scispace - formally typeset
Search or ask a question

Showing papers by "Stephen V. Faraone published in 1992"


Journal ArticleDOI
TL;DR: Previous findings indicating family-genetic influences in attention deficit hyperactivity disorder are extended by using both pediatrically and psychiatrically referred proband samples, and the distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficithyperactivity disorder byComorbidity.
Abstract: • We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 firstdegree 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.

781 citations


Journal ArticleDOI
TL;DR: Psychopathology was assessed in children from a nonclinical sample originally identified as behaviorally inhibited or uninhibited at 21 months and followed through 7 1/2 years, suggesting that the association between behavioral inhibition and anxiety disorder is accounted for by children who have stable behavioral inhibition.
Abstract: "Behavioral inhibition to the unfamiliar" is a temperamental construct reflecting the tendency to be shy, timid, and constrained in novel situations. Previous work has suggested that it may be associated with anxiety disorders in children. Psychopathology was assessed in children from a nonclinical sample originally identified as behaviorally inhibited or uninhibited at 21 months and followed through 7 1/2 years. Children who remained inhibited at 4, 5 1/2 and 7 1/2 years (Stable Inhibited) had higher rates of anxiety disorders than children who were not consistently inhibited. Their parents had higher rates of multiple childhood anxiety disorders and of continuing anxiety disorder. These results suggest that the association between behavioral inhibition and anxiety disorder is accounted for by children who have stable behavioral inhibition.

490 citations


Journal ArticleDOI
TL;DR: Findings show that a liberal definition of LD overidentifies LD not only in ADDH children but also in normal children.
Abstract: A widely variable overlap ranging from 10 to 92% has been reported in the literature between attention deficit disorder with hyperactivity (ADDH) and learning disability (LD), most likely a result of inconsistencies in the criteria used to define LD in different studies. The following study seeks to more accurately determine rates of LD in clinically referred children. Using a psychometrically reliable methodological approach, it was expected that the rate of LD in ADDH children would be far more modest than previously reported. Subjects were referred children with ADDH (N = 60), children with academic problems (N = 30), and normal controls (N = 36) of both sexes with available psychological and achievement testing. Using a liberal definition of LD, significant differences were found between the groups (ADDH = 38% versus academic problems = 43% versus normals = 8%; p = 0.002). In contrast, more modest rates were found using two more stringent methods of assessment (23 and 17%; 10 and 3%; 2 and 0%, respectively; p = 0.02). Arithmetic-based LD appears to be equally identified by both stringent methods, whereas the liberal definition overidentified children in all three groups. These findings show that a liberal definition of LD overidentifies LD not only in ADDH children but also in normal children.

448 citations


Journal ArticleDOI
TL;DR: This work suggests that subgroups of children with ADHD might be delineated based on the presence of comorbidity, and these subgroups may have differing risk factors, clinical course, and pharmacologic responses.

157 citations


Journal ArticleDOI
TL;DR: This article applied segregation analysis to a sample of 257 children with attention deficit hyperactivity disorder (ADHD) and found that its familial transmission is consistent with known genetic mechanisms, including twin and adoption.
Abstract: Although family, twin and adoption studies suggest that genetic factors are involved in attention deficit hyperactivity disorder, further evidence is needed to demonstrate that its familial transmission is consistent with known genetic mechanisms. We applied segregation analysis to a sample of 257 c

145 citations


Journal ArticleDOI
TL;DR: The results indicate that the presence of parental loading for anxiety disorders may help to identify the subgroup of inhibited children at very high risk for developing childhood-onset anxiety disorders.
Abstract: Objective Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders However, the factors determining which inhibited children were at risk for childhood onset of anxiety disorders remained unknown The authors of this study hypothesized that greater anxiety loading in parents would increase the risk for anxiety disorders in children with behavioral inhibition Method Using DSM-III structured interviews, the authors examined patterns of aggregation of anxiety disorders in parents of two existing cohorts of children, one cross-sectional and clinically derived (31 children, 60 parents) and the other epidemiologically derived and longitudinal (40 children, 75 parents) Within each cohort, parents were stratified into three groups based on the presence (behavioral inhibition and anxiety) or absence (behavioral inhibition only, no behavioral inhibition and no anxiety) of behavioral inhibition and two or more anxiety disorders in their child Results Parents of children with behavioral inhibition and anxiety, from both the clinical and nonclinical cohorts, had significantly higher rates of two or more anxiety disorders than did parents of children with behavioral inhibition only and parents of children with no behavioral inhibition and no anxiety Conclusions These results indicate that the presence of parental loading for anxiety disorders may help to identify the subgroup of inhibited children at very high risk for developing childhood-onset anxiety disorders

108 citations


Journal ArticleDOI
TL;DR: The scores of attention/information-processing measures derived from neuropsychological testing of 34 chronic psychotic, primarily schizophrenic patients were subjected to a principal components analysis and it was concluded that the flexibility factor requires further clarification.
Abstract: The scores of attention/information-processing measures derived from neuropsychological testing of 34 chronic psychotic, primarily schizophrenic patients were subjected to a principal components analysis. Measures were chosen a priori on the basis of a previous factor-analytic study by A.F. Mirsky (1987, Behavioral and psychophysiological markers of disordered attention, Environmental Health Perspectives 74:191-199). The factor pattern in the present study was strikingly similar to that reported by Mirsky on a largely nonpsychotic sample. In both studies, four factors emerged that may be identified as: a) perceptual motor speed; b) mental control (numerical-mnemonic); c) flexibility; and d) vigilance. This replication provides support for previously postulated types of attention and suggests that schizophrenic and other psychotic disorders are not associated with atypical organization of attention/information-processing dimensions. The authors discuss questions raised by Mirsky's previous results in light of the present findings. In particular, it was concluded that the flexibility factor requires further clarification. Implications of the findings for clinical evaluation and research in schizophrenia are discussed as well.

65 citations


Journal ArticleDOI
TL;DR: Results showed that the effect of gender on the transmission of schizophrenia could not be explained by gender differences in age at onset, symptom expression, premorbid history, and winter birth, however, premOrbid history had an effect on familial risk independent of gender, indicating that probands with a poor premor bid history had a lower familial risk for schizophrenia than those with a good premorbrid history.

40 citations


Journal ArticleDOI
TL;DR: This article delineates several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives and presents them for heuristic purposes so that they may serve to guide the interpretation of data.
Abstract: The search for indicators of vulnerability has been important in schizophrenia research, but, as in many areas, progress has been impeded due to the heterogeneity of schizophrenic disorders. How one conceptualizes the observed heterogeneity is dependent upon the particular genetic model to which one subscribes. In this article, we delineate several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives. We present these models for heuristic purposes so that they may serve to guide the interpretation of data with respect to the issue of teasing apart familial and nonfamilial environmental components of putative vulnerability indicators. It is suggested that investigators will profit by: a) efforts to combine psychiatric genetic paradigms in order to maximize the yield of family study data, and b) thinking in terms of comparing the ability of different models to account for research findings.

38 citations


Journal ArticleDOI
TL;DR: The results indicate that to be certain of adequate statistical power, linkage analyses of schizophrenia will require very large samples that do not have a marked degree of genetic heterogeneity.
Abstract: In planning for a linkage study, it is important to determine the number of pedigrees needed to show linkage. Our study overcomes some of the limitations of previous power studies by simulating multigeneration pedigrees to be compatible with the demographic and genetic epidemiological features of schizophrenia; these are variable age at onset, reduced fertility, and increased mortality after onset. We evaluate the power of these pedigrees by first simulating an ascertainment rule requiring at least three ill family members per pedigree and then simulating the trait and marker genotypes according to a single gene model known to fit epidemiological family study data. Our analysis allows for incomplete and age-dependent penetrance, phenocopies, and interpedigree heterogeneity. We present the power to detect linkage at several lod score thresholds since the multiple tests and phenotypic models required for complex diseases may necessitate using a lod score significance level greater than three. The sample size needed to achieve sufficient power is feasible if 50% of the pedigrees are linked to the marker under test. It may not be feasible to detect linkage if only 25% of the pedigrees are linked, even if a very closely linked marker is used. Our results indicate that to be certain of adequate statistical power, linkage analyses of schizophrenia will require very large samples that do not have a marked degree of genetic heterogeneity. © 1992 Wiley-Liss, Inc.

31 citations


Journal ArticleDOI
TL;DR: A mathematical model is developed to account for the complex relationship between drug dose and clinical response in psychopharmacologic research which indicates that random assignment to two fixed doses is more powerful and less sensitive to heterogeneity than assignment to clinically determined doses.
Abstract: We develop a mathematical model to account for the complex relationship between drug dose and clinical response in psychopharmacologic research. The model specifies relationships among drug dose, drug bioavailability, pharmacokinetic factors, course moderators, clinical response and the heterogeneity of the disorder, and allows for the derivation of results that have implications for experimental design in psychopharmacologic research. These results form the basis for computer simulations which indicate that random assignment to two fixed doses is more powerful and less sensitive to heterogeneity than assignment to clinically determined doses. Fixed dose designs, however, tend to overestimate the magnitude of drug bioavailability-clinical response relationships. Clinically determined dose designs are useful in some experimental situations; their effectiveness is enhanced by systematically reducing the clinically determined dose. Larger dose reductions improve the ability to detect bioavailability-clinical response relationships.


Journal ArticleDOI
TL;DR: In this paper, the authors comprehensively review methods for estimating the age at onset distribution of a disease and make recommendations for use of current methods and suggestions for future investigations of the issue.
Abstract: Since many genetic diseases have a variable age at onset, knowing the age at onset distribution of a disease facilitates genetic analyses in several ways. Age at onset distributions are used to estimate the risk of illness among relatives of probands and can improve estimates of recurrence rates in genetic counselling. The age at onset distribution is also useful when we test genetic hypotheses in segregation and linkage analyses. Unfortunately, estimation of a disease's age at onset distribution is not straightforward. The distribution we observe in a series of cases is biased towards younger ages and the magnitude of the bias is not negligible. In this paper we comprehensively review methods for estimating the age at onset distribution. We classify these methods based on the type of data required for the analysis: (1) independently ascertained probands; and (2) pedigree data. In presenting these methods, we focus on their conceptual derivation, mathematical formulation and critical assumptions. We also examine factors that limit the applicability of these methods to psychiatric disorders. We conclude with recommendations for use of current methods and suggestions for future investigations of the issue.

Book ChapterDOI
01 Jan 1992
TL;DR: Looking back at the proceedings of the last conference, I saw that I had discussed unreliability in psychiatric diagnoses, but the primary problem in psychiatric diagnosis no longer can be said to be unreliability, and the validity of diagnosis now faces a more complex and perhaps less tractable issue.
Abstract: Looking back at the proceedings of our last conference, I saw that I had discussed unreliability in psychiatric diagnoses. However, the primary problem in psychiatric diagnosis no longer can be said to be unreliability. Fortunately, substantial and impressive progress has been made during the past two decades. We now face a more complex and perhaps less tractable issue — the validity of diagnosis. One reason to be less sanguine about progress in improving validity compared to reliability is that, while we can reliably measure reliability, identifying a clear-cut criterion for validity is problematic. If one wants to improve something, it is helpful, if not necessary, to be able to measure it.