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Biomedical subjects

S V Faraone

Publications and source records attributed to S V Faraone.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

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

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.

Adolescent↗
PubMed1999

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗
PubMed1999

Poor perception of nonverbal social-emotional cues in relatives of schizophrenic patients.

The present study compared nonverbal social perception in relatives of schizophrenic patients (n = 21) with that of normal controls (n= 19). We hypothesized that relatives would display deficits in social perception and we sought to determine the skills that are associated with this deficit. Relatives performed significantly worse than controls on the Profile of Nonverbal Sensitivity Test (PONS), despite comparable performance on skills hypothesized to be related to nonverbal social perception: visual perception, nonverbal problem solving, facial recognition, facial affect recognition, naming, social judgment, and vigilance. To further explore the relationships among these skills, we calculated correlations between the PONS score and associated skills separately within both the relative and control groups and assessed whether the values of these correlations differed between groups. Correlations that differed significantly indicated a greater association, within relatives, between slower reaction times on vigilance tasks and poor PONS performance. Further research is needed to clarify the nature of this relationship, to better characterize social perception deficits in relatives, and to determine whether these perceptual deficits are part of the genetic diathesis to schizophrenia.

Adult↗
PubMed1999

Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.

BACKGROUND: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.

Adult↗
PubMed1999

Treatment of nonpsychotic relatives of patients with schizophrenia: four case studies.

BACKGROUND: Substantial evidence now shows that the genetic vulnerability to schizophrenia can be manifested clinically in first-degree relatives of people with schizophrenia, even without the full manifestations of the disorder. One pattern of problems observed involves the combination of negative symptoms and neuropsychological deficits. We have investigated whether a low dose of a novel antipsychotic medication, risperidone, could attenuate these clinical problems in non-psychotic, first-degree relatives, and report here findings from our first 4 cases. METHODS: Twelve adults who were first-degree relatives of patients with schizophrenia were evaluated for the presence of negative symptoms and neuropsychological deficits (in attention and working memory, long-term verbal memory and executive functions). Four subjects who met our predetermined criteria, and who did not demonstrate medical contraindications, were enrolled in a 6-week trial of risperidone. Clinical and medical measures were assessed before, during and after treatment. Doses of risperidone started at 0.25 mg and were increased to 1.0-2.0 mg/day. RESULTS: These subjects showed substantial reductions in negative symptoms, and one subject showed modest reductions. All four subjects showed substantial improvements on some tests of attention and working memory. Side effects of risperidone were temporary and mainly mild. CONCLUSIONS: These initial findings support two conclusions. First, clinical deficits in non-psychotic first-degree relatives of people with schizophrenia are identifiable, and to a significant extent, reversible. Second, risperidone may eventually serve as an effective treatment for people whose lives are impaired by similar or related problems.

Adult↗
PubMed1999

Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging.

BACKGROUND: Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. METHODS: Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. RESULTS: The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and frontoorbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. CONCLUSION: Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.

Adult↗
PubMed1999

The genetics of schizophrenia.

Behavioral genetic studies provide overwhelming evidence that genes contribute to schizophrenia. Recently, genetic studies have provided promising evidence that schizophrenia genes are linked to several chromosomal locations in affected family members. Despite this progress, individual genes for schizophrenia have yet to be identified. Future progress will depend, in part, on the selection of phenotypes that best reflect effects of etiologic genes. One such phenotype is schizotaxia, a clinically meaningful syndrome that reflects the genetic liability to schizophrenia in nonpsychotic individuals. The potential importance of schizotaxia, or similar concepts, for use in genetic studies, is discussed.

Chromosome Mapping↗