A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands

BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability. DESIGN: Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account. RESULTS: Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.     

Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.     

Family history and diagnosis of alcohol dependence in cocaine dependence

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.     

The clinical course of alcoholism in 243 Mission Indians

OBJECTIVE: This study was conducted to describe the order of appearance and the progression of alcohol-related life events in Mission Indian men and women with a lifetime diagnosis of alcohol dependence. METHOD: A total of 407 participants completed a structured interview that gathered information on alcohol diagnoses, remissions, abstinences, and treatments as well as alcohol-related life events. RESULTS: A total of 70% of the men and 50% of the women sampled met lifetime diagnostic criteria for alcohol dependence. The age at onset of alcohol dependence was younger (20 years) and the course proceeded more rapidly (6 years) than what has been described in other large studies of alcoholics. A high degree of similarity in the type and progression of alcohol-related life events was found between Mission Indian men and women and alcoholics from the Collaborative Study on the Genetics of Alcoholism (COGA). However, Mission Indians in this study were significantly more likely than alcoholics in the COGA to experience binge drinking, physical fighting, driving while intoxicated, and alcohol-related health problems and were less likely to consider themselves excessive drinkers, drinking where and when they had not intended to, and to experience guilt concerning their drinking. Rates of abstention after an alcohol dependence diagnosis (61%) and remission from alcohol dependence symptoms (77%) were also high in Mission Indians. CONCLUSIONS: Understanding the course of Mission Indian alcoholism can help identify unique alcohol-related phenotypes as well as guide the development of treatment and prevention programs in this underserved population.     

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).     

Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence.

OBJECTIVE: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. METHOD: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. RESULTS: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. CONCLUSIONS: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.     

Hidden severe psychiatric morbidity in sentenced prisoners: an Australian study

OBJECTIVE: The aim of this survey was to estimate the prevalence of severe mental disorders in a representative sample of sentenced prisoners. METHOD: The subjects were selected as a random sample of sentenced prisoners in Melbourne's three metropolitan prisons. Interviews were conducted with 158 men and 31 women. Clinicians used the Structured Clinical Interview for DSM-III-R (SCID) to diagnose psychotic, affective, and substance use disorders. RESULTS: Six prisoners (3%) received current diagnoses of psychotic disorders, and 23 (12%) were diagnosed as having current mood disorders, mainly major depression. A lifetime diagnosis of at least one mental disorder each was made for 82% of the respondents, and in 26% more than one lifetime disorder was diagnosed. Sixty-nine percent received lifetime diagnoses of dependence on or abuse of alcohol, other psychoactive substances, or a combination of these. CONCLUSIONS: These findings do not indicate a large-scale shift of deinstitutionalized psychotically ill people from mental hospitals to prisons. They do, however, highlight the diversion into the corrections system of substance-dependent people and the apparent pool of prisoners with largely untreated major depression.     

Nicotine dependence, major depression, and anxiety in young adults.

To determine whether nicotine dependence, classified by level of severity, was associated with other substance dependence, major depression, and anxiety disorders, we studied a random sample of 1007 young adults in the Detroit (Mich) area using the National Institute of Mental Health Diagnostic Interview Schedule, revised according to DSM-III-R. The systematic coverage of DSM-III-R criteria of nicotine dependence provides an unprecedented opportunity to separate persons with nicotine dependence from the larger class of persons with a history of smoking and to examine the prevalence of psychiatric disorders among persons with nicotine dependence and among nondependent smokers. The lifetime prevalence of nicotine dependence was 20%. Nicotine dependence was associated with alcohol, cannabis, and cocaine dependence. Controlling for the effects of other substance dependencies, persons with nicotine dependence had higher rates of major depression and anxiety disorders. The strength of these associations varied by level of severity of nicotine dependence. Nondependent smokers had higher rates of other substance dependencies, but not of major depression or anxiety disorders.     

DSM-III-R classification of murderous youth: help or hindrance?

Fourteen homicidal juveniles were evaluated through clinical interviews, review of police and delinquency records, and administration of the Diagnostic Interview for Children and Adolescents to investigate the presence of psychiatric disorders in homicidal juveniles and to examine the usefulness of DSM-III-R in this population. A wide range of DSM-III-R diagnoses were established, primarily in conjunction with conduct disorder. DSM-III-R diagnoses were also made in conjunction with mood disorders, psychoactive substance use/dependence disorders, anxiety disorders, and several other disorders, but no diagnoses of psychotic disorder could be made. The average number of lifetime prevalence diagnoses made per individual was 2.4, and 13 (93%) of the subjects met DSM-III-R criteria for at least one current diagnosis at the time of their homicidal behavior. These findings have potentially important treatment, prognostic, and forensic implications.     

Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence

Alcohol dependence frequently co-occurs with cigarette smoking, another common addictive behavior. Evidence from genetic studies demonstrates that alcohol dependence and smoking cluster in families and have shared genetic vulnerability. Recently a candidate gene study in nicotine dependent cases and nondependent smoking controls reported strong associations between a missense mutation (rs16969968) in exon 5 of the CHRNA5 gene and a variant in the 3'-UTR of the CHRNA3 gene and nicotine dependence. In this study we performed a comprehensive association analysis of the CHRNA5-CHRNA3-CHRNB4 gene cluster in the Collaborative Study on the Genetics of Alcoholism (COGA) families to investigate the role of genetic variants in risk for alcohol dependence. Using the family-based association test, we observed that a different group of polymorphisms, spanning CHRNA5-CHRNA3, demonstrate association with alcohol dependence defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) criteria. Using logistic regression we replicated this finding in an independent case-control series from the family study of cocaine dependence. These variants show low linkage disequilibrium with the SNPs previously reported to be associated with nicotine dependence and therefore represent an independent observation. Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA.     

Lifetime history of traumatic events in a young adult Mexican American sample: Relation to substance dependence,affective disorder,acculturation stress,and PTSD

Mexican Americans comprise one of the most rapidly growing populations in the United States, and within this population, trauma and post-traumatic stress disorder (PTSD) are associated with physical and mental health problems. Therefore, efforts to delineate factors that may uniquely contribute to increased likelihood of trauma, PTSD, and substance use disorders over the lifetime in Mexican Americans are important to address health disparities and to develop treatment and prevention programs. Six hundred fourteen young adults (age 18–30 yrs) of Mexican American heritage, largely second generation, were recruited from the community and assessed with the Semi-Structured Assessment for the Genetics of Alcoholism and an acculturation stress scale. More males (51.2%) reported experiencing traumas than females (41.1%), however, a larger proportion of females received a PTSD diagnosis (15%) than males (8%). Alcohol dependence and affective disorders, but not anxiety disorders, antisocial disorders, nicotine, marijuana, or stimulant dependence, were significantly comorbid with PTSD. Endorsing higher levels of acculturation stress was also significantly associated with both trauma exposure and a diagnosis of PTSD. Logistic regression revealed that female gender, having an affective disorder, alcohol dependence, higher levels of acculturation stress, and lower levels of education were all predictors of PTSD status. Additionally, alcohol dependence generally occurred after the PTSD diagnosis in early adulthood in this high-risk population. These studies suggest that treatment and prevention efforts should particularly focus on young adult second generation Mexican American women with higher levels of acculturation stress, who may be at higher risk for PTSD, affective disorder, and alcohol dependence following trauma exposure.     

Increasing diagnosis of nicotine dependence in adolescent mental health patients

OBJECTIVE: The aim of this study was to investigate the routine recording patterns of patients' smoking by clinical staff of an adolescent mental health service over a 3-year period. METHOD: A systematic examination of the clinical files of all patients who underwent an initial assessment or reassessment at the Youth Specialty Service (Mental Health; YSS) over a 2-month period (1 April-31 May) was carried out in 1996, 1997 and 1998. A range of data were collected including: demographics; diagnoses; amount of total information recorded and history of nicotine dependence. RESULTS: A stable historical record of cigarette smoking in the region of 30-40% across the 3 years sampled was found, but the rate of formal diagnosis of nicotine dependence rose from 3.6% in 1996 to 26.3% in 1998. This rise was in the context of relative stability over this time period of: size of reports and relevant sections (alcohol and drug history, cigarette smoking history); three other key diagnoses, major depression, conduct disorder and alcohol dependence; and demographic data. The rise in rate of diagnosis proceeded specific discussion within the clinical team about nicotine dependence. CONCLUSIONS: Adolescent mental health settings are a key venue to address heavy and potentially chronic cigarette smoking, but nicotine dependence has been traditionally a neglected diagnosis in mental health patients. The rate of diagnosis is likely to rise when specific discussion is undertaken within clinical teams.     

Validity of the Michigan Alcoholism Screening Test (MAST) for the detection of alcohol-related problems among male geriatric outpatients.

Alcoholism is a frequent and underdiagnosed mental health problem of later life. Its detection often relies on the use of screening instruments such as the Michigan Alcoholism Screening Test (MAST). The authors investigated the properties of the scale in a sample of 122 older adults recruited from a geriatric outpatient service in S?o Paulo, Brazil. Thirty-five subjects met criteria for the diagnosis of alcohol abuse or dependence according to DSM-III-R. The cutoff point 4/5 was associated with a sensitivity of 91.4%, specificity of 83.9%, and positive and negative predictive values of 69.6% and 96.0%, respectively. These results indicate that the MAST is a good screening test for the detection of alcohol abuse and dependence in an elderly male population and that the MAST should be used in combination with a questionnaire assessing the frequency/quantity of alcohol consumption to optimize the detection of cases and characterize their current drinking patterns.     

Comorbidity of phobic disorders with alcoholism in a Canadian community sample.

OBJECTIVES: To examine the relation between phobic disorders and alcoholism in a Canadian community sample. METHOD: Data came from the Mental Health Supplement of the Ontario Health Survey. The University of Michigan revision of the Composite International Diagnostic Interview (UM-CIDI) was used to diagnose DSM-III-R psychiatric disorders in 8116 Canadian respondents between ages 15 and 64 years. Since the cross-system agreement (ICD-10 and DSM-III-R or DSM-IV) on the diagnosis of alcohol abuse is much lower than that for alcohol dependence, we also examined a WHO category, "hazardous alcohol use." Logistic regression controlling for age and sex was used to determine odds ratios (ORs) for phobic disorders and alcohol-use diagnoses. RESULTS: Individuals with lifetime alcohol abuse or dependence had two- to threefold increased odds of having a phobic disorder. Simple phobia and social phobia with multiple fears were significantly associated (ORs 1.5 to 2) with hazardous alcohol use (which had a prevalence of approximately 10%). CONCLUSIONS: Given the early onset of most phobic disorders, the findings suggest that these are a risk factor for hazardous patterns of alcohol use.     

Coexisting obsessive compulsive disorder and alcoholism

Fifty patients with the diagnosis of alcohol dependence or abuse who were admitted to a university-based alcohol rehabilitation program were screened for obsessions and compulsions. Six percent (3) of the patients met DSM-III-R criteria for obsessive compulsive disorder (OCD), which is three times the lifetime prevalence for OCD found in the general population. The diagnosis of OCD is easily overlooked, so screening questions should be asked of all alcoholics during the routine clinical interview. Identifying those patients with dual diagnoses is important because treatment of the underlying OCD should improve overall clinical outcome.     

Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians

OBJECTIVE: Two alcohol dehydrogenase genes (ADH2 and ADH3 on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms. The goal of this study was to determine whether any associations exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a group of Native Americans. An additional goal was to determine if any associations exist between these polymorphisms and the endophenotype, maximum number of drinks ever consumed in a 24-hour period. METHOD: Mission Indian adults (N=340) were recruited for participation from reservations in southern California. Each participant completed an interview with the Semi-Structured Assessment for the Genetics of Alcoholism. A blood sample was collected from each participant for genotyping at the ALDH2, ADH2, and ADH3 loci. RESULTS: Sixty percent of all participants (72% of men and 53% of women) met lifetime DSM-III-R criteria for alcohol dependence. A significant difference in the ADH2 allele distributions was found between alcohol-dependent and non-alcohol-dependent participants. Those with alcohol dependence were significantly less likely to have the ADH2*3 allele (odds ratio=0.28) and significantly more likely to have the ADH2*1 allele (odds ratio=2.00) than those who were not alcohol dependent. Individuals with ADH2*3 reported a lower number of maximum drinks ever consumed in a 24-hour period, compared to those without this allele. CONCLUSIONS: These results are consistent with genetic linkage studies showing protective associations for alcohol dependence and related behavior on chromosome 4 and suggest that ADH2 polymorphisms may account for these findings. These results also highlight the utility of evaluating protective factors in populations with high rates of alcohol dependence.     

The structure and stability of common mental disorders: the NEMESIS study

BACKGROUND: We analyzed the underlying latent structure of 12-month DSM-III-R diagnoses of 9 common disorders for the general population in the Netherlands. In addition, we sought to establish (1) the stability of the latent structure underlying mental disorders across a 1-year period (structural stability) and (2) the stability of individual differences in mental disorders at the level of the latent dimensions (differential stability). METHODS: Data were obtained from the first and second measurement of the Netherlands Mental Health Survey and Incidence Study (NEMESIS) (response rate at baseline: 69.7%, n = 7076; 1 year later, 79.4%, n = 5618). Nine common DSM-III-R diagnoses were assessed twice with the Composite International Diagnostic Interview with a time lapse of 1 year. Using structural equation modeling, the number of latent dimensions underlying these diagnoses was determined, and the structural and differential stability were assessed. RESULTS: A 3-dimensional model was established as having the best fit: a first dimension underlying substance use disorders (alcohol dependence, drug dependence); a second dimension for mood disorders (major depression, dysthymia), including generalized anxiety disorder; and a third dimension underlying anxiety disorders (simple phobia, social phobia, agoraphobia, and panic disorder). The structural stability of this model during a 1-year period was substantial, and the differential stability of the 3 latent dimensions was considerable. CONCLUSIONS: Our results confirm the 3-dimensional model for 12-month prevalence of mental disorders. Results underline the argument for focusing on core psychopathological processes rather than on their manifestation as distinguished disorders in future population studies on common mental disorders.     

Prevalence of mental disorders and utilization of mental health services in two American Indian reservation populations: mental health disparities in a national context

OBJECTIVE: The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP) provided estimates of the prevalence of DSM-III-R disorders and utilization of services for help with those disorders in American Indian populations. Completed between 1997 and 1999, the AI-SUPERPFP was designed to allow comparison of findings with the results of the baseline National Comorbidity Survey (NCS), conducted in 1990-1992, which reflected the general United States population. METHOD: A total of 3,084 tribal members (1,446 in a Southwest tribe and 1,638 in a Northern Plains tribe) age 15-54 years living on or near their home reservations were interviewed with an adaptation of the University of Michigan Composite International Diagnostic Interview. The lifetime and 12-month prevalences of nine DSM-III-R disorders were estimated, and patterns of help-seeking for symptoms of mental disorders were examined. RESULTS: The most common lifetime diagnoses in the American Indian populations were alcohol dependence, posttraumatic stress disorder (PTSD), and major depressive episode. Compared with NCS results, lifetime PTSD rates were higher in all American Indian samples, lifetime alcohol dependence rates were higher for all but Southwest women, and lifetime major depressive episode rates were lower for Northern Plains men and women. Fewer disparities for 12-month rates emerged. After differences in demographic variables were accounted for, both American Indian samples were at heightened risk for PTSD and alcohol dependence but at lower risk for major depressive episode, compared with the NCS sample. American Indian men were more likely than those in NCS to seek help for substance use problems from specialty providers; American Indian women were less likely to talk to nonspecialty providers about emotional problems. Help-seeking from traditional healers was common in both American Indian populations and was especially common in the Southwest. CONCLUSIONS: The results suggest that these American Indian populations had comparable, and in some cases greater, mental health service needs, compared with the general population of the United States.     

Effects of major depression on remission and relapse of substance dependence

BACKGROUND: The effects of major depressive disorder (MDD) on the course of substance dependence may differ depending on the temporal relationship of depression to dependence. We investigated the effects of MDD on the outcome of substance dependence under 3 circumstances: (1) lifetime onset of MDD prior to lifetime onset of dependence onset, (2) current MDD occurring during a period of abstinence, and (3) current MDD during substance use that exceeded the expected effects of intoxication or withdrawal. METHODS: A sample of 250 inpatients with DSM-IV cocaine, heroin, and/or alcohol dependence were followed up at 6, 12, and 18 months. The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was used to make DSM-IV diagnoses. Using Cox proportional hazards models, stable remissions (those lasting at least 26 weeks) from DSM-IV cocaine, heroin, and/or alcohol dependence and from use were studied, as well as subsequent relapses of dependence and use. RESULTS: Patients with current substance-induced MDD were less likely to remit from dependence (adjusted hazards ratio, 0.11) than patients with no baseline MDD. A history of MDD prior to lifetime onset of substance dependence also reduced the likelihood of remission relative to the absence of such a history (adjusted hazard ratio, 0.49). Major depressive disorder during sustained abstinence predicted dependence relapse (adjusted hazards ratio, 3.07) and substance use after hospital discharge compared with those without abstinence MDD (adjusted hazards ratio, 1.45). CONCLUSION: The timing of depressive episodes relative to substance dependence served as an important factor in the remission and relapse of substance dependence and substance use.     

Comorbidity of panic and somatization disorder: A genetic-epidemiological approach

Although recent diagnostic systems support the distinctiveness of panic disorder (PD) and somatization disorder, a high level of comorbidity of these two diagnoses has been reported, indicating a need for investigations with external validators. One hundred fifty-nine outpatients with DSM-III-R PD and 76 surgical controls were screened for lifetime presence of DSM-III-R somatization disorder, and the risks for some types of psychiatric disorders in their families were computed. In our sample, 23% of women and 5% of men with PD also had DSM-III-R somatization disorder. Women patients with PD plus somatization disorder did not differ from women with PD only in age at onset of panic, agoraphobia, childhood history of separation anxiety, or lifetime diagnoses of other disorders. Familial risks for PD, PD-agoraphobia, and alcohol dependence were significantly higher for families of women with PD and women with PD plus somatization disorder than for controls. The familial risks for antisocial personality (ASP) disorder (a familial indicator for the somatization disorder spectrum of liability, phenomenologically independent from both PD and somatization disorder) were significantly higher for families of women with PD plus somatization disorder than for families of women with PD only or for controls. Application of DSM-IV criteria for somatization disorder substantially decreased the comorbidity with PD. Our data suggest that somatization disorder is not simply a form of PD, and that the two disorders may coexist in the same subject without sharing a common genetic diathesis. Compared with DSM-III-R, DSM-IV criteria for somatization disorder appear to be simpler in structure and of less complicated application.