Showing papers by "Stephen V. Faraone published in 2000"

Age-Dependent Decline of Symptoms of Attention Deficit Hyperactivity Disorder: Impact of Remission Definition and Symptom Type

Abstract: OBJECTIVE: Symptom decline in attention deficit hyperactivity disorder (ADHD) was examined with different definitions of remission.METHOD: Symptoms in 128 boys were measured five times over 4 years. The prevalences of syndromatic (less than full syndrome), symptomatic (less than subthreshold diagnosis), and functional (full recovery) remission were estimated as a function of age with multivariate logistic regression.RESULTS: Age was significantly associated with decline in total ADHD symptoms and symptoms of hyperactivity, impulsivity, and inattention. Symptoms of inattention remitted for fewer subjects than did symptoms of hyperactivity or impulsivity. The proportion of subjects experiencing remission varied considerably with the definition used (highest for syndromatic remission, lowest for functional remission).CONCLUSIONS: These results indicate that differences in reported remission rates reflect the definition used rather than the disorder’s course. They provide systematic support for the clinical o...

Adoptive and biological families of children and adolescents with ADHD.

Abstract: Objective Using an adoption study design, the authors addressed the issue of genetics in attention-deficit hyperactivity disorder (ADHD). Method This study examined the rates of ADHD and associated disorders in the first-degree adoptive relatives of 25 adopted probands with ADHD and compared them with those of the first-degree biological relatives of 101 nonadopted probands with ADHD and 50 nonadopted, non-ADHD control probands. Results Six percent of the adoptive parents of adopted ADHD probands had ADHD compared with 18% of the biological parents of nonadopted ADHD probands and 3% of the biological parents of the control probands. Conclusion Results of this study lend support to the hypothesis that ADHD has a genetic component.

Patterns of alcohol and drug use in adolescents can be predicted by parental substance use disorders.

Abstract: Objective. To examine the specificity of risk for alcohol or drug abuse or dependence (substance use disorders [SUDs]) in offspring exposed to particular subtypes of parental SUDs. Methods. The original sample was derived from 2 groups of index children: 140 attention-deficit/hyperactivity disorder (ADHD) probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. Results. Independent of familial risk, exposure to parental SUDs predicted SUDs in the offspring. Controlling for duration of exposure, we found that adolescence was a critical developmental period for exposure to parental SUDs. Because all our analyses controlled for social class, ADHD status, and parental lifetime history of SUDs, these results show that exposure to parental SUDs predicts offspring SUDs independently of these risk factors. Conclusions. These results support the critical importance of familial environmental risk factors for the development of SUDs in youth in general and particularly in those at high risk for these disorders. These results highlight adolescence as a critical period for the deleterious effects of exposure to parental SUDs, supporting the need to develop preventive and early intervention strategies targeted at adolescents at high risk for SUDs.

Toward reformulating the diagnosis of schizophrenia.

Abstract: OBJECTIVE: The authors assess implications of DSM criteria for schizophrenia by reviewing the criteria’s 1) emphasis on psychotic features, 2) dissociation of symptoms from their etiology, 3) exclusive reliance on clinical features but exclusion of biological indicators, and 4) classification of schizophrenia as a discrete category. The authors then discuss alternative conceptions of schizophrenia that take into account recent data concerning its genetic and neurodevelopmental origins and its pathophysiological substrates.METHOD: The historical development of diagnostic criteria for schizophrenia is reviewed in the context of recent published data on the biology and development of schizophrenia.RESULTS: Growing evidence suggests that symptoms of psychosis may be a common end-state in a variety of disorders, including schizophrenia, rather than a reflection of the specific etiology of schizophrenia. Features occurring before the advent of psychosis that are clinical, biological, and/or neuropsychological i...

Diagnostic efficiency of neuropsychological test scores for discriminating boys with and without attention deficit-hyperactivity disorder.

Abstract: A growing literature has documented group differences between boys with and without attention deficit-hyperactivity disorder (ADHD) on neuropsychological tests; however, whether or not such tests can discriminate individuals with ADHD from non-ADHD controls remains unclear. This study used conditional probability and receiver operating characteristic analyses to examine the efficiency of test-based diagnostic discriminations in a large sample of referred boys with and without ADHD. Single neuropsychological tests had limited discriminating ability at various cutoff scores. When multiple tests were used together, prediction of ADHD status improved but overall diagnostic efficiency remained limited. Diagnostic efficiency did not differ when medicated and nonmedicated index children were considered separately. Results suggest that children with ADHD show variable deficits on neuropsychological tests of attention and executive functions. Impairments on multiple neuropsychological tests are predictive of ADHD, but normal scores do not rule out the diagnosis. The prognostic implications of variable neuropsychological deficits in children with ADHD require further investigation.

Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder

Abstract: Converging evidence from family, twin, and adoption studies points to a substantial genetic component of the etiology of attention deficit hyperactivity disorder (ADHD). These data about ADHD have motivated molecular genetic studies of the disorder, which have produced intriguing but somewhat conflicting results. Some studies have reported associations with candidate genes and others not. Our review of the literature shows that one problem facing molecular genetic studies of ADHD is that its recurrence risk to first-degree relatives is only about five times higher than the population prevalence. This suggests that, to produce consistently replicated results, molecular genetic studies should either use much larger samples or should select those families in which genes exert the largest effect. Risch [(1990a) Am J Hum Genet 46:222-228; (1990b) Am J Hum Genet 46:229-241] proved that the statistical power of a linkage study increases with the magnitude of risk ratios (lambda's) computed by dividing the affection rate among each relative type to the rate of affection in the population. Our prior work suggests two dimensions of genetic heterogeneity that might be useful for selecting ADHD subjects for molecular genetic studies: comorbidity with conduct disorder and persistence of ADHD into adolescence. This paper shows that these sub-phenotypes are useful for molecular genetic studies because (1) they have much higher empirical lambda values and (2) they affect a substantial minority of ADHD patients.

A controlled study of behavioral inhibition in children of parents with panic disorder and depression.

Abstract: OBJECTIVE: “Behavioral inhibition to the unfamiliar” has been proposed as a precursor to anxiety disorders. Children with behavioral inhibition are cautious, quiet, introverted, and shy in unfamiliar situations. Several lines of evidence suggest that behavioral inhibition is an index of anxiety proneness. The authors sought to replicate prior findings and examine the specificity of the association between behavioral inhibition and anxiety. METHOD: Laboratory-based behavioral observations were used to assess behavioral inhibition in 129 young children of parents with panic disorder and major depression, 22 children of parents with panic disorder without major depression, 49 children of parents with major depression without panic disorder, and 84 children of parents without anxiety disorders or major depression (comparison group). A standard definition of behavioral inhibition based on previous research (“dichotomous behavioral inhibition”) was compared with two other definitions. RESULTS: Dichotomous behav...

Sustained attention deficits as markers of genetic susceptibility to schizophrenia.

Abstract: This article reviews recent evidence regarding the potential of the visual sustained attention deficits as measured by the Continuous Performance Test (CPT) as an endophenotype of the genetic susceptibility to schizophrenia. Findings in community subjects indicate that sustained attention develops during the primary school ages, reaches its maximum around early adolescence, and declines with age after adulthood. The assertion that CPT performance deficits, and especially on the more difficult versions, are reliable and valid genetic susceptibility indicators of schizophrenia is supported by the following results: 1) CPT deficits are present in schizophrenic patients, are particularly associated with negative and disorganized symptoms, and deficits on the more difficult CPT versions are not amenable to neuroleptic treatment; 2) subjects with schizotypal personality features also exhibit CPT deficits, which are specifically associated with the negative factor of schizotypy; 3) a substantial proportion of nonpsychotic relatives of schizophrenic patients (19-34%) have CPT deficits, which can also be predicted from their probands' CPT performance. Thus, using a CPT deficits as an endophenotype of schizophrenia would not only provide a valuable measure of genetic risk, but would also greatly enhance our understanding of etiology, and may help identify susceptibility genes for schizophrenia.

The paradox of normal neuropsychological function in schizophrenia.

Abstract: Mounting evidence suggests that compromised neurocognitive function is a core feature of schizophrenia. However, some studies have found neuropsychologically normal schizophrenia patients. To address this apparent contradiction, we blindly rated individual neuropsychological profiles of 75 schizophrenia patients and 91 control participants on the basis of methods developed by L. J. Seidman, S. V. Faraone, W. S. Kremen, J. R. Pepple, M. J. Lyons, and M. T. Tsuang (1993). Almost one-quarter of the patients were classified as neuropsychologically within normal limits (WNL). Despite significantly worse neuropsychological performance, WNL patients had higher estimated premorbid ability than did controls. Compared to a subset of controls matched on overall neuropsychological function, WNL patients had higher estimated premorbid ability and current IQs. Our results favor the view that even neuropsychologically normal schizophrenia patients have compromised cognitive function relative to their presumed expected or premorbid level of intellectual ability.

Family study of girls with attention deficit hyperactivity disorder.

Abstract: OBJECTIVE: Because attention deficit hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the causes of ADHD in girls. To help fill this gap in the literature, the authors assessed the familial transmission of ADHD in families ascertained through girls.METHOD: Interviewers who were blind to diagnosis administered structured psychiatric interviews to 140 girls with ADHD and their 417 first-degree relatives and to 122 girls without ADHD and their 369 first-degree relatives.RESULTS: The relatives of the ADHD girls had a significantly higher prevalence of ADHD, according to either the DSM-III-R or DSM-IV definition, than the relatives of the comparison girls. However, this did not differ from the prevalence the authors reported previously for families of boys with ADHD. Like the boys’ families, the relatives of the girl probands also had significantly higher prevalences of antisocial, mood, anxiety, and substance use disorders, although the prevalence of familial antisocia...

Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions.

Abstract: We extend the methodology for family-based tests of association and linkage to allow for both variation in the phenotypes of subjects and incorporation of covariates into general-score tests of association. We use standard association models for a phenotype and any number of predictors. We then construct a score statistic, using likelihoods for the distribution of phenotype, given genotype. The distribution of the score is computed as a function of offspring genotypes, conditional on parental genotypes and trait values for offspring and parents. This approach provides a natural extension of the transmission/disequilibrium test to any phenotype and to multiple genes or environmental factors and allows the study of gene-gene and gene-environment interaction. When the trait varies among subjects or when covariates are included in the association model, the score statistic depends on one or more nuisance parameters. We suggest two approaches for obtaining parameter estimates: (1) choosing the estimate that minimizes the variance of the test statistic and (2) maximizing the statistic over a nuisance parameter and using a corrected P value. We apply our methods to a sample of families with attention-deficit/hyperactivity disorder and provide examples of how covariates and gene-environment and gene-gene interactions can be incorporated.

Sleep Disturbances Associated with Attention Deficit Hyperactivity Disorder: The Impact of Psychiatric Comorbidity and Pharmacotherapy

Abstract: Objective: To estimate the relative risk of sleep problems associated with attention deficit hyperactivity disorder (ADHD), its pharmacotherapy, and its comorbid psychopathology. Method: Standard sleep questionnaires were used to assess sleep problems and characteristics in ADHD (n = 122) and non-ADHD (n = 105) comparison youths. Results: ADHD was associated with 10 of 19 sleep problems assessed. However, after controlling for psychiatric comorbidity and pharmacotherapy with stimulants, the majority of these differences were no longer evident. Rather, treatment with stimulants and comorbidity with anxiety and behavior disorders were significantly associated with sleep disturbances. Positive family history of ADHD was associated with none of the sleep problems assessed here after adjusting for age, psychiatric comorbidity, and treatment with anti-ADHD medication. Conclusions: Although subjective sleep difficulties are common in ADHD youths, they are frequently accounted for by comorbidity and pharmacothera...

Validity of DSM-IV Subtypes of Attention-Deficit/Hyperactivity Disorder: A Family Study Perspective

Abstract: Objective To test the hypothesis that the clinical severity of subtypes paralleled a gradient of familial severity. Method One hundred forty children with attention-deficit/hyperactivity disorder (ADHD) and 120 normal control children and their biological relatives were studied. Because these data had been collected prior to the publication of DSM-IV, DSM-III-R symptoms were used to approximate DSM-IV subtypes using a method the authors had validated in prior work. Results The first prediction from the hypothesis was true: rates of ADHD among relatives of each subtype group were greater than rates among relatives of controls. But the second prediction did not hold: rates of ADHD were not significantly higher among relatives of combined-typed probands compared with relatives of other probands. The "gradient model" also predicted that subtypes would not "breed true" (i.e., the subtype of the relative would not be the same as that of the proband). The prediction of non-specificity was refuted for the inattentive and combined subtypes, but hyperactive-impulsive ADHD was found almost exclusively among relatives of hyperactive-impulsive probands. Conclusions Although the results are limited by some small subsamples along with the use of a DSM-III-R -ascertained sample, they provide little evidence for the idea that DSM-IV subtypes of ADHD correspond to familially distinct conditions. They also do not confirm the idea that the subtypes fall along a gradient of familial severity. Instead, they suggest that symptom differences among subtypes are due to nonfamilial, environmental causes.

Assessing symptoms of attention deficit hyperactivity disorder in children and adults: which is more valid?

Abstract: The assessment of attention deficit hyperactivity disorder (ADHD) in adults has been a source of controversy. The authors tested competing ideas by evaluating familial transmission among adult and nonadult relatives of ADHD children. They analyzed ADHD symptom data collected by structured interviews from the members of 280 ADHD and 242 non-ADHD families. For both past and current symptoms, both the boys' and girls' families showed significantly more familial aggregation for adult relatives than for nonadult relatives. The results were similar for inattentive and hyperactive-impulsive symptoms and for relatives with and without psychiatric comorbidity. The results provide further evidence for the validity of adult ADHD and support the intriguing idea that, from a familial perspective, the assessment of ADHD may be more valid in adults than in children. They do not support the idea that parents of ADHD children are biased to report ADHD symptoms in themselves because of their exposure to an ADHD child.

Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder.

Abstract: The goal of this study was to assess neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987) and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level. Information on attention, executive, and memory functions was obtained in a standardized manner without knowledge of clinical status. Compared with siblings of controls, siblings with ADHD were significantly impaired on the Stroop test and on verbal learning and memory. In contrast, siblings without ADHD were similar to controls on virtually all measures. These data suggest that some executive, attention, and verbal learning deficits are found in nonreferred individuals with ADHD but that neuropsychological deficits are unlikely to constitute an endophenotype to ADHD.

Therapeutic Dilemmas in the Pharmacotherapy of Bipolar Depression in the Young

Abstract: Pediatric bipolar disorder is commonly mixed with co-occurring symptoms of major depression and mania. Knowledge has begun to accumulate on the treatment of the mania component, but limited information is available to guide the therapeutic approach to bipolar depression. To this end, we reviewed the medical charts of 59 patients with diagnosis of DSM-III-R bipolar disorder from an outpatient pediatric psychopharmacology clinic. Multivariate methods were used to model the probability of improvement and relapse at each visit of clinical follow-up. Serotonin-specific antidepressants were significantly associated with both an increased rate of improvement of bipolar depression-relative risk = 6.7 (1.9-23.6); p = 0.003-and a significantly greater probability of relapse of manic symptomatology-relative risk = 3.0 (1.2-7.8); p = 0.02. Although mood stabilizers improved manic symptomatology, they had no demonstrable effect on the symptoms of bipolar depression. Despite the increased risk of mood destabilization, serotonin-specific antidepressants did not interfere with the antimanic effects of mood stabilizers. Because bipolar youth commonly come to clinical practice with depression, these results underscore the importance of assessing a lifetime history of bipolar disorder in making treatment decisions in depressed youth.

Pediatric mania: a developmental subtype of bipolar disorder?

Abstract: Despite ongoing controversy, the view that pediatric mania is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: - its pattern of comorbidity may be unique by adult standards, especially its overlap with ADHD, aggression and conduct disorder; - its overlap with substance use disorders; - its association with trauma and adversity; - its response to treatment is atypical by adult standards. These issues will be reviewed in the presentation.

Genetic influences on attention deficit hyperactivity disorder.

Abstract: In this article we review behavioral and molecular genetics studies of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, all support the hypothesis that both genetic and environmental factors contribute to the etiology of ADHD. Despite this strong evidence for the familial transmission of ADHD, the mode of transmission requires further clarification. In addition, because ADHD appears to be genetically heterogeneous, more work is needed to delineate genetically homogeneous subtypes and describe the range of expression of their underlying genotypes.

Clinical correlates of obsessive compulsive disorder in children and adolescents referred to specialized and non-specialized clinical settings.

Abstract: The objective of this study was to assess the extent of referral bias by comparing children and adolescents with Obsessive Compulsive Disorder (OCD) ascertained through a specialized pediatric OCD and a general child psychiatry clinic. Subjects were juveniles meeting DSM-III-R and DSM IV criteria for OCD referred to a general pediatric psychopharmacology clinic and to a specialized OCD clinic within the same academic medical center. Subjects were evaluated clinically and with structured diagnostic interviews using the Kiddie SADS-E. OCD was identified in 8.6% of the general psychiatry clinic subjects. The only differences between ascertainment sources in clinical or sociodemographic characteristics of OCD subjects were higher rates of social phobia and ADHD in the non-specialized clinic, while specialty clinic subjects had a greater lifetime severity of OCD and were more likely to have received treatment of their OCD. Because we found limited evidence for referral biases, our results suggest that findings from studies using either of these sources may generalize to the other. It also suggests that pooling subjects from the two sources is justified. Nevertheless, because some group differences did emerge, researchers should acknowledge referral bias as a potential limitation of their work.

Attention Deficit Hyperactivity Disorder in Adults Implications for Theories of Diagnosis

Abstract: The diagnosis of attention deficit hyperactivity disorder (ADHD) in adults has been a source of controversy, with some prominent researchers questioning its very existence and others suggesting it is an urgent clinical problem. This article reviews five domains of data addressing the validity of adult ADHD: clinical correlates, family history, treatment response, laboratory studies, and long-term outcome. It then shows how the debate over adult ADHD reflects a clash of theoretical paradigms and concludes by suggesting ways in which psychological science can collect the data needed to clarify the validity of adult ADHD.