Biomedical subjects

Stephen V Faraone

Publications and source records attributed to Stephen V Faraone.

At least 109 records · Page 6Linked to original sources

PubMed2005

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Adolescent↗

PubMed2005

Clinical correlates of bipolar disorder in a large, referred sample of children and adolescents.

OBJECTIVE: To compare the prevalence, clinical correlates, and comorbidity among children and adolescents with bipolar disorder (BPD) assessed in the early 1990s (first cohort) with those evaluated over the last 7 years (second cohort). METHODS: Subjects were consecutively referred children (N=108) and adolescents (N=197) with a DSM-III-R BPD diagnosis, referred to a child psychiatry service and evaluated with identical structured assessment methods. RESULTS: Mania was identified in 16% of referred youth in both age groups and cohorts; in both age groups and cohorts, the clinical picture was predominantly irritable and mixed, and the course was chronic. Youth with BPD in both age groups and cohorts frequently had comorbidity with ADHD, psychosis and anxiety disorders. They also had high rates of psychiatric hospitalization and evidence of severely impaired psychosocial functioning. CONCLUSIONS: The consistency of clinical features of bipolar disorder seen across age groups (children vs. adolescents) and cohorts (early and late cohorts) over the past decade supports the hypothesis that BPD in the young is a severe condition afflicting a sizeable minority of referred youth. These findings replicate and extend our previous characterization of an early onset mania, which may represent a developmental subtype of BPD.

Adolescent↗

PubMed2005

Neuropsychological functioning in relatives of girls with and without ADHD.

BACKGROUND: A limited number of studies have examined neuropsychological functioning in the family members of ADHD youth, and none have focused exclusively on relatives of females. METHOD: Structured diagnostic interviews and neuropsychological batteries were administered to parents and siblings enrolled in a family study of girls with and without ADHD. Relatives were stratified into three groups: relatives of DSM-IV ADHD probands with ADHD (n = 106), relatives of ADHD probands without ADHD (n = 189) and relatives of controls without ADHD (n = 243). Analyses were also conducted on a subgroup of families in which more than one member had RESULTS: The neuropsychological battery as a whole distinguished affected and unaffected ADHD relatives from controls. The Wechsler Oral Arithmetic subtest, the Stroop Word, Color and Color-Word subscales were impaired in affected ADHD relatives, as were the WRAT-R Arithmetic and Reading subtests. Only the Stroop Color-Word and Interference subtests and the WRAT-R Arithmetic subtest showed significant impairments in unaffected relatives. In multiplex families, additional impairments were found in unaffected relatives on the Stroop Color subtest and the Wechsler Oral Arithmetic subtest. Analyses based on DSM-III-R diagnoses produced nearly identical results. Minor differences emerged across relatives of probands with different DSM-IV subtypes. CONCLUSIONS: Data were consistent with our previous study of relatives of boys with ADHD. Neuropsychological impairments in relatives of female ADHD probands were primarily associated with the diagnosis of ADHD, but subtle cognitive impairments that index familial vulnerability to the disorder may exist.

Adolescent↗

PubMed2005

Serotonin gene polymorphisms and bipolar I disorder: focus on the serotonin transporter.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

Bipolar Disorder↗

PubMed2005

Long-term effects of extended-release mixed amphetamine salts treatment of attention- deficit/hyperactivity disorder on growth.

OBJECTIVE: The aim of this study was to examine the long-term effects of extended-release mixed amphetamine salts (MAS-XR) with 10-30-mg doses on the growth of children being treated for attention-deficit/hyperactivity disorder (ADHD). METHODS: Long-term growth data were collected from 568 children, 6-12 years of age, enrolled in a multicenter, open-label study of the safety of MAS-XR for the treatment of ADHD symptoms over the course of 6-30 months. RESULTS: Children taking MAS-XR grew less than expected, based on the norms provided by the Centers for Disease Control (CDC). The losses in expected weight and body mass index (BMI) were greatest for the heaviest children, and the losses in expected height were greatest for the tallest children. For weight, height, and BMI, we found that nearly all of the growth deficits occurred in year one. For each of these growth parameters, the loss in expected growth was not significant in the second year of treatment. CONCLUSIONS: Our results suggest that treatment with MAS-XR can lead to reductions in expected height and weight that are not fully rectified over the course of treatment, although they did show attenuation with treatment over time. Although this does not eliminate the need for clinicians to monitor growth, as they should for all stimulant formulations, it suggests that deficits in growth are not likely to be a clinical concern for most children treated with MAS-XR.

Amphetamine↗

PubMed2005

An open-label trial of risperidone in children and adolescents with bipolar disorder.

OBJECTIVE: The aim of this study was to evaluate the potential of risperidone as a treatment of pediatric bipolar disorder. METHODS: This was an 8-week, open-label, prospective study of risperidone monotherapy (1.25 +/- 1.5 mg/d) for 30 bipolar youths (manic, mixed, or hypomanic; 6-17 years of age). RESULTS: Twenty-two of the 30 youths (73%) completed the study. Using predefined criteria for improvement (a Clinical Global Impressions Improvement in Mania score of < or =2 at endpoint), the response rate for manic symptoms was 70%. The significant reduction in symptoms of mania resulted in a mean Young Mania Rating Scale (YMRS) score 13.5 at endpoint, indicating mild residual symptoms. Weight increased significantly from baseline (2.1 +/- 2.0 kg; p < 0.001) and there was a four-fold increase in prolactin levels from baseline (p < 0.001). CONCLUSIONS: Open-label risperidone treatment was associated with a significant shortterm improvement of symptoms of pediatric bipolar disorder. Future placebo-controlled, double-blind studies are needed to confirm these preliminary results.

Adolescent↗

PubMed2005

Searching for the liability to schizophrenia: concepts and methods underlying genetic high-risk studies of adolescents.

Conceptualizations of the liability for schizophrenia help guide the development of research protocols, which, in turn, provide empirical confirmations or disconfirmations of the conceptualization's tenets. This paper focuses on a conception of liability and its relationships to genetic adolescent high-risk studies. Specifically, the derivation and nature of a proposed multidimensional syndrome of liability to schizophrenia ("schizotaxia") are outlined, followed by a representative review of features reported in previous high-risk studies that may be related to schizotaxia, and a perspective on future high-risk investigations. Overall, genetic high-risk studies generally confirm the concept of liability in the offspring of parents with schizophrenia, as expressed by deficits or abnormalities in multiple dimensions. It is concluded that high-risk studies on the liability to schizophrenia provide an important tool with which to explore the etiology and development of schizophrenia, in part by contributing to the identification and validation of specific liability syndromes.

Adolescent↗

PubMed2005

Childhood antecedents to panic disorder in referred and nonreferred adults.

OBJECTIVE: We used a recursive partitioning method to examine antecedent childhood anxiety disorders in large samples of referred and nonreferred subjects with and without panic disorder. METHODS: Referred subjects included adults treated for panic disorder (n = 131) and comparison adults with neither major anxiety nor mood disorders (n = 61). The nonreferred adult group derived from an opportunistic sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD), yielding 58 adults with panic disorder and 587 who were free of major anxiety and mood disorders. RESULTS: The majority of referred (65%) and nonreferred (52%) adults with panic disorder had antecedent childhood anxiety or disruptive behavior disorders. Classification and Regression Trees (CART) analysis showed that both separation anxiety disorder and overanxious disorder were independent predictors of subsequent panic disorder in both referred and nonreferred samples. CONCLUSIONS: These results confirm and extend previously reported findings by documenting that childhood anxiety disorders are important antecedent risk factors for panic disorder, independently of referral bias.

Adult↗

PubMed2005

Atomoxetine and stroop task performance in adult attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, for executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Two identical studies using a double-blind, placebo-controlled, parallel design were conducted. Patients were adults (Study 1, n = 280; Study 2, n = 256) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-defined ADHD recruited by referral and advertising. They were randomized to 10 weeks of treatment with atomoxetine or placebo. Executive functions were measured by the Stroop task. RESULTS: There was no evidence of cognitive deterioration associated with atomoxetine treatment. Atomoxetine treatment was associated with an improvement of the Stroop colorword score. CONCLUSIONS: Our results provide further support for Spencer et al.'s (1998) report that atomoxetine improves inhibitory capacity, as measured by the Stroop task. The absence of cognitive deterioration from atomoxetine, along with improved performance in a subgroup of patients in this large study, supports the safety of atomoxetine in this regard and its potential for improving a significant source of impairment for adults with ADHD.

Adult↗

PubMed2005

Family, twin, adoption, and molecular genetic studies of juvenile bipolar disorder.

Juvenile bipolar disorder (JBD) has been a subject of significant research and debate. Phenotypic differences between JBD and adult-onset bipolar disorder have led researchers to question whether or not similar neuropathologic mechanisms will be found. While much is known about the genetic and environmental contributions to the adult-onset phenotype, less is known about their contributions to JBD. Here, we review family, twin, adoption, and molecular genetic studies of JBD. Behavioral genetic data suggest both genetic and environmental contributions to JBD, while molecular genetic studies find linkage to age of onset of bipolar disorder to chromosomes 12p, 14q, and 15q. Additionally, changes associated with symptom age of onset have been recently reported in the brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK3-beta) genes. We contend that further progress in discovering the precise genetic and environmental contributions to JBD may depend on advances in phenotypic refinement, an increased appreciation of comorbid conditions, and more investigation of the longitudinal course of the disorder.

Adoption↗

PubMed2005

The CBCL predicts DSM bipolar disorder in children: a receiver operating characteristic curve analysis.

BACKGROUND: No clear consensus has been reached yet on how best to characterize children who suffer from pediatric bipolar disorder (PBD). The CBCL-PBD profile on the Child Behavior Checklist (CBCL) has been consistently reported showing deviant findings on the Attention Problems, Aggressive Behavior, and Anxious-Depressed subscales. AIM: To examine the sensitivity and specificity of the proposed CBCL-PBD profile for determining DSM diagnosis of PBD. METHODS: We applied receiver operating characteristic (ROC) curve analysis to data from 471 probands from two family studies of attention-deficit hyperactivity disorder and their 410 siblings. RESULTS: The CBCL-PBD score demonstrated an area under the curve (AUC) of 0.97 for probands and 0.82 for siblings for current diagnosis of PBD, suggesting that the CBCL-PBD provided a highly efficient way of identifying subjects with a current diagnosis of PBD in this sample. CONCLUSIONS: These findings suggest that the CBCL-PBD may provide a highly efficient way of screening for childhood bipolar disorder.

Adolescent↗

PubMed2005

Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?

BACKGROUND: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. METHOD: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. RESULTS: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless, studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. CONCLUSIONS: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Collaborative analysis of DRD4 and DAT genotypes in population-defined ADHD subtypes.

BACKGROUND: It has been proposed that some of the variability in reporting of associations between attention deficit hyperactivity disorder (ADHD) and candidate genes may result from mixing of genetically heterogeneous forms of ADHD using DSM-IV criteria. The goal of the current study is to test whether population-based ADHD subtypes defined by latent class analysis help resolve issues of variable findings across individual gene association studies. METHODS: Three studies which had previously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD subtypes. RESULTS: Across studies no significant associations were found for either DRD4 or DAT polymorphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3' DAT VNTR polymorphism and population-defined severe combined ADHD (OR=1.25, p=.01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD. CONCLUSION: Use of alternative population-based defined ADHD subtypes may help resolve some of the variable results presented for candidate gene association studies in ADHD.

Adolescent↗

PubMed2005

Absence of gender effects on attention deficit hyperactivity disorder: findings in nonreferred subjects.

OBJECTIVE: In a previous study, the authors found that, compared with referred boys with attention deficit hyperactivity disorder (ADHD), girls are less likely to manifest comorbid disruptive behavior disorders and learning disabilities--characteristics that could adversely affect identification of ADHD in girls. However, because referral bias can affect outcome, these findings require replication in nonreferred groups of ADHD subjects. METHOD: The authors evaluated gender effects in a large group of nonreferred siblings (N=577) of probands with ADHD and non-ADHD comparison subjects. Ninety-eight of the nonreferred siblings (N=73 males, N=25 females) met the criteria for diagnosis of ADHD, and 479 (N=244 males, N=235 females) did not meet those criteria. All siblings were systematically and comprehensively assessed with measures of emotional, school, intellectual, interpersonal, and family functioning. The assessment battery used for the siblings was the same as that used for the probands. RESULTS: The nonreferred males and females with ADHD did not differ in DSM-IV subtypes of ADHD, psychiatric comorbidity, or treatment history. They also showed similar levels of cognitive, psychosocial, school, and family functioning. CONCLUSIONS: These findings suggest that the clinical correlates of ADHD are not influenced by gender and that gender differences reported in groups of subjects seen in clinical settings may be caused by referral biases.

Adolescent↗

PubMed2005

Training raters to assess adult ADHD: reliability of ratings.

The standardization of ADHD ratings in adults is important given their differing symptom presentation. The authors investigated the agreement and reliability of rater standardization in a large-scale trial of atomoxetine in adults with ADHD. Training of 91 raters for the investigator-administered ADHD Rating Scale (ADHDRS-IV-Inv) occurred prior to initiation of a large, 31-site atomoxetine trial. Agreement between raters on total scores was established in two ways: (a) by Kappa coefficient (rater agreement for each item with the percentage of raters that had identical item-by-item scores) and (b) intraclass correlation coefficients (reliability). For the ADHDRS-IV-Inv, rater agreement was moderate, and reliability, as measured by Cronbach's alpha, was substantial. The data indicate that clinicians can be trained to reliably evaluate ADHD in adults using the ADHDRS-IV-Inv.

Adult↗

PubMed2005

Reexamining the familial association between asthma and ADHD in girls.

The objective of this study is to further evaluate the association between asthma and ADHD, addressing issues of familiality in female probands. A case control study of referred ADHD proband girls, controls, and relatives are used. Participants include 140 ADHD proband girls and 122 non-ADHD comparisons, with 417 and 369 first-degree biological relatives, respectively. Relatives are stratified into four groups according to proband ADHD and asthma status. The authors compare rates of asthma and ADHD in relatives. ADHD does not increase the risk for asthma in probands. Patterns of familial aggregation are mostly consistent with independent transmission of ADHD and asthma in families of girl probands. The results extend to female probands' previously reported findings that asthma and ADHD are independently transmitted in families. These findings further support the conclusion that ADHD symptoms should not be dismissed as part of asthma symptomatology or a consequence of its treatment.

Adult↗

PubMed2005

What is the prevalence of adult ADHD? Results of a population screen of 966 adults.

To provide a better estimate of the prevalence of ADHD in adulthood, the authors complete a telephone survey of 966 randomly selected adults. They compute two diagnoses from the survey data. Participants meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for both childhood and adulthood are defined as narrow ADHD. Broad ADHD adds to that definition those meeting subthreshold criteria. Cronbach's alpha is .90 for the 18 DSM-IV symptoms in childhood and .88 when rated for current symptoms in adulthood. No one item unduly influences the reliability of the total score. The authors find similar results in separate analyses of hyperactive-impulsive and inattentive symptoms. They estimate prevalences of 2.9% for Narrow ADHD and 16.4% for Broad ADHD. Having ADHD is associated with lower levels of education and employment status. These findings suggest that adult ADHD is a common disorder associated with impaired functioning.

Adult↗

PubMed2005

Impact of gender and age on executive functioning: do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years?

ADHD is known to have neuropsychological correlates, characterized mainly by executive function (EF) deficits. However, most available data are based on studies of boys through age 12. Our goal was to assess whether girls with ADHD express neuropsychological features similar to those found in boys, and whether these impairments are found in both preteen and teen samples. Participants were 101 girls and 103 boys with DSM-III-R ADHD, and 109 comparison girls and 70 boys without ADHD, ages 9 to 17 years. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. Primary regression analyses controlled for age, socioeconomic status, learning disability, and psychiatric comorbidity. Girls and boys with ADHD were significantly more impaired on some measures of EFs than healthy comparisons but did not differ significantly from each other. With the exception of 1 test score there were no significant Sex x Diagnosis interactions. Moreover, there were no more significant interactions among age, gender, and diagnosis than would be expected by chance. Neuropsychological measures of EFs were comparably impaired in girls compared to boys with ADHD, and these impairments are found at ages 9 to 12 and ages 13 to 17. These findings suggest that executive dysfunctions are correlates of ADHD regardless of gender and age, at least through the late teen years.

Adolescent↗