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.     

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.     

Separating attention deficit hyperactivity disorder and learning disabilities in girls: a familial risk analysis

OBJECTIVE: Familial risk analysis was used to clarify the relationship in girls between attention deficit hyperactivity disorder (ADHD) and learning disabilities in either mathematics or reading. METHOD: The authors assessed the presence of ADHD and learning disabilities in 679 first-degree relatives of three groups of index children: girls with ADHD and a comorbid learning disability, girls with ADHD but no learning disabilities, and a comparison group of girls without ADHD. RESULTS: The risk for ADHD was similarly higher in families of ADHD probands with and without learning disabilities; both groups had significantly higher rates of ADHD than did families of the comparison girls. In contrast, only among relatives of ADHD probands with a learning disability was there a higher risk for learning disabilities. A strong (although statistically nonsignificant) difference emerged that suggested at least some degree of cosegregation of ADHD and learning disabilities in family members. There was no evidence of nonrandom mating between spouses with ADHD and learning disabilities. CONCLUSIONS: These results extend previously reported findings regarding the relationship of ADHD and learning disabilities to female subjects and raise the possibility that, in girls, the relationship between ADHD and learning disabilities is due to shared familial risk factors.     

The influence of gender in the familial association between ADHD and major depression

This study estimated the impact of gender on the familial associations between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD). The risk for ADHD and MD in first degree relatives was stratified by the presence of MD in boy and girl ADHD probands. In families ascertained via boy probands, the risk for MD was greater in the relatives of both the depressed ADHD and nondepressed ADHD probands. In families ascertained via girl probands, there was cosegregation and the risk of MD was greater only for those relatives of depressed ADHD probands. The results indicate that there may be two mechanisms underlying MD in ADHD families: 1) an etiologically distinct familial subtype of ADHD and MD that is more evident in females, and 2) a familial, gender-specific susceptibility to nonfamilial risk factors that mediate the onset of either ADHD or MD in males and females.     

A Pilot Controlled Family Study of DSM-III-R and DSM-IV ADHD in African-American Children

BackgroundVery little is known about attention-deficit hyperactivity disorder (ADHD) in African-American children, and although the familial transmission of ADHD has been well established in white samples, prior work has not evaluated this feature of ADHD in African-American families.MethodSubjects were 37 first-degree relatives of children with DSM-III-R-defined ADHD and 52 first-degree relatives of non-ADHD comparison children matched for ethnicity, age, and gender. DSM-III-R-based structured interviews (modified to include DSM-IV diagnoses) provided the basis for psychiatric diagnoses in relatives.ResultsThe risks for both DSM-III-R and DSM-IV ADHD were significantly greater in first-degree relatives of ADHD probands than in relatives of controls. In addition, the relatives of ADHD probands also were at higher risk for oppositional defiant disorder, antisocial personality disorder, major depression, generalized anxiety, and substance use disorders.ConclusionsThese results suggest that ADHD and related disorders are familial in African-Americans. Further work is needed to confirm the familial transmission of ADHD in African-American children and to explore the role of genetics as well as environmental factors in the transmission of the disorder. J. Am. Acad. Child Adolesc. Psychiatry, 1999, 38(1):034–39.     

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.     

Familial risk analyses of attention deficit hyperactivity disorder and substance use disorders

OBJECTIVE: A robust and bidirectional comorbidity between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (alcohol or drug abuse or dependence) has been consistently reported in the extant literature. METHOD: First-degree relatives from a large group of pediatrically and psychiatrically referred boys with (112 probands, 385 relatives) and without (105 probands, 358 relatives) ADHD were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first-degree relatives for ADHD, psychoactive substance use disorder, alcohol dependence, and drug dependence after stratifying probands by the presence and absence of these disorders. RESULTS: ADHD in the proband was consistently associated with a significant risk for ADHD in relatives. Drug dependence in probands increased the risk for drug dependence in relatives irrespective of ADHD status, whereas alcohol dependence in relatives was predicted only by ADHD probands with comorbid alcohol dependence. In addition, ADHD in the proband predicted drug dependence in relatives, and drug dependence in comparison probands increased the risk for ADHD in relatives. Both alcohol dependence and drug dependence bred true in families without evidence for a common risk between these disorders. CONCLUSIONS: Patterns of familial risk analysis suggest that the association between ADHD and drug dependence is most consistent with the hypothesis of variable expressivity of a common risk between these disorders, whereas the association between ADHD and alcohol dependence is most consistent with the hypothesis of independent transmission of these disorders. Findings also suggest specificity for the transmission of alcohol and drug dependence.     

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.     

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.     

A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. METHODS: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. RESULTS: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. CONCLUSIONS: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.     

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.     

Examining the association between attention deficit hyperactivity disorder and substance use disorders: A familial risk analysis

ObjectiveThe main aim of this study was to use familial risk analysis to examine the association between attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) attending to sex effects and the specificity of alcohol and drug use disorder risks.MethodsSubjects were derived from two longitudinal case-control family studies of probands aged 6–17 years with and without DSM-III-R ADHD of both sexes and their first degree relatives followed from childhood onto young adult years. Cox proportional hazard models were used to estimate rates of ADHD and SUDs (any SUD, alcohol dependence, and drug dependence). Logistic regression was used to test both co-segregation and assortative mating.ResultsOur sample included 404 probands (ADHD: 112 boys and 96 girls; Control: 105 boys and 91 girls) and their 1336 relatives. SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status. The risk for dependence to drug or alcohol in relatives was non-specific. There was evidence that even in the absence of a SUD in the proband, ADHD by itself increased the risk of SUDs in relatives. Proband sex did not moderate the familial relationship between ADHD and SUDs. There was evidence of co-segregation between ADHD and SUD.ConclusionsFindings indicate that various independent pathways are involved in the transmission of SUD in ADHD and that these risks were not moderated by proband sex. ADHD children and siblings should benefit from preventive and early intervention strategies to decrease their elevated risk for developing a SUD.     

Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: a family study perspective

OBJECTIVE: To test the hypothesis that the clinical severity of subtypes paralleled a gradient of familial severity. METHOD: One hundred forty children with attention-deficit/hyperactivity disorder (ADHD) and 120 normal control children and their biological relatives were studied: Because these data had been collected prior to the publication of DSM-IV, DSM-III-R symptoms were used to approximate DSM-IV subtypes using a method the authors had validated in prior work. RESULTS: The first prediction from the hypothesis was true: rates of ADHD among relatives of each subtype group were greater than rates among relatives of controls. But the second prediction did not hold: rates of ADHD were not significantly higher among relatives of combined-typed probands compared with relatives of other probands. The "gradient model" also predicted that subtypes would not "breed true" (i.e., the subtype of the relative would not be the same as that of the proband). The prediction of nonspecificity was refuted for the inattentive and combined subtypes, but hyperactive-impulsive ADHD was found almost exclusively among relatives of hyperactive-impulsive probands. CONCLUSIONS: Although the results are limited by some small subsamples along with the use of a DSM-III-R-ascertained sample, they provide little evidence for the idea that DSM-IV subtypes of ADHD correspond to familially distinct conditions. They also do not confirm the idea that the subtypes fall along a gradient of familial severity. Instead, they suggest that symptom differences among subtypes are due to nonfamilial, environmental causes.     

Parsing the familiality of oppositional defiant disorder from that of conduct disorder: a familial risk analysis

Background

Family risk analysis can provide an improved understanding of the association between attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), attending to the comorbidity with conduct disorder (CD).

Methods

We compared rates of psychiatric disorders in relatives of 78 control probands without ODD and CD (Control, N = 265), relatives of 10 control probands with ODD and without CD (ODD, N = 37), relatives of 19 ADHD probands without ODD and CD (ADHD, N = 71), relatives of 38 ADHD probands with ODD and without CD (ADHD + ODD, N = 130), and relatives of 50 ADHD probands with ODD and CD (ADHD + ODD + CD, N = 170).

Results

Rates of ADHD were significantly higher in all three ADHD groups compared to the Control group, while rates of ODD were significantly higher in all three ODD groups compared to the Control group. Evidence for co-segregation was found in the ADHD + ODD group. Rates of mood disorders, anxiety disorders, and addictions in the relatives were significantly elevated only in the ADHD + ODD + CD group.

Conclusions

ADHD and ODD are familial disorders, and ADHD plus ODD outside the context of CD may mark a familial subtype of ADHD. ODD and CD confer different familial risks, providing further support for the hypothesis that ODD and CD are separate disorders.     

Evidence of familial association between attention deficit disorder and major affective disorders

With the use of family study methods and assessments by "blinded" raters, we tested hypotheses about patterns of familial association between DSM-III attention deficit disorder (ADD) and affective disorders (AFFs) among first-degree relatives of clinically referred children and adolescents with ADD (73 probands, 264 relatives) and normal controls (26 probands, 92 relatives). Among the 73 ADD probands, 24 (33%) met criteria for AFFs (major depression, n = 15 [21%]; bipolar disorder, n = 8 [11%]; and dysthymia, n = 1 [1%]). After stratification of the ADD sample into those with AFFs (ADD + AFF) and those without AFF (ADD), familial risk analyses revealed the following: (1) the relatives of each ADD proband subgroup were at significantly greater risk for ADD than were relatives of normal controls; (2) the age-corrected morbidity risk for ADD was not significantly different between relatives of ADD and ADD + AFF (27% vs 22%); however, these two risks were significantly greater than the risk to relatives of normal controls (5%); (3) the risk for any AFF (bipolar disorder, major depressive disorder, or dysthymia) was not significantly different between relatives of ADD probands and ADD + AFF probands (28% and 25%), but these two risks were significantly greater than the risk to relatives of normal controls (4%); (4) ADD and AFFs did not cosegregate within families; and (5) there was no evidence for nonrandom mating. These findings are consistent with the hypothesis that ADD and AFFs may share common familial vulnerabilities.     

Family aggregation of mental disorders in the nationwide Danish three generation study

Objective  The study of familial aggregation of major mental disorders in a national population. Method  Within a Danish register-based cohort study, aggregation of mental disorders was analysed in all case-probands with first psychiatric contact before the age of 19 years in the time period between 1 April 1969 and 29 June 2004 followed up until the age of 35 years, their first-degree relatives, and a matched group of control-probands including their first-degree relatives. Results  Hazard rate ratios were significantly elevated for cases as compared to controls for all diagnoses among probands, parents, and siblings. Among children of the probands, these ratios were significantly elevated for neurotic (anxiety) disorders, mental retardation, developmental disorders, behavioural and emotional disorders of childhood and adolescence, and miscellaneous disorders. Family aggregation of any diagnosis was significantly higher in probands with substance use disorder, schizophrenia, affective disorders, neurotic (anxiety) disorders, and miscellaneous disorders. There was specificity of familial transmission for affective and neurotic (anxiety) disorders. Conclusion  This large nationwide study found some differential patterns of familial aggregation of major mental disorders.     

Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: a familial risk analysis.

BACKGROUND: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. METHODS: We assessed for ADHD and OCD in the 1533 first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. RESULTS: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p = .91), and both groups had significantly higher rates of ADHD compared with controls (4.6%; p < or = .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0%) compared with controls (.5%; p < or = .001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a significantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 1.3%; p < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. CONCLUSIONS: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype.     

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.     

Increased risk of ADHD in families with ASD

Attention Deficit and Hyperactive Disorder (ADHD) and Autism Spectrum Disorders (ASD) are frequent comorbid neurodevelopmental conditions and the overlap between both disorders remains to be delineated. A more complete understanding of the shared genetic and environmental factors is needed. Using a family-based method, we evaluated the risk of ADHD in a group of relatives with an ASD proband (ASD−) and a group of relatives with an ASD and ADHD proband (ASD+). We enrolled 1245 individuals in the study: 499 probands, their 746 first-degree relatives and 140 controls. We used a multivariate generalized estimating equation (GEE) model, in which the dependent variable was the ADHD diagnosis in the relatives and the independent variable the ASD+ or ASD− in probands. We adjusted for sociodemographic factors (age, sex, IQ) and for the nature of the familial relationship with the affected proband (parent or sibling). Among the probands, there were 287 ASD− and 212 ASD+ individuals. ADHD was more frequent in relatives (19%) than in the control group (7%) (p = 0.001). The risk of ADHD was higher in the ASD+ relatives group than in the ASD− relatives group (GEE model OR 1.58 [95% CI 1.04–2.38], p = 0.032). This result was found in parents (OR 1.96 [95% CI  1.14–3.36], but not in siblings (OR 1.28 [95% CI 0.84–1.94], p = 0.434). Our study provides a representative estimate of the family distribution of ADHD in relatives of ASD probands but supports the modest effect of shared genetic and environmental factors between both disorders.

     

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.