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Stephen V Faraone

Publications and source records attributed to Stephen V Faraone.

At least 145 records · Page 8Linked to original sources
PubMed2004

Further evidence of unique developmental phenotypic correlates of pediatric bipolar disorder: findings from a large sample of clinically referred preadolescent children assessed over the last 7 years.

BACKGROUND: A comparison of the prevalence, clinical correlates, and patterns of comorbidity among children with bipolar disorder (BPD) assessed in the early 1990s (1st cohort) with those evaluated over the last 7 years (2nd cohort). METHOD: Subjects in both cohorts were children aged <or=12 years referred to a child psychiatry service and evaluated with identical assessment methods. Children with a DSM-III-R BPD diagnosis (1st cohort, n=43; 2nd cohort, n=129) were identified. For comparison purposes, we used attention-deficit/hyperactivity disorder (ADHD) children without BPD referred to the same clinic during the same time period (1st cohort, n=164; 2nd cohort, n=450). RESULTS: Analogous to 1st cohort findings, 2nd cohort results showed that (1) mania was identified in 17% of subjects; (2) the clinical picture was predominantly irritable and mixed, and the course was chronic; (3) BPD children frequently met criteria for major depression, ADHD, psychosis, and anxiety disorders; and (4) BPD children had high rates of psychiatric hospitalization and had evidence of severely impaired psychosocial functioning. CONCLUSION: These findings confirm that pediatric BPD is a severe clinical disorder afflicting a sizable number of referred preadolescent children. Its unique phenotypic features and patterns of comorbidity support the hypothesis that clinically referred pediatric bipolar disorder represents a very severe developmental subtype of bipolar disorder.

Age of Onset↗
PubMed2004

Absence of gender differences in pediatric bipolar disorder: findings from a large sample of referred youth.

BACKGROUND: Because little is known about gender differences in pediatric bipolar disorder, we evaluated whether gender moderates the expression of pediatric bipolar disorder in a large clinical sample. METHODS: Subjects were consecutively referred youth aged 18 years or less who met full criteria for DSM-III-R bipolar disorder (BPD) (females, n=74; BD males, n=224). All subjects were assessed with a structured diagnostic interview and measures of psychosocial and family functioning. RESULTS: Most of the bipolar subjects (91% of males, 70% of females) also had ADHD. Bipolar disorder was equally prevalent in both genders. Among females and males, severe irritability (83% and 80%, respectively), mixed presentation (87% and 84%, respectively), chronic course (84% and 77%, respectively) and prepubertal onset (78% and 93%, respectively) predominated the clinical picture. We found no meaningful differences between genders in the number of BPD symptoms, type of treatment for BPD (counseling, medication, hospitalization), severity of educational deficits, severity of family and interpersonal functioning or patterns of psychiatric comorbidity. CONCLUSIONS: Because gender does not moderate the clinical expression of pediatric bipolar disorder, our data does not suggest that gender specific criteria for the disorder are warranted.

Adolescent↗
PubMed2004

The Massachusetts General Hospital studies of gender influences on attention-deficit/hyperactivity disorder in youth and relatives.

With the single exception of SUDs, no statistically significant gender-by ADHD interactions were identified in the multiple, outcomes evaluated. These results suggest that with the exception of SUDs, ADHD expresses itself similarly in boys and girls relative to comparison subjects of the same gender, indicating that ADHD-associated impairments are correlates of ADHD in both genders. Gender differences, such as the higher prevalence of symptoms of inattention and lower rates of comorbidity with disruptive behavior disorders, major depression, and learning disability, were identified among the ADHD subjects. Because these differences were caused by the main effects of gender rather than effect modification of ADHD by gender, these findings indicate that girls were at the same relative risk for these adverse outcomes as boys, but that female gender resulted in a different clinical presentation than that affecting boys. The single statistically significant gender-by-ADHD interaction identified was the association between ADHD and SUDs (alcohol or drug abuse or dependence). ADHD in females was a more serious risk factor for SUDsthan it was in males was an unanticipated and surprising finding. In light of ongoing concerns regarding ADHD as a putative risk factor of SUDs [12],this finding may indicate that girls are particularly at risk in early adolescence. Considering that the age of onset of ADHD and SUDs are separated by at least a decade [13.14], this finding would support targeting of substance abuse prevention programs to girls with ADHD.Furthermore, results show that although the combined type of ADHDwas the predominant type in both genders, girls with ADHD were twice as likely as boys with ADHD to manifest the predominantly inattentive type of the disorder. Because symptoms of inattention are more covert than those of hyperactivity and impulsivity, their higher prevalence in girls with ADHDrelative to boys also may explain partially the markedly higher male-to-female ratios in referred versus nonreferred samples of children withADHD. This work also showed that the pattern of transmission of ADHD and comorbid disorders is not influenced by the proband's gender. This is true for the type of disorder transmitted and the degree of risk to relatives. The finding of no interactions between proband ADHD diagnosis and pro-band gender clearly rejects the idea that gender differences in comorbid disorders can be attributed to genes or other familial causes. Prior work had shown this to be true for the diagnosis of ADHD in relatives [15-20].Thus, gender and ADHD appear to be independent risk factors for comorbid psychopathology and for the familial transmission of comorbid psychopathology. In summary, these results suggest that gender was a limited effect modifier of ADHD as a risk factor for ADHD-associated dysfunction in referred children and adolescents. Gender, however, did impact the clinical presentation of the disorder. This was largely because girls with ADHDwere less likely than boys to have comorbid disruptive behavior problems and higher prevalence of symptoms of inattention. Because these features could result in gender-based referral bias unfavorable to girls, more work is needed in referred and nonreferred samples of youth with ADHD to more fully assess this issue. These results also showed similar patterns in the familial transmission of comorbid disorders in families of boys and girls with ADHD. Thus, although ADHD is associated with the familial trans-mission of comorbid disorders, the pattern of transmission is not influenced by the proband's gender. These similar patterns provide further evidence for the idea that, when ADHD is diagnosed in girls it corresponds to the same disorder diagnosed in boys.

Adolescent↗
PubMed2004

Age-dependent expression of attention-deficit/hyperactivity disorder symptoms.

The authors' research indicates that most adults with ADHD continue to struggle with substantial number of ADHD symptoms and high levels of dysfunction despite a sizable syndromatic remission. Furthermore, in-attention was more persistent than hyperactivity or impulsivity as children progress throughout adolescence and into early adulthood. These results stress the critical importance of carefully choosing the appropriate definition of remission in longitudinal studies of youth with ADHD and that symptom clusters and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined ADHD subtypes (ie, combined, inattentive., or hyperactive/'impulsive) should be considered separately.

Age Factors↗
PubMed2004

An overview of the genetics of psychotic mood disorders.

This article presents a conceptual review of the genetic underpinnings of psychotic mood disorders. Both unipolar and bipolar forms of mood disorder sometimes feature psychotic symptoms. Some evidence from epidemiological research suggests that psychotic forms of mood disorder specifically might be heritable. Linkage studies of mood disorders in general have also provided some support for that notion, as have associated studies involving serotonin and dopamine genes and psychotic mood disorder. Some research suggests there might be a genetic connection between schizophrenia and bipolar disorder, undermining the Kraepelinian dichotomous classification of the psychoses. Future research should continue to examine psychotic forms of mood disorder using both epidemiological and molecular approaches.

Affective Disorders, Psychotic↗
PubMed2004

Genetics of adult attention-deficit/hyperactivity disorder.

Results of behavioral genetic investigations using family twin and adoption studies converge with those of molecular genetic studies in showing that genes influence susceptibility to'attention-deficit/hyperactivity disorder (ADHD). These finding suggest that genetic mechanisms that predispose individuals to ADHD are complex. It seems likely that the disorder is caused by the combined actions of several genes. It is equally clear that aberrant genes create a vulnerability to the disorder that is not expressed in all environments. The literature about the genetics of adult ADHD is relatively small, but it suggests not only that the persistent form of ADHD is familial, but that it is more familial than the nonpersistent form. More work from twin and molecular genetic studies is needed to determine if the increased familiality of persistent ADHD reflects the actions of genes or of familial environmental causes.

Adoption↗
PubMed2004

A twin study of sexual behavior in men.

The role of genetic and environmental influences on age of initiation of first sexual relations and engaging in sexual activity with multiple partners (10 or more partners in 1 year) was investigated in male twins (N = 6,744) from the Vietnam Era Twin Registry. Individual differences in both types of sexual behaviors were heritable, but only age of onset of sexual relations was significantly influenced by the environment shared by the twins. There was a moderate negative correlation between age of initiation of sexual relations and the multiple partners variable; initiating sexual relations earlier was associated with a higher probability of having multiple partners. The additive genetic influence on age of initiation also influenced the multiple partners variable. The substantial unique environmental influences on each variable were uncorrelated with each other. The data suggest that the observed association between age of initiation of sexual relations and having multiple partners is due to genetic influences common to both behaviors.

Adult↗
PubMed2004

Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children.

The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.

Achievement↗
PubMed2004

Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy.

OBJECTIVES: While stimulants are the recognized first-line choice of pharmacotherapy for ADHD, reports that they may induce or exacerbate tics have tended to limit their use in ADHD children who have a history of tics or a family history of Tourette's syndrome. This study analyzes the incidence of tics reported across five studies of children with ADHD who received methylphenidate (MPH)-based therapy as part of the clinical development program for once-daily OROS MPH (CONCERTA McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA). METHODS: Data were analyzed from three placebo-controlled, active-controlled studies (studies 1-3) lasting 1-4 weeks, and two open-label studies lasting 2 years (study 4) and 9 months (study 5), respectively. During the course of the studies, parents were asked at the end of each week of treatment (studies 1 and 2), biweekly (study 3), or monthly (for the first year of study 4, then at 3-month intervals thereafter) whether their child had experienced tics. Tics could also be reported as adverse events in the two open-label studies. RESULTS: Pooled data from the three placebo-controlled studies showed that the incidence of tics was not significantly different across all three treatment groups (OROS MPH, 4.0%; MPH tid, 2.3%; placebo, 3.7%, p = 0.5249). During the first year of the 2-year open-label study, the monthly incidence of tics remained constant, at approximately 5%. Analysis of tic episodes per patient in this study found no correlation between an OROS MPH dose and the frequency of tic episodes. The risk of tic episodes was higher in patients with a history of tics than in those with no history of tics (33% versus 7%, p < 0.0001). However, only 2 children with a history of tics (4%) withdrew from therapy because of their tics. CONCLUSIONS: These data suggest that MPH-based therapy does not significantly induce or exacerbate tics in children with ADHD.

Adolescent↗
PubMed2004

Association of norepinephrine transporter gene with methylphenidate response.

OBJECTIVE: This study aimed to explore the association between alleles of the norepinephrine transporter gene and the methylphenidate response. METHOD: Chinese Han youths with attention-deficit/hyperactivity disorder recruited in the Outpatient Department of the Institute of Mental Health from 2001 to 2004 were treated with methylphenidate in doses of 0.45 to 0.60 mg/kg per day. Behavior changes were measured by the ADHD Rating Scale-IV when optimal doses were reached. The single-nucleotide polymorphic allele of norepinephrine transporter gene G1287A was used as the genetic marker, and the genotypes were identified by restriction fragment length polymorphism analysis. RESULTS: A significant association was found between norepinephrine transporter gene G1287A genotypes and response to methylphenidate for hyperactive-impulsive subscale scores (mean score reduction was 7.15 and 6.94 for G/G and G/A genotype, respectively, and 2.13 for A/A; p = .012) but not inattentive scores. CONCLUSIONS: These findings suggest an association between the G1287A polymorphism of the norepinephrine transporter gene and variation in methylphenidate response. Further work is needed to confirm this finding and to assess its generalization to other ethnic groups.

Adolescent↗
PubMed2004

Risk of substance use disorders in adolescents with bipolar disorder.

OBJECTIVE: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD. METHOD: Probands with DSM-IV BPD (n=57, mean age +/- SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected. RESULTS: Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or =13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi1=9.3, p=.002). CONCLUSIONS: These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder.

Adolescent↗
PubMed2004

Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder.

This article reviews the efficacy of methylphenidate (MPH) for adult attention-deficit/hyperactivity disorder (ADHD). A literature search identified double-blind placebo-controlled MPH treatment studies of ADHD adults. Meta-analysis estimated the pooled effect size for MPH treatment and tested for publication bias. Meta-analysis regression assessed the influence of study design features on medication effects. Six trials met criteria and were included in this meta-analysis. These studies included a total of 140 MPH-treated ADHD adults and 113 placebo-treated ADHD adults. The mean effect size of 0.9 was statistically significant and there was no evidence of publication bias. Larger MPH effect sizes were associated with physician ratings of outcome and use of higher doses. When treatment is optimized to high doses, the effect size for MPH in adults was 1.3. We found strong support for the assertion that MPH is efficacious for treating adult ADHD. Because the degree of efficacy of MPH in treating ADHD adults is similar to what has been reported from meta-analyses of the child and adolescent literature, our work provides further assurance to clinicians that the diagnosis of ADHD can be validly applied in adulthood.

Adult↗
PubMed2004

Phenomenology of childhood psychosis: findings from a large sample of psychiatrically referred youth.

Our objective was to evaluate the scope and clinical correlates of psychotic phenomena in psychiatrically referred children and adolescents. Subjects were 1657 psychiatrically referred youth (mean age = 10.9 years) evaluated from 1991 to 2002. DSM-III-R diagnoses were obtained through maternal report by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version. Childhood-onset psychosis was defined by the presence of delusions or hallucinations. Childhood-onset psychosis was identified in 8% of psychiatrically referred youth. It was associated with a chronic course and high levels of impairment. Comorbidity with disruptive, mood, and anxiety disorders was very severe, with only one of the 132 identified youth with psychosis not having at least one comorbidity. In conclusion, childhood-onset psychosis in referred youth is common and highly morbid. It remains an important topic of research deserving full clinical and scientific attention.

Academic Medical Centers↗
PubMed2004

Reexamining Tic persistence and Tic-associated impairment in Tourette's Disorder: findings from a naturalistic follow-up study.

The objective of this study was to assess tic persistence and tic-associated impairment in referred youth with Tourette's Disorder (TD). Subjects were 50 youth (ages 6-17 years) who met DSM-IV diagnostic criteria for TD, were referred to a specialized TD program, and were evaluated by clinical and structured diagnostic interview. Tic severity and impairment was measured using the Yale Global Tic Severity Scale. The total tic score at or above minimal range defined tic persistence, and a TD impairment score at or above moderate range defined tic-associated impairment. Results were assessed during administration of the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiological Version. Mean age of onset of TD was 5.1 +/- 2.3 years, and mean illness duration was 5.6 +/- 3.2 years. At baseline, 88% of subjects met threshold criteria for at least mild tics, but only 30% met criteria for tic-associated impairment. At 2-year follow-up, 82% of these subjects met criteria for tic persistence (NS change from baseline), but only 14% met criteria for TD-associated impairment (p < .04 change from baseline). Although tics followed a persistent course in the majority of youth with TD, they were infrequently associated with impairment. There was a significant reduction in the proportion of youth with TD impairment from baseline to follow-up. These results support the view that TD is a persistent disorder, but suggest a dissociation between tic persistence and tic-associated dysfunction.

Adolescent↗
PubMed2004

A novel permutation testing method implicates sixteen nicotinic acetylcholine receptor genes as risk factors for smoking in schizophrenia families.

Smoking is a common correlate of schizophrenia, which leads to medical morbidity. Although twin and adoption studies have consistently implicated genes in the etiology of both smoking and schizophrenia, finding genes has been difficult. Several authors have suggested that clinical or neurobiological features associated with schizophrenia, such as smoking, might improve the ability to detect schizophrenia susceptibility genes by identifying genes related to the etiology of that feature. The objective of this study is to assess evidence for linkage of sixteen nicotinic acetylcholine receptor genes and smoking in schizophrenia families, using data from the NIMH Genetics Initiative for schizophrenia. Sixteen nicotinic acetylcholine receptor genes were selected prior to analysis. We used a multipoint sibling pair linkage analysis program, SIBPAL2, with a smoking trait in schizophrenia families. The significance of the group of candidate genes, in addition to each individual candidate gene, was assessed using permutation testing, which adjusted for multiple comparisons. The group of genes showed significant linkage to the smoking trait after adjusting for multiple comparisons through permutation testing (p = 0.039). In addition, two of the individual candidate genes were significant (CHRNA2, p = 0.044) and (CHRNB2, p = 0.015) and two genes were marginally significant (CHRNA7, p = 0.095; CHRNA1, p = 0.076). The significance of the complex hypothesis, involving sixteen genes, implicates the nicotinic system in smoking for schizophrenic families. Individual gene analysis suggests that CHRNA2 and CHRNB2 may play a particular role in this involvement. Such findings help prioritize genes for future case control studies. In addition, we provide a novel permutation method that is useful in future analyses involving a single hypothesis, with multiple candidate genes.

Adult↗
PubMed2004

Lack of association between behavioral inhibition and psychosocial adversity factors in children at risk for anxiety disorders.

OBJECTIVE: In a previous controlled study of offspring at risk for anxiety disorders, the authors found that parental panic disorder with comorbid major depression was associated with child behavioral inhibition, the temperamental tendency to be quiet and restrained in unfamiliar situations. To explore whether this association was mediated by environmental factors, the authors examined associations between psychosocial adversity variables and behavioral inhibition in this group of children. METHOD: Subjects included 200 offspring of parents with panic disorder and/or major depression and 84 comparison children of parents without mood or anxiety disorders. Behavioral inhibition was assessed through laboratory observations. The associations between behavioral inhibition and the following psychosocial factors were examined: socioeconomic status; an index of adversity factors found in previous studies to be additively associated with child psychopathology; family intactness, conflict, expressiveness, and cohesiveness; exposure to parental psychopathology; sibship size; birth order; and gender. RESULTS: The results showed no associations between behavioral inhibition and any of the psychosocial factors in the study group as a whole, despite adequate power to detect medium effect sizes. Among low-risk comparison children only, some definitions of behavioral inhibition were associated with low socioeconomic status, low family cohesion, and female gender. CONCLUSIONS: The results suggest that the psychosocial adversity factors examined in this study do not explain the previous finding that offspring of parents with panic disorder are at high risk for behavioral inhibition.

Anxiety Disorders↗