Biomedical subjects

S V Faraone

Publications and source records attributed to S V Faraone.

At least 217 records · Page 12Linked to original sources

PubMed1993

Unipolar relatives in bipolar pedigrees: a search for indicators of underlying bipolarity.

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 unipolars. Using data from the Collaborative Study of the Psychobiology 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 somewhat more likely to be male and to have subthreshold bipolar features, and less likely to have panic symptoms. In addition, they had a small but significant decrease in the number of depressive symptoms and a large decrease in all treatment indicators. A multiple logistic regression model for these differences was highly significant, but had limited ability to discriminate between the two groups. These differences are not large enough to effectively discriminate between the groups for the purposes of classification. These particular results may result from a number of factors, most likely the choice of comparison group. Nonetheless, the work demonstrates a potential method for the construction of caseness indices for use in genetic studies of bipolar and other psychiatric disorders.

Adult↗

PubMed1993

Estimating age at onset distributions: the bias from prevalent cases and its impact on risk estimation.

Since many disorders have a variable age at onset, knowing the age at onset distribution of a disease facilitates epidemiologic analyses in several ways. The age at onset distribution is commonly used to estimate morbidity risks or the recurrence risks in genetic counseling. Unfortunately, estimation of a disease's age at onset distribution is not straightforward. The observed age at onset distribution obtained from prevalent cases is usually used in these epidemiologic analyses. Through simulation studies, we show that, in certain situations, the observed age at onset distribution has a non-negligible downward bias. This bias can lead to a substantial underestimation of the morbidity risk or the recurrence risk. The simulations also demonstrate that a non-parametric approach for correcting the age at onset distribution works well even when mortality increases after onset. The results have implications for diseases that have adult onset and/or increased mortality after onset. We suggest that researchers should use corrected age at onset distributions, rather than relying on observed distributions, in the calculation of either morbidity risks or recurrence risks.

Adolescent↗

PubMed1993

Identification of the phenotype in psychiatric genetics.

Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.

Aged↗

PubMed1993

A family study of self-reported personality traits and DSM-III-R personality disorders.

Personality traits and DSM-III-R personality disorders of first-degree relatives of patients with psychoses were studied using the NEO Five-Factor Inventory (NEO-FFI) and the Personality Diagnostic Questionnaire-Revised (PDQ-R), two self-report instruments. The relatives were compared on their scores for the five personality factors in the NEO-FFI, the prevalence of individual DSM-III-R personality disorders, and their scores for each personality disorder scale in the PDQ-R. The results suggest that there is no difference in personality traits and prevalence of personality disorders, including schizophrenia spectrum disorders, when relatives of patients with schizophrenia, bipolar disorder, and major depression are compared to each other. Relatives of patients with "atypical psychosis," psychotic disorders that do not meet DSM-III-R criteria for any specific nonorganic psychotic disorder, may be a distinctive group.

Adult↗

PubMed1993

Efficiency of diagnostic criteria for attention deficit disorder: toward an empirical approach to designing and validating diagnostic algorithms.

Using structured psychiatric interviews, 73 attention deficit disorder (ADD) patients, 26 psychiatric control patients, 26 normal controls, and all available first degree relatives of these index children were examined. ADD subgroups with and without comorbid psychiatric disorders did not differ on rates of specific ADD symptoms. The construct of ADD is internally consistent as measured by Cronbach's alpha. The diagnostic efficiency of individual items is presented. A receiver operating characteristic-based procedure is used to create an ADD diagnostic algorithm that is more efficient in discriminating ADD children from controls than the DSM-III-based clinical diagnosis. Cross-validation with family study data shows this procedure to be superior to the procedure used for the DSM-III-R diagnosis. The results show that proponents of conditional probability and receiver operating characteristic analyses are correct in asserting that the examination of symptom combinations may result in better diagnostic algorithms.

Algorithms↗

PubMed1993

Diagnoses of attention-deficit hyperactivity disorder from parent reports predict diagnoses based on teacher reports.

OBJECTIVE: For DSM-III attention deficit disorder (ADD), it was previously reported that, when a parent report leads to a diagnosis of ADD, it is highly likely that the teacher report will also be positive. This report seeks to generalize that finding to DSM-III-R attention-deficit hyperactivity disorder (ADHD). METHOD: In a population of 34 children meeting clinical criteria for DSM-III-R ADHD, parents and teachers independently responded to questions about individual ADHD symptoms. RESULTS: Correlations between parents and teachers for individual symptoms were low to moderate; however, there was a 77% probability that the teacher report would result in a positive diagnosis given a positive parent diagnosis. This probability increased to 88% if "broad" teacher diagnoses of ADHD, defined by 35% of the 14 DSM-III-R symptoms, were included. CONCLUSIONS: In clinically-referred children, a clinical diagnosis of ADHD based on parent report is likely to be corroborated by a teacher report.

Attention Deficit Disorder with Hyperactivity↗

PubMed1993

A 3-year follow-up of children with and without behavioral inhibition.

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. Although these findings suggested that "behavioral inhibition to the unfamiliar" may be associated with risk for anxiety disorders in children, longitudinal data were needed to confirm the initial impressions. METHOD: Using DSM-III structured interviews, the authors examined psychiatric disorders at 3-year follow-up in children of two independently ascertained, previously described, and preexisting samples of children. One sample was cross sectional and clinically derived (Massachusetts General Hospital at-risk sample), and the other was epidemiologically derived and longitudinal (Kagan et al. Longitudinal Cohort). RESULTS: Analyses of follow-up findings revealed significant differences between inhibited and not inhibited children in the rates of multiple > or = 4 psychiatric disorders, multiple > or = 2 anxiety disorders, avoidant disorder, separation anxiety disorder, and agoraphobia. Among inhibited children, the rates of anxiety disorders increased markedly from baseline to follow-up assessments, attaining statistical significance for multiple > or = 2 anxiety disorders and avoidant disorder. Our findings also show there were significant differences between inhibited and not inhibited children in the emergence of multiple > or = 2 anxiety disorders, avoidant disorder, and separation anxiety disorder in children who did not have these diagnoses at baseline. CONCLUSIONS: These findings indicate that inhibited children are at high risk for developing childhood-onset anxiety disorders and provide additional support for the hypothesis that behavioral inhibition is a predictor of later anxiety disorder.

Adolescent↗

PubMed1993

Are perinatal complications relevant to the manifestation of ADD? Issues of comorbidity and familiality.

OBJECTIVE: We evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit disorder (ADD) addressing issues of comorbidity and familiarity by formulating and testing multiple hypotheses. METHOD: Subjects were six to 17-year-old boys with DSM-III attention deficit disorder (ADD, N = 73), psychiatric (N = 26), and normal (N = 26) controls and their relatives. Information on PDICs was obtained from the mothers in a standardized manner blind to the proband's clinical status. RESULTS: Using odds ratio analyses, an association was found between ADD and PDICs that was strongest for the comorbid and nonfamilial subtypes. In contrast, noncomorbid and familial ADD subgroups differed less from normal controls in the risk for PDICs. CONCLUSIONS: The increased risk for PDICs in nonfamilial ADD children and the lack of evidence for increased risk among familial ADD patients suggests that PDICs may be part of nongenetic etiologic mechanisms in this disorder, especially for children who have comorbid disorders.

Adolescent↗

PubMed1993

Social Adjustment Inventory for Children and Adolescents: concurrent validity in ADHD children.

OBJECTIVE: The assessment of children's adaptive functioning has broad-range implications for clinical practice, research, and public health, and relatively few well-developed assessment instruments are available. The validity of the Social Adjustment Inventory for Children and Adolescents (SAICA), a semistructured interview schedule that assesses adaptive functioning in children and adolescents, was examined. METHOD: Two groups of index children were examined: 140 attention-deficit hyperactivity disorder (ADHD) children (both psychiatric and pediatric referrals) and 120 normal comparisons. RESULTS: Concurrent validity was found for the SAICA in its significant association with the social competence scales of the Child Behavior Checklist and DSM-III-R's Global Assessment of Functioning. It was also found that among ADHD children, psychiatric comorbidity conferred an increased risk for worse adaptive functioning. CONCLUSIONS: These findings suggest the SAICA is an effective way to assess adaptive functioning. Moreover, its ability to discriminate ADHD from control children and its association with psychiatric comorbidity indicate the SAICA measures adaptive functioning within a range relevant for studies of psychopathology.

Adolescent↗

PubMed1993

Convergence of the Child Behavior Checklist with structured interview-based psychiatric diagnoses of ADHD children with and without comorbidity.

We evaluated the convergence of CBCL scales with the diagnosis of ADHD and comorbid disorders in 133 ADHD and 118 normal control boys, aged 6-17 years old. We evaluated the strength of association between each CBCL scale and structured-interview derived diagnoses with Total Predictive Value (TPV) and the odds-ratio (OR). Excellent convergence was found between the CBCL Attention Problems scale with the diagnosis of ADHD, between the Delinquent Behavior scale and the diagnosis of CD, and between the Anxiety/Depression scale and the diagnoses of Anxiety Disorders. These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify comorbid and non-comorbid cases of ADHD.

Adolescent↗

PubMed1993

Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder.

OBJECTIVE: Although attention deficit hyperactivity disorder is a common disorder of childhood, its status as a disorder in adults is not clear. The authors reasoned that if the adult diagnosis of the disorder is a valid clinical entity, it should be similar to the childhood disorder with regard to patterns of psychiatric and cognitive findings. METHODS: Eighty-four adults with a clinical diagnosis of childhood-onset attention deficit hyperactivity disorder confirmed by structured interview who were referred for treatment were studied. Findings were compared with those from a preexisting study group of referred children with attention deficit hyperactivity disorder, nonreferred adult relatives of those children who also had attention deficit hyperactivity disorder, and adults without the disorder who were relatives of normal children. Subjects were evaluated with a comprehensive battery of psychiatric, cognitive, and psychosocial assessments. RESULTS: The referred and nonreferred adults with attention deficit hyperactivity disorder were similar to one another but more disturbed and impaired than the comparison subjects without the disorder. The pattern of psychopathology, cognition, and functioning among the adults with attention deficit hyperactivity disorder approximated the findings for children with the disorder. CONCLUSIONS: These results show that referred and nonreferred adults with attention deficit hyperactivity disorder have a pattern of demographic, psychosocial, psychiatric, and cognitive features that mirrors well-documented findings among children with the disorder. These findings further support the validity of the diagnosis for adults.

Adult↗

PubMed1993

Evidence for the independent familial transmission of attention deficit hyperactivity disorder and learning disabilities: results from a family genetic study.

OBJECTIVE: The purpose of the study was to clarify the relationship between attention deficit hyperactivity disorder and learning disabilities. METHOD: The authors assessed learning disabilities in a sample of 140 children with attention deficit hyperactivity disorder and in 120 normal comparison children. They also assessed a sample of the probands' 822 first-degree relatives. RESULTS: The risk for learning disabilities was highest among relatives of probands with both attention deficit hyperactivity disorder and learning disabilities. The two disorders did not cosegregate in families. There was nonrandom mating between spouses with attention deficit hyperactivity disorder and learning disabilities. CONCLUSIONS: The two disorders are transmitted independently in families, and their co-occurrence may be due to nonrandom mating. Attention deficit hyperactivity disorder is likely to be etiologically independent from learning disabilities.

Adult↗

PubMed1993

The role of gender in understanding the familial transmission of schizoaffective disorder.

The purpose of this study was to test the effect of gender on the familial risk for schizophrenia and affective disorders in probands with schizoaffective disorder. The sample consisted of 42 DSM-III schizoaffective probands and 149 first-degree relatives from the retrospective cohort family studies, the Iowa 500 and non-500. Survival analysis estimated differences in morbidity risks, analysed by sex of proband and of relative. Findings showed that, among probands, relatives of females had significantly higher rates of schizophrenia and unipolar disorder than relatives of males. Further, among relatives, males were at significantly higher risk for schizophrenia spectrum disorders than females. Results were similar when probands were subdivided into their primary symptom patterns, that is 'mainly schizophrenic' or 'mainly affective', as well as by 'schizoaffective, depressed' or 'schizoaffective, manic'. Implications for the taxonomy of schizoaffective disorder suggest a stronger relationship with schizophrenia, although the relationship with affective disorder remains unclear.

Adolescent↗

PubMed1992

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.

Adolescent↗

PubMed1992

Linkage studies of schizophrenia: a stimulation study of statistical power.

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.

Adult↗

PubMed1992

Mathematical models of complex dose-response relationships: implications for experimental design in psychopharmacologic research.

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.

Antipsychotic Agents↗

PubMed1992

Gender and the familial risk for schizophrenia. Disentangling confounding factors.

Recent studies of the effect of gender on the familial risk for schizophrenia have shown that relatives of females have a higher risk for schizophrenia than relatives of males. This study attempts to explain the effect by examining factors found to differentiate schizophrenic men and women and found to be related to the familial risk for schizophrenia. Cox proportional hazard regression model was used to examine the simultaneous effects of age at onset, season of birth, and premorbid history, controlled for symptoms that have been found to differ by gender (dysphoria, paranoia, and flat affect). 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 premorbid history had a lower familial risk for schizophrenia than those with a good premorbid history. Implications of the findings are discussed.

Adult↗

PubMed1992

Stable behavioral inhibition and its association with anxiety disorder.

"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.

Anxiety Disorders↗