Showing papers by "Stephen V. Faraone published in 1994"

Neuropsychological Risk Indicators for Schizophrenia: A Review of Family Studies

Abstract: We reviewed potential neuropsychological risk indicators for schizophrenia by addressing two broad questions about neuropsychological performance in biological relatives of schizophrenia patients: (1) Is there evidence of deficits, and, if so, (2) are those deficits similar to deficits found in schizophrenia patients themselves? There has not yet been adequate validation of most neuropsychological risk indicators, but promising leads have emerged from studies of relatives of persons with schizophrenia. The strongest evidence of impairment in relatives was in sustained attention, perceptual-motor speed, and concept formation and abstraction; to a slightly lesser extent, mental control/encoding (primarily with distraction) was implicated as well. Impairments in verbal memory and verbal fluency were also found, although these have been less well studied. The pattern of deficits paralleled that found in schizophrenia patients, thus suggesting dysfunction in prefrontal, temporal-limbic, and attentional systems. Findings were similar for children and adult relatives of schizophrenia patients. It is suggested that future studies (1) emphasize comprehensive test batteries, (2) develop composite neuropsychological measures, (3) use profile and deviant-responder analyses, (4) include psychiatric comparison groups, and (5) integrate neuropsychological assessments with brain imaging techniques.

Diagnostic Accuracy of the Child Behavior Checklist Scales for Attention-Deficit Hyperactivity Disorder: A Receiver-Operating Characteristic Analysis.

Abstract: The diagnostic accuracy of the Child Behavior Checklist (CBCL) scales for attention-deficit hyperactivity disorder (ADHD) were examined using receiver-operating characteristic (ROC) analysis. Three logistic regression models were estimated in an initial sample of 121 children with and without ADHD. These models were then tested in a cross-validation sample (N = 122) and among the 111 brothers and 108 sisters of the initial and cross-validation samples. In all four groups, the CBCL Attention Problems scale had the highest discriminating power for ADHD. Adding other scales did not increase the area under the curve of the ROC significantly. These findings suggest that the CBCL Attention Problems scale could serve as a rapid and useful screening instrument not only to help identify cases likely to meet criteria for ADHD in clinical settings but also to identify cases of ADHD among the siblings of children with ADHD.

Gender differences in a sample of adults with attention deficit hyperactivity disorder.

Abstract: Although originally conceptualized as a childhood disorder, attention deficit hyperactivity disorder (ADHD) may also be an adult disorder. However, despite increasing media attention to adult ADHD, its validity has only recently been studied in a systematic fashion. The overrepresentation of females in adult samples in comparison to pediatric samples of ADHD raises additional questions about the validity of this disorder in adults. The goal of this article is to explore whether ADHD is a valid clinical entity in female subjects and whether it is expressed differently in male and female adults. To this end, we examined the clinical, cognitive, and functional characteristics of 128 referred adult ADHD cases of both sexes. Each subject had a clinical diagnosis of childhood-onset ADHD confirmed by structured interview. The male and female ADHD adults were similar to one another but more disturbed and impaired than non-ADHD adult control subjects. Compared with normal control females, ADHD women had higher rates of major depression, anxiety disorders, and conduct disorder; and more evidence of school failure and cognitive impairment. The consistency of these findings in both genders further supports the validity of the diagnosis of ADHD in adults. Our results stress the viability and importance of identification of female subjects with ADHD. The underidentification and undertreatment of females with ADHD may have substantial mental health and educational implications, suggesting that research is needed to develop a better understanding of clinical indicators of ADHD in females.

Measuring diagnostic accuracy in the absence of a "gold standard".

Abstract: Objective As the nation debates issues of national health care reform, psychiatrists seek equal status with other medical colleagues. To defend psychiatry in the national arena, the accuracy of psychiatric diagnoses must be measured. Indexes of accuracy such as sensitivity and specificity provide valuable information, yet they are rarely computed because there is no "gold standard" with which to compare them. The goal of this article is to show how this problem can be overcome and to encourage nosologists to use accuracy statistics in assessing the adequacy of psychiatric diagnoses. Method The authors reviewed the literature on medical decision making to find methodological approaches to assessing diagnostic accuracy in the absence of gold standards. Results A lack of such standards is not unique to psychiatry and has been addressed with a variety of novel analytic procedures. Although these methods differ in many respects, each recognizes that the conventional 2 x 2 table of interrater agreement does not provide enough data for estimating diagnostic accuracy. After defining the data needed, each method provides a mathematical model that estimates accuracy statistics and the prevalence of a disorder. Most of these methods are variants of latent class analysis. The authors reanalyzed data from one of the reviewed papers to show that similar inferences about accuracy of diagnoses could be drawn from a conventional latent class analysis. Conclusions There are potential pitfalls in using latent structure methods, but their cautious use would provide valuable information for psychiatric nosology. These methods supplement, but do not replace, data about outcome, family history, laboratory studies, and other validating criteria in making accurate diagnoses.

Tourette's syndrome: what are the influences of gender and comorbid obsessive-compulsive disorder?

Abstract: Objective To explore the influence of gender and comorbid obsessive-compulsive disorder (OCD) on the phenomenology of Tourette's syndrome (TS). Method TS proband groups defined by gender and comorbid OCD status were compared on a variety of sociodemographic variables, clinical characteristics, and perinatal complications. Results Compared to females, males more often onset with rage and had ever experienced any form of simple tics. Females onset with compulsive tics more often than males. Probands with comorbid OCD were more likely than those without OCD to onset with complex tics. Delivery complications, especially forceps deliveries, were associated with being male and with having OCD. Fetal exposure to relatively high levels of coffee, cigarettes, or alcohol predicted OCD in TS probands. Diagnosis of TS occurred at later ages among females than among males. Males and females displayed different age distributions. Conclusions Males and females tend to experience different kinds of symptoms at onset. However, the overall experience of TS appears to be similar for both groups. Perinatal brain injury is implicated in the etiology of TS in some boys. Early brain injury may cause or exacerbate the development of OCD in some TS sufferers.

Is Attention-Deficit Hyperactivity Disorder in Adults a Valid Disorder?

Abstract: Concerns have been raised regarding the validity of the diagnosis of attention-deficit hyperactivity disorder in adults. The purpose of this report is to evaluate critically whether this diagnosis in adults meets acceptable standards for diagnostic validity. A systematic search was conducted of the psychiatric and psychological literature for empirical studies dealing with adult attention-deficit hyperactivity disorder with childhood onset. These studies were examined for evidence of descriptive, predictive, and concurrent validity. The literature shows that this disorder can be reliably diagnosed in adults and that the diagnosis confers considerable power to forecast complications and treatment response. In addition, evidence is mounting for genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals. Evidence from the literature is increasingly pointing to the validity of adult attention-deficit hyperactivity disorder.

Gender differences in age at onset of schizophrenia.

Abstract: Numerous studies have found that male schizophrenic patients have earlier ages at onset than females. However, none of these studies have corrected the observed ages for known gender differences in the age distribution of the population. Using a pre-existing data set, we applied a non-parametric method to correct the male and female distributions of observed age at onset for sex-specific age distributions. The distributions of observed age at onset indicated earlier onset among males. After correction, the age-at-onset distributions shifted toward older ages, but the difference between males and females remained statistically significant. Thus, gender differences in the age at onset of schizophrenia are not artefactual.

Associations between childhood asthma and ADHD : issues of psychiatric comorbidity and familiality

Abstract: Objective In this paper we evaluate the association between asthma and attention-deficit hyperactivity disorder (ADHD), addressing issues of comorbidity and familiality by formulating and testing competing hypotheses. Method Subjects were 6− to 17-year-old boys with DSM-III-R ADHD ( N = 140) and normal controls ( N = 120) and their first-degree relatives. Information on asthma was obtained from the mothers in a standardized manner blind to the proband's clinical status. Results The risk for asthma did not meaningfully differ between ADHD and control children. Relatives of ADHD probands with and without asthma were at significantly greater risk for ADHD than relatives of normal controls. In contrast, the risk for asthma was significantly elevated only among relatives of children with ADHD plus asthma. Conclusions These findings argue against a substantial etiological or pathophysiological relationship between the two conditions but suggest that ADHD and asthma are independently transmitted in families. Thus, the observation of ADHD symptoms in an asthmatic child should not be dismissed out of hand as being a consequence of asthma since many asthmatic ADHD children may actually have ADHD.

Is Attention Deficit Hyperactivity Disorder Familial

Abstract: Using two sources of data, we review methodologic issues pertinent to family studies of attention deficit hyperactivity disorder to evaluate whether such studies define attention deficit hyperactivity disorder as a familial disorder. We systematically evaluate the relevant literature and provide a detailed overview of the Massachusetts General Hospital family-genetic studies of attention deficit disorder as defined in DSM-III and attention deficit hyperactivity disorder as defined in DSM-III-R. The available literature, and our double-blind, controlled studies indicate that attention deficit disorder and attention deficit hyperactivity disorder are familial. Moreover, the pattern of transmission of comorbid disorders suggests that attention deficit hyperactivity disorder is, from a familial perspective, distinct from anxiety disorders and learning disabilities. In contrast, attention deficit hyperactivity disorder with conduct disorder appears to be a familial subtype, and major depression appears to be a variable expression of the familial predisposition to attention deficit hyperactivity disorder. Although the available literature provides strong evidence for the familial transmission of attention deficit hyperactivity disorder, the mode of transmission requires further clarification. In addition, attention deficit hyperactivity disorder appears to be genetically heterogeneous, indicating that more work is needed to delineate genetically homogeneous subtypes and to describe the range of expression of their underlying genotypes. Family-genetic studies will continue to clarify the etiology and nosology of attention deficit hyperactivity disorder.

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

Abstract: 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 individ ual symptoms were low to moderate; however, there was a 77% probability that the teacher report would result in a positive diagnosis given a positive parental 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.

Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease.

Abstract: Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.

Comparison of schizotypal relatives of schizophrenic versus affective probands

Abstract: In order to investigate possible heterogeneity in schizotypal personality disorder (SPD), two groups of schizotypals, one related to schizophrenic probands (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14), ascertained in the same family study, were compared. The FSPD group had more inadequate rapport; the groups did not differ in the frequency of any other symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher rates of anxiety disorders. There was a higher risk of bipolar disorder in the relatives of NFSPDs and higher risk for anxiety disorders in the relatives of FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and atypical PDs and for having at least one PD.

ELISA method for evaluation of anti-A60 IgG in patients with pulmonary and extrapulmonary tuberculosis.

Abstract: Several studies on the IgG mediated humoral immune response against the mycobacterial antigen A60 are available in the literature. However extensive variability in observed responses has been reported. In the present study we measured by ELISA the titers of IgG antibodies against A60 in 50 tuberculin negative healthy subjects, (Group I); 44 tuberculin positive healthy subjects, (Group II); 13 patients with healed Tuberculosis (Group III); 22 patients with a defined acute or chronic Non Tuberculous Pulmonary Pathology (Group IV); 42 patients suffering from sputum positive Active Pulmonary Tuberculosis, (Group V); 15 patients with sputum negative Active Pulmonary Tuberculosis (Group VI) and 16 patients with Active Extrapulmonary Tuberculosis (Group VII). The assay was performed at the time of recruitment into the study, corresponding for patients of Groups IV to VII to the day of hospital admission; in patients from Groups III to VII the assay was repeated two weeks later. The cut-off point was defined as mean +2SD of values found in Groups I-IV and was 0.372 (expressed in Optical Density). By using this cut-off, the test on first blood samples was positive in 1/50 subjects from Group I, 1/44 from Group II, 0/13 from Group III, 3/22 patients from Group IV, 35/42 from Group V, 9/15 from Group VI, 9/16 from Group VII. On second blood samples, kept 9-12 days after starting anti-TB chemotherapy in Groups V, VI and VII, the test resulted positive in 0/13 patients from Group III, 3/22 from Group IV, 39/42 from Group V, 13/15 from Group VI and 14/16 from Group VII.

Estimating the morbidity risk for diseases having a variable age at onset.

Abstract: The morbidity risk assesses the risk of manifesting illnesses having a variable age at onset. We reviewed the conceptual derivation and critical assumptions of various methods for estimating morbidity risk by classifying them into two approaches. One approach uses an age at onset distribution as a weighting system. A second approach uses methods from survival analysis. Because survival methods estimate the morbidity risk and age at onset distribution simultaneously, they are preferable to weighting methods. Among weighting methods, Stromgren's estimator or Risch's maximum likelihood estimate are the methods of choice; the Kaplan-Meier estimator is the preferred survival analysis approach.