of the mother's body build. These data point toward the importance of considering paternal genotype in studies exploring the developmental origins of osteoporotic fracture and raise intriguing mechanistic questions about the gender specificity of influences on intrauterine bone mineral accrual.     

Psychiatric comorbidity in treatment-seeking alcoholics: the role of childhood trauma and perceived parental dysfunction

BACKGROUND: This study among treatment-seeking alcoholics examined the relationship between childhood abuse (sexual abuse only [CSA], physical abuse only [CPA], or dual abuse [CDA]) and the presence of comorbid affective disorders, anxiety disorders, and suicide attempts, controlling for the potential confounding effects of other childhood adversities (early parental loss, witnessing domestic violence, parental alcoholism, and/or dysfunction) and adult assault histories. METHOD: We assessed 155 (33 females, 122 males) treatment-seeking alcoholics using the European Addiction Severity Index, the Structured Trauma Interview, and the Composite International Diagnostic Interview. RESULTS: The severity of childhood abuse was associated with posttraumatic stress disorder (PTSD) and suicide attempts in females and with PTSD, social phobia, agoraphobia, and dysthymia in males. Among men, multiple logistic regression models showed that CPA and CDA were not independently associated with any of the examined comorbid disorders or with suicide attempts. However, CSA independently predicted comorbid social phobia, agoraphobia, and PTSD. For the presence of comorbid affective disorders (mainly major depression) and suicide attempts, maternal dysfunctioning was particularly important. CSA also independently contributed to the number of comorbid diagnoses. For females, small sample size precluded the use of multivariate analyses. CONCLUSION: Childhood abuse is an important factor in understanding clinical impairment in treated alcoholics, especially regarding comorbid phobic anxiety disorders, PTSD, and suicidality. These findings underline the importance of routine assessment of childhood trauma and possible trauma-related disorders in individuals presenting to alcohol treatment services. More studies with bigger samples sizes of female alcohol-dependent patients are needed.     

Common genetic mechanisms in alcoholism and psychiatric disorders: negative evidence from a study of ethnic group patients

Alcoholism in the male relatives of patients with various (nonalcoholic) psychiatric disorders is consistently elevated above population risk. Over the years, this finding has given rise to theories which propose that some forms of alcoholism are attributable to the pleiotropic expression of genes underlying these disorders. This mechanism was tested in the fathers of patients from ethnic groups associated with culturally suppressed alcohol abuse where it was predicted that decreased alcoholism would be substituted for by increased psychiatric disorder. Results, however, failed to support such a mechanism. Other explanations of this elevated alcoholism were considered.     

Geschlechterunterschiede in der neuropsychiatrischen Pharmakotherapie

At least half of all patients with psychiatric disorders are female. Depressive disorders occur twice as often in women than in men. Despite the need for a gender-specific approach in treating psychiatric disorders, little is known about gender issues in psychopharmacology. It has been recognized that women respond better than men to serotonin-modulating substances but that this effect is reversed after menopause. Furthermore, women develop gynecological complications under medication with certain psychopharmacological agents which calls the use of these drugs into question. Side effects such as weight gain, hyperglycemia, cardiac arrhythmias, and sexual dysfunction also occur more frequently in women than in men. Pregnancy is a particularly sensitive aspect. The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications.     

Gender differences in psychopharmacology

At least half of all patients with psychiatric disorders are female. Depressive disorders occur twice as often in women than in men. Despite the need for a gender-specific approach in treating psychiatric disorders, little is known about gender issues in psychopharmacology. It has been recognized that women respond better than men to serotonin-modulating substances but that this effect is reversed after menopause. Furthermore, women develop gynecological complications under medication with certain psychopharmacological agents which calls the use of these drugs into question. Side effects such as weight gain, hyperglycemia, cardiac arrhythmias, and sexual dysfunction also occur more frequently in women than in men. Pregnancy is a particularly sensitive aspect. The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications.     

Lack of excess maternal transmission of type 2 diabetes in a Korean population

The purpose of this study was to assess the familial clustering of type 2 diabetes and to investigate the presence of excess maternal transmission of type 2 diabetes in Korea. The medical records of 56,492 subjects (31,680 men and 24,812 women), who attended the Health Promotion Center were examined. The subjects were questioned about their parents' diabetes status. All study subjects were classified into the three groups (normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetes). Offspring with paternal diabetes (odds ratio 2.54, 95% CI 2.22-2.91, P < 0.001) and those with maternal diabetes (odds ratio 3.10, 95% CI 2.76-3.49, P < 0.001) were at increased risk for diabetes when compared to subjects without parental diabetes and adjusted for other clinical and biochemical variables. Offspring with bilineal parental diabetes were at a greater risk for diabetes (odds ratio 6.09, 95% CI 4.55-8.16, P < 0.001) when compared to subjects without parental diabetes. In both genders, offspring with maternal diabetes showed no increased risk for diabetes (odds ratio 1.22, 95% CI 0.92-1.37, P + 0.266 in men; odds ratio 1.31, 95% CI 0.95-1.81, P = 0.104 in women) when compared with those with paternal diabetes. The data suggested that parental type 2 diabetes was an independent risk factor for offspring type 2 diabetes in this Korean population. Excess maternal transmission of type 2 diabetes was not observed.     

The association between cannabis abuse and dependence and childhood physical and sexual abuse: evidence from an offspring of twins design

AIM: This study examines the association between childhood physical abuse (CPA) and sexual abuse (CSA) and the development of cannabis abuse and dependence among adolescents and young adults while controlling for genetic and environmental risk factors. DESIGN: To control for familial risk differences related to paternal drug dependence that might confound the relationship between CSA and CPA and cannabis abuse/dependence, we created four groups based on father's and uncle's substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: (i) high genetic, high environmental risk; (ii) high genetic, low environmental risk; (iii) medium genetic, low environmental risk; and (iv) low genetic, low environmental risk. PARTICIPANTS: Adolescent and young adult offspring of monozygotic and dizygotic US military veteran twin fathers (n = 819). MEASUREMENTS: Data on CPA and CSA, DSM-IV offspring cannabis abuse/dependence, other SUD and psychopathology and maternal and paternal SUD and psychopathology were collected via semi-structured telephone interview. FINDINGS: Twenty-three per cent of the offspring sample met life-time criteria for cannabis abuse/dependence and 8.55% and 12.82% reported CSA and CPA, respectively. Offspring exposed to CSA, but not CPA, were at significantly greater risk of developing cannabis abuse/dependence compared to those who had not experienced CSA (hazard ratio = 2.16; 95% confidence interval = 1.48-3.16) after controlling for genetic and familial environmental risk and offspring gender, alcohol abuse and dependence and conduct disorder. CONCLUSIONS: These results indicate that there are effects of CSA on development of cannabis abuse/dependence in addition to the genetic and familial environmental risk imparted by having a drug-dependent father.     

Gender Differences in Lifetime Psychiatric Disorders Between Sons and Daughters of Alcoholic Mothers: A Pilot Study

Lifetime prevalence of selected psychiatric disorders was assessed in 24 independent pairs of adult siblings (brother-sister) with an alcoholic mother, using the Diagnostic interview Schedule. Adult females were as likely as adult males to have had one or more lifetime diagnosis of psychiatric disorder. Lifetime prevalence of affective disorders was the same in male and female siblings. Although not statistically significant, compared with their sister, men were 3 times more likely to have had a diagnosis of alcohol abuse/dependence, and 3.5 times more likely to have had a diagnosis of general anxiety disorder. When compared with their brother, women were 1.66 times more likely to have had a diagnosis of drug abuse/dependence, 3 times more likely to have had a diagnosis of panic disorder, and 6 times more likely to have been diagnosed with phobia; however, these differences were not significant.     

A Comparison of Male and Female Physicians Treated for Substance Use and Psychiatric Disorders

The authors compared physicians admitted for psychiatric or substance use disorders on demographic, clinical, and gender variables. The records of 92 physicians admitted to a private psychiatric hospital over a 6-year period were reviewed to compare characteristics of those admitted for psychiatric disorders with those admitted for substance abuse problems, and to compare female and male physician-patients. Of physicians who presented for substance abuse treatment, 58% had an additional Axis I psychiatric disorder, whereas 22% of physicians admitted for psychiatric treatment had substance use disorder; 59% of this sample of physicians received a personality disorder diagnosis. “Dual disorder” is a common clinical presentation in physicians. Male (n= 76) and female (n= 16) physicians were similar on compared variables except that they showed differing patterns of substance abuse. Compared with previous studies of treated physicians, the percentage of female physicians and the overall percentage of physicians with substance abuse diagnoses are increasing.     

Substance use disorders in high-risk adolescent offspring.

OBJECTIVE: To examine the risk for substance use disorders (SUD) in offspring of SUD parents who were not selected due to referral to SUD treatment centers. METHODS: The original sample was ascertained through two groups of index children: 140 ADHD probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. RESULTS: We found that: 1) parental SUD was associated with SUD and all SUD subtypes in the offspring; 2) parental alcohol use disorders were associated with alcohol use disorders in the offspring as well as co-occurring alcohol and drug use disorders but not drug use disorders alone in the offspring; and 3) drug use disorders in the parents were associated with drug use disorders but not alcohol use disorders in the offspring. CONCLUSIONS: These findings suggest that alcoholism and drug abuse may breed true from parents to their offspring, but further work with larger samples is needed to confirm this idea. Our findings also suggest a possible common diathesis that is expressed as comorbid alcohol and drug use in the offspring of alcoholic parents. If confirmed, these findings may be useful for the development of preventive and early intervention strategies for adolescents at high risk for SUD based on parental history of SUD.     

Comorbid psychiatric disorders and nicotine dependence in adolescence

Aims To examine bidirectional influences of onset of psychiatric disorders and nicotine dependence among adolescent smokers. Design A prospective longitudinal cohort of adolescents and mothers drawn from a large city school system. Adolescents were interviewed five times and mothers three times over 2 years. Setting Chicago, Illinois. Participants Subsample of adolescent smokers (n = 814). Measurements Selected DSM‐IV psychiatric disorders, nicotine dependence and selected risk factors were ascertained. Findings Among lifetime smokers, 53.7% experienced at least one nicotine dependence criterion; 26.1% full dependence; 14.1% experienced an anxiety disorder, 18.8% a mood disorder and 29.5% a disruptive disorder. Nicotine dependence and psychiatric disorders were comorbid: nicotine‐dependent youths had higher rates of individual and multiple disorders than those not dependent. Controlling for other covariates, mood disorder and nicotine dependence did not predict each other; anxiety disorder predicted nicotine dependence. Bidirectional influences were observed for disruptive disorder and nicotine dependence. Predictors of onset of full nicotine dependence included earlier onset age of tobacco use, high initial pleasant sensitivity to tobacco, alcohol and illicit drug use, abuse and dependence and parental nicotine dependence. Predictors of psychiatric disorder onset included gender, race/ethnicity, other psychiatric disorders, illicit drug abuse or dependence and parental depression and delinquency. Conclusions Initial pleasant experiences of smoking are predictive of later development of nicotine dependence. There may be reciprocal influences between disruptive disorder and development of nicotine dependence in adolescence, and intergenerational transmission of parental nicotine dependence and psychopathology.