Morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of patients with eating disorders

OBJECTIVE: A hypothesis that eating disorders are a phenomenological variant of obsessive-compulsive disorder (OCD) has been proposed. This study was conducted to determine whether anorexia nervosa and bulimia, the two main eating disorders, are familial and whether the risk for obsessive-compulsive spectrum disorders (OCD and tic disorders) is higher in families of patients with eating disorders. METHOD: The morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of 136 female probands with eating disorders (84 with anorexia nervosa, 52 with bulimia) was compared to that for first-degree relatives of 72 female comparison subjects. RESULTS: The morbidity risk for obsessive-compulsive spectrum disorders was significantly higher among the 436 relatives of the eating disorder probands than among the 358 relatives of the comparison subjects (9.69% versus 0%). This finding was independent of any comorbid diagnosis of an obsessive-compulsive spectrum disorder in the eating disorder probands. The eating disorder group and the comparison group did not differ in familial risk for eating disorders and tic disorders. CONCLUSIONS: To better understand the genetic components of eating disorders, these disorders should be considered as part of the obsessive-compulsive spectrum of disorders.     

Binge eating disorder: a stable syndrome

OBJECTIVE: This study assessed the stability of binge eating disorder in a community sample. METHOD: The authors interviewed 888 first-degree relatives of 300 overweight or obese probands (150 with binge eating disorder and 150 with no lifetime eating disorder) who were recruited during a family study. They compared the total duration of illness among relatives with lifetime diagnoses of binge eating disorder (N=131), bulimia nervosa (N=17), and anorexia nervosa (N=18). RESULTS: The mean lifetime duration of binge eating disorder was 14.4 years (SD=13.9), significantly longer than for either bulimia nervosa (mean=5.8 years, SD=9.1) or anorexia nervosa (mean=5.9 years, SD=7.4). These differences changed little when analysis was restricted to female relatives or to relatives of the probands with no lifetime eating disorder. CONCLUSIONS: These findings suggest that binge eating disorder is at least as chronic as the well-validated disorders anorexia nervosa and bulimia nervosa and likely represents a stable syndrome.     

Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes

OBJECTIVE: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands. CONCLUSIONS: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.     

Family study of chronic depression in a community sample of young adults

OBJECTIVE: The validity of the distinctions between dysthymic disorder, chronic major depressive disorder, and episodic major depressive disorder was examined in a family study of a large community sample of young adults. METHOD: First-degree relatives (N=2,615) of 30 probands with dysthymic disorder, 65 probands with chronic major depressive disorder, 313 probands with episodic major depressive disorder, and 392 probands with no history of mood disorder were assessed by using direct interviews and informant reports. RESULTS: The rates of major depressive disorder were significantly greater among the relatives of probands with dysthymic disorder and chronic major depressive disorder than among the relatives of probands with episodic major depressive disorder, who in turn exhibited a higher rate of major depressive disorder than the relatives of probands with no history of mood disorder. The relatives of probands with dysthymic disorder had a significantly higher rate of dysthymic disorder than the relatives of probands with no history of mood disorder, and the relatives of probands with chronic major depressive disorder had a significantly higher rate of chronic major depressive disorder than the relatives of probands with no history of mood disorder. However, the relatives of the three groups of probands with depression did not differ on rates of dysthymic disorder and chronic major depressive disorder. CONCLUSIONS: Chronic depression is distinguished from episodic depression by a more severe familial liability. This familial liability may contribute to the more pernicious course of chronic depression.     

Phenomenologic relationship of eating disorders to major affective disorder

We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder.     

Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder

To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.     

Comorbidity of psychiatric diagnoses in anorexia nervosa

The comorbidity of psychiatric diagnoses was examined with the Diagnostic Interview Schedule in 62 women who participated in a 10-year follow-up study of anorexia nervosa. Sixty-two age- and sex-matched controls, their parents, and parents of the anorectic probands were also interviewed with the Diagnostic Interview Schedule. There was a statistically significant comorbidity of the affective and anxiety disorders with anorexia nervosa. The first-degree relatives of the anorectic probands had significantly more alcoholism and total number of psychiatric diagnoses compared with the first-degree relatives of controls. There were two mothers with bulimia nervosa, two cases of anorexia nervosa and two of bulimia nervosa in other first-degree relatives of anorectic probands, and no cases of eating disorders in the first-degree relatives of controls.     

Family history of suicidal behavior and mood disorders in probands with mood disorders

OBJECTIVE: First-degree relatives of persons with mood disorder who attempt suicide are at greater risk for mood disorders and attempted or completed suicide. This study examined the shared and distinctive factors associated with familial mood disorders and familial suicidal behavior. METHOD: First-degree relatives' history of DSM-IV-defined mood disorder and suicidal behavior was recorded for 457 mood disorder probands, of whom 81% were inpatients and 62% were female. Probands' lifetime severity of aggression and impulsivity were rated, and probands' reports of childhood physical or sexual abuse, suicide attempts, and age at onset of mood disorder were recorded. Univariate and multivariate analyses were carried out to identify predictors of suicidal acts in first-degree relatives. RESULTS: A total of 23.2% of the probands with mood disorder who had attempted suicide had a first-degree relative with a history of suicidal behavior, compared with 13.2% of the probands with mood disorder who had not attempted suicide (odds ratio=1.99, 95% CI=1.21-3.26). Thirty percent (30.8%) of the first-degree relatives with a diagnosis of mood disorder also manifested suicidal behavior, compared with 6.6% of the first-degree relatives with no mood disorder diagnosis (odds ratio=6.25, 95% CI=3.44-11.35). Probands with and without a history of suicide attempts did not differ in the incidence of mood disorder in first-degree relatives (50.6% versus 48.1%). Rates of reported childhood abuse and severity of lifetime aggression were higher in probands with a family history of suicidal behavior. Earlier age at onset of mood disorder in probands was associated with greater lifetime severity of aggression and higher rates of reported childhood abuse, mood disorder in first-degree relatives, and suicidal behavior in first-degree relatives. CONCLUSIONS: Risk for suicidal behavior in families of probands with mood disorders appears related to early onset of mood disorders, aggressive/impulsive traits, and reported childhood abuse in probands. Studies of such clinical features in at-risk relatives are under way to determine the relative transmission of these clinical features.     

A controlled family study of anorexia nervosa

A family study of eating disorders in first and second-degree relatives of anorexia nervosa and nonanorexic psychiatrically ill control probands found increased rates of anorexia-nervosa, bulimia nervosa, and subclinical anorexia nervosa in relatives of anorexic probands. The pattern of familial clustering suggests that these disorders may represent variable expressions of a common underlying psychopathology, although restricter and bulimic subforms of eating disorder may segregate within families. Implications of these findings for understanding factors important to the pathogenesis and subclassification of eating disorders are discussed.     

A family study of anxiety disorders: familial transmission and relationship to mood disorder and psychoactive substance use disorder

The prevalence of mental disorders in 76 first-degree relatives (parents and nontwin siblings) of 33 subjects with anxiety disorder was compared with the prevalence of mental disorders in 45 first-degree relatives of 20 subjects with mood disorder and 13 first-degree relatives of 6 subjects with psychoactive substance use disorder. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID I). Interrater reliability was high for most diagnoses. Significantly more first-degree relatives of subjects with anxiety disorder had panic disorder and generalized anxiety disorder compared with relatives of probands with mood disorder. Significantly more female than male relatives of anxiety subjects suffered from anxiety disorders; there were no gender differences in the prevalence of anxiety disorders in relatives of mood and psychoactive substance use disorder (PSUD) subjects. The combination of anxiety and mood disorder was overrepresented in first-degree relatives of subjects with the same type of comorbidity. In relatives of subjects with mixed anxiety and psychoactive substance use disorder, but no mood disorder, there was an overrepresentation of PSUD; mainly alcohol abuse or dependence.     

A family study of pathological gambling

The cause of pathological gambling (PG) is unknown. The current study was conducted to determine whether PG is familial, and to examine patterns of familial aggregation of psychiatric disorder. To that end, 31 case probands with DSM-IV PG and 31 control probands were recruited and interviewed regarding their first degree relatives (FDRs). Available and willing FDRs were directly interviewed with structured instruments of known reliability, and best estimate final diagnoses were blindly assigned for 193 case and 142 control relatives over age 18 years. The results were analyzed using logistic regression by the method of generalized estimating equations. The lifetime rates of PG and "any gambling disorder" were significantly greater among the relatives of case probands (8.3% and 12.4%, respectively) than among the control relatives (2.1% and 3.5%, respectively) (OR=3.36 for "any gambling disorder"). PG relatives also had significantly higher lifetime rates of alcohol disorders, "any substance use disorder," antisocial personality disorder (ASPD), and "any mental disorder". "Any gambling disorder," alcohol disorder, and "any substance use disorder" remained significant after a conservative Bonferroni correction. Interestingly, PG families were significantly larger than control families. We conclude that gambling disorders are familial and co-aggregate with substance misuse. The data are also suggestive that PG co-aggregates with ASPD. Further research on the heritability of PG is warranted.     

Psychiatric disorders in the first-degree relatives of probands with bulimia nervosa

Data from a family study of psychiatric disorders showed higher rates of major affective disorders, eating disorders, and alcoholism in first-degree relatives of 40 bulimic probands than in first-degree relatives of 24 control subjects. More importantly, the data showed higher rates of major affective disorders in relatives of bulimic probands who themselves had no history of major affective disorders than in relatives of control subjects. This significant finding indicates a familial relationship between bulimia nervosa and major affective disorders, which suggests the possibility of a common diathesis.     

The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study.

BACKGROUND: Obsessive-compulsive disorder (OCD) and tic disorders have phenomenological and familial-genetic overlaps. An OCD family study sample that excludes Tourette's syndrome in probands is used to examine whether tic disorders are part of the familial phenotype of OCD. METHODS: Eighty case and 73 control probands and their first-degree relatives were examined by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. DSM-IV psychiatric diagnoses were ascertained by a best-estimate consensus procedure. The prevalence and severity of tic disorders, age-at-onset of OCD symptoms, and transmission of OCD and tic disorders by characteristics and type of proband (OCD + tic disorder, OCD - tic disorder) were examined in relatives. RESULTS: Case probands and case relatives had a greater lifetime prevalence of tic disorders compared to control subjects. Tic disorders spanning a wide severity range were seen in case relatives; only mild severity was seen in control relatives. Younger age-at-onset of OCD symptoms and possibly male gender in case probands were associated with increased tic disorders in relatives. Although relatives of OCD + tic disorder and OCD - tic disorder probands had similar prevalences of tic disorders, this result is not conclusive. CONCLUSIONS: Tic disorders constitute an alternate expression of the familial OCD phenotype.     

The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study.

BACKGROUND: The familial relationship between obsessive-compulsive disorder (OCD) and "obsessive-compulsive spectrum" disorders is unclear. This study investigates the relationship of OCD to somatoform disorders (body dysmorphic disorder [BDD] and hypochondriasis), eating disorders (e.g., anorexia nervosa and bulimia nervosa), pathologic "grooming" conditions (e.g., nail biting, skin picking, trichotillomania), and other impulse control disorders (e.g., kleptomania, pathologic gambling, pyromania) using blinded family study methodology. METHODS: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives, were examined by psychiatrists or Ph.D. psychologists using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. Two experienced psychiatrists independently reviewed all diagnostic information and made final consensus diagnoses using DSM-IV criteria. RESULTS: Body dysmorphic disorder, hypochondriasis, any eating disorder, and any grooming condition occurred more frequently in case probands. In addition, BDD, either somatoform disorder, and any grooming condition occurred more frequently in case relatives, whether or not case probands also had the same diagnosis. CONCLUSIONS: These findings indicate that certain somatoform and pathologic grooming conditions are part of the familial OCD spectrum. Though other "spectrum" conditions may resemble OCD, they do not appear to be important parts of the familial spectrum.     

Familial psychiatric illness and posttraumatic stress disorder: findings from a family study of substance abuse and anxiety disorders.

BACKGROUND: Aside from the possibility of a direct relationship between individual and familial posttraumatic stress disorder (PTSD), there is accumulating evidence that implicates a family history of psychiatric and substance use disorders as an important risk factor in the development of PTSD and associated symptoms. METHOD: The familial risk of DSM-III-R PTSD was examined within a family study of clinical- and community-ascertained probands (N = 263) and their 1206 adult first-degree relatives. RESULTS: Although PTSD among probands was not found to significantly elevate the risk of PTSD among first-degree relatives, an elevated rate of PTSD was found among the relatives of drug abusing probands compared with the relatives of probands with alcoholism, other anxiety disorders, and normal controls. Additionally, affective disorders were significantly associated with PTSD in relatives (p < .01). When these familial and individual associations were examined according to gender, drug disorders in probands were significantly associated with PTSD only among male relatives (p < .01), while the association between PTSD and comorbid affective disorders was seen primarily among female relatives (p < .01). CONCLUSION: Although probands in the present family study were not selected specifically for PTSD, the data afforded a unique opportunity to examine the profile of familial psychopathology as a part of the complex picture of susceptibility for PTSD. Future family study research will be able to determine the generalizability of the present findings through more complete measurement of diverse forms of trauma.     

Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients

To evaluate whether probands from a clinical sample diagnosed as having DSM-III schizotypal and/or paranoid personality disorder have a familial relationship to the schizophrenia-related disorders, the morbid risk for schizophrenia-related disorders and other psychiatric disorders were evaluated in the first-degree relatives of patients with schizotypal and/or paranoid personality disorder and compared with the corresponding risk for these disorders in the first-degree relatives of patients with other non-schizophrenia-related personality disorders. The morbid risk for all schizophrenia-related disorders, and specifically for schizophrenia-related personality disorders, was significantly greater among the relatives of the probands with schizotypal and/or paranoid personality disorder than among the relatives of probands with other personality disorder. The morbid risk for other psychiatric disorders did not differ significantly between the first-degree relatives of the schizotypal/paranoid personality disorder and the other personality disorder control proband samples. These results suggest a specific familial association between schizophrenia-related disorders, particularly schizophrenia-related personality disorders, and clinically diagnosed schizotypal patients.     

Affective and impulsive personality disorder traits in the relatives of patients with borderline personality disorder

OBJECTIVE: This study tested the hypothesis that the risk for affective and impulsive personality disorder traits commonly found in patients with borderline personality disorder would be greater in the first-degree relatives of probands with borderline personality disorder than in two comparison groups. METHOD: Blind family history interviews were conducted with family informants to assess the extent to which first-degree relatives of 29 probands with borderline personality disorder, 22 probands with other personality disorders who met three or fewer of the criteria for borderline personality disorder, and 43 probands with schizophrenia fulfilled operationalized criteria for the two kinds of personality disorder traits and for other diagnostic categories. The crude proportions of adult relatives with each diagnosis, as well as the age-adjusted morbid risks, were assessed in the three groups of relatives. RESULTS: The risks for affective and impulsive personality disorder traits were independently greater in the 129 relatives of the borderline probands than in the 105 relatives of the probands with other personality disorders and the 218 relatives of the schizophrenic probands. There was no similarly greater risk for any other psychiatric disorder assessed, including major affective disorder. In addition, the relatives of borderline probands with current or past major depressive disorder showed a greater risk for major affective disorders than the relatives of never-depressed probands with other personality disorders but not the relatives of never-depressed borderline probands. CONCLUSIONS: These results suggest familial transmission of the hallmark borderline-related personality characteristics and raise the possibility that these familial traits may be partially independent.     

A blind re-analysis of the Iowa family study of obsessive-compulsive disorder

We present results from a re-analysis of the Iowa family study of obsessive-compulsive disorder (OCD) that previously concluded the disorder was not familial. These conclusions were based on Diagnostic Interview Schedule results of first-degree relatives (FDRs) and not a best estimate diagnosis (BED). For the re-analysis we reviewed raw data on OCD and control probands and their FDRs. Relatives had been assessed through structured interviews, validated questionnaires, family history, and medical records in some cases. BEDs were assigned through a blind consensus procedure employing DSM-IV criteria. The data were analyzed using logistic regression with generalized estimating equations to account for within family correlations. BEDs were assigned to 32 OCD probands, 31 control probands, and 352 FDRs, including 249 FDRs who were interviewed directly and 103 FDRs who were unavailable or deceased. Lifetime prevalence of definite/probable OCD was significantly higher in the FDRs of OCD probands than controls (10.7% vs. 3.8%, OR=3.04, p=0.026). FDRs of OCD probands had significantly higher rates of depressive illness than relatives of controls. Depression of any type in relatives was predicted by the proband's depression history. We conclude that OCD is familial. The re-analysis highlights the importance of the BED procedure in family studies.     

Prävalenz von Essstörungen unter Studierenden

A sample of 507 social work students completed the Bulimic Investigatory Test Edinburgh (BITE). Simulating diagnoses according to DSM-IV criteria, we found three women suffering from bulimia nervosa (BN). This represents a total prevalence of 0.6%, 0.8% in women, and 0.9% in female probands up to the age of 30 years. In the same way, we identified one case of anorexia nervosa (AN), i.e. a total prevalence of 0.2%, 0.3% in women, and 0.3% in female probands up to the age of 30. Nineteen students also fulfilled DSM-IV research criteria for binge-eating disorder (BED), showing a total prevalence of 3.7%, 3.8% in women, 3.5% in men, and 4.3% in female probands up to the age of 30. Thus, BED is the most common eating disorder and also occurs in men. In light of the association between weight discontent and eating disorders, suggestions are made for the management of overweight patients and both normal and underweight clients with eating disorders.     

Family study of affective spectrum disorder

BACKGROUND: Affective spectrum disorder (ASD) represents a group of psychiatric and medical conditions, each known to respond to several chemical families of antidepressant medications and hence possibly linked by common heritable abnormalities. Forms of ASD include major depressive disorder (MDD), attention-deficit/hyperactivity disorder, bulimia nervosa, cataplexy, dysthymic disorder, fibromyalgia, generalized anxiety disorder, irritable bowel syndrome, migraine, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social phobia. Two predictions of the ASD hypothesis were tested: that ASD, taken as a single entity, would aggregate in families and that MDD would coaggregate with other forms of ASD in families. METHODS: Probands with and without MDD, together with their first-degree relatives, were interviewed using the Structured Clinical Interview for DSM-IV and a supplemental interview for other forms of ASD. The familial aggregation and coaggregation of disorders were analyzed using proband predictive logistic regression models, including a novel bivariate model for the presence or absence of each of 2 disorders in a relative as predicted by the presence or absence of each of 2 disorders in the associated proband. RESULTS: In the 178 interviewed relatives of 64 probands with MDD and 152 relatives of 58 probands without MDD, the estimated odds ratio (95% confidence interval) for the familial aggregation of ASD as a whole was 2.5 (1.4-4.3; P =.001) and for the familial coaggregation of MDD with at least one other form of ASD was 1.9 (1.1-3.2; P =.02). CONCLUSIONS: Affective spectrum disorder aggregates strongly in families, and MDD displays a significant familial coaggregation with other forms of ASD, taken collectively. These results suggest that forms of ASD may share heritable pathophysiologic features.