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.     

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.     

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.     

A controlled family history study of Tourette's syndrome, II: Alcoholism, drug abuse, and obesity

The behaviors associated with Gilles de la Tourette's syndrome (TS), including impulsive, compulsive, attentional, learning, conduct, and mood disorders, have often been described as substrates for the development of alcoholism and/or drug abuse. As the authors' experience with TS pedigrees indicated that alcoholism and/or drug abuse were common in relatives of TS probands, they examined, by the family history technique, 1750 relatives over 14 years of age in 130 TS proband and 25 control families. Significant, life-disrupting problems with alcoholism and/or drug abuse were present in 14.5% of the relatives of TS probands compared with 4.4% of the control relatives (p less than .00001). Among parents of TS probands, the ratio of affected fathers to mothers was 2:1. Marked obesity (greater than 100 lb) was present in 10.8% of the mothers and 3.2% of all relatives of TS probands compared with 0.8% of all control relatives (p = .01). In parents of TS probands, the ratio of marked obesity in fathers to that in mothers was 1:4.5. When the categories of alcoholism and/or drug abuse and marked obesity were combined, 17.4% of all relatives of TS probands were affected compared with 4.6% of all control relatives (p less than .0001) and the ratio of fathers to mothers with these disorders was 1.1:1. Among all relatives of TS probands, 20.8% of those with tics and 17.4% of those without tics had problems with alcoholism and/or drug abuse or obesity or both. This finding suggests that when the Gts gene(s) is expressed in this form it is about equally likely to occur in persons with and persons without tics. The similarities between TS and early onset, male predominant, Type II alcoholism suggest that in some cases, alcoholism and/or drug abuse in males and severe obesity in females are related, genetically controlled, compulsive behaviors.     

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.     

Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship

Previous studies have suggested that obsessive-compulsive symptoms frequently occur among patients with Gilles de la Tourette's syndrome (TS). To examine the relationship between TS and obsessive-compulsive disorder (OCD), data from all first-degree relatives of TS probands were obtained with a semistructured interview designed to collect information on the presence of TS, other tic disorders, and neuropsychiatric illnesses during the lifetime of the individual. The rate of OCD among first-degree relatives was significantly increased over estimates from the general population and a control sample of adoptive relatives. The rates of TS, OCD, and chronic multiple tics (CMT) were virtually the same in families of probands with OCD (TS +/- OCD) when compared with families of probands without OCD (TS - OCD). Finally, the frequency of OCD without TS or CMT among first-degree relatives was significantly elevated in families of both TS + OCD and TS - OCD probands, suggesting that some forms of OCD may represent an alternative expression of the factors responsible for TS and/or CMT.     

A controlled family history study of Tourette's syndrome, I: Attention-deficit hyperactivity disorder and learning disorders

Gilles de la Tourette's syndrome (TS) is a common, hereditary neuropsychiatric disorder. While its diagnostic feature is the presence of suppressible motor and vocal tics, a wide range of impulsive, compulsive, attentional, learning, mood, and anxiety disorders are also present in many patients. To determine if attentional and learning problems are part of the expression of the Gts gene (or genes), the authors analyzed family histories of 130 TS probands with 1851 relatives and 25 control probands with 541 relatives--a total of 2392 relatives. The frequency of attention-deficit hyperactivity disorder (ADHD) or learning disorders was significantly increased in the relatives of the TS probands. The data on first-degree relatives suggest that when the Gts gene is expressed in this form, in two thirds of the cases tics are also present and in one third they are not. These observations are consistent with the proposal that ADHD and learning disorders form an integral part of the expression of the Gts gene or genes.     

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.     

Family-genetic and psychosocial risk factors in DSM-III attention deficit disorder

Using family study methodology and assessments made by blind raters, this study evaluated family-genetic and psychosocial risk factors for DSM-III attention deficit disorder (ADD) among the 457 first-degree relatives of clinically referred children and adolescents with ADD (N = 73), compared with psychiatric (N = 26) and normal controls (N = 26). Relatives of ADD probands had a higher morbidity risk for ADD (25.1% versus 5.3% versus 4.6%, ps less than 0.00001), antisocial disorders (25.3% versus 6.9% versus 4.2%, ps less than 0.00001), and mood disorders (27.1% versus 13.9%, p = 0.038 and 27.1% versus 3.6%, p = 0.00001) than did relatives of psychiatric and normal controls. The increased risk for ADD could not be accounted for by gender or generation of relative, the age of proband, social class, or the intactness of the family. These results confirm and extend previous findings indicating important family-genetic risk factors in ADD.     

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.     

Alcohol use disorders in relatives of patients with panic disorder

OBJECTIVE: The aim of this study was to use data from a family study of anxiety disorders to examine the familial association between alcohol use disorders and panic disorder (PD), controlling for alcohol use disorders in the proband. METHOD: Data from a family study of anxiety disorders were used to compare rates of alcohol use disorders in the relatives of 3 proband groups (PD with lifetime alcohol use disorders, PD without lifetime alcohol use disorders, and not-ill controls). RESULTS: There was a significantly higher rate (12%) of alcohol use disorders among the relatives of PD probands compared with relatives of controls (5%), even in the absence of alcohol use disorders in the proband and after adjusting for differences in sociodemographic characteristics and lifetime drug use disorders (chi2 = 5.4; df = 1; P = .02). Anxiety symptoms were more frequent among the male relatives of panic probands who received an alcohol diagnosis, compared with those who did not have alcohol use disorders (10/25 vs 22/111; chi2 = 4.6; df = 1; P = .03). A similar pattern was found in women (8/11 vs 63/156; chi2 = 4.4; df = 1; P = .036). CONCLUSIONS: These findings suggest a familial association between PD and alcohol use disorders. Future studies with more refined alcohol diagnoses are needed to replicate and investigate the mechanism of this association.     

Family study of affective spectrum disorder

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

Increased frequency of arousal parasomnias in families with nocturnal frontal lobe epilepsy: A common mechanism?

Purpose: Retrospective observations disclosed an overlap between parasomnias and nocturnal frontal lobe epilepsy (NFLE) not only in patients but also in their relatives, suggesting a possible common pathogenetic mechanism. This study aimed to verify whether relatives of patients with NFLE have a higher frequency of parasomnias, namely arousal disorders, and thereby shed light on the still unknown pathophysiologic mechanisms underlying NFLE. Methods: We undertook a case–control family study in which we recruited NFLE probands and healthy controls, matched for age, sex, education, and geographic origin. At least four relatives were included for each proband and control. Each subject underwent a standardized interview, with application of the International Classification of Sleep Disorders–Revised (ICSD‐R 2001) minimal criteria to diagnose the lifetime prevalence of the main parasomnias. Results: Four hundred fifty‐eight individuals were recruited: 33 NFLE probands, 200 relatives of probands, 31 controls, and 194 control relatives. All NFLE probands but one have sporadic NFLE. The lifetime prevalence of the following parasomnias differed in proband relatives versus control relatives: arousal disorders [odds ratio (OR) 4.7, 95% confidence interval (CI) 2.0–11.6; p < 0.001] and nightmares (OR 2.6, 95% CI 1.6–4.2; p < 0.001) were more frequent among NFLE proband relatives. In the secondary analysis comparing NFLE probands to controls, arousal disorders (OR 6.3, 95% CI 1.3–31.7; p = 0.023) and bruxism (OR 5.4, 95% CI 1.3–21.7; p = 0.017) were more frequent among NFLE probands. Discussion: The higher frequency of arousal disorders in NFLE families suggests an intrinsic link between parasomnias and NFLE and an abnormal (possibly cholinergic) arousal system as a common pathophysiologic mechanism.     

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.     

Psychiatric morbidity in the relatives of patients with DSM-III schizophreniform disorder: comparisons with the relatives of schizophrenic and bipolar disorder patients

Risks for psychiatric disorders (RDC) among first degree relatives of DSM-III schizophreniform, bipolar, and schizophrenic probands obtained from an epidemiologic sample using family history methods were examined. The relatives of the schizophreniform probands differed from the relatives of the schizophrenic and bipolar probands. The relatives of schizophreniform probands had significantly higher rates of affective illnesses (with the exception of bipolar illness) than the relatives of schizophrenic probands, and they had a significantly higher rate of psychotic affective disorders than the relatives of the bipolar probands.     

Parsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis

BACKGROUND: A growing literature suggests that anxiety disorders (ANX) co-occur with bipolar disorder (BPD), but the nature of this overlap is unknown. Thus, we investigated the familial association between BPD and ANX among the first-degree relatives of children with BPD with and without comorbid ANX. METHODS: We compared relatives of four proband groups defined by the presence or absence of BPD and ANX in the proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2) BPD without ANX (n = 11 probands, 38 relatives), (3) ANX without BPD (n = 48 probands, 167 relatives), and (4) controls without BPD or ANX (n = 118 probands, 385 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. RESULTS: The results show high rates of both BPD and ANX in relatives of children with BPD + ANX. Moreover, BPD and ANX cosegregated among the relatives of children with BPD + ANX. Although relatives of both ANX proband groups (with and without BPD) had high rates of ANX, and relatives of both BPD proband groups (with and without ANX) had high rates of BPD, the combined condition BPD + ANX was the predominant form of BPD among relatives of probands with BPD + ANX. CONCLUSIONS: These family-genetic findings suggest that the comorbid condition BPD+ANX may be a distinct clinical entity. More work is needed to evaluate whether the presence of comorbid ANX may be a marker of very early onset BPD.     

A family study of juvenile obsessive-compulsive disorder.

OBJECTIVES: To determine whether juvenile obsessive-compulsive disorder (OCD) is familial and whether the rate of Tourette syndrome (TS) and tic disorders is higher among relatives of patients with OCD than among relatives of controls subjects. METHOD: We assessed first-degree relatives of 35 juvenile OCD probands (aged 16 years or less) and 34 matched, psychiatrically unaffected control subjects, using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) (unpublished), a Questionnaire for tic disorders, the Children's Version of Leyton's Obsessional Inventory (CV-LOI), and the Children's Version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Similarly, we assessed adult relatives, using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Leyton's Obsessional Inventory (LOI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and a Questionnaire for tic disorders. The diagnoses were determined by consensus, using DSM-III-R criteria. We calculated age-corrected morbid risk, using Weinberg's method. RESULTS: The morbid risk for OCD among the relatives of OCD probands was 4.96%, while none of the relatives of unaffected control subjects had OCD. We did not diagnose TS in any of the relatives of either OCD probands or control subjects. We diagnosed chronic motor tic disorders in only 1 of the relatives of OCD probands, while none of the relatives of control subjects had any tic disorder. CONCLUSION: Most juvenile cases of OCD are nonfamilial and unrelated to tic disorders, while only a few are familial. There is a need to re-examine the issue of familiality in cases of OCD, as well as its relation to TS, using larger community samples to better understand the hypotheses of familial transmission and comorbidity with tic disorders.     

Interstitial cystitis and panic disorder: a potential genetic syndrome

BACKGROUND: Evidence from a genetic linkage study had suggested a possible syndrome in some families with panic disorder (PD). This syndrome includes bladder problems (possibly urinary interstitial cystitis [IC]), thyroid disorders, chronic headaches/migraine, and/or mitral valve prolapse. In 19 multiplex families with PD, one marker (D13S779) on chromosome 13 gave a logarithm of odds score of more than 4 when individuals with any of the syndrome conditions were analyzed as affected. Families with the bladder problems yielded the highest logarithm of odds scores. These findings were replicated in an extended sample of 60 families. Whereas PD had been well characterized by direct interview, the urologic problems had been found only via medical history checklists and records. A case review by a board-certified urologist suggested they could be IC. OBJECTIVE: To determine whether patients diagnosed as having IC by urodynamics and/or cystoscopy and their first-degree relatives (FDRs) have increased rates of the syndrome conditions, thus validating that the bladder problems observed in the linkage study could be IC and providing further support for the panic syndrome. DESIGN: Case-control and family history study. SETTING: Two metropolitan urology clinics. PARTICIPANTS: One hundred forty-six probands (67 with IC and 79 with other urologic disorders) and 815 FDRs. MAIN OUTCOME MEASURES: Lifetime rates of syndrome conditions in probands and FDRs who were blind to urologic or psychiatric diagnoses in the proband. RESULTS: Compared with patients without IC, patients with IC had a significantly higher lifetime prevalence of PD (controlling for age and sex) (odds ratio, 4.05; 95% confidence interval, 1.22-13.40; P =.02) and a higher lifetime prevalence of any of the syndrome disorders (controlling for age and sex) (odds ratio, 2.22; 95% confidence interval, 0.89-5.54; P =.09). First-degree relatives of probands with (vs without) IC were significantly more likely to have PD, thyroid disorder, urologic problems, and any of the syndrome disorders (controlling for age and sex of the relative and sex of the proband) (adjusted odds ratio, 1.95; 95% confidence interval, 1.13-3.38; P =.02). These results in relatives were not influenced by PD in probands, and did not change substantially when controlling for the proband-relative relationship, modeling age as a categorical (vs continuous) variable, or excluding FDRs with PD. There were no interactions between proband IC status and sex of the relative. CONCLUSIONS: The increased frequency of seemingly disparate disorders in patients with IC and their FDRs is consistent with the genetic linkage findings in families with PD. These findings suggest that the bladder problems observed in the linkage study may be IC. The hypothesis that there is a familial, possibly pleiotropic, syndrome that may include IC, PD, thyroid disorders, and other disorders of possible autonomic or neuromuscular control deserves further investigation.     

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.     

Neurocognitive functioning and schizophrenia spectrum disorders can be independent expressions of familial liability for schizophrenia in community control children: the UCLA family study

This study provided a further test of the hypothesis that certain neuromotor, language and verbal memory dysfunctions reflect genetic predisposition to schizophrenia, by examining the effects of family loading for schizophrenia (FLS) in normal controls without personal histories of schizophrenia or attention deficit hyperactivity disorder. In a case control design, 11 community controls (CC) with FLS were compared to 47 CC without FLS on tests of expressive and receptive language, visual motor coordination, full scale intelligence and verbal memory. In this study, FLS primarily reflects the incidence of schizophrenia spectrum diagnoses in the second-degree relatives of CC probands. CC probands with FLS had significantly poorer general intelligence, expressive and receptive vocabulary abilities, visual motor coordination and slower motor speed than CC probands without FLS. The variance in neurocognitive functioning associated with FLS is not due to the presence of any psychiatric disorders in CC probands, nor the presence of schizophrenia spectrum disorders in their parents. The relation between FLS and neurocognitive and neuromotor functioning in CC probands was moderated by the parent's cognitive functioning. The results of the present study indicate that familial liability to schizophrenia can be transmitted across two generations, independent of the presence of schizophrenia spectrum disorders in either the parent or proband, and account for significant variance in proband neurocognitive and neuromotor functioning.These findings suggest the neurocognitive and neuromotor functioning and schizophrenia spectrum disorders can be relatively independent expressions of familial liability to schizophrenia.