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.     

Psychopathology and substance abuse in parents of young children with attention-deficit/hyperactivity disorder

OBJECTIVE: To compare the prevalence of psychological disorders in parents of young children with and without attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behavior disorders (DBD). METHOD: Subjects included 98 three- to seven-year-old children with DSM-IV ADHD (68 with ADHD and comorbid oppositional defiant or conduct disorder [ADHD+ODD/CD]) and 116 non-ADHD comparison children recruited in 1995-96 during the first wave of a longitudinal study. Biological mothers were administered interviews to assess ADHD and DBD in their children and mood, anxiety, and substance use disorders in themselves. In addition, they were queried about symptoms of childhood ADHD and DBD, and antisocial personality disorder in themselves and their children's biological fathers. RESULTS: Child ADHD was associated with increased rates of maternal and paternal childhood ADHD relative to comparison children. Child ADHD+ODD/CD was associated with maternal mood disorders, anxiety disorders, and stimulant/cocaine dependence, and paternal childhood DBD. Mothers of children with ADHD+ODD/CD also reported increased drinking problems in their children's fathers. CONCLUSIONS: These findings indicate that many young children with ADHD, particularly those with comorbid ODD/CD, require comprehensive services to address both their ADHD and the mental health needs of their parents.     

Patterns of psychiatric comorbidity with attention-deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is frequently comorbid with a variety of psychiatric disorders. These disorders include oppositional defiant (ODD) and conduct disorders (CD), and affective, anxiety, and learning disorders. Studies which have examined the comorbidity of these disorders with ADHD are reviewed. ADHD and ADHD with CD seem to be distinct subtypes; children with ADHD/CD are at higher risk of antisocial personality as adults. Coexisting anxiety may attenuate impulsivity in ADHD. Studies examining stimulant response in children with ADHD/anxiety have recently yielded conflicting results. Anxiety and ADHD seem to be inherited independently. The prevalence of major depressive disorder (MDD) and bipolar disorder among children with ADHD is controversial, but there clearly exists a subgroup of severely emotionally labile children with ADHD who present serious management issues for the clinician. About 20% to 25% of children with ADHD meet criteria for a learning disorder (LD), but LD seems to be independent of ADHD.     

Lifetime criminality among boys with attention deficit hyperactivity disorder: a prospective follow-up study into adulthood using official arrest records

This study investigates the relationship between childhood attention deficit hyperactivity disorder (ADHD) and later criminality. White boys (n=207, ages 6-12) with ADHD, free of conduct disorder, were assessed at ages 18 and 25 by clinicians who were blind to childhood status. A non-ADHD group served as comparisons. Lifetime arrest records were obtained when subjects were 38 years old for subjects who resided in New York State throughout the follow-up interval (93 probands, 93 comparisons). Significantly more ADHD probands than comparisons had been arrested (47% vs. 24%), convicted (42% vs. 14%), and incarcerated (15% vs. 1%). Rates of felonies and aggressive offenses also were significantly higher among probands. Importantly, the development of an antisocial or substance use disorder in adolescence completely explained the increased risk for subsequent criminality. Results suggest that even in the absence of comorbid conduct disorder in childhood, ADHD increases the risk for developing antisocial and substance use disorders in adolescence, which, in turn, increases the risk for criminal behavior in adolescence and adulthood.     

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.     

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD‐only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD‐only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ—including 36 boys with ADHD‐only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.     

Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity

CONTEXT: A key question is whether a prepubertal and early-adolescent bipolar I disorder phenotype (PEA-BP-I) is the same illness as adult BP-I. This question arises because of the greater severity, longer current episode duration, preponderance of mania, and high rates of ultradian rapid cycling and comorbid attention-deficit/hyperactivity disorder (ADHD) in PEA-BP-I. OBJECTIVES: To examine morbid risk (MR) of BP-I in first-degree relatives of PEA-BP-I, ADHD, and healthy control probands, as well as imprinting, sibling recurrence risk, and anticipation. DESIGN: Controlled, blind direct interview. There were no family psychopathology exclusions for any proband group. SETTING: University medical school research unit. PARTICIPANTS: First-degree relatives 6 years and older (n = 690) of 219 probands (95 with PEA-BP-I, 47 with ADHD, and 77 healthy controls). The PEA-BP-I and ADHD probands were obtained by consecutive new case ascertainment, and healthy controls were from a random survey; proband diagnoses were validated via 4-year prospective follow-up. The PEA-BP-I probands had a mean +/- SD age of 10.8 +/- 2.6 years.Main Outcome Measure Morbid risk. RESULTS: The MR of BP-I was higher in relatives of PEA-BP-I probands compared with ADHD or healthy controls (P<.001 for both); the MR in relatives of ADHD and healthy controls was similar. The MR of BP-I in relatives with ADHD was higher (P<.001) and age at onset of BP-I was younger in parents with ADHD than in those without (P<.001). The MR of BP-I in relatives with oppositional, conduct, or antisocial disorders was higher than in those without (P<.001). Anticipation was evidenced by a younger age at onset of BP-I in probands than in their parents (P<.001). No imprinting was found. CONCLUSIONS: Findings support that PEA-BP-I and adult BP-I are the same diathesis, 7 to 8x greater familiality in child vs adult BP-I, and family study validation of PEA-BP-I, including its differentiation from ADHD.     

Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis.

BACKGROUND: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders. METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives. CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders.     

Response to emotional stimuli in boys with conduct disorder

OBJECTIVE: Boys with conduct disorder are at risk of persistently showing antisocial behavior in adult life, particularly if they have an additional diagnosis of attention deficit hyperactivity disorder (ADHD). In the search for biological risk factors that predispose children to the development of antisocial personality disorder, research has provided substantial data suggesting that autonomic hyporesponsiveness indicates a greater likelihood of future antisocial behavior. The purpose of this study was to examine autonomic arousal in boys with conduct disorder, comorbid conduct disorder and ADHD, and ADHD only. METHOD: In addition to self-ratings, electrodermal responses to pleasant, neutral, and unpleasant slides were obtained for 21 boys with conduct disorder and 54 boys with ADHD plus conduct disorder. Forty-three boys with a diagnosis of ADHD only were recruited as a clinical comparison group, and 43 boys with no conduct disorder or ADHD were included as a healthy comparison group. All subjects were ages 8-13 years. RESULTS: Compared to the healthy subjects and the subjects with ADHD only, the boys with conduct disorder and with ADHD plus conduct disorder reported lower levels of emotional response to aversive stimuli and lower autonomic responses to all slides independent of valence. CONCLUSIONS: Although the self-report data supported a deficit in reactivity to explicit fear cues, the psychophysiological data indicated that boys with conduct disorder both with and without a comorbid condition of ADHD are characterized by a generalized deficit in autonomic responsivity in an experimental situation in which children were exposed to complex visual stimuli of unpredictable affective quality. Psychophysiological findings may point to a deficit in associative information processing systems that normally produce adaptive cognitive-emotional reactions.     

Comorbidity of attention deficit hyperactivity disorder in juvenile bipolar disorder

OBJECTIVE: There is some evidence to suggest that attention deficit hyperactivity disorder (ADHD) and juvenile bipolar disorder could be related. This is based on studies of comorbidity and some preliminary family study data. However, doubts continue to be raised about the relationship between the two disorders. This study examined the comorbidity of disruptive behavior disorders (DBD) that include ADHD, oppositional defiant disorder (ODD) and conduct disorder (CD) in juvenile bipolar disorder. METHOD: Seventy-three subjects with onset of bipolar disorder at age 18 years or younger were evaluated using structured interviews (Missouri Assessment of Genetics Interview for Children, Structured Clinical Interview for DSM-IV Axis I disorders--Clinician Version, and Operational Criteria Checklist for Psychotic Disorders version 3.4). Information was collected from subjects as well as from their parents. Patients with comorbid DBD were compared with patients without DBD. RESULTS: Ten subjects (14%) had one or more comorbid DBD. ADHD, CD, and ODD were present in three (4%), two (3%), and eight (11%) subjects, respectively. Those with DBD had earlier onset of bipolar disorder and spent more time ill compared to those without DBD. CONCLUSIONS: The rates of comorbid DBD in juvenile bipolar disorder are low. The study does not support a definite relationship between ADHD and juvenile bipolar disorder. Higher rates reported previously may be due to differing methods of subject ascertainment. Samples recruited from community and general psychiatric settings may help to clarify the relationship between bipolar disorder and ADHD.     

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.     

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8–25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.     

Deficient social problem-solving in boys with ODD/CD, with ADHD, and with both disorders

OBJECTIVE: To study social problem-solving skills in psychiatrically defined aggressive boys, starting from Dodge's social information-processing model. METHOD: Videotaped stimuli of problematic social situations and questions were presented to elicit responses that indicate boys' social problem-solving skills (encoding and interpretation of social cues, generation of possible responses, evaluation of responses, self-efficacy evaluation, and response selection). Boys aged 7 to 12 years with oppositional defiant or conduct disorder (ODD/CD) (n = 48), attention-deficit hyperactivity disorder (ADHD) (n = 27), and both disorders (ODD/CD + ADHD) (n = 29) were involved as well as a normal control group (n = 37) and a psychiatric control group with internalizing disorders (n = 23). RESULTS: When compared with normal controls, boys with ADHD, with ODD/CD, and with ODD/CD + ADHD encoded fewer social cues and generated fewer responses. Boys with ODD/CD and with ODD/CD + ADHD moreover were more confident in their ability to enact an aggressive response than normal controls. When ODD/CD boys and ODD/CD + ADHD boys were given the opportunity to select a response from various types of responses shown, they selected an aggressive response more often than normal controls. Thus, in ADHD boys social problem-solving was affected only in encoding and in the generation of responses, whereas in ODD/CD and ODD/CD + ADHD boys social problem-solving was affected throughout the process. CONCLUSION: For the further study of social problem-solving in aggressive children, it is essential to differentiate between children with ADHD and children with ODD/CD and ODD/CD + ADHD.     

Attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder or conduct disorder

Comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) are common in clinically referred children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Early recognition and treatment of co-occurring ADHD and ODD and/or CD is important because comorbidity influences symptom severity, prognosis, and treatment. Research on treatment supports the importance of behavior therapies for ODD and multimodal psychosocial interventions delivered simultaneously and intensively for CD with adjunctive medication for ADHD symptoms. Clinical trials are beginning to show that stimulants and atomoxetine are effective for ADHD and ODD symptoms when the disorders occur together. It is presently unclear if ODD in the absence of ADHD responds to pharmacotherapy. More research is needed examining the effects of commonly prescribed ADHD medications on CD symptoms. Research suggests a high prevalence of lifetime comorbidity with ODD in clinically referred patients with ADHD.     

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.     

Psychophysiological responses in ADHD boys with and without conduct disorder: implications for adult antisocial behavior

OBJECTIVE: Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. However, because previous research did not consider comorbid conduct disorder (CD), the question of whether ADHD by itself or only the association of ADHD with CD implies a risk of adult antisocial behavior developing is still under discussion. METHOD: Because several characteristics of psychophysiological response had been shown to be associated with future increased likelihood of adult antisocial behavior, autonomic arousal as well as electrodermal responses to orienting and aversive stimuli were assessed in 26 boys with ADHD+CD compared with 21 boys with ADHD alone and 21 controls. RESULTS: Boys with a comorbid condition of ADHD+CD showed a decrement of autonomic responses and a more rapid habituation to orienting and aversive startling stimuli compared with age-matched children with ADHD alone. CONCLUSIONS: Boys with ADHD+CD show a psychophysiological response pattern that is very similar to that reported in antisocial personalities. These findings give further support for a high persistence of antisocial behavior from childhood to adulthood, while no evidence was found that ADHD itself is associated with a predisposition to antisocial behavior.     

Diagnostic threshold for conduct disorder in girls and boys

Concerns about gender bias in the diagnostic criteria for conduct disorder (CD) have prompted some researchers to recommend that the diagnostic threshold in girls be lowered. Since CD is a highly familial condition, the authors assessed the diagnostic validity of subthreshold CD in girls using family study methodology. They compared the rates of antisocial disorders (CD and antisocial personality disorder) in relatives of four groups of index children: children with attention deficit hyperactivity disorder (ADHD) and full, subthreshold, or no CD diagnoses and non-ADHD/non-CD control subjects. Results showed no interaction between gender and familiality across the four groups. Furthermore, there was no significant evidence of familiality of subthreshold CD. From a family genetic perspective, the diagnostic threshold for CD does not appear to differ by gender. The current results support the possibility that differential rates of CD reflect actual differences in rates of antisocial behavior across gender.     

Neuroanatomical correlates of attention‐deficit–hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder

Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention‐deficit–hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel‐based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age‐ and gender‐matched typically developing subjects underwent high‐spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel‐by‐voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.     

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.     

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.