Showing papers by "Stephen V. Faraone published in 1996"

A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders

Abstract: Background: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. Methods: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school, and family functioning. Results: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted conduct disorder and substance use disorders at follow-up, major depression at baseline predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. Conclusions: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.

Predictors of persistence and remission of ADHD into adolescence : results from a four-year prospective follow-up study

Abstract: Objective To evaluate the predictors of persistence and the timing of remission of attention-deficit hyperactivity disorder (ADHD). Method Subjects were 6− to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses, cognitive achievement, social, school, and family functioning at a 4-year follow-up assessment. Results At the 4-year follow-up assessment, 85% of children with ADHD continued to have the disorder and 15% remitted. Of those who remitted, half did so In childhood and the other half in adolescence. Predictors of persistence were familiality of ADH D, psychosocial adversity, and comorbidity with conduct, mood, and anxiety disorders. Conclusions The findings prospectively confirm that the majority of children with ADHD will continue to express the disorder 4 years later. For a minority of children, ADHD was a transient disorder that remits early in development. In addition, we have shown that persistence of ADHD is predictable. Familiality, adversity, and psychiatric comorbidity may be clinically useful predictors of which children with ADHD are at risk for a persistent disorder. J. Am. Acad. Child Adolesc. Psychiatry, 1996, 35(3):343–351.

Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs.

Abstract: Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individual's risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Attention-Deficit Hyperactivity Disorder and Juvenile Mania: An Overlooked Comorbidity?

Abstract: Objective To evaluate the psychiatric, cognitive, and functional correlates of attention-deficit hyperactivity disorder (ADHD) children with and without comorbid bipolar disorder (BPD). Method DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses at baseline and 4-year follow-up in ADHD and control children. In addition, subjects were evaluated for cognitive, academic, social, school, and family functioning. Results BPD was diagnosed in 11% of ADHD children at baseline and in an additional 12% at 4-year follow-up. These rates were significantly higher than those of controls at each assessment. ADHD children with comorbid BPD at either baseline or follow-up assessment had significantly higher rates of additional psychopathology, psychiatric hospitalization, and severely impaired psychosocial functioning than other ADHD children. The clinical picture of bipolarity was mostly irritable and mixed. ADHD children with comorbid BPD also had a very severe symptomatic picture of ADHD as well as prototypical correlates of the disorder. Comorbidity between ADHD and BPD was not due to symptom overlap. ADHD children who developed BPD at the 4-year follow-up had higher initial rates of comorbidity, more symptoms of ADHD, worse scores on the CBCL, and a greater family history of mood disorder compared with non-BPD, ADHD children. Conclusions The results extend previous results documenting that children with ADHD are at increased risk of developing BPD with its associated severe morbidity, dysfunction, and incapacitation.

Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children

Abstract: OBJECTIVE This study investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). METHOD Subjects were 6-17-year-old boys with DSM-III-R ADHD (N = 140) and normal comparison subjects (N = 120) and their first-degree biological relatives. Information on maternal smoking was obtained from mothers in a standardized manner by raters who were blind to the proband's clinical status. RESULTS Twenty-two percent of the ADHD children had a maternal history of smoking during pregnancy, compared with 8% of the normal subjects. This positive association remained significant after adjustment for socioeconomic status, parental IQ, and parental ADHD status. Significant differences in IQ were found between those children whose mothers smoked during pregnancy and those whose mothers did not smoke (mean IQ = 104.9, SD = 12.3, and mean = 115.4, SD = 12.2, respectively). CONCLUSIONS These findings suggest that maternal smoking during pregnancy is a risk factor for ADHD. If confirmed, these findings will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age.

Is Childhood Oppositional Defiant Disorder a Precursor to Adolescent Conduct Disorder? Findings from a Four-Year Follow-up Study of Children with ADHD

Abstract: Objective To evaluate the overlap between attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), addressing whether ODD is a subsyndromal form of conduct disorder (CD) and, if so, whether it is a precursor or prodrome syndrome of CD. Method Assessments from multiple domains were used to examine 140 children with ADHD and 120 normal controls at baseline and 4 years later. Results Of children who had ADHD at baseline, 65% had comorbid ODD and 22% had CD. Among those with ODD, 32% had comorbid CD. All but one child with CD also had ODD that preceded the onset of CD by several years. ODD+CD children had more severe symptoms of ODD, more comorbid psychiatric disorders, lower Global Assessment of Functioning Scale scores, more bipolar disorder, and more abnormal Child Behavior Checklist clinical scale scores compared with ADHD children with nonCD ODD and those without ODD or CD. In addition, ODD without CD at baseline assessment in childhood did not increase the risk for CD at the 4-year follow-up, by midadolescence. Conclusions Conclusions: Two subtypes of ODD associated with ADHD were identified: one that is prodromal to CD and another that is subsyndromal to CD but not likely to progress into CD in later years. These ODD subtypes have different correlates, course, and outcome.

Six-Week, Double-Blind, Placebo-Controlled Study of Desipramine for Adult Attention Deficit Hyperactivity Disorder

Abstract: Objective : Despite the increasing awareness of attention deficit hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder ; most of the trials have focused on the psychostimulants. Because the tricyclic antidepressant desipramine has been found to be effective in treating ADHD in pediatric groups, the authors tested its efficacy in adults with ADHD. Method : The authors conducted a randomized, 6-week, placebo-controlled, parallel-design study of desipramine at a target daily dose of 200 mg in 41 adult patients with DSM-III-R ADHD. They used standardized structured psychiatric instruments for diagnosis and, as the dependent variables (outcome), used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. Results : There were highly significant differences in the reduction of ADHD symptoms between adults receiving desipramine and placeho. Within the desipramine-treated group, there were clinically and statistically significant differences between baseline and the week 6 end point for 1) reduction of 12 of 14 symptoms of ADHD and 2) decreases in the broad categories of hyperactivity, impulsivity, and inattentivenes. In contrast, placebo-treated patients showed no differences between baseline and end point for any of the A DHD symptoms assessed. According to strict, predefined criteria for response, 68% of desipramine-treated subjects and no subjects in the placebo group were considered positive responders. Response to desipramine was independent of dose, level of impairment, gender, or lifetime psychiatric comorbidity with anxiety or depressive disorders. Conclusions : These results, similar to findings in children and adolescents with ADHD, indicate that desipramine is effective in the treatment of ADHD in adults.

Growth Deficits in ADHD Children Revisited: Evidence for Disorder-Associated Growth Delays?

Abstract: Objective To reevaluate the hypothesis that stimulants cause growth deficits in children with attention-deficit hyperactivity disorder (ADHD). Method Growth deficits in height and weight were examined in 124 children and adolescents with ADHD and 109 controls, using appropriate correction by age and parental height measures and attending to issues of pubertal stage, treatment, and psychiatric comorbidity. Results Small but significant differences in height were identified between ADHD children and controls. However, height deficits were evident in early but not late adolescent ADHD children and were unrelated to use of psychotropic medications. There was no evidence of weight deficits in ADHD children relative to controls, and no relationship between measures of malnutrition and short stature was identified. Conclusions ADHD may be associated with temporary deficits in growth in height through mid-adolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not its treatment.

Toward a new psychometric definition of social disability in children with attention-deficit hyperactivity disorder.

Abstract: Objective To investigate a new mechanism for identifying social disability in children with attention-deficit hyperactivity disorder (ADHD), employing psychometric methodology used in defining learning disabilities. Method Two groups of index children were examined: 140 children with ADHD (referred from both psychiatric and pediatric sources) and 120 non-ADHD comparison children. Subjects were defined as socially disabled if they had a value greater than 1.65 on a standardized discrepancy score between observed and expected scores on a measure of social functioning (with expected scores derived as a function of the child's estimated Full Scale IQ). Children identified as socially disabled were compared with non-socially disabled probands on psychopathology, familiality, cognitive functioning, school history, and treatment history. Results Using this psychometric approach, 22% of the ADHD probands qualified as socially disabled, whereas none of the comparison probands qualified ( p ≤ .001). Socially disabled ADHD probands were significantly more impaired than were non-socially disabled ADHD probands in global and specific measures of social functioning and patterns of psychiatric comorbidity. Conclusions The psychometrically defined construct of social disability may identify children with ADHD who are at very high risk for severe social dysfunction and whose course and prognosis may vary from those of other children with ADHD. This subgroup of children with ADHD may be at heightened risk for poor outcome, and their identification may facilitate the development of clinical interventions aimed at ameliorating their specific difficulties.

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome.

Abstract: Background Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. Objective To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. Method DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. Results At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. Conclusions The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.

Child Behavior Checklist Findings Further Support Comorbidity between ADHD and Major Depression in a Referred Sample

Abstract: Objective To examine the convergence of categorical and empirical diagnostic systems to evaluate whether psychiatric comorbidity of juvenile major depression with attention-deficit hyperactivity disorder (ADHD) is due to assessment bias. Method Using total predictive value and the odds ratio, the authors evaluated the convergence of Child Behavior Checklist (CBCL) scales with structured interview-derived diagnoses in 94 children with major depression, 97 with ADHD, and 115 normal control children with neither diagnosis. Results The CBCL Anxious/Depressed scale discriminated depressed from nondepressed children irrespective of comorbidity with ADHD, and the Attention Problems scale discriminated ADHD from non-ADHD children irrespective of comorbidity with major depression. Children with major depression comorbid with ADHD had CBCL correlates of both syndromes. Conclusions Since the CBCL is an empirically derived taxonomic system, the correspondence between the content-congruent CBCL scales and DSM-III-R categorical diagnoses of major depression and of ADHD indicates that previously reported findings of high overlap between these two disorders using structured diagnostic interview methodology and trained raters were not due to rater biases.

Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.

Abstract: The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other.

Is Season of Birth a Risk Factor for Attention-Deficit Hyperactivity Disorder?

Abstract: Objective To investigate seasonal variations in the birth patterns of children with attention-deficit hyperactivity disorder (ADHD) in reference to a group of normal control children, attending to issues of comorbidity, familiality, and learning disability. Method Subjects were boys with DSM-III-R ADHD ( n = 140) and normal controls ( n = 120). The ADHD children were stratified by the presence of comorbid psychiatric disorders, learning disability, and family history of ADHD, and logistic regression was used to estimate relative risks. Results No statistically major effect for season of birth was observed in the comparison of ADHD and control children. However, significant effects were found for September births for ADHD children with learning disability (odds ratio=5.4) and for ADHD children without psychiatric comorbidity (odds ratio=4.5). A trend was also noted for winter births in ADHD children with learning disabilities, no psychiatric comorbidity, and positive family history for ADHD. Conclusions These preliminary results suggest that there may be a seasonal pattern of birth for subtypes of ADHD. If season of birth serves as a proxy for the timing of seasonally mediated viral infections, it may lead to a greater understanding of the etiology and pathophysiology of ADHD.

Unipolar relatives in bipolar pedigrees: A search for elusive indicators of underlying bipolarity

Abstract: In an effort to identify features indicative of underlying bipolarity within the unipolar relatives of bipolar probands, we compared unipolar relatives of bipolars with unipolar relatives of controls. Using data from the Yale-NIMH Collaborative Study of Depression, we compared a number of demographic and clinical features individually, and then developed a logistic regression model for the differences found. Unipolar relatives of bipolars were generally similar to relatives of controls, but they were older and more likely to suffer from more severe, even psychotic, depression, and somewhat less likely to report a brief transition into their illness. A multiple logistic regression model for observed differences was highly statistically significant, but had limited ability to discriminate effectively between the two groups. These findings suggest that more stringent diagnostic criteria might be beneficial if unipolar relatives are counted as affected in linkage studies of bipolar disorder. The ability of this strategy to improve the “clinical phenotype” is limited, however, and other approaches may be needed to identify features of underlying bipolarity and thus to define “caseness” for unipolar relatives in linkage analyses of bipolar disorder. © 1996 Wiley-Liss, Inc.

Assessing risk for the Tourette spectrum of disorders among first‐degree relatives of probands with Tourette syndrome

Abstract: Previous studies have indicated that genetic investigations of Tourette syndrome (TS) should focus on a phenotype that includes not only TS, but chronic tics (CT) and obsessive-compulsive disorder (OCD) as well. These studies have shown that sex may play a role in determining which of the disorders in the TS spectrum is expressed in a susceptible individual. Female relatives of TS probands far more often express OCD, while male relatives more often express TS or CT. Data from the Yale Family Study of TS were used to model risk to first-degree relatives of probands with TS for a variety of TS disease phenotypes. Risk to relatives was modeled using multivariate Cox regression analysis, a method appropriate for assessing risk when there is correlation among disease onsets. This is the first known application of this method to family data. The study identified two proband characteristics that increase the risk for disease onset among both male and female relatives for all TS spectrum disorders, lending credence to the hypothesis that TS spectrum disorders share a common etiology. These were a relatively younger age-at-onset, and no experience of simple motor tics. The predictive ability of two additional factors varied by both sex and disease phenotype. These characteristics, i.e., proband onset with compulsive tics, and proband onset with range, appear to increase risk primarily in female relatives, and for the OCD part of the spectrum.

New phenotype definition of attention deficit hyperactivity disorder in relatives for genetic analyses

Abstract: The goal of the present investigation was to create a phenotype definition in relatives of probands that reflects a more genetic form of attention deficit hyperactivity disorder (ADHD). Logistic regression was applied to the first-degree relatives of ADHD and normal control probands to create a quantitative phenotype that combined information across psychiatric, cognitive, and demographic domains. Models were run separately in mothers, fathers, sisters, and brothers. Although there was some overlap between the variables retained in each model, no two models had exactly the same variables. Our results suggest that the use of fitted logits may be valuable as a potential index of caseness. Since different characteristics were included in different groups of relatives, our results suggest that gender and generation may moderate the expression of ADHD.

The Inheritance of Mood Disorders

Abstract: In this Chapter we will show that although much is known about the inheritance of mood disorders, we still have much to learn. Available studies weave a complex pattern of results that inform clinicians, educate students, and stimulate researchers. A complete review of relevant work is beyond the scope of a single Chapter; those who wish to learn more should consult comprehensive reviews (Faraone, Kremen, & Tsuang, 1990; Tsuang and Faraone, 1990) along with the original studies. Our goal for this Chapter is to provide an overview that orients readers to basic findings and future directions. However, before doing so, we briefly review the spectrum of conditions called mood disorders to create a nosological foundation for the studies to be reviewed.

Detection of IgA against the mycobacterial antigen A60 in serum and saliva in patients with active pulmonary tuberculosis: preliminary results

Abstract: Humoral immune response against the mycobacterial antigen A60 was evaluated in 38 subjects: 13 healthy volunteers (Group I), 10 patients with a defined acute or chronic non tuberculous lung disease (Group II), 15 patients suffering from pulmonary tuberculosis (Group III). Saliva IgA in samples diluted in various concentrations (1:10, 1:30, 1:50) and serum IgG and IgA levels were measured by ELISA. Positive values of IgG were found in sera of 0/13 subjects from Group I, 1/10 from Group II, 12/15 from Group III; searching for IgA in serum was positive in 1/13 subjects from Group I, 2/10 from Group II, 11/15 from Group III, 1:30 dilution of saliva led to positive results in 0/13 subjects from Group I, 0/10 from Group II and 10/15 from Group III. The measurement of anti-A60 IgA levels in both saliva and serum might be a useful complement to serology based on detection of anti-A60 IgG in blood samples.

Neuropsychological among the elderly nonpsychotic relatives of schizophrenic patients

Abstract: In our prior work with a young sample (age <60), we showed that three neuropsychological functions were impaired among relatives of schizophrenic patients: abstraction, verbal memory, and auditory attention. In the present work we show that these results do not generalize to an older sample aged 60 years and greater. Thus, although we and others have put forth measures of neuropsychological function as indicators of the schizophrenia genotype, the present study suggests that conclusions may be limited to non-elderly samples. Further work is needed to address this issue definitively.