Family study of fibromyalgia and affective spectrum disorder.

BACKGROUND: Fibromyalgia is one member of a proposed group of psychiatric and medical disorders, collectively termed affective spectrum disorder (ASD), hypothesized to share possibly heritable pathophysiologic features. Two predictions of the ASD hypothesis were tested: ASD, taken as a single entity, aggregates in families; and fibromyalgia coaggregates with other forms of ASD in families. METHODS: Probands with and without fibromyalgia, together with their first-degree relatives, were administered structured diagnostic interviews. Noninterviewed relatives were diagnosed according to information provided by interviewed relatives. Aggregation and coaggregation of disorders were analyzed with proband predictive logistic and linear regression models. RESULTS: In 533 relatives of 78 probands with fibromyalgia and 272 relatives of 40 probands without fibromyalgia, the estimated odds ratio (OR) (95% confidence interval) for the familial aggregation of ASD was 1.8 (.97, 3.2), p = .065, and the increase in number of forms of ASD in a relative for each additional form of ASD in a proband was .076 (.027, .1240), p = .002. The OR for the coaggregation of fibromyalgia with other forms of ASD was 2.0 (1.2, 3.2), p = .004; this remained significant even after excluding all mood-disorder diagnoses: 1.8 (1.1, 3.0), p = .012. CONCLUSIONS: These findings support familial aggregation of ASD collectively and familial coaggregation of fibromyalgia with other forms of ASD.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Familial aggregation of delusional depression: Re-examination in a recent family study

Background: Delusional (D-MDD) and nondelusional depression (ND-MDD) differ in clinical presentation, biological abnormalities, course of illness, and treatment response. Family data, however, have been less consistent regarding differential risk both for any major depression (MDD) and specifically D-MDD in relatives of D-MDD probands. In an earlier family study, we observed a 1.5-fold increase in rates of any MDD, specificity of transmission of D-MDD, and increased rates of bipolar disorders in relatives of D-MDD compared to relatives of ND-MDD probands. In a new family study, we attempted to replicate these findings. Method: A family study of 361 directly interviewed adult first-degree relatives (FDRs) of 163 probands (118 with MDD and 45 screened normal controls) was used to examine familial aggregation of any MDD, D-MDD, and bipolarity by proband delusional status. Results: Compared to FDRs of ND-MDD probands, FDRs of D-MDD probands were at modestly increased risk for any MDD. These results were unaffected by adjustment for proband ascertainment source, comorbidity, or whether probands had chronologically primary MDD. There was a trend toward increased rates of broadly defined bipolarity (bipolar I, bipolar II, or cyclothymia) in FDRs of D-MDD compared to FDRs of ND-MDD probands. Conclusion: Results from the present study were broadly consistent with those from our previous work. While other lines of evidence for D-MDD as a distinct subtype are more compelling than family data, it would be of methodologic interest to identify sources of inconsistency across studies in findings concerning the familial aggregation of delusional depression. Depression and Anxiety 8:160–165, 1998. © 1998 Wiley-Liss, Inc.     

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.     

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.     

Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands

Objective: This study examined the comorbidity of obsessive–compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. Method: This study assessed the lifetime prevalence of MDD in 141 first‐degree relatives (FDR) and 452 second‐degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best‐estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Results: Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). Conclusions: MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest.     

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.     

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.     

Revisiting the association between attention-deficit/hyperactivity disorder and anxiety disorders: a familial risk analysis.

BACKGROUND: This study tested competing hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders using familial risk analysis methodology. METHODS: The risk for ADHD and anxiety disorders in first-degree relatives was examined after stratifying ADHD probands by the presence or absence of comorbid anxiety disorders. The presence of anxiety disorders in probands and relatives was defined as meeting DSM-III-R diagnostic criteria for > or = 2 anxiety syndromes in the same subject. RESULTS: Familial risk analyses revealed that 1) the risk for anxiety disorders was significantly higher in ADHD probands and their relatives than in control probands and their relatives; 2) the risk for anxiety disorders among the relatives of ADHD probands was limited to those families in which the proband had a diagnosis of ADHD; 3) the risk for anxiety disorders was significantly higher among the relatives of ADHD probands with anxiety disorders than in relatives of ADHD probands without anxiety disorders, but these two groups did not differ in the familial risk for ADHD; and 4) ADHD and anxiety disorders did not cosegregate within families, and there was no evidence for nonrandom (assortative) mating. CONCLUSIONS: These findings are most consistent with the hypothesis that ADHD and anxiety disorders segregate independently in families.     

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.     

A family study of major depressive disorder in a community sample of adolescents

BACKGROUND: Family studies provide a useful approach to exploring the continuities and discontinuities between major depressive disorder (MDD) in children and adolescents and MDD in adults. We report a family study of MDD in a large community sample of adolescents. METHODS: Probands included 268 adolescents with a history of MDD, 110 adolescents with a history of nonmood disorders but no history of MDD through age 18 years, and 291 adolescents with no history of psychopathology through age 18 years. Psychopathology in their 2202 first-degree relatives was assessed with semistructured direct and family history interviews, and best-estimate diagnoses were derived with the use of all available data. RESULTS: The relatives of adolescents with MDD exhibited significantly elevated rates of MDD (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.46-2.31), dysthymia (HR, 1.79; 95% CI, 1. 11-2.87), and alcohol abuse or dependence (HR, 1.29; 95% CI, 1.05-1. 53), but not anxiety disorders, drug abuse or dependence, or antisocial and borderline personality disorder. In contrast, anxiety, substance use, and disruptive behavior disorders in adolescents were not associated with elevated rates of MDD in relatives. However, the relatives of probands with anxiety and substance use disorders exhibited elevated rates of anxiety and substance use disorders, respectively. CONCLUSIONS: The results provide evidence of the familial aggregation of adolescent MDD, and also indicate that there is a considerable specificity in the pattern of familial transmission. In addition, we found preliminary evidence of the familial aggregation of adolescent anxiety and substance use disorders.     

Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives

BACKGROUND: Brain function, as indexed by brain electrical activity, is heritable in humans, and it may be impaired in autism. Autism also has strong genetic determinants, and like all major psychiatric disorders, its complex clinical phenotype renders genetic studies difficult. Innovative strategies focused on alternative biological phenotypes are needed. METHODS: The early brain auditory-evoked response was assessed in 73 autistic probands and 251 relatives who were compared with 521 normal controls. RESULTS: We first confirmed in the autistic probands the presence of a slowing in nerve conduction in the auditory system as expressed by the prolongation of early brain auditory-evoked response under the form of I-III interpeak latencies (IPLs). Furthermore, we observed the same I-III IPL prolongation in the unaffected first degree relatives of the autistic probands compared with controls. Despite clear evidence of a coaggregation of autism and I-III IPL prolongation in families, the IPLs did not seem to be the sole liability factor for autism as suggested by the observation of 52% of families in which the autistic proband and relatives showed normal IPLs. CONCLUSION: A prolongation of the early brain auditory-evoked response IPLs may be a marker for one of several deficits underlying autism and deserves further analysis as a potential alternative phenotype for the disorder.     

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.     

Association of bipolar and substance use disorders in parents of adolescents with bipolar disorder.

BACKGROUND: We have previously shown that juvenile bipolar disorder (BPD) is a risk for substance use disorders (SUD). Here we examine the expression of both disorders in families of youth with BPD to evaluate the familial risk mechanism. METHODS: We studied 108 adolescent BPD probands with 187 parents (34 with SUD and 58 parents) and 96 control probands with 177 parents with structured interviews. We compared the prevalence of BPD and SUD with Cox proportional hazards models with time to onset of BPD or SUD as the dependent variable and proband diagnosis (Control, BPD, or BPD+SUD) as the independent variable. RESULTS: The parents of the proband youth with BPD (without SUD) and BPD+SUD were more likely to develop BPD than the parents of control subjects [omnibus test chi2=10.18, p=.006]; we found no differences between the two bipolar groups. Parents of proband youth with BPD and with BPD+SUD were more likely than relatives of control subjects to develop SUD [omnibus test chi2=14.69, p<.001]; however, we found no differences between the parents of the two proband bipolar groups. Within the parents of proband youth with BPD+SUD, we found higher risk of SUD in parents with BPD than in those without BPD [chi2=8.39, p=.004], although the frequency of BPD was low in this group of parents. CONCLUSIONS: Bipolar disorder and SUD are prevalent in the first-degree relatives of adolescents with BPD. Adults with BPD were more likely to manifest SUD with preliminary evidence of BPD and SUD cosegregation.     

Specificity of familial transmission of anxiety and comorbid disorders

This study examines the specificity and impact of comorbid disorders in probands on the familial transmission of panic and social anxiety disorders. It employs a contemporary family study design with 225 probands (with and without panic and social anxiety disorders) sampled from outpatient clinics and the local community. Their 1053 adult first-degree relatives were assessed for lifetime disorders, based on best estimate diagnoses derived from semi-structured psychiatric diagnostic interviews (Schedule for Affective Disorders and Schizophrenia), multi-informant family history information, and medical records. Generalized estimating equations were used to examine the familial aggregation of panic and social anxiety disorders, and the contributions of comorbid disorders. Results show specificity of familial aggregation of both panic disorder and social anxiety in probands and relatives (i.e., panic odds ratio=3.7, 95%CI 1.5-9.3; social anxiety odds ratio=1.8, 95%CI 1.1-2.9) after controlling for comorbid disorders. There was no contribution of common comorbid disorders (depression, alcoholism, generalized anxiety disorder and agoraphobia) in probands on the familial aggregation of either disorder. These findings confirm prior studies of specificity of familial transmission of panic and social anxiety disorders, and demonstrate that the association between these disorders in probands is not attributable to comorbid mood, anxiety or substance use disorders. Therefore, despite the high magnitude of co-occurrence of panic disorder and social anxiety, there may be distinct etiologic factors underlying each disorder. These findings have implications for studies of the etiology, genetics, and treatment of these disorders.     

Familial association between attention deficit disorder and anxiety disorders

BACKGROUND AND METHOD: This study tested hypotheses about patterns of familial association between attention deficit disorder (ADD) and anxiety disorders among 356 first-degree relatives of 73 clinically referred children with ADD and 26 normal comparison children. Through structured diagnostic interviews with trained raters, relatives were assessed for adult and childhood psychopathology. After stratifying the sample of ADD probands into those with anxiety disorders and those without, the authors examined patterns of aggregation of ADD and anxiety disorders in the relatives of these probands as well as in the relatives of the normal comparison subjects. RESULTS: Familial risk analyses revealed that 1) familial risk for anxiety disorders was higher among all ADD probands than among the normal subjects; 2) familial risk for ADD was similar in the relatives of the ADD probands and of the probands with ADD and anxiety disorder; 3) the relatives of the ADD probands with and without anxiety disorders were at greater risk for ADD than the relatives of the normal subjects; 4) the risk for anxiety disorders was two times higher in the relatives of the probands who had ADD with anxiety disorder than in those of the ADD probands without anxiety disorders; and 5) there was a tendency for ADD probands' relatives who themselves had ADD to have a higher risk for anxiety disorders than ADD probands' relatives who did not have ADD (cosegregation). CONCLUSIONS: The results were most consistent with the hypotheses indicating that ADD and anxiety disorders segregate independently in families.     

Attention-deficit disorder and conduct disorder in girls: evidence for a familial subtype.

BACKGROUND: The frequent comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) raises the possibility that ADHD+CD is a distinct and separate condition. METHODS: We tested hypotheses about patterns of familial association between ADHD, CD, oppositional defiant disorder (ODD) and adult antisocial personality disorder (ASPD). Using family study methodology in a sample of girls, we found 11 children with diagnoses of ADHD+ CD, 39 with ADHD+ODD, and 90 with ADHD only. These were compared with 122 non-ADHD, non-CD control probands. Familial risk analysis was utilized. RESULTS: Relatives of each ADHD proband subgroup were at significantly greater risk for ADHD, and the relatives of ADHD-only subjects were at a greater risk of ODD than relatives of control subjects. Also, rates of CD were elevated among relatives of ADHD+CD probands only, and the coaggregation of ADHD and the antisocial disorders could not be accounted for by marriages between ADHD and antisocial spouses. Both ADHD and antisocial disorders occurred in the same relatives more often than expected by chance. CONCLUSIONS: These findings suggest that ADHD with and without antisocial disorders may be etiologically distinct disorders and provide evidence for the nosologic validity of ICD-10 hyperkinetic conduct disorder.     

Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples.

We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 first-degree relatives using "blind" raters and structured diagnostic interviews. Compared with controls, probands with attention deficit hyperactivity disorder were more likely to have conduct, mood, and anxiety disorders. Compared with relatives of controls, relatives of probands with attention deficit hyperactivity disorder had a higher risk for attention deficit hyperactivity disorder, antisocial disorders, major depressive disorder, substance dependence, and anxiety disorders. Patterns of comorbidity indicate that attention deficit hyperactivity disorder and major depressive disorders may share common familial vulnerabilities, that attention deficit hyperactivity disorder plus conduct disorder may be a distinct subtype, and that attention deficit hyperactivity disorder and anxiety disorders are transmitted independently in families. These results extend previous findings indicating family-genetic influences in attention deficit hyperactivity disorder by using both pediatrically and psychiatrically referred proband samples. The distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficit hyperactivity disorder by comorbidity.     

Family study of girls with attention deficit hyperactivity disorder

OBJECTIVE: Because attention deficit hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the causes of ADHD in girls. To help fill this gap in the literature, the authors assessed the familial transmission of ADHD in families ascertained through girls.METHOD: Interviewers who were blind to diagnosis administered structured psychiatric interviews to 140 girls with ADHD and their 417 first-degree relatives and to 122 girls without ADHD and their 369 first-degree relatives.RESULTS: The relatives of the ADHD girls had a significantly higher prevalence of ADHD, according to either the DSM-III-R or DSM-IV definition, than the relatives of the comparison girls. However, this did not differ from the prevalence the authors reported previously for families of boys with ADHD. Like the boys' families, the relatives of the girl probands also had significantly higher prevalences of antisocial, mood, anxiety, and substance use disorders, although the prevalence of familial antisocial disorders was lower than had been observed in the boys' families. There was no association between the DSM-IV subtypes of the probands and relatives.CONCLUSIONS: The familial transmission of ADHD and comorbid disorders generalizes to families of girls with ADHD. Neither proband gender nor subtype influences the familial transmission of ADHD.