Showing papers by "Stephen V. Faraone published in 1998"

Psychiatric, Neuropsychological, and Psychosocial Features of DSM-IV Subtypes of Attention-Deficit/Hyperactivity Disorder: Results From a Clinically Referred Sample

Abstract: Objective To assess the validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD). Method Using structured diagnostic interviews and psychometric measures of cognitive and social functioning, the authors assessed 413 children and adolescents consecutively referred to a pediatric psychopharmacology clinic since 1991. Results Marked psychiatric differences were found among DSM-IV subtypes of ADHD, but few differences were found in cognitive or psychosocial functioning. The greatest psychiatric differences were found between the combined-type subjects (who tended to show more impairment in multiple domains) and the other two subgroups. The inattentive patients, however, were more likely to have required extra help in school. The hyperactive-impulsive patients were not different from controls on rates of depression, Child Behavior Checklist measures of social functioning, or psychometric measures of intellectual functioning and academic achievement. Conclusions The results suggest that, regarding clinical features, combined-type patients have a more severe disorder than the other DSM-IV subtypes.

Effectiveness and Tolerability of Tomoxetine in Adults With Attention Deficit Hyperactivity Disorder

Abstract: OBJECTIVE: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide supp...

NIMH genetics initiative millennium schizophrenia consortium: Linkage analysis of African‐American pedigrees

Abstract: The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

Abstract: The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241–247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241–247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z=3.2, P = .0006). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:290–295, 1998. © 1998 Wiley-Liss, Inc.

Further evidence of an association between maternal smoking during pregnancy and attention deficit hyperactivity disorder: findings from a high-risk sample of siblings.

Abstract: Investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). Siblings of ADHD (N = 174) and non-ADHD (N = 129) probands were studied. Information on maternal smoking was obtained from mothers in a standardized manner blind to the sibling's ADHD and high-risk status (i.e., whether a sibling of an ADHD or non-ADHD proband). Fifteen (47%) of the high-risk siblings with ADHD had a history of maternal smoking during pregnancy compared with 33 (24%) of the siblings without ADHD (p = 0.009). This positive association remained significant after adjusting for socioeconomic status, parental IQ, and parental ADHD status. Lower IQ scores were found among those high-risk siblings whose mothers smoked during pregnancy compared with those whose mothers did not smoke. These findings extend our previous findings of an association between maternal smoking during pregnancy and ADHD. Moreover, they highlight the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of child-bearing age.

Disentangling the Overlap between Tourette's Disorder and ADHD

Abstract: Objective: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method: The sample consisted of children with Tourette's syndrome with ADHD(N=79), children with Tourette's syndrome without ADHD (N=18), children with ADHD (N=563), psychiatrically referred children (N=212), and healthy controls (N=140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCDbut suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.

Adults with attention-deficit/hyperactivity disorder: a controversial diagnosis.

Abstract: The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has remained controversial. This paper reviews the empirical evidence to date as to whether the diagnosis of ADHD in adults is valid and consistent with the childhood syndrome. Evidence of descriptive, divergent, predictive, and concurrent validity were examined. The available literature provides evidence that adult ADHD can be reliably diagnosed and that the diagnosis confers considerable power to forecast complications and treatment response. Studies of genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals are also consistent with studies in childhood ADHD. There is converging evidence that adult ADHD is a not rare, valid clinical diagnosis. In addition, studies suggest that adult and child patients with ADHD may share a similar treatment-responsive, underlying neurobiological substrate.

A Registry-Based Twin Study of Depression in Men

Abstract: Background The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men. Methods Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Probandwise concordance rates and biometric modeling were used to analyze the data. Results The diagnosis of major depression (MD), as defined by DSM-III-R , and the subtype of severe/psychotic MD were significantly affected by genetic ( h 2 =0.36 and 0.39, respectively) and nonshared environmental ( e 2 =0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental ( c 2 =0.27, 0.08, and 0.14, respectively) and nonshared environmental ( e 2 =0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic ( h 2 =0.47 and 0.10, respectively) and nonshared environmental ( e 2 =0.53 and 0.90, respectively) factors. Early-onset MD was significantly more heritable than late-onset MD. Conclusions The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.

Diagnostic continuity between child and adolescent ADHD: findings from a longitudinal clinical sample.

Abstract: Objective To determine whether there are differences in the clinical expression and correlates of attention-deficit hyper-activity disorder (ADHD) between children and adolescents. Method Subjects were 6− to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews, psychometric measures, and blind raters assessed psychiatric diagnoses, intellectual performance, social disability, school failure, and family functioning. Results Children and adolescents with ADHD had an almost identical pattern of correlates in multiple domains of assessment including psychosocial adversity and comorbidity with conduct, mood, and anxiety disorders. Although the rate of substance abuse differed in comparison between child and adolescent subjects, this was independent of ADHD status. Conclusions These findings document the diagnostic continuity of ADHD between childhood and adolescence and support the inclusion of adolescent samples in ADHD research protocols. J. Am. Acad. Child Adolesc. Psychiatry, 1998, 37(3):305–313.

Factor structure of the Wisconsin Card Sorting Test: Dimensions of deficit in schizophrenia.

Abstract: The aim of this study was to explore the factorial structure of the Wisconsin Card Sorting Test (WCST) and to identify the dimensions of deficit in schizophrenia. WCST scores in patients with schizophrenia and schizophrenia-related psychosis (n = 292), 1st degree relatives of schizophrenic patients (n = 91), and normal controls (n = 141) were subjected to a principal factor analysis followed by orthogonal rotation. This led to 3 factors, perseveration, failure to maintain set, and idiosyncratic sorting. The detected factor structure was found to be invariant across the schizophrenic and control subsamples. Moreover, it replicated previous findings from 2 smaller samples. Only perseverations and, to a lesser degree, idiosyncratic sorting appeared to differentiate schizophrenic patients from comparisons. Only perseveration had good sensitivity and specificity, as well as the most robust significant correlations with estimates of IQ, attention, and other measures of executive functioning. Thus, perseveration appears to be the most diagnostically useful and characteristic WCST feature of schizophrenia.

The naturalistic course of pharmacologic treatment of children with maniclike symptoms: a systematic chart review.

Abstract: Objective: To assess the effectiveness of mood stabilizers in treating maniclike symptoms in children. Method: Subjects were consecutively referred pediatric patients who, at initial intake, satisfied DSM-III-R criteria for mania on a structured diagnostic interview. We systematically reviewed their clinical records to assess (1) the course of maniclike symptoms and (2) all medications prescribed at each follow-up visit. Survival analysis was used to determine the effect of mood stabilizers and other medications on the course of maniclike symptoms. Results: Of the 59 subjects meeting criteria for mania, 44 (75%) exhibited evidence of maniclike symptoms during follow-up. The occurrence of manic symptoms significantly predicted the subsequent prescription of mood stabilizers (rate ratio = 2.9, 95% confidence interval [CI = 1.6 to 5.5), and use of mood stabilizers predicted decreases in manic symptoms (rate ratio = 4.9, 95% CI = 1.2 to 20.8). However, improvement was slow and associated with a substantial risk for relapse. Conclusion: Mood stabilizers were frequently used in children with maniclike symptoms, and their use was associated with significant improvement of maniclike symptoms, whereas use of antidepressant, antipsychotic, and stimulant medications was not.

Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH genetics initiative

Abstract: Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia.

Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands.

Abstract: Evidence of subtle neuropsychological deficits in relatives of schizophrenic probands (REL-SZs) suggests that these are risk indicators for schizophrenia, but little is known about whether neuropsychological performance in REL-SZs differs from that in other groups of relatives. We compared neuropsychological function in female REL-SZs (n = 39), relatives of primarily psychotic bipolar disorder probands (REL-BPs; n = 15), and a normal control group (n = 44). After adjustment for expected intellectual ability (based on reading recognition), REL-SZs showed deficits in verbal and visual memory (Wechsler Memory Scale-Revised logical memories, visual reproductions), and auditory attention (dichotic digits) compared with either REL-BPs or control subjects. Memory, but not dichotic listening differences remained significant after adjusting for current IQ; however, average effect sizes after controlling for either reading or IQ were roughly comparable for these three parameters (d = 0.80, 0.71, and 0.69, respectively). REL-BPs and control subjects showed little difference. Although both schizophrenic and bipolar patients often manifest neuropsychological dysfunction, these preliminary findings indicate subtle neuropsychological deficits only in REL-SZs. Such differences suggest different underlying processes; neuropsychological impairment may, in part, reflect an expression of genetic liability to schizophrenia but not bipolar disorder. Replication with a larger REL-BP sample and with male relatives is needed to evaluate the generalizability of the results.

Familial Subtypes of Attention Deficit Hyperactivity Disorder: A 4‐year Follow‐up Study of Children from Antisocial‐ADHD Families

Abstract: ADHD is a familial disorder with high rates of comorbidity with conduct disorder in childhood and antisocial personality and substance use disorders in adulthood. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. Previously, we proposed a family-based stratification that defined Antisocial families as those with either conduct disorder or antisocial personality disorder in the probands or relatives. To provide predictive validity for that stratification, we assessed psychopathology in these families 4 years after their initial assessment. Results show that the probands and siblings from Antisocial families had higher rates of psychopathology during the 4-year follow-up period compared with siblings from Non-antisocial and control families. They also had more deviant ratings on the Child Behavior Checklist (especially for anxious/depressed, delinquent, and aggressive behavior). We found fewer group differences in the academic, psychosocial, and intellectual correlates of ADHD. These results confirm and extend previous work indicating that Antisocial ADHD may be a nosologically and clinically meaningful subform of ADHD.

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

Abstract: Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

Negative, Positive, and Disorganized Symptom Dimensions in Schizophrenia, Major Depression, and Bipolar Disorder

Abstract: We compared the factor structure of positive and negative symptoms in schizophrenia (N = 214), major depression (N = 97), and bipolar disorder (N = 58) to determine whether schizophrenia factors would generalize to mood disorders. A study of schizophrenia and mood disorders identified patients whose symptoms were evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. We conducted principal component analyses with orthogonal rotation on the global ratings. The factor structure replicated earlier findings of three factors (negative, positive, and disorganization) in groups with schizophrenia, combined mood disorders, and psychotic symptoms, regardless of diagnosis. An additional negative symptom factor was found in the major depression group. The bipolar group did not have a disorganization factor. Similar symptom factors in schizophrenia and mood disorders suggest a continuity in the major affective and psychotic disorders that appears to reflect the underlying dimension of a psychotic process.

Genome-wide search for schizophrenia susceptibility loci : The NIMH Genetics Initiative and Millennium Consortium

Abstract: Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

Informativeness of child and parent reports on substance use disorders in a sample of ADHD probands, control probands, and their siblings.

Abstract: Objective To evaluate parent-child agreement on psychoactive substance use disorder (PSUD) reporting among children with attention-deficit hyperactivity disorder (ADHD) and to test whether agreement level could be predicted from measures of parent and child psychopathology and substance use severity. Method The authors examined 348 pairs of child and parent assessments in a sample of 108 ADHD and 68 normal control probands and their 172 siblings aged 12 and older. Results PSUD rates were higher when the child was the reporter than when the parent was. Agreement between parent and child reports was strongest for cigarette smoking, alcohol dependence, and any PSUD. Although parental reports were frequently endorsed by the child's report, the reverse was rarely true. Predictors of parental awareness of the child's PSUD included impaired social functioning, younger age of the child, presence of multiple substance use disorders in the child, and comorbid bipolar disorder. Conclusions PSUD rates vary by informant and are higher when the child is the reporter. Because severity of PSUD and multiple substance use were the strongest predictors of parental awareness, more efforts are needed to identify the more covert and milder cases of PSUD that may not reach clinical attention. J.Am.Acad. Child Adolesc. Psychiatry, 1998, 37(7):752–758.

Clinical Characteristics of Attention Deficit Hyperactivity Disorder in African American Children

Abstract: OBJECTIVE: The authors' goal was to explore the nature of attention deficit hyperactivity disorder (ADHD) in African American children, which has received scant attention by psychiatric researchers. METHOD: Subjects were 19 African American children with DSM-III-R ADHD and 24 African American children without ADHD. Ethnically sensitive methods were used to evaluate the children comprehensively. The findings were compared with those from an earlier study of Caucasian children with ADHD. RESULTS: African American children with ADHD had higher levels of psychiatric disorders other than ADHD than did African American children who did not have ADHD. CONCLUSIONS: Among African American children, ADHD may be characterized by a narrower pattern of psychiatric comorbidity and dysfunction than has been observed in Caucasians. Given the small number of subjects studied, these findings are preliminary and must be replicated to confirm their validity.

Detection of IgG and IgA against the mycobacterial antigen A60 in patients with extrapulmonary tuberculosis

Abstract: Background—Diagnosis of extrapulmonary tuberculosis is often diYcult to establish using standard methods. Serological techniques based on detection of antibodies against mycobacterial antigen A60 have shown good sensitivity and specificity in pulmonary tuberculosis.The present study was undertaken to define the diagnostic accuracy of testing for IgG and IgA against A60 in extrapulmonary tuberculosis. Methods—One hundred and ninety eight subjects were studied: 42 patients with extrapulmonary tuberculosis confirmed by microbiology and/or histology, 24 subjects with healed pulmonary or extrapulmonary tuberculosis, 44 patients with a defined non-tuberculous disease, and 88 healthy volunteers (44 PPD negative and 44 PPD positive). Detection of IgG and IgA against A60 antigen was carried out by enzyme-linked immunosorbent assay. Cut oV values were determined by receiver operating characteristic curves. Results—Sensitivity of the IgG test was 73.8% in extrapulmonary tuberculosis, while the specificity was 96.1%. The IgA test showed a sensitivity of 69.0% with a specificity of 93.6%. Combination of the IgG and IgA tests showed a sensitivity of 80.9% and a specificity of 92.3%. Patients with extrapulmonary tuberculosis showed significantly higher titres of both IgG and IgA against A60 than other groups. Conclusions—Anti-A60 IgG or IgA tests are characterised by good sensitivity and specificity. The combined use of both tests allows an increase in diagnostic accuracy of extrapulmonary tuberculosis. (Thorax 1998;53:377‐380)

Familial Risk Analysis of the Association Between Attention-Deficit/Hyperactivity Disorder and Psychoactive Substance Use Disorders

Abstract: Objective To test hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUDs) by using the family study method. Design The first-degree relatives of clinically referred children and adolescents with ADHD (131 probands, 413 relatives) and healthy control probands (106 probands, 323 relatives) were assessed by blind raters. Results After stratifying the probands with ADHD and the control probands into those with PSUD (group 1 and group 3, respectively) and those without PSUD (group 2 and group 4, respectively), familial risk analyses revealed the following: (1) the risk for ADHD was not significantly different between relatives of group 2 and group 1 probands (19.6% vs 18.0%; P =.88), but these 2 risks were significantly greater than the risk to relatives of group 3 probands (1.0%; P =.01 and P =.02, respectively) and group 4 probands (7.0%; P =.001 and P =.01, respectively); (2) there were no significant differences in the risk for PSUD between relatives of group 1 (47.5%) and group 3 probands (39.7%; P =.40), but these risks were greater than the risk to relatives of group 2 (30.0%; P =.32) and group 4 probands (20.9%; P Conclusions These findings are consistent with the hypothesis that ADHD and PSUD are transmitted independently in families. Because the probands were young adolescents, many have not lived through the age at risk for PSUD. Thus, the hypothesis stating that ADHD and PSUD represent variable expressions of a common underlying risk factor cannot be ruled out.