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Stephen V Faraone

Publications and source records attributed to Stephen V Faraone.

At least 55 records · Page 3Linked to original sources
PubMed2006

Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: an fMRI study of working memory.

OBJECTIVE: Adult first-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness, demonstrate working memory (WM) impairments, and manifest alterations in dorsolateral prefrontal cortical (DLPFC) function during WM. Because substantially less is known about these phenotypes in adolescent subjects we sought to demonstrate that young relatives of persons with schizophrenia manifest impaired WM and altered prefrontal activation. METHODS: Participants were 21 non-psychotic, unmedicated first-degree relatives of persons with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type and 24 unmedicated controls, recruited from the community and hospitals in metropolitan Boston (ages 13-28). We compared groups on an auditory WM task with interference prior to scanning and used functional magnetic resonance imaging (fMRI) to compare groups while performing visual 2-back WM and control vigilance tasks. Blood oxygen level dependent signal change was measured using two whole-brain gradient echo EPI pulse acquisitions (21 contiguous, 5mm axial slices), acquired on a Siemens 1.5T MR scanner. Data were analyzed using Statistical Parametric Mapping-99. RESULTS: The high risk subjects were significantly impaired on the auditory WM task, had significantly greater Phobic Anxiety, and marginally greater Psychoticism than controls on the Symptom Checklist-90-Revised, and showed significantly greater task-elicited activation in the right DLPFC (BA 46). Psychopathology, IQ, and in-scanner WM performance did not account for group differences in brain activation. CONCLUSIONS: Data support a physiological difference (an exaggerated fMRI response) in DLPFC in adolescents at genetic risk for schizophrenia, independent of psychosis. Future work can study the relationship of these measures to possible onset of schizophrenia.

Adolescent↗
PubMed2006

Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor gene polymorphisms in Han Chinese subjects.

Attention-deficit/hyperactivity disorder (ADHD) is an important public health problem. Although serotonin is believed to be an important neurotransmitter in the etiology of this disorder, it remains unclear which specific 5-HT receptors are involved in regulating the symptoms of ADHD. Previous studies have provided favorable evidence for the association of ADHD with both the serotonin transporter gene and serotonin 1B receptor gene. To further investigate the role of other genes of the serotonergic pathway in ADHD, the current study examined variants of the serotonin 4 receptor gene in a relatively large sample of ADHD nuclear families. The T allele of the 83097 C>T polymorphism of HTR4 showed a tendency of preferential transmission to probands with ADHD (chi(2)=2.699, P=0.100). When haplotype TDT analysis of HTR4 was performed, we further found that the C/G haplotype of the 83097 C>T and 83198 A>G polymorphisms (chi(2)=8.783, P=0.003) and the C/G/C haplotype of these and the -36 C>T polymorphism (chi(2)=5.762, P=0.016) were under-transmitted to probands with ADHD. These results suggest that the HTR4 gene may play a role in the genetic predisposition to ADHD.

Asian People↗
PubMed2006

Possible association of the alpha-2A adrenergic receptor gene (ADRA2A) with symptoms of attention-deficit/hyperactivity disorder.

A dysfunction of the central noradrenergic system has long been suggested to be involved in attention-deficit/hyperactivity disorder (ADHD). Pharmacological evidence from animal studies and clinical practice has identified the alpha-2A adrenergic receptor gene (ADRA2A) as a candidate gene in ADHD. Some findings from Caucasian populations seem to support a role for this gene in ADHD. The current study first examined the association of the ADRA2A MspI and DraI polymorphisms with ADHD in the Han Chinese population, which differs quite substantially from the Caucasian population in the frequencies of alleles at these polymorphisms. No biased transmission of alleles of either polymorphism was observed using transmission disequilibrium test (TDT) analysis in a sample of 268 nuclear families with an ADHD proband; however, haplotype analysis only identified a trend toward over-transmission of the M/C haplotype to probands with the combined subtype of ADHD (chi(2) = 3.233, P = 0.072). The mm genotype of the MspI polymorphism was also marginally related (P = 0.051) to lower ADHD symptom scores in a sample of 559 Chinese children with ADHD, which is inconsistent with data from Caucasian samples. Our results provide weak evidence for a possible role of ADRA2A in ADHD symptom expression.

Adolescent↗
PubMed2006

Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population.

Attention deficit hyperactivity disorder (ADHD) is a severe behavioral disorder in children known to have a substantial genetic component. Prior studies have implicated serotonin genes in the etiology of ADHD but have not examined tryptophan hydroxylase (TPH), which is a rate-limiting enzyme in serotonin biosynthesis. The current study examined the relationship between the A218C and A-6526G polymorphisms of the TPH gene and ADHD. Three hundred sixty-two unrelated ADHD probands and their biological parents were recruited to participate in this study. No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD (chi(2) = 4.4995, P = 0.034), regardless of subtype. Although this finding for ADHD in the Chinese Han population.

Adolescent↗
PubMed2006

Decreased volume of left and total anterior insular lobule in schizophrenia.

The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.

Adolescent↗
PubMed2006

The genetics of ADHD: a literature review of 2005.

Investigations into the genetic basis of attention-deficit/hyperactivity disorder (ADHD) continue to yield compelling results as candidate gene studies reveal more information about this elusive disorder. Family, twin, and adoption studies further the notion that ADHD is a highly heritable disorder with direct genetic and environmental influence. The year 2005 saw many ADHD candidate gene studies, with most focused on the catecholaminergic candidates. Although many genes were studied in 2005, a large portion of findings has been supportive of the roles of dopaminergic genes' relationship to clinical phenotypes and drug response. These studies often require replication. Clinical implications continue to be speculative, as larger sample sizes are needed to validate findings to the general population. Further understanding of endophenotypes and the impact of comorbidities also is necessary for proper clinical intervention. Forthwith, we provide a summary of ADHD genetic studies published in 2005.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Risperidone for the treatment of affective symptoms in children with disruptive behavior disorder: a post hoc analysis of data from a 6-week, multicenter, randomized, double-blind, parallel-arm study.

BACKGROUND: Despite the increasing recognition of bipolar disorder in childhood, there have been no controlled, randomized clinical trials of atypical antipsychotics in this population. Preliminary data from open-label trials in children suggest that these agents might be effective in treating pediatric bipolar disorder, however. OBJECTIVE: The purpose of this post hoc analysis of data from Aman et al was to determine the effects of risperidone in the management of affective symptoms in children with disruptive behavioral disorders (DBDs). METHODS: This report presents a secondary analysis of a previously reported 6-week, multicenter, double-blind, randomized, parallel-arm trial comparing 6 weeks of administration of risperidone (flexible dosing starting at 0.02 mg . kg .1 . d(-1) and titrated up to 0.06 mg kg(-1) d(-1)) versus placebo in children with DBDs and subaverage intelligence. Twenty-four candidate affective symptoms of mania and depression were extracted from the 64-item Nisonger Child Behavior Rating Form (NCBRF). To define independent dimensions of mood-disorder psychopathology, these 24 symptoms were assigned 1 of 3 independent dimensions (symptoms of mania) based on loading: explosive irritability; agitated, expansive, grandiose; and depression. A fourth, nonaffective independent dimension encompassed a combination of nonaffec tive symptoms on the NCBRF Conduct Problem subscale. To assess treatment effect, each independent dimension was assigned a score derived from the sum of the symptoms that loaded on that dimension at weeks 2, 4, and 6 of study drug administration. RESULTS: A total of 110 patients were included in the independent-dimension analysis (89 boys, 21 girls; risperidone, 49 patients; placebo, 61 patients; mean [SD] age, 8.6 [2.3] and 8.1 [2.4] years in the risperidone and placebo groups, respectively; mean [SD] weight, 33.9 [12.8] and 32.1 [12.0] kg in the risperidone and placebo groups, respectively). The treatment-effect analysis found that the mean scores of all 3 independent dimensions were significantly reduced with risperidone compared with placebo at weeks 2, 4, and 6 (all, P <or= 0.03). The effect sizes of improvement in these factors ranXged from 0.44 to 0.95 at end point. CONCLUSIONS: The results of this post hoc analysis of affective symptoms of DBDs using data from a previously published randomized, double-blind clinical comparison of risperidone and placebo in the treatment of children with DBDs and subaverage intelligence suggest that risperidone was effective in treating the factors of explosive irritability; agitated, expansive, grandiose; and depression.

Affective Symptoms↗
PubMed2006

The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies.

BACKGROUND: This study examined the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood. METHOD: We analyzed data from published follow-up studies of ADHD. To be included in the analysis, these additional studies had to meet the following criteria: the study included a control group and it was clear from the methods if the diagnosis of ADHD included subjects who did not meet full criteria but showed residual and impairing signs of the disorder. We used a meta-analysis regression model to separately assess the syndromatic and symptomatic persistence of ADHD. RESULTS: When we define only those meeting full criteria for ADHD as having 'persistent ADHD', the rate of persistence is low, approximately 15% at age 25 years. But when we include cases consistent with DSM-IV's definition of ADHD in partial remission, the rate of persistence is much higher, approximately 65%. CONCLUSIONS: Our results show that estimates of ADHD's persistence rely heavily on how one defines persistence. Yet, regardless of definition, our analyses show that evidence for ADHD lessens with age. More work is needed to determine if this reflects true remission of ADHD symptoms or is due to the developmental insensitivity of diagnostic criteria for the disorder.

Age Factors↗
PubMed2006

Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study.

BACKGROUND: Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD: We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS: The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS: By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies.

Adolescent↗
PubMed2006

Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood. METHOD: This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults > or =18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S). RESULTS: Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P<.001), and 18.5 for the 60-mg group (P<.001). Adults with severe symptoms (ADHD Rating Scale score >32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P<.05) improvements in CAARS-S-S ADHD index scores occurred at 4- and 12-hours postdose for all MAS XR groups, indicating a 12-hour duration of effect. Symptoms improved within the first treatment week. Most adverse events reported were mild or moderate in intensity, and the most commonly reported adverse events were consistent with the known profile of stimulant medications. Vital signs and electrocardiograms showed no clinically significant cardiovascular changes. CONCLUSION: These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours.

Adolescent↗
PubMed2006

Neuropsychological functioning in girls with attention-deficit/hyperactivity disorder with and without learning disabilities.

The authors' goal was to assess neuropsychological performance in girls with attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls without ADHD, ages 6-17 years. Neuropsychological performance was measured in a standardized manner, blind to clinical status. LD was defined by a combined regression-based and low-achievement classification. ADHD was associated with modest, but significant, neuropsychological impairment, as measured with an aggregate measure of performance and with the Stroop Color-Word Test, independent of age, social class, IQ, and psychiatric comorbidity. Neuropsychological deficits were most pronounced in girls with both ADHD and an LD and in those without medications. These results extend to females the previously documented association of LDs with neuropsychological functioning in males with ADHD.

Adolescent↗
PubMed2006

A discordant twin study of premorbid cognitive ability in schizophrenia.

Twin studies are advantageous because sources of genetic and environmental variation are equated in ways that are not possible in standard case-control designs. We examined premorbid cognitive ability by comparing Armed Forces Qualification Test scores administered at the time of military enlistment in 21 schizophrenia-discordant twin pairs and 860 matched control twins. Scores were significantly lower in schizophrenia probands than in their nonpsychotic co-twins; co-twins were midway between probands and control twins. Effects were reduced when the discordant pairs were extended to include 33 psychosis-discordant pairs. Compared with controls, education at enlistment was significantly lower in psychosis probands and in co-twins from both schizophrenia- and psychosis-disordant pairs. Co-twins from psychosis-discordant pairs had significantly lower education at midlife than controls. Results suggest that cognitive ability is influenced by familial vulnerability for schizophrenia or psychosis, and that premorbid cognitive ability is lower in schizophrenia versus psychosis in general. Educational advancement may be slightly slowed by this familial vulnerability, but results were equivocal with regard to attenuation of one's ultimate educational attainment.

Adult↗
PubMed2006

Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD?

OBJECTIVE: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the first year and every 3 months thereafter. RESULTS: At baseline, subjects were approximately the expected height for their age and somewhat heavier than expected. Subjects gained height steadily throughout the study and were on average 0.23 cm less than expected at month 21. Weight did not increase and BMI decreased slightly in the first 4 months. Thereafter, weight Z score and BMI Z score remained relatively constant and children were on average 1.23 kg less than expected at month 21. Previous stimulant therapy tended to be associated with a smaller decrease in Z score during the study compared with no previous stimulant therapy. Drug holidays did not significantly affect growth. CONCLUSIONS: The effects of prolonged OROS MPH therapy on growth were clinically insignificant and limited to slight decreases in weight during the first months of therapy. Drug holidays did not reduce any impact on growth and are thus of questionable utility for limiting potential effects of treatment on growth.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Absence of significant associations between four AKT1 SNP markers and schizophrenia in the Taiwanese population.

AKT1 (V-akt murine thymoma viral oncogene homolog 1) is a protein kinase isoform of AKT. Five single-nucleotide polymorphisms, rs3803300, rs1130214, rs3730358, rs2498799 and rs2494732, at the genomic region of AKT1 have been reported to be significantly associated with schizophrenia. We tested for the presence of these five single-nucleotide polymorphisms in a Taiwanese population by genotyping 218 co-affected schizophrenia families. Both single locus and haplotypes analyses showed no association of these single-nucleotide polymorphisms with schizophrenia. These findings fail to support AKT1 as a susceptibility gene for schizophrenia in the Taiwanese population.

Genetic Markers↗
PubMed2006

Early onset bipolar disorder: possible linkage to chromosome 9q34.

OBJECTIVES: Bipolar disorder (BD) is characterized by manic and depressive states that onset at various times in life. Research shows that early onset forms of BD are associated with a stronger genetic loading for the illness. We hypothesized that using age at onset to look at subsets of BD families in a genetic linkage analysis would prove useful in separating etiologically homogeneous BD sub-groups and subsequently identifying genetic susceptibility regions. METHODS: We used the wave-I National Institute of Mental Health (NIMH) Genetics Initiative BD sample, which includes 540 individuals from 97 families with BD, in an ordered-subsets linkage analysis with age at onset of mania as the subset-identifying covariate. This analysis was performed using GENEHUNTER-PLUS followed by the ordered-subsets analysis program. This program generates empirical p-values for the subset with the largest LOD score to determine whether this value was significantly higher than the baseline LOD score using all families. RESULTS: Three chromosomal regions resulted in LOD scores above 2.0: 2.21 (6q25), 3.21 (9q34), and 2.16 (20q11). The largest increase in LOD score was observed on chromosome 9q34 between markers D9S290 and D9S915 in the subset of 58 families that had mania onset before age 20. Families with a minimal mania onset less than 20 years had a significantly greater number of psychiatric comorbidities (p = 0.02) and a marginal increase in depressive symptoms (p = 0.10). CONCLUSIONS: Further investigation into chromosomal region 9q34 is necessary to determine whether this region may harbor a gene specific to families with a minimal age at onset of less than 20.

Age Factors↗
PubMed2006

Diagnosing adult attention deficit hyperactivity disorder: are late onset and subthreshold diagnoses valid?

OBJECTIVE: Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM's diagnosis threshold. METHOD: The authors addressed the validity of DSM-IV's age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. RESULTS: Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. CONCLUSIONS: The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV's threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV's age-at-onset criterion is too stringent.

Adolescent↗
PubMed2006

Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder.

OBJECTIVE: The association between deficits in executive functioning and functional outcomes was examined among adults with attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were adults who did (N=213) and did not (N=145) meet DSM-IV criteria for ADHD. The authors defined having deficits in executive functioning as having at least two measures of executive functioning with scores 1.5 standard deviations below those of matched comparison subjects. RESULTS: Significantly more adults with ADHD had deficits of executive functioning than comparison subjects. Deficits of executive functioning were associated with lower academic achievement, irrespective of ADHD status. Subjects with ADHD with deficits of executive functioning had a significantly lower socioeconomic status and a significant functional morbidity beyond the diagnosis of ADHD alone. CONCLUSIONS: Psychometrically defined deficits of executive functioning may help identify a subgroup of adults with ADHD at high risk for occupational and academic underachievement. More efforts are needed to identify cost-effective approaches to screen individuals with ADHD for deficits of executive functioning.

Accidents, Traffic↗