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S V Faraone

Publications and source records attributed to S V Faraone.

At least 37 records · Page 2Linked to original sources
PubMed2001

Genetic association analysis of behavioral inhibition using candidate loci from mouse models.

Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.

Animals↗
PubMed2001

Genetic counseling for psychiatric disorders.

Like other medical conditions, some psychiatric disorders are inherited, whereas others are not. Human genetics research is moving at a rapid pace. Genes for over 450 genetic disorders have been cloned and many disease-causing mutations have also been identified. The explosion of this new knowledge has created many new exciting opportunities in the diagnosis of these heritable disorders. The rapid pace of gene discovery will aid the identification of susceptibility genes for psychiatric disorders. Indeed, we can look forward to answers to many clinical and research questions. These are some of the gifts that the expanding field of human genetics research will continue to bring to medical science. However, as genetic tests for the detection of psychiatric disorders become available, many ethical, legal, and social implications will need to be considered. In this article, we review the principles of genetic counseling for psychiatric disorders, as well as the social and ethical dilemmas that genetic testing may bring. Although medical and scientific advances may bring many gifts, we should approach this new knowledge with caution, as one of the gifts may be a Pandora's box.

Ethics, Medical↗
PubMed2001

Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype?

BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.

Adolescent↗
PubMed2001

Heterogeneity of childhood conduct disorder: further evidence of a subtype of conduct disorder linked to bipolar disorder.

BACKGROUND: Although a small literature suggests that conduct disorder (CD) co-occurs with bipolar disorder (BPD), little is known about this overlap. Thus, we investigated the familial association of antisocial disorders (CD and/or antisocial personality disorder (ASPD)) and BPD among the first degree relatives of children with CD with and without comorbid BPD. METHODS: We compared relatives of four proband groups defined by the presence or absence of CD and BPD in the proband: (1) CD+BPD (N=26 probands, 92 relatives; (2) BPD without CD (BPD) (N=19 probands, 53 relatives); (3) CD without BPD (CD) (N=16 probands, 58 relatives); and (4) controls without BPD or CD (N=102 probands, 338 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. RESULTS: The results show high rates of antisocial disorders and BPD in relatives of children with CD+BPD. Moreover, antisocial disorders and BPD cosegregated among the relatives of children with CD+BPD. While relatives of both CD proband groups with and without BPD had high rates of CD/ASPD, the combined condition CD/ASPD+BPD was found exclusively among relatives of probands with CD+BPD. LIMITATIONS: Since we pooled two datasets, subjects were not all evaluated at the same time. Also, the lack of direct psychiatric interviews with children younger than 12 may have decreased the sensitivity of some diagnoses. CONCLUSIONS: These family-genetic findings suggest that CD and BPD represent separate disorders. Furthermore, they suggest that the comorbid condition of CD+BPD may be a distinct nosological entity. This suggests that clinicians treating CD or BPD children should consider the treatment implications of this comorbid condition.

Adolescent↗
PubMed2001

Disentangling chronological age from age of onset in children and adolescents with obsessive--compulsive disorder.

Although paediatric obsessive--compulsive disorder (OCD) is increasingly recognized as a putative developmental subtype of the disorder, it remains uncertain as to whether additional subtyping by age at onset in childhood or adolescence is warranted. Subjects included children and adolescents meeting DSM-III-R and DSM-IV criteria for OCD referred to a specialized OCD clinic. All youth were systematically evaluated with structured diagnostic interviews and clinical assessment by an OCD expert. Irrespective of current age, an earlier age at onset predicted increased risk for attention deficit hyperactivity disorder, simple phobia, agoraphobia and multiple anxiety disorders. In contrast, mood and psychotic disorders were associated with chronological age and were more prevalent in older subjects. Tourette's disorder showed associations with both chronological age and age at onset. Chronological age and age at onset predicted different patterns of comorbidity and dysfunction in children and adolescents with OCD. Considering the heterogeneity of OCD, age at onset may help identify meaningful developmental subtypes of the disorder beyond chronological age.

Adolescent↗
PubMed2001

Learning disabilities and executive dysfunction in boys with attention-deficit/hyperactivity disorder.

The effect of comorbid reading or arithmetic learning disabilities (LDs) on neuropsychological function in attention-deficit/hyperactivity disorder (ADHD) was studied. Participants were young males diagnosed with ADHD, with and without LD, and non-ADHD, non-LD male controls of similar age. LD was defined by combined regression-based and low-achievement classifications. Analyses adjusted for the effect of psychiatric comorbidity, age, and socioeconomic status on neuropsychological function. Children who had both ADHD and LD were significantly more impaired on both executive and nonexecutive functions than ADHD children without LD. Neuropsychological performance was most impaired in ADHD with combined arithmetic and reading disability. These data indicate that comorbid LD, especially arithmetic disability, significantly increases the severity of executive function impairment in ADHD.

Adolescent↗
PubMed2001

Methodological complexities in the diagnosis of major depression in youth: an analysis of mother and youth self-reports.

OBJECTIVE: Considering the well-documented low level of agreement between youth and parent reports on the diagnosis of major depressive disorder (MDD), uncertainties remain as to the informativeness of discrepant youth and parent reports in clinical studies. To this end we evaluated whether morbidity and functional correlates on the diagnosis of MDD in youth vary by informant source. METHODS: The sample consisted of 186 pairs of independently assessed mother and youth self-reports on the diagnosis of MDD using structured diagnostic interviews ascertained in a large study of youth with and without attention deficit hyperactivity disorder of both genders. Subjects were also assessed on measures of interpersonal, school, and family functioning as well as prior treatment history. RESULTS: The diagnosis of MDD endorsed by youth self-report only when compared with that reported by the mother was characterized by significantly: shorter duration episode, later age at onset, milder depression-associated impairment, less impairment in interpersonal functioning, lower rates of comorbid disorders, and decreased likelihood to receive any course of treatment for depression. The morbidity and dysfunction associated with MDD varied significantly by informant source, and followed a dose-response association with the highest morbidity associated with the concurrent reports of the youth and the mothers, followed by mother report alone, with the least morbidity and dysfunction when endorsed by youth alone. CONCLUSIONS: These findings suggest that exclusive reliance on youth self-reports may identify a mild form of depression associated with limited morbidity and disability compared with that identified by parental reports.

Adolescent↗
PubMed2001

An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to evaluate the tolerability and effectiveness of the experimental, noradrenergic specific reuptake inhibitor atomoxetine in the treatment of children with attention deficit hyperactivity disorder (ADHD). METHODS: This was an open, prospective, dose-ranging study of atomoxetine monotherapy in the treatment of 30 children with ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on response and adverse effects. Twenty-two children completed the full 11 weeks. We assessed efficacy with weekly clinician and parent ratings of ADHD and oppositional symptoms and monitored adverse effects, laboratory findings, and cardiovascular parameters. RESULTS: Treatment with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very well tolerated without meaningful adverse effects. Atomoxetine significantly reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of subjects who completed 10 weeks of treatment showed > 25% decrease in ADHD symptoms. CONCLUSIONS: These findings extend to children the positive results previously reported in adults diagnosed with ADHD who were treated with atomoxetine. These results support additional controlled trials of atomoxetine in cases of pediatric ADHD.

Adolescent↗
PubMed2001

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology.

Because methylphenidate (MPH) is currently the most widely prescribed medication for attention deficit hyperactivity disorder (ADHD), several studies have used this as the touch-stone for evaluating the efficacy of a newer stimulant, Adderall. In a parallel-groups study of MPH (n = 20), Adderall (n = 20), and placebo (n = 18), Pliszka et al. (2000) reported that both medications were superior to placebo in improving parent, teacher, and clinician ratings of ADHD and associated behaviors. Compared with MPH, Adderall led to significantly more improvements in teacher and clinician ratings. The present study extends these results by addressing the issue of clinical significance using drug-placebo and drug-drug response curve analyses of the same data. The goal of this method is to answer the following questions about drug-placebo or drug-drug differences: Is the effect clinically meaningful? What does the effect tell us about individual responses? Is the effect due to symptom improvement, the prevention of worsening, or both? Our results show that the efficacy of Adderall to improve functioning is seen throughout the full range of improvement scores. In contrast, MPH showed a substantial effect for "mildly" and "much improved" but not for "very much improved." Our analyses also show that both Adderall and MPH prevent worsening of symptoms. They further suggest that, compared with the Conners Teacher Rating Scale, the Clinical Global Impressions scale may be more sensitive to improvements at the "well end" of the spectrum of functioning.

Algorithms↗
PubMed2001

Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.

The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T(1)-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans.

Adult↗
PubMed2001

"Schizotaxia": clinical implications and new directions for research.

We sought to show that (1) schizotaxia (Meehl's term for the predisposition to schizophrenia) is a clinically consequential condition, and (2) distinguishing it from schizotypal personality disorder may be useful from both clinical and scientific perspectives. We review the features of schizotaxia that may be relevant in clinical settings and discuss their implications for the diagnosis, psychosocial functioning, family intervention and treatment of people in schizophrenia families. Our review indicates that prior work finds some of the nonpsychotic and nonschizotypal relatives of schizophrenia patients to have a psychiatric syndrome characterized by negative symptoms, neuropsychological impairment, and psychosocial dysfunction. Following Meehl, we call this constellation of clinical and neurobiological features schizotaxia. The studies we review suggest it may be worthwhile to consider schizotaxia as a separate diagnostic class. Doing so would alert clinicians to a neurobehavioral syndrome not adequately covered by current diagnostic criteria and would motivate researchers to develop diagnostic and therapeutic approaches aimed at helping schizotaxic individuals and, perhaps, preventing the onset of schizophrenia.

Diagnosis, Differential↗
PubMed2001

Patterns of remission and symptom decline in conduct disorder: a four-year prospective study of an ADHD sample.

OBJECTIVE: To evaluate systematically the longitudinal course of conduct disorder (CD) in a sample of youths with attention-deficit hyperactivity disorder (ADHD) to determine the effects of a persistent course on outcome. METHOD: One hundred forty children with ADHD and their nuclear families were assessed at baseline and again at 1 and 4 years. Subjects were examined by means of DSM-III-R-based structured interviews. They were also evaluated for cognitive and social functioning. Persistent (exhibiting symptoms of CD at either follow-up) and desistent (symptoms of CD at neither follow-up) cases were identified. RESULTS: Forty-two percent of CD cases followed a persistent course. Although both persistent and desistent subjects had high rates of antisocial disorders in relatives, increased family conflict and decreased family cohesion were selectively associated with a persistent course. In addition, subjects with persistent symptoms of CD exhibited more impaired ratings on the Aggression and Delinquency subscales of the Child Behavior Checklist, as well as higher rates of bipolar, oppositional defiant, and substance use disorders. CONCLUSIONS: These findings suggest that the poor prognosis associated with CD is limited to an identifiable subgroup with a persistent course.

Adolescent↗
PubMed2001

Social impairment in girls with ADHD: patterns, gender comparisons, and correlates.

OBJECTIVE: To investigate social impairment in girls with attention-deficit/hyperactivity disorder (ADHD), compare the social functioning of boys and girls with ADHD, and explore the association between social dysfunction and conditions comorbid with ADHD. METHOD: Four groups of index children were studied: 267 children (127 girls) with ADHD and 234 non-ADHD comparison children (114 girls). Groups were compared on social functioning, psychopathology, and demographic characteristics. RESULTS: Girls with ADHD manifested significant deficits in interpersonal functioning compared with girls without ADHD and evidenced a similar degree of social impairment compared with boys with ADHD. ADHD and associated comorbid disorders were significant correlates of specific domains of social dysfunction in boys and girls with ADHD. CONCLUSIONS: Interpersonal deficits are a major correlate of ADHD, irrespective of gender, and appear to stem from the behaviors associated with ADHD as well as behaviors characteristic of conditions comorbid with ADHD.

Adolescent↗
PubMed2001

Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression.

OBJECTIVE: The purpose of the study was to evaluate 1) whether an underlying familial predisposition is shared by all anxiety disorders or whether specific risks are associated with specific disorders, and 2) whether panic disorder and major depression have a familial link. METHOD: The study compared four groups of children: 1) offspring of parents with panic disorder and comorbid major depression (N=179), 2) offspring of parents with panic disorder without comorbid major depression (N=29), 3) offspring of parents with major depression without comorbid panic disorder (N=59), and 4) offspring of parents with neither panic disorder nor major depression (N=113). RESULTS: Parental panic disorder, regardless of comorbidity with major depression, was associated with an increased risk for panic disorder and agoraphobia in offspring. Parental major depression, regardless of comorbidity with panic disorder, was associated with increased risks for social phobia, major depression, disruptive behavior disorders, and poorer social functioning in offspring. Both parental panic disorder and parental major depression, individually or comorbidly, were associated with increased risk for separation anxiety disorder and multiple (two or more) anxiety disorders in offspring. CONCLUSIONS: These findings confirm and extend previous results documenting significant associations between the presence of panic disorder and major depression in parents and patterns of psychopathology and dysfunction in their offspring.

Adolescent↗
PubMed2001

Separating attention deficit hyperactivity disorder and learning disabilities in girls: a familial risk analysis.

OBJECTIVE: Familial risk analysis was used to clarify the relationship in girls between attention deficit hyperactivity disorder (ADHD) and learning disabilities in either mathematics or reading. METHOD: The authors assessed the presence of ADHD and learning disabilities in 679 first-degree relatives of three groups of index children: girls with ADHD and a comorbid learning disability, girls with ADHD but no learning disabilities, and a comparison group of girls without ADHD. RESULTS: The risk for ADHD was similarly higher in families of ADHD probands with and without learning disabilities; both groups had significantly higher rates of ADHD than did families of the comparison girls. In contrast, only among relatives of ADHD probands with a learning disability was there a higher risk for learning disabilities. A strong (although statistically nonsignificant) difference emerged that suggested at least some degree of cosegregation of ADHD and learning disabilities in family members. There was no evidence of nonrandom mating between spouses with ADHD and learning disabilities. CONCLUSIONS: These results extend previously reported findings regarding the relationship of ADHD and learning disabilities to female subjects and raise the possibility that, in girls, the relationship between ADHD and learning disabilities is due to shared familial risk factors.

Adolescent↗