Psychopathology in adopted-away offspring of biologic parents with antisocial behavior.

A study of 246 adoptees aged 10 to 37 years separated at birth from biologic parents is used to study genetic heritability of antisocial behavior and to delineate the extent and quality of "antisocial spectrum" conditions. Evidence is presented for a genetic factor in adoptee antisocial behavior and for the following as "spectrum" conditions: (1) hysteria in adult females (Briquet's syndrome) or multiple somatic complaints without medical explanation in younger female subjects and (2) mood swings possibly associated with the symptom of audible thoughts.

Sex differences in predictors of antisocial behavior in adoptees.

The present study follows up adoptees separated at birth from the biologic parents to assess the importance of genetic and environmental factors in adolescent antisocial behavior. The dependent variable is an antisocial symptom count that tallies antisocial but not necessarily criminal behaviors in adolescence. The independent variables are of two types, genetic and environmental. Genetic variables refer to psychiatric diagnoses of the biologic family. Environmental variables are those identified by previous research as associated with adolescent antisocial behavior. Our results indicate that boys are more vulnerable than girls to the adverse effects of a psychiatrically ill adoptive family member or divorce in the adoptive parents. There is not a significant sex difference in genetic predictors. In the total sample, the genetic variables that predict antisocial behavior are having an antisocial or alcoholic biologic relative. This finding is in agreement with other heritability studies of antisocial behavior.

Development of alcoholism in adoptees raised apart from alcoholic biologic relatives.

Male adoptees raised apart from alcoholic biologic parents were followed up and compared with adoptees of nonalcoholic biologic parents. Significant associations were found between adoptee alcoholism and an alcoholic biologic background and between childhood conduct disorder and the development of alcoholism as an adult. None of the environmental factors--psychiatric or alcohol problems in adoptive family, socioeconomic status of the adoptive family, or exposure to discontinuous mothering as an infant--predicted adoptee alcoholism. These findings suggest the importance of a genetic factor in alcoholism and are in accord with previous work that failed to show an independent effect of an alcoholic environment in development of adoptee alcoholism.

Alcoholism and antisocial personality. Interrelationships, genetic and environmental factors.

In a sample of 127 male and 87 female adult adoptees, antisocial personality and alcohol abuse were related to biologic backgrounds and to environmental factors. In the men, alcohol abuse was increased by a background of problem drinking in first-degree biologic relatives and by drinking problems in the adoptive home. Antisocial personality occurred more frequently in men whose first-degree biologic relatives had antisocial behavior problems. In the women, alcohol abuse was increased in adoptees whose first-degree relatives had problem drinking. Increased alcohol abuse in men and women was not predicted by biologic first-degree relatives with antisocial problems, nor did increased frequency of antisocial personality occur in adoptees with biologic relatives with problem drinking. The results suggest specificity of inheritance of antisocial and alcoholic conditions and the importance of environmental factors.

An adoption study of genetic and environmental factors in drug abuse.

In a sample of 242 male and 201 female adoptees who had been separated at birth from biologic parents, adult adoptee diagnoses of alcohol abuse, drug abuse and antisocial personality were correlated with biologic and environmental factors. Three etiologic relationships with drug abuse were found: drug abuse was highly correlated with antisocial personality, which in turn was predicted from antisocial biologic background; a biologic background of alcohol problems predicted increased drug abuse in adoptees who did not have antisocial personalities; and environmental factors of divorce and psychiatric disturbance in the adoptive family were associated with increased drug abuse.

Genetic-environmental interaction in the genesis of aggressivity and conduct disorders.

BACKGROUND: The purpose of this study was to determine the effect of an adverse adoptive home environment on adoptee conduct disorder, adult antisocial behavior, and two measures of aggressivity, all of which are behaviors that contribute to adult antisocial personality disorder and that also are associated with increased vulnerability to drug abuse and/or dependence. METHODS: The study used an adoption paradigm in which adopted offspring who were separated at birth from biologic parents with documented (by prison and hospital records) antisocial personality disorder and/or alcohol abuse or dependence were followed up as adults. They and their adoptive parents were interviewed in person. These adoptees were compared with controls whose biologic background was negative for documented psychopathologic behavior. Subjects were 95 male and 102 female adoptees and their adoptive parents. RESULTS: Multiple regression analysis was used to measure separately genetic and environmental effects. It showed that (1) a biologic background of antisocial personality disorder predicted increased adolescent aggressivity, conduct disorder, and adult antisocial behaviors, and (2) adverse adoptive home environment (defined as adoptive parents who had marital problems, were divorced, were separated, or had anxiety conditions, depression, substance abuse and/or dependence, or legal problems) independently predicted increased adult antisocial behaviors. Adverse adoptive home environment interacted with biologic background of antisocial personality disorder to result in significantly increased aggressivity and conduct disorder in adoptees in the presence of but not in the absence of a biologic background of antisocial personality disorder. CONCLUSIONS: Environmental effects and genetic-environmental interaction account for significant variability in adoptee aggressivity, conduct disorder, and adult antisocial behavior and have important implications for the prevention and intervention of conduct disorder and associated conditions such as substance abuse and aggressivity.

Distinct contributions of conduct and oppositional defiant symptoms to adult antisocial behavior: evidence from an adoption study.

BACKGROUND: We conducted an exploratory multivariate analysis of juvenile behavior symptoms in an adoption data set. One goal was to see if a few DSM-interpretable symptom dimensions economically captured information within the data. A second goal was to study the relationships between any such dimensions, biological and environmental background, and eventual adult antisocial behavior. METHODS: The data originated from a retrospective adoption study. Probands with a biological background for parental antisocial personality or alcoholism were heavily oversampled. Symptoms were ascertained by proband and adoptive parent interview. We performed, by gender, orthogonal rotated principal component analyses of juvenile behavior disturbance symptoms (females, n = 87; males, n = 88). We used structural equation modeling to examine the relationships hypothesized above. RESULTS: For both genders, an oppositional defiant disorder (ODD) component and at least 1 conduct component emerged. Regardless of the conduct component scores, the ODD components were significant predictors of adult antisocial behavior. For males, the ODD component was predicted by an antisocial biological background, but not by scores on the Adverse Adoptive Environment Scale. The conduct components were predicted by adoptive environment alone. For females, biological background or biological-environmental interactions predicted each of the components. CONCLUSIONS: There has been little previous distinction between conduct disorder and ODD in studies of genetic and environmental influences on juvenile behavior. The study suggests that adolescent ODD symptoms may be a distinct antecedent of adult antisocial personality. In males, adolescent ODD symptoms may represent early expression of genetic sociopathic personality traits.

Adoption study demonstrating two genetic pathways to drug abuse.

BACKGROUND: Studies of adoptees have demonstrated that there are two genetic factors leading to alcohol abuse and/or dependence (abuse/dependence). In addition, environmental factors found in the adoptive family also predict alcohol abuse/dependency independently. One study has found evidence that a similar model of two genetic factors and independent adoptive family factors were involved in drug abuse. Our study was designed to test the hypothesis that genetic factors defined by alcohol abuse/dependency and anti-social personality disorder in biologic parents were etiologic in drug abuse/dependency and that psychiatric problems in adoptive parents were an additional factor associated with drug abuse/dependence. METHODS: A sample of 95 male adoptees, separated at birth from their biologic parents, were followed up as adults to determine their psychiatric diagnosis and their substance use/abuse in a structured interview administered blind to biologic parent diagnoses. A high-risk, case-control design was used wherein half of the adoptees came from biologic parents known to be alcohol abuser/dependent and/or have antisocial personalities (diagnoses from hospital or prison records). These adoptees were matched for age, sex, and adoption agency to a control group of adoptees whose biologic parents were not found in the hospital and prison record search. Adoptive home environment was assessed by structured interviews, including psychiatric assessment of both adoptive parents. RESULTS: Data were analyzed by log-linear modeling, which showed evidence of two genetic pathways to drug abuse/dependency. One pathway went directly from a biologic parent's alcoholism to drug abuse/dependency. The second pathway was more circuitous, and started with anti-social personality disorder in the biologic parent and proceeded through intervening variables of adoptee aggressivity, conduct disorder, antisocial personality disorder, and, eventually, ended in drug abuse/dependency. Environmental factors defined by psychiatric conditions in adoptive families independently predicted increased antisocial personality disorder in the adoptee. Adoptees born of alcohol-abusing mothers showed evidence of fetal alcohol syndrome, but controlling for this did not diminish the evidence for the direct genetic effect between an alcohol-abusing biologic parent and drug abuse/dependency in offspring. CONCLUSIONS: This study confirms the model of two independent genetic factors involved in drug abuse/dependence and previous findings that disturbed adoptive parents are associated with adoptee drug abuse/dependency.

Evidence for genetic inheritance of primary affective disorder in adoptees.

Offspring of psychiatrically disturbed and normal biologic parents, adopted away at birth, were followed up as adults. The psychiatric status of the adoptees was determined by adoptive parent and adoptee interviews. The incidence of depression was significantly higher in the affective-parented adoptees (3 depressed of 8 adoptees) than in the remaining adoptees whose biologic parents had other psychiatric conditions or were apparently psychiatrically well (8 depressed of 118). The results suggest a genetic factor in affective disorders.

Genetic contributions to human fatness: an adoption study.

A strong relationship was found between the degree of fatness of biologic mothers and that of their adult offspring who had been separated from their mothers at birth and adopted during the first year of life. This relationship persisted even after age, height, and possible confounding environmental factors were controlled. There was little evidence for either selective placement on the basis of parental fatness or gene-environment interaction. There was no relationship between the degree of fatness of adoptive parents and that of the adoptees. Two indexes of environmental influence--rural upbringing and disturbance in the adoptive home--predicted fatness among adoptees.

Studies of adoptees from psychiatrically disturbed biological parents. III. Medical symptoms and illnesses in childhood and adolescence.

Analysis of data gathered from interviews with adoptive parents supports the hypothesis that female adoptees of antisocial biological backgrounds might have higher percentages of somatic symptoms. The authors compared female adoptees of antisocial parentage with male and female controls, male adoptees of antisocial parentage, and male and female adoptees whose biological parents had other psychiatric conditions. They stress the importance of this hypothesis in the diagnosis and management of childhood and adolescent "medical" and behavioral problems.

Depression spectrum disease, I: The role of gene-environment interaction.

OBJECTIVE: This study used an adoption study design to separate genetic from environmental factors in the etiology of depression spectrum disease, a type of major depression characterized by families in which male relatives are alcoholic and females are depressed. The genetic etiology hypothesis of depression spectrum disease proposes that an alcoholic genetic diathesis predisposes to depression in females but alcoholism, not depression, in males. METHOD: The study examined 197 adult offspring (95 male and 102 female) of alcoholic biological parents and used logistic regression models to determine the contribution to major depression in male and female adoptees that could be explained by the genetic alcoholic diathesis combined with an environmental factor that was characterized by psychiatrically or behaviorally disturbed adoptive parents. RESULTS: Major depression in females was predicted by an alcoholic diathesis only when combined with the disturbed adoptive parent variable. The same regression model failed to predict depression in males. Other possible environmental confounding factors contributing to an increased chance of depression were found in females: fetal alcohol exposure, age at the time of adoption, and a family with an adopted sibling who had a psychiatric problem. These variables did not diminish the significance of the prediction of depression with the alcohol genetic diathesis and disturbed parent model. CONCLUSIONS: The results show that a genetic factor is present for which alcoholism is at least a marker, and which exerts its effect in women as a gene-environment interaction leading to major depression. This finding suggests that an important etiologic factor in depression spectrum disease is gene-environment interaction.

Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients.

OBJECTIVE: Clozapine, an atypical antipsychotic, has been estimated to be effective in 30% of treatment-refractory schizophrenic patients. The authors hypothesized that if a dose-response relationship was obvious for this drug, the response rate could be significantly amplified. METHOD: Following an 8-24-day dose titration phase, 29 inpatients with treatment-resistant schizophrenia diagnosed according to DSM-III-R were given a clozapine dose of approximately 400 mg/day for 4 weeks; blood samples were obtained weekly during this period. RESULTS: A receiver operator curve demonstrated that the threshold clozapine plasma concentration for therapeutic response was 350 ng/ml. Sixty-four percent of the patients with clozapine plasma concentrations greater than 350 ng/ml responded, whereas only 22% of the patients with concentrations less than 350 ng/ml responded. CONCLUSIONS: Use of clozapine blood levels as a predictor for treatment response in treatment-refractory schizophrenic patients appears worthwhile, since the measurement's sensitivity for response was 64% and the specificity for nonresponse was 78%.

Anorexia nervosa in a 45-year-old man.

A case of anorexia nervosa diagnosed at age 45 in a man with a 20-year history of eating disorder is described. The reasons why anorexia may go undiagnosed in men are reviewed. The need to consider the possibility of this "unusual" diagnosis in men presenting with weight loss, no matter what their age, is emphasized.

Genetics of aggressive and violent behavior.

This article develops the topic of the genetics of aggressive and violent behavior from three directions. Firstly, evidence from twin, family, and adoption studies will establish the case for the importance of genetically transmitted factors in the genesis of aggressivity from childhood through adulthood. Secondly, evidence from adoption studies will be presented to show that some environmental conditions interact with genetic factors in such a way as to suggest that the development of aggressivity requires that both genetic and environmental factors be present. Thirdly, additional and direct evidence of genetic factors in aggressivity is presented from the perspective of molecular genetics, where underlying biochemical mechanisms associated with aggressivity have been found to be caused by specific genes in animal models with confirmation of similar physiologic mechanisms in humans.

An adoption study of DSM-IIIR alcohol and drug dependence severity.

OBJECTIVE: The objective of this study was to evaluate the role of genetic factors in alcohol and drug dependence at various levels of DSM-IIIR psychoactive substance dependence severity. METHOD: One-hundred-and-ninety-seven adoptees (95 case adoptees with biological parental alcoholism, drug dependence or antisocial personality disorder and 102 control adoptees) were interviewed for the presence of alcohol abuse or dependence and drug abuse or dependence using the Diagnostic Interview Schedule-DIS IIIR. RESULTS: Adoptees with five or more DSM-IIIR criteria for alcohol dependence demonstrated evidence of a genetic effect using this adoption paradigm (odds ratio = 2.3, 95% C.I. (1.1, 4.9)). Adoptees with one or more DSM-IIIR criteria for drug dependence demonstrated a genetic effect (odds ratio = 2.4, 95% C.I. (1.3, 4.4). CONCLUSIONS: This study suggests genetic factors influence the risk for alcohol and drug dependence at different thresholds of severity as determined by DSM-IIIR symptom severity count.

Genetic and environmental factors in major depression.

A study of 48 individuals with major depression in a sample of 443 adoptees has shown that depression is positively but not significantly correlated with a biologic background of affective disorder. Both primary and secondary depression was positively and significantly correlated with several environmental factors. In males, an adoptive home where another individual had an alcohol problem increased depression; in females, death of an adoptive parent prior to adoptee age 19 and an adoptive family where another individual had a behavior disturbance increased depression. Results suggest that the environmental factors occurring prior to adoptees age 18 predisposed to depression.

Factors associated with suicide attempts in alcohol abusers.

Alcoholics with and without previous suicide attempts were compared on a variety of clinical variables. Drug abuse and major depression especially if accompanied by crying spells, hopelessness, or seeking psychiatric help were found more frequently in the suicide attempter group. Additionally, total psychiatric symptoms were found to be higher in the suicide attempters in various categories including somatic, obsessive-compulsive, and total number of psychiatric symptoms reported on the structured interview. These results indicate that certain psychopathological symptoms are associated with suicide attempts in alcoholics and may be predictive of completed suicide.

Somatic symptoms. A major feature of depression in a family practice.

The complaints of depressed patients were investigated in a private, single-physician family practice clinic. Complaints and visits of depressives were compared to those of age- and sex-matched non-depressed controls over a period of 3 years beginning 18 months prior to the diagnosis of depression. Pain, functional and anxiety complaints signalled the onset and paralleled the course of depression. Somatic complaints were a conspicuous mode of presentation in this family practice. These somatic features are not among the usual diagnostic and research criteria for depression (DSM-III, Feighner Criteria and RDC) although they appear to be a major feature in the natural history of depression.

Anxiety in family practice.

The time course of patient initiated visits, somatic, functional, and other medical complaints was studied in a group of 58 patients from a family practice who had been diagnosed and treated for anxiety. The findings were contrasted with two other groups of patients from the same practice: 101 depressives and 101 controls. Results indicate that the anxiety patients differed markedly from the depressives in having a very short-lived episode of anxiety or somatic complaints in contrast to depressives' much longer history of somatic and functional complaints which appeared to precede by months the diagnosis of depression. The findings suggest that the anxiety patients in this practice either had a qualitatively different condition from the depressives, or possibly suffered from a short-lived and unrecognized depression.