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Biomedical subjects

S V Faraone

Publications and source records attributed to S V Faraone.

At least 109 records · Page 6Linked to original sources
PubMed1999

Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder.

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.

Adult↗
PubMed1999

Further validation of social impairment as a predictor of substance use disorders: findings from a sample of siblings of boys with and without ADHD.

Examined predictors of substance use disorders in nonreferred siblings of boys with and without attention deficit hyperactivity disorder to further investigate whether previous findings documenting the role of social impairment in predicting substance use disorders would be replicated. Participants were comprehensively assessed at Time 1 and at 4-year follow-up. We found that social impairment was the sole significant predictor of alcohol and substance abuse and smoking after controlling for other variables previously shown to be predictors of substance use disorders. These results confirmed prior findings documenting the critical role of social impairment in predicting later substance use disorders.

Adolescent↗
PubMed1999

Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder.

OBJECTIVE: To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). METHODS: The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. RESULTS: Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8-21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04-0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. CONCLUSIONS: Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Adolescent↗
PubMed1999

Absence of effect of stimulants on the phamacokinetics of desipramine in children.

We conducted a retrospective chart review to examine the pharmacokinetic interaction between desipramine and the stimulants methylphenidate and dexedrine using routinely monitored desipramine serum concentrations in children receiving desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking desipramine, 29 taking desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 desipramine, 68 desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66+/-1.36 mg/kg, desipramine; 3.66+/-1.09 mg/kg, desipramine-stimulants; p=0.97), weight- and dose-normalized serum concentrations (47.26+/-39.26 [microg/L]/[mg/kg], desipramine, 39.02+/-19.92 [microg/L]/[mg/kg], desipramine-stimulants; p=0.09), and clearance (0.690+/-0.913 [L/kg]/hr, desipramine; 0.613+/-0.514 [L/kg]/hr, desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between desipramine and stimulants.

Adolescent↗
PubMed1998

Neurobiology of attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is an early-onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. Family, twin, adoption, segregation analysis, and molecular genetic studies show that is has a substantial genetic component. Although their results are still tentative, molecular genetic studies suggest that three genes may increase the susceptibility to ADHD: the D4 dopamine receptor gene, the dopamine transporter gene, and the D2 dopamine receptor gene. Studies of environmental adversity have implicated pregnancy and delivery complications, marital distress, family dysfunction, and low social class. The pattern of neuropsychological deficits found in ADHD children implicate executive functions and working memory; this pattern is similar to what has been found among adults with frontal lobe damage, which suggests that the frontal cortex or regions projecting to the frontal cortex are dysfunctional in at least some ADHD children. Moreover, neuroimaging studies implicate frontosubcortical pathways in ADHD. Notably, these pathways are rich in catecholamines, which have been implicated in ADHD by the mechanism of action of stimulants--the class of drugs that effectively treats many ADHD children. Yet human studies of the catecholamine hypothesis of ADHD have produced conflicting results, perhaps due to the insensitivity of peripheral measures.

Adult↗
PubMed1998

Sex differences in self-reported schizotypal traits in relatives of schizophrenic probands.

We used the Schizotypal Personality Questionnaire to evaluate schizotypal traits in 44 normal volunteers and 40 non-psychotic, biological relatives of schizophrenic probands. Relatives endorsed more cognitive-perceptual traits than did controls; a group-by-sex interaction indicated that male relatives accounted for this difference. Although not statistically significant, a similar pattern was observed for interpersonal traits. Thus, elevated rates of some schizotypal traits appear to be more prominent in male than in female relatives of schizophrenic probands, at least when assessed by self-report. Subscale analysis indicated that differences were accounted for primarily by suspiciousness and ideas of reference, suggesting that paranoid-like phenomena from both the cognitive-perceptual and interpersonal factors may constitute an important dimension of schizotypy in relatives. Unlike previous studies, we did not find any differences in constricted affect or disorganization signs. Interviews and other non-self-report techniques are probably best suited for an assessment of these features, although the question remains as to whether the combination of both approaches might provide some incremental discriminatory power.

Adult↗
PubMed1998

The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study.

The goal of this study was to assess whether degree of information processing load differentially affects vigilance performance in patients with schizophrenia as compared to normal controls or patients with other attentional disorders. We contrasted the performance of clinically stable outpatients with schizophrenia (n = 18), with that of normal controls (n = 17), and adults with developmental attentional/learning disorders (n = 13) on simple and demanding versions of a visual continuous performance test (CPT). Patients with schizophrenia were significantly impaired on both versions of the CPT compared to normal controls, and showed a significant decline in perceptual sensitivity and significantly more omission errors with increased processing demands. Compared to adults with developmental attentional/learning disorders, patients with schizophrenia manifested a tendency toward a decline in perceptual sensitivity. There were no significant differences between groups on a measure of response bias. The data support the hypothesis that patients with schizophrenia have insufficient information processing resources to cope with higher processing demands on effortful attention tasks. Further study comparing schizophrenic patients with patients who have other neuropsychiatric disorders, controlling for severity of illness, is required to determine the specificity of this deficit in schizophrenia.

Adult↗
PubMed1998

Neuropsychological function in adults with attention-deficit hyperactivity disorder.

BACKGROUND: Recent studies indicate that attention-deficit hyperactivity disorder (ADHD) persists into adulthood, but little is known about the neuropsychological features of adult ADHD. Our objective was to assess neuropsychological functioning in adults with ADHD with a battery of executive function tests. METHODS: Subjects were 64 unmedicated adults, 19-59 years of age, with DSM-III-R ADHD of childhood onset who met criteria for ADHD when referred in adulthood and 73 non-ADHD controls of similar age and gender. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Compared with controls, adults with ADHD were significantly impaired on measures of vigilance, semantic encoding for verbal memory, and written arithmetic, irrespective of age, gender, psychiatric comorbidity, or presence of learning disability. Despite comparable educational level and IQ, ADHD adults had a trend to lower occupational attainment and had significantly more academic problems in school. CONCLUSIONS: These executive, attention, and achievement dysfunctions demonstrated in adults with ADHD provide additional support for the validity of the syndrome in adults.

Adult↗
PubMed1998

Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence?

BACKGROUND: The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. METHODS: An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. RESULTS: ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). CONCLUSIONS: ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.

Adult↗
PubMed1998

Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands.

Evidence of subtle neuropsychological deficits in relatives of schizophrenic probands (REL-SZs) suggests that these are risk indicators for schizophrenia, but little is known about whether neuropsychological performance in REL-SZs differs from that in other groups of relatives. We compared neuropsychological function in female REL-SZs (n = 39), relatives of primarily psychotic bipolar disorder probands (REL-BPs; n = 15), and a normal control group (n = 44). After adjustment for expected intellectual ability (based on reading recognition), REL-SZs showed deficits in verbal and visual memory (Wechsler Memory Scale-Revised logical memories, visual reproductions), and auditory attention (dichotic digits) compared with either REL-BPs or control subjects. Memory, but not dichotic listening differences remained significant after adjusting for current IQ; however, average effect sizes after controlling for either reading or IQ were roughly comparable for these three parameters (d = 0.80, 0.71, and 0.69, respectively). REL-BPs and control subjects showed little difference. Although both schizophrenic and bipolar patients often manifest neuropsychological dysfunction, these preliminary findings indicate subtle neuropsychological deficits only in REL-SZs. Such differences suggest different underlying processes; neuropsychological impairment may, in part, reflect an expression of genetic liability to schizophrenia but not bipolar disorder. Replication with a larger REL-BP sample and with male relatives is needed to evaluate the generalizability of the results.

Adolescent↗
PubMed1998

Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative.

Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia.

Chromosomes, Human, Pair 15↗
PubMed1998

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium.

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

Adolescent↗
PubMed1998

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.

The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Adolescent↗
PubMed1998

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006).

Adolescent↗
PubMed1998

Association of neuropsychological vulnerability markers in relatives of schizophrenic patients.

We investigated the association of neuropsychological risk indicators in a matched sample of first-degree relatives of schizophrenic patients (n = 54) and normal controls (n = 72). We focussed on three functions previously identified in a smaller, initial sample as putative risk indicators of the schizophrenia genotype: abstraction, verbal memory and auditory attention. The expanded sample of relatives displayed significantly lower scores than controls on abstraction, verbal memory and auditory attention. The relatives demonstrated significant intercorrelations among these three functions. The significant correlations among relatives between attention and verbal memory and between attention and abstraction differed significantly from these correlations among controls. We discuss how the use of multiple risk indicators may help us better identify those relatives that carry the schizophrenia genotype.

Adult↗
PubMed1998

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness.

Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

Adolescent↗
PubMed1998

Familial risk analysis of the association between attention-deficit/hyperactivity disorder and psychoactive substance use disorders.

OBJECTIVE: To test hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUDs) by using the family study method. DESIGN: The first-degree relatives of clinically referred children and adolescents with ADHD (131 probands, 413 relatives) and healthy control probands (106 probands, 323 relatives) were assessed by blind raters. RESULTS: After stratifying the probands with ADHD and the control probands into those with PSUD (group 1 and group 3, respectively) and those without PSUD (group 2 and group 4, respectively), familial risk analyses revealed the following: (1) the risk for ADHD was not significantly different between relatives of group 2 and group 1 probands (19.6% vs 18.0%; P= .88), but these 2 risks were significantly greater than the risk to relatives of group 3 probands (1.0%; P= .01 and P= .02, respectively) and group 4 probands (7.0%; P=.001 and P=.01, respectively); (2) there were no significant differences in the risk for PSUD between relatives of group 1 (47.5%) and group 3 probands (39.7%; P = .40), but these risks were greater than the risk to relatives of group 2 (30.0%; P = .32) and group 4 probands (20.9%; P<.001); and (3) there was no evidence for nonrandom mating. CONCLUSIONS: These findings are consistent with the hypothesis that ADHD and PSUD are transmitted independently in families. Because the probands were young adolescents, many have not lived through the age at risk for PSUD. Thus, the hypothesis stating that ADHD and PSUD represent variable expressions of a common underlying risk factor cannot be ruled out.

Adolescent↗