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Biomedical subjects

S V Faraone

Publications and source records attributed to S V Faraone.

At least 73 records · Page 4Linked to original sources
PubMed2000

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

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.

Adolescent↗
PubMed2000

Genetic influences on attention deficit hyperactivity disorder.

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.

Adolescent↗
PubMed2000

The paradox of normal neuropsychological function in schizophrenia.

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.

Adult↗
PubMed2000

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

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.

Alleles↗
PubMed2000

Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young.

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.

Adolescent↗
PubMed2000

Sleep disturbances associated with attention deficit hyperactivity disorder: the impact of psychiatric comorbidity and pharmacotherapy.

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 pharmacotherapy. Furthermore, the lack of an association between a positive family history of ADHD and sleep difficulties suggests that ADHD is not a misdiagnosis of the consequences of disruption of normal sleep.

Adolescent↗
PubMed2000

Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: a family study perspective.

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 nonspecificity 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.

Adolescent↗
PubMed2000

Adoptive and biological families of children and adolescents with ADHD.

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.

Adolescent↗
PubMed2000

The drug-placebo response curve: a new method for assessing drug effects in clinical trials.

Unlike many other areas of medicine, psychiatric clinical trials have no gold standard laboratory tests with which to measure drug effects. Although reliable and valid psychometric measures are available, the standard analysis of such measures obscures the clinical relevance of drug effects. In this study, the authors sought to address this problem by developing a graphical display called the drug-placebo response curve. The features of the drug-placebo response curve are described by applying it to a previously published, controlled clinical trial of desipramine in the treatment of adults with attention-deficit/hyperactivity disorder. Unlike the standard analysis, the drug-placebo response curve showed that desipramine was effective over the full range of response and that it prevented worsening, in addition to increasing the likelihood of improvement. The drug-placebo response curve provides clinically relevant information about the effect of drugs on continuous outcomes in controlled clinical trials.

Adrenergic Uptake Inhibitors↗
PubMed2000

Informativeness of structured diagnostic interviews in the identification of Tourette's disorder in referred youth.

Although specialized programs have greatly advanced the treatment of youth with Tourette's disorder (TD), not all children with TD reach such programs, raising questions as to whether TD is adequately identified outside specialized settings. There is thus a need for evidence that cases identified in the nonspecialty setting are "true cases." Because structured diagnostic interview methodology can reduce errors of omission, this approach can facilitate the identification of TD in referred youth outside specialized programs. Similarities between cases ascertained in specialty and nonspecialty settings would suggest that those identified in the nonspecialty setting were indeed "true cases." Comparisons were made between youth with TD ascertained through a specialized TD program who had both a structured diagnostic interview-derived diagnosis of TD plus an expert evaluation of TD (N = 103), with youth ascertained through a non-TD specialized pediatric psychopharmacology program who had a structured diagnostic interview-derived diagnosis of TD (N = 92). Irrespective of ascertainment source, children with structured interview-derived diagnosis of TD shared similar correlates in terms of tic severity, mean age of onset and duration of tics, as well as patterns of comorbidity well known to be associated with TD in clinical samples. Children meeting diagnostic criteria for TD on structured diagnostic interviews share similarities and patterns of clinical correlates, irrespective of ascertainment through a specialized TD or non-TD specialized clinic. These findings support the usefulness of structured diagnostic interview methodology as a diagnostic aid for the identification of TD in non-TD specialized settings and facilitate delineation of patterns of comorbidity.

Adolescent↗
PubMed2000

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

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 behavioral inhibition was most frequent among the children of parents with panic disorder plus major depression (29% versus 12% in comparison subjects). For all definitions, the univariate effects of parental major depression were significant (conferring a twofold risk for behavioral inhibition), and for most definitions the effects of parental panic disorder conferred a twofold risk as well. CONCLUSIONS: These results suggest that the comorbidity of panic disorder and major depression accounts for much of the observed familial link between parental panic disorder and childhood behavioral inhibition. Further work is needed to elucidate the role of parental major depression in conferring risk for behavioral inhibition in children.

Adult↗
PubMed2000

Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type.

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 observation that hyperactivity and impulsivity symptoms tend to decline at a higher rate than inattention symptoms.

Adolescent↗
PubMed2000

Toward reformulating the diagnosis of schizophrenia.

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 in nature may constitute evidence of a genetic predisposition toward schizophrenia ("schizotaxia") and may provide more specific information about the genetic, pathophysiological, and developmental origins of schizophrenia. CONCLUSIONS: The success of efforts to treat and prevent schizophrenia will depend to an important extent on an accurate understanding of its causes. This goal can be furthered by conducting field trials to develop research criteria to assess the value of a developmentally sensitive, biologically informed approach to classification that would consider schizotaxia with psychosis (schizophrenia) and schizotaxia alone as distinct diagnostic conditions.

Genetic Predisposition to Disease↗
PubMed2000

Family study of girls with attention deficit hyperactivity disorder.

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 antisocial disorders was lower than had been observed in the boys' families. There was no association between the DSM-IV subtypes of the probands and relatives. CONCLUSIONS: The familial transmission of ADHD and comorbid disorders generalizes to families of girls with ADHD. Neither proband gender nor subtype influences the familial transmission of ADHD.

Adolescent↗
PubMed2000

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

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.

Adolescent↗
PubMed2000

Lifetime prevalence of mood and anxiety disorders in twin pairs discordant for schizophrenia.

There have been long questions about the relationship of schizophrenia to other mental disorders. Lifetime DSM-III-R diagnoses of mood and anxiety disorders in twins with clinically diagnosed schizophrenia (n = 24) and their non-affected co-twins (n = 24) were compared with twins from pairs without schizophrenia (n = 3327) using a sample from the Vietnam Era Twin Registry. Schizophrenic probands had significantly elevated rates of all included disorders (bipolar disorder, major depression, dysthymia, generalized anxiety disorder, panic disorder, and PTSD) compared with controls (P<0.01). The odd ratios comparing co-twins of schizophrenic probands with controls was greater than three for every disorder, but did not attain statistical significance. A similar pattern was observed when analyses were restricted to only monozygotic twins (n = 12). Consistent with other studies, schizophrenics appeared to have higher rates of a range of mental disorders. Our results suggest that schizophrenia per se represents a risk factor for other psychiatric disorders, but the absence of significantly elevated risk among non-schizophrenic co-twins suggested that family environmental and/or genetic factors that contribute to risk of schizophrenia do not increase the risk of mood and anxiety disorders to the same extent that the risk of these other disorders is increased by the presence of schizophrenia.

Adult↗