Faculty Bibliography

OBJECTIVES: This study examined whether high levels of television viewing are associated with attention problems and hyperactivity in preschool children. METHODS: Parent and teacher ratings of inattention, hyperactivity and impulsivity, objectively measured activity level, and parental estimation of early television exposure were collected for a sample of preschool children. Separate linear regression analyses were conducted with parent and teacher behavioral ratings and objectively assessed activity level as outcome variables. RESULTS: Results indicated that after controlling for demographic factors (i.e., age, sex, and SES), television exposure accounted for a significant proportion of the variance in teacher ratings of inattentive/hyperactive behaviors, as well as objectively measured activity level. CONCLUSIONS: These findings partially replicate those from a recent, highly publicized study indicating a correlation between television exposure and attention-deficit/hyperactivity disorder (ADHD)-associated behaviors. However, it remains unclear as to whether elevated levels of television viewing are the cause or result of ADHD symptoms.

The oxytocin receptor gene (OXTR) has been studied in autism because of the role of oxytocin (OT) in social cognition. Linkage has also been demonstrated to the region of OXTR in a large sample. Two single nucleotide polymorphisms (SNPs) and a haplotype constructed from them in OXTR have been associated with autism in the Chinese Han population. We tested whether these associations replicated in a Caucasian sample with strictly defined autistic disorder. We genotyped the two previously associated SNPs (rs2254298, rs53576) in 57 Caucasian autism trios. Probands met clinical, ADI-R, and ADOS criteria for autistic disorder. Significant association was detected at rs2254298 (p=0.03) but not rs53576. For rs2254298, overtransmission of the G allele to probands with autistic disorder was found which contrasts with the overtransmission of A previously reported in the Chinese Han sample. In both samples, G was more frequent than A. However, in our Caucasian autism trios and the CEU Caucasian HapMap samples the frequency of A was less than that reported in the Chinese Han and Chinese in Bejing HapMap samples. The haplotype test of association did not reveal excess transmission from parents to affected offspring. These findings provide support for association of OXTR with autism in a Caucasian population. Overtransmission of different alleles in different populations may be due to a different pattern of linkage disequilibrium between the marker rs2254298 and an as yet undetermined susceptibility variant in OXTR

Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder

We present a novel method of statistical surface-based morphometry based on the use of non-parametric permutation tests and a spherical wavelet (SWC) shape representation. As an application, we analyze two brain structures, the caudate nucleus and the hippocampus, and compare the results obtained to shape analysis using a sampled point representation. Our results show that the SWC representation indicates new areas of significance preserved under the FDR correction for both the left caudate nucleus and left hippocampus. Additionally, the spherical wavelet representation provides a natural way to interpret the significance results in terms of scale in addition to knowing the spatial location of the regions.

OBJECTIVE: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. METHOD: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. RESULTS: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. CONCLUSION: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo

Despite the importance of the family in the treatment of pediatric obsessive-compulsive disorder (OCD), relatively little empirical attention has been directed to family accommodation of symptoms. This study examined the relations among family accommodation, OCD symptom severity, functional impairment, and internalizing and externalizing behavior problems in a sample of 57 clinic-referred youth 7 to 17 years old (M = 12.99 +/- 2.54) with OCD. Family accommodation was a frequent event across families. Family accommodation was positively related to symptom severity, parent-rated functional impairment (but not child-rated impairment), and externalizing and internalizing behavior problems. Family accommodation mediated the relation between symptom severity and parent-rated functional impairment

OBJECTIVE: The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies. METHOD: The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. RESULTS: The original observations were confirmed, with an overall odds ratio of 1.4 across samples. CONCLUSIONS: These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required