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S V Faraone

Publications and source records attributed to S V Faraone.

At least 19 recordsLinked to original sources
PubMed2006

Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families.

Evidence for association with schizophrenia has been reported for NOTCH4, although results have been inconsistent. Previous studies have focused on polymorphisms in the 5' promoter region and first exon of NOTCH4. Our aim was to test the association of the entire genomic region of NOTCH4 in 218 families with at least two siblings affected by schizophrenia in Taiwan. We genotyped seven single nucleotide polymorphisms (SNPs) of this gene, with average intermarker distances of 5.3 kb. Intermarker linkage disequilibrium (LD) was calculated using gold software, and single-locus and haplotype association analyses were performed using transmit software. We found that the T allele of SNP rs2071285 (P= 0.035) and the G allele of SNP rs204993 (P= 0.0097) were significantly preferentially transmitted to the affected individuals in the single-locus association analysis. The two SNPs were in high LD (D' > 0.8). Trend for overtransmission was shown for the T-G haplotype of the two SNPs to affected individuals (P= 0.053), with the A-A haplotype significantly undertransmitted (P= 0.034). The associated region distributed across the distal portion of the NOTCH4 gene and overlapped with the genomic region of the G-protein signaling modulator 3 and pre-B-cell leukemia transcription factor 2. In summary, we found modest association evidence between schizophrenia and the distal genomic region of NOTCH4 in this Taiwanese family sample. Further replication for association with the distal genomic region of NOTCH4 is warranted.

Gene Frequency↗
PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗
PubMed2005

Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14.

Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD = 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004).

Adult↗
PubMed2005

The CBCL as a screen for psychiatric comorbidity in paediatric patients with ADHD.

AIMS: To examine the informativeness of the Child Behavior Checklist (CBCL) as a screening tool to identify comorbid and non-comorbid cases of attention deficit hyperactivity disorder (ADHD) in a paediatrically referred population. It was hypothesised that specific scales of the CBCL would help identify specific comorbidities within ADHD cases in the primary care setting. METHODS: The sample consisted of children and adolescents 6-17 years old of both genders with ADHD (n = 121). A receiver operating curve (ROC) approach was used to determine which CBCL scales best differentiated between ADHD cases with and without its comorbidities with conduct, anxiety, and mood disorders. RESULTS: ROC analysis showed that the CBCL Delinquent Behavior and Aggressive Behavior scales predicted the structured interview derived diagnoses of conduct and bipolar disorder, the Anxious/Depressed and Aggressive Behavior scales predicted major depression, and the Anxious/Depressed and Attention problems scales predicted anxiety disorders. CONCLUSIONS: These results extend to a paediatrically referred population with previously reported findings in psychiatric samples documenting good convergence between structured interview diagnoses and syndrome congruent CBCL scales. These findings support the utility of the CBCL as a screening tool for the identification of psychiatric comorbidity in ADHD youth in the primary care setting.

Adolescent↗
PubMed2004

Relapse of depression during pregnancy following antidepressant discontinuation: a preliminary prospective study.

OBJECTIVE: Pregnancy has frequently been referred to as a time of emotional well-being for patients. However, systematic data about the risk for relapse of depression during pregnancy are sparse. METHOD: We completed a longitudinal cohort study of thirty-two (N = 32) women with histories of depression who were euthymic at conception and who either discontinued or attempted to discontinue antidepressant therapy proximate to conception. Subjects were prospectively followed across pregnancy once per trimester using structured clinical interviews. Rates of relapse and time to relapse were examined. Factors distinguishing the population with respect to risk for relapse including demographic characteristics and illness history were also examined. RESULTS: Seventy-five percent (N = 24) of patients relapsed during pregnancy. The majority of relapses (79%, N = 19) occurred in the first trimester, and relapse was more prevalent in women with histories of more chronic depression. CONCLUSIONS: Pregnancy is not "protective" with respect to risk for relapse of depression. Careful treatment planning is necessary for those women on antidepressants who plan to conceive or who become pregnant.

Adult↗
PubMed2004

Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature.

OBJECTIVE: To review the extant literature on the long-term outcome of child/adolescent-onset obsessive-compulsive disorder (OCD). METHOD: Medline and Psychlit databases were systematically searched for articles regarding long-term outcomes of child/adolescent-onset OCD. Meta-analysis regression was applied to evaluate predictors and persistence of OCD. RESULTS: Sixteen study samples (n = 6-132; total = 521 participants) in 22 studies had follow-up periods ranging between 1 and 15.6 years. Pooled mean persistence rates were 41% for full OCD and 60% for full or subthreshold OCD. Earlier age of OCD onset (z = -3.26, P = 0.001), increased OCD duration (z = 2.22, P = 0.027) and in-patient vs. out-patient status (z = 2.94, P = 0.003) predicted greater persistence. Comorbid psychiatric illness and poor initial treatment response were poor prognostic factors. Although psychosocial function was frequently compromised, most studies lacked comprehensive outcome measures. CONCLUSION: Long-term persistence of pediatric OCD may be lower than believed. Future studies should include broader measures of outcome including symptomatic persistence and functional impairment in multiple domains.

Adolescent↗
PubMed2003

Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large Veterans Affairs Cooperative Study sample.

Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP21 and haplotypes SNP2-(CTG)(n) and SNP12-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n = 62, 37%), African Americans (n = 60, 36%), and racially mixed or other races (n = 44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD = 1.25) and found excess transmission of the 8 (P = 0.06) and 13 (P = 0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively.

Alleles↗
PubMed2003

Meta-analysis identifies an association between the dopamine D2 receptor gene and schizophrenia.

The D2 subtype of dopamine receptor has been widely implicated in the pathogenesis of schizophrenia. Early evidence supporting an association between the Cys311Ser polymorphism of the D2 receptor gene (DRD2) and schizophrenia was subsequently refuted and, eventually, dismissed. From all 24 published case-control studies, we calculated a pooled estimate of this association. The pooled odds ratio was 1.3 for the Cys allele, which was highly significant (P=0.007). The odds ratio derived from each study was unrelated to the ethnicity or gender composition of the sample, or the age of the control group. There was no evidence of publication bias or excessive influence attributable to any given study. Although more family-based studies are needed to confirm this relation, our results provide strong evidence that DRD2 influences susceptibility to schizophrenia.

Genetic Predisposition to Disease↗
PubMed2002

Impact of exposure to parental attention-deficit hyperactivity disorder on clinical features and dysfunction in the offspring.

BACKGROUND: Although genes are known to influence the aetiology of ADHD, the impact of exposure to parental ADHD has received limited scientific scrutiny. This study investigated the impact of exposure to parental ADHD on clinical features and dysfunction in offspring. METHODS: We studied 1099 offspring (53% male, mean age 12.4 years) of non-ADHD, remitted ADHD, and persistent ADHD parents, using structured diagnostic interviews and a battery of cognitive and psychosocial measures. Offspring across these three groups were compared on clinical, cognitive and psychosocial outcomes, adjusting for exposure to other parental psychopathology, offspring ADHD status and social class. RESULTS: Parental ADHD was associated with an increased risk for ADHD in offspring relative to no parental ADHD, but no significant differences were found between children of remitted versus persistent ADHD parents. Exposure to parental ADHD predicted higher levels of family conflict and lesser levels of family cohesion relative to families without parental ADHD, independent of other psychopathological conditions in parents or ADHD status. Significant interactions were detected in which parental ADHD had a deleterious impact on measures of school performance in offspring without ADHD but not in those with the disorder. CONCLUSIONS: These results find no support for the hypothesis that exposure to parental ADHD increases the risk for ADHD in children beyond that conveyed by the liability associated with the diagnosis in the parent. However, since exposure to parental ADHD was associated with a disruptive family environment, the identification and treatment of adults with ADHD may be an important component of the treatment plan of youth with ADHD.

Adolescent↗
PubMed2002

Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, Its prevalence In adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritability data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.

Adult↗
PubMed2002

Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis.

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Several studies have shown Adderall , to be efficacious for measures of inattention, hyperactivity-impulsivity, aggression, disruptive behavior, and academic productivity. Although these studies provide useful information for clinicians treating ADHD children and adults, the variability in efficacy among the different types of measures used within each study has not been comprehensively examined. Thus, to provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the six available studies of standard release Adderall show it to be efficacious for symptoms of inattention, hyperactivity-impulsivity, and aggression, as well as global ratings. Its efficacy was significant for clinician, parent, and teacher ratings, and for both fixed- and best-dose designs.

Adolescent↗
PubMed2001

Evidence for the multigenic inheritance of schizophrenia.

Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.

Alleles↗
PubMed2001

Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.

Adult↗
PubMed2001

A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. METHODS: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. RESULTS: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. CONCLUSIONS: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.

Adolescent↗
PubMed2001

Intelligence quotient and neuropsychological profiles in patients with schizophrenia and in normal volunteers.

BACKGROUND: The objective of this study was to examine neuropsychological performance at different intelligence quotient (IQ) levels in schizophrenia. METHODS: Thirty-six patients with schizophrenia were matched with 36 normal control subjects in two IQ groups: low average (81-94) and average (95-119). Performance level (IQ group main effects) and profile shape (IQ group x function interactions) were compared. RESULTS: Current IQ was lower than estimated premorbid intellectual ability in both patient groups. Patients also displayed poorer neuropsychological function than same-IQ control subjects, suggesting neuropsychological dysfunction beyond their already compromised IQ. Patients had different profile shapes than control subjects, but profile shapes were consistent within patients and control subjects at each IQ level. Patients at both levels had higher verbal and lower performance IQ than control subjects. Abstraction-executive function was one of the lowest neuropsychological scores in both patient groups. Average IQ patients had nonsignificantly better overall neuropsychological performance than low average control subjects, but the effect size (.43) was quite small relative to the IQ difference (effect size = 2.57). CONCLUSIONS: Neuropsychological patterns in schizophrenia tend to be consistent at different IQ levels. Even schizophrenia patients with normal current IQs manifest substantial neuropsychological compromise relative to their level of general intellectual ability. The results strengthen the argument that neurocognitive deficits are core deficits of schizophrenic illness.

Adult↗
PubMed2001

Concurrent validation of schizotaxia: a pilot study.

BACKGROUND: Many first-degree relatives of patients with schizophrenia show deficits in clinical, neuropsychological, neurobiological and social domains, in the absence of psychosis. We recently reformulated Meehl's concept of schizotaxia to conceptualize the liability to schizophrenia, and we proposed preliminary criteria based on the presence of negative symptoms and neuropsychological deficits. Here we investigate the concurrent validity of schizotaxia by comparing a group of subjects who met criteria for schizotaxia with a group who did not on independent measures of clinical function, and on lifetime rates of selected comorbid psychiatric disorders. METHODS: Twenty-seven adults who were first-degree, biological relatives of patients with schizophrenia were evaluated for schizotaxia based on our predetermined criteria involving negative symptoms and neuropsychological deficits. Subjects also received portions of the Diagnostic Interview for Genetic Studies, the Structured Interview for Schizotypy, the Family Interview for Genetic Studies, the DSM-IV Global Assessment of Functioning, the Physical Anhedonia Scale, the Social Adjustment Scale and the Symptom Checklist-90-Revised. Subjects who met criteria for schizotaxia were compared with those who did not on each of the clinical measures, and on their rates of comorbid DSM-IV psychiatric diagnoses. RESULTS: Eight subjects met criteria for schizotaxia, and 19 did not. Subjects with schizotaxia showed significantly lower levels of function on each of the clinical scales. Differences in comorbid psychiatric diagnoses were not significant, although the rate of lifetime substance abuse diagnoses in the schizotaxic group (50%) approached levels that are often seen in schizophrenia. CONCLUSIONS: These findings provide the first evidence of concurrent validation for a proposed syndrome of schizotaxia. They are also consistent with the view that the vulnerability to schizophrenia may be defined, at least partially, although larger studies to assess both the concurrent and predictive validity of schizotaxia will be required to confirm these results.

Adult↗
PubMed2001

Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders.

The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article.

Attention Deficit Disorder with Hyperactivity↗