Faculty Bibliography

BACKGROUND: The dopamine receptor D4 (DRD4) 7-repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (GxE) interaction of the DRD4 7-repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-repeat allele differs between ADHD affected and unaffected children. METHODS: Linear mixed models were used to assess main and interactive effects of the DRD4 7-repeat allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6-17 years. RESULTS: There was some evidence pointing to differential effects of the DRD4 7-repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for GxE interactions. CONCLUSION: Despite the large sample size, no GxE interactions were found. The impact of the DRD4 7-repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater-specific behaviors

Theory of Mind (ToM) and Executive Function (EF) have been associated with autism and with attention-deficit hyperactivity disorder (ADHD), and hence might play a role in similar syndromes found following profound early institutional deprivation. In order to examine this possibility the current study included a group of 165 Romanian adoptees, of whom 144 were adopted into the UK from deprived institutional settings before 43months of age, and a group of 52 within-UK adoptees, all adopted before 6months of age. Both groups were assessed at 6 and 11years. The Strange Stories task was used to assess ToM and the Stroop task was used to assess EF, both at age 11. The Romanian adoptees displayed deficits in both ToM and EF compared with the within-UK adoptee group. The degree of deficit was greater for children who had experienced more than 6months of institutional deprivation. Deficits in both domains (ToM and EF) were associated with each of the three apparently deprivation-specific problems, namely quasi-autism, disinhibited attachment and inattention/overactivity. Statistical analyses indicated a mediating role for both ToM and EF with respect to quasi-autism; possibly a partial mediating role for EF with respect to inattention/overactivity; and probably no mediating role for either ToM or EF in the case of disinhibited attachment. In conclusion, there is evidence for a possible mediating role for ToM and EF in the development of some apparently deprivation-specific difficulties in institution-reared Romanian adoptees, but neither accounts for the overall pattern of deprivation-related difficulties

OBJECTIVE: We conducted a retrospective, observational study of aripiprazole for the treatment of tics and/or co-morbid explosive outbursts in 37 children and adolescents with Tourette disorder (TD). METHOD: Thirty seven children and adolescents with TD, with and without explosive outbursts, and refractory to previous treatment were treated at one of two university affiliated specialty clinics. All diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) criteria. Tic severity was rated using the Clinical Global Impressions Scale for tics (CGI-Tics) and frequency of explosive outbursts was assessed using the CGI-Rage; both measures were obtained at pretreatment baseline and at posttreatment follow up. RESULTS: High rates of psychiatric co-morbidity were observed in these subjects: 31 of 37 (84%) subjects met criteria for obsessive-compulsive disorder (OCD), and 31 of 37 (84%) met criteria for attention-deficit/hyperactivity disorder (ADHD). Twenty nine of 37 (78%) subjects met criteria for intermittent explosive disorder (IED) minus criterion C; the remaining 8 subjects had TD only. Eight subjects (22%) discontinued treatment before 12 weeks due to inability to tolerate the drug. At follow up, tics reduced at a mean daily dose of 12.3 (7.50) mg in 29 of 29 (100%) subjects who completed the study, and explosive outbursts improved in 24/25 subjects (96%) who completed the study. Aripiprazole was tolerated reasonably well, although 8/37 (22%) subjects discontinued treatment; most common side effects included weight gain, akathisia, and sedation. CONCLUSION: Aripiprazole should be investigated further as a treatment option for TD with and without co-morbid explosive outbursts

Treatment with psychostimulant medication has been shown to improve scholastic functioning in children with attention-deficit/hyperactivity disorder (ADHD). However, the extent to which long-term academic gains are apparent in those having received such treatment remains elusive. This study examined prospectively the relationship of childhood stimulant treatment to academic functioning during adolescence. Children (n = 169) were initially recruited and diagnosed with ADHD when they were 7-11 years old. A subsample of those with childhood ADHD (n = 90) was reevaluated on average 9.13 (SD = 1.5) years later. Probands who did and did not receive treatment with stimulant medication were compared to each other and to a never-ADHD comparison group (n = 80) on three subtests from the Wechsler Individual Achievement Test-II (WIAT-II), as well as high school grade point average (GPA) and number of retentions in school as derived from school records. Analyses of covariance controlling for severity of childhood ADHD symptoms indicated that probands treated with psychostimulant medication achieved better academic outcomes, as measured by WIAT-II subtests and high school GPA, than those not treated with psychostimulants (p < .05). However, treated probands did not fare as well as the never-ADHD comparison group. Psychostimulant treatment for children with ADHD may benefit long-term adolescent academic performance, although the extent of improvement is likely to vary as a function of multiple factors.

Children with attention deficit/hyperactivity disorder (ADHD) are at heightened risk for maltreatment and later substance use disorders (SUDs). We investigated the relationship of childhood maltreatment and other risk factors to SUDs among adolescents diagnosed with ADHD in childhood. Eighty adolescents diagnosed with ADHD when they were 7 to 11 years old were screened for histories of childhood maltreatment, and SUD diagnoses were formulated in accordance with the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders. Lifetime history of problematic substance use was obtained for each parent at baseline. Childhood maltreatment predicted SUD outcome over and above that accounted for by childhood conduct disorder and problematic parental substance use, two potent predictors of adolescent SUDs.

CONCLUSION: The olfactory event-related potential (OERP) method provides a means of objectively assessing olfactory function. However, further validation is needed before OERPs can be routinely applied in clinical assessment of olfactory dysfunction. OBJECTIVE: To assess OERPs in patients with olfactory impairment and in healthy controls to investigate possible dose-response effects of odor concentration on OERP parameters in these groups, thereby exploring possibilities and limitations regarding the clinical utility of the OERP method. SUBJECTS AND METHODS: Twenty-three patients with a history of impaired olfactory function and 24 controls participated in the study. Olfactory function was assessed with psychophysical tests, i.e. assessment of the odor threshold, and odor identification. OERPs were obtained in response to the olfactory stimulant butanol at two different concentrations, presented via an olfactometer. RESULTS: The OERP amplitudes increased and the latencies shortened with increasing stimulus concentration. Furthermore, a difference between the groups was found, with higher OERP amplitudes and shorter latencies in healthy subjects compared with patients.

This study compared the Piers-Harris 2 scores of youth with PTSD (n=30) to the scores of traumatized youth without PTSD (n=60) and a non-traumatized comparison group (n=39). In the absence of major comorbid disorders, youth with PTSD evidenced significantly lower scores than the traumatized PTSD negatives and controls on five of six Piers-Harris 2 scales. With the exception of scores on an index of perceived parental acceptance of child behavior, trauma exposure in the absence of PTSD was not associated with lower Piers-Harris 2 scores