Faculty Bibliography

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. METHODS: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. RESULTS: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. CONCLUSIONS: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life

A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made

In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy

OBJECTIVE: To evaluate whether training primary care clinicians in maintenance care for patients who have changed their drinking influences practice behavior. DESIGN: We randomized 15 physician and 3 mid-level clinicians in 2 primary care offices in a 2:1 design. The 12 intervention clinicians received a total of 2 (1/4) hours of training in the maintenance care of alcohol problems in remission, a booster session, study materials and chart-based prompts at eligible patients' visits. Six controls provided usual care. Screening forms in the waiting rooms identified eligible patients, defined as those who endorsed: 1 or more items on the CAGE questionnaire or that they had an alcohol problem in the past; that they have 'made a change in their drinking and are trying to keep it that way'; and that they drank <15 (men) or <10 (women) drinks per week in the past month. Exit interviews with patients evaluated the clinician's actions during the visit. RESULTS: Of the 164 patients, 62% saw intervention clinicians. Compared with patients of control clinicians, intervention patients were more likely to report that their clinician asked about their alcohol history (odds ratio, 2.8; 95% confidence interval, 1.3, 5.8). Intervention clinicians who asked about the alcohol history were more likely to assess prior and planned alcohol treatment, assist through offers for prescriptions and treatment referral, and receive higher satisfaction ratings for the visit. CONCLUSIONS: Systemic prompts and training in the maintenance care of alcohol use disorders in remission might increase primary care clinicians' inquiries about the alcohol history as well as appropriate assessment and intervention after an initial inquiry

In this article, the authors introduce a latent difference score (LDS) approach to analyzing longitudinal data in trauma research. The LDS approach accounts for internal sources of change in an outcome variable, including the influence of prior status on subsequent levels of that variable and the tendency for individuals to experience natural change (e.g., a natural decrease in posttraumatic stress disorder [PTSD] symptoms over time). Under traditional model assumptions, the LDSs are maximally reliable and therefore less likely to introduce biases into model testing. The authors illustrate the method using a sample of children who experienced significant burns or other injuries to examine potential influences (i.e., age of child-adolescent at time of trauma and ongoing family strains) on PTSD symptom severity over time

OBJECTIVE: The serotonin transporter gene (SLC6A4) is a strong autism candidate gene because of its association with anxiety, aggression and attention, and the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in treating certain behavioral symptoms. In families with individuals with autism, several reports of biased transmission of both alleles (short, long) at the serotonin transporter gene promotor polymorphism (5-HTTLPR) locus of SLC6A4 now exist. The heterogeneity in these reports may be due to clinical heterogeneity. The authors hypothesized that 5-HTTLPR genotypes would be related to variation in specific symptoms in children with autism. METHOD: The authors explored whether variants of two functional polymorphisms of SLC6A4 (5-HTTLPR, intron 2 variable number tandem repeat [2 VNTR]) were related to behavioral characteristics measured by the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Subjects (N=73, age 3-19 years old) met diagnostic criteria for autistic disorder based on both measures. RESULTS: Evidence of genotype-phenotype interactions on the Autism Diagnostic Interview-Revised was found with the 5-HTTLPR short group of HTTLPR (S/L or S/S genotypes) being rated as more severe on the subdomain 'failure to use nonverbal communication to regulate social interaction,' and the long group (L/L genotype) being more severe on the subdomain 'stereotyped and repetitive motor mannerisms' and on an aggression measure. In contrast, on the Autism Diagnostic Observation Schedule, the long group was associated with greater severity on directed facial expressions and unusual sensory interests. There were no significant relationships between the intron 2 VNTR genotypes and subdomains or domains of symptoms on the Autism Diagnostic Interview-Revised or the Autism Diagnostic Observation Schedule. CONCLUSIONS: These findings provide initial support for genotype-specific phenotypes for 5-HTTLPR in autism based on ratings from the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule