Faculty Bibliography

This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

The authors investigated prospectively assessed eating pathology (body image dissatisfaction and bulimia nervosa symptoms) among an ethnically and socioeconomically diverse sample of adolescent girls with attention-deficit/hyperactivity disorder-combined type (ADHD-C; n=93), ADHD-inattentive type (ADHD-I; n=47), and a comparison group (n=88). The sample, initially ages 6-12 years, participated in a 5-year longitudinal study (92% retention rate). After statistical control of relevant covariates, girls with ADHD-C at baseline showed more eating pathology at follow-up than did comparison girls; girls with ADHD-I were intermediate between these two groups. Baseline impulsivity symptoms, as opposed to hyperactivity and inattention, best predicted adolescent eating pathology. With statistical control of ADHD, baseline peer rejection and parent- child relationship problems also predicted adolescent eating pathology. The association between punitive parenting in childhood and pathological eating behaviors in adolescence was stronger for girls with ADHD than for comparison girls. Results are discussed in terms of the expansion of longitudinal research on ADHD to include female-relevant domains of impairment, such as eating pathology.

Many studies show that early and active parent involvement reduces discipline problems in school, increases academic success, and leads to better outcomes in adult life. The best outcomes are seen when both parents are highly involved. The February issue of our Parent Letter discusses some of the things that fathers and other male role models can do to increase their impact on children’s academic success and overall well-being.

We have previously shown that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/ MAPK) is transiently activated in anatomically restricted regions of the lateral amygdala (LA) following Pavlovian fear conditioning and that blockade of ERK/MAPK activation in the LA impairs both fear memory consolidation and long-term potentiation (LTP) in the amygdala, in vitro. The present experiments evaluated the role of the ERK/MAPK signaling cascade in LTP at thalamo-LA input synapses, in vivo. We first show that ERK/MAPK is transiently activated/phosphorylated in the LA at 5 min, but not 15 or 60 min, after high-frequency, but not low-frequency, stimulation of the auditory thalamus. ERK activation induced by LTP-inducing stimulation was anatomically restricted to the same regions of the LA previously shown to exhibit ERK regulation following fear conditioning. We next show that intra-LA infusion of U0126, an inhibitor of ERK/MAPK activation, impairs LTP at thalamo-LA input synapses. Collectively, results demonstrate that ERK/MAPK activation is necessary for synaptic plasticity in anatomically defined regions of the LA, in vivo

Identification and validation of novel drug targets continues to be a major bottleneck in drug development, particularly for polygenic complex diseases such as type 2 diabetes. Here, the authors describe an approach that allows researchers to rapidly identify and validate potential drug targets by combining chemical tools and RNA interference technology. As a proof-of-concept study, the known mechanism Sigma LOPAC library was used to screen for glucose-dependent insulin secretion (GDIS) in INS-1 832/13 cells. In addition to several mechanisms that are known to regulate GDIS (such as cyclic adenosine monophosphate-specific phosphodiesterases, adrenoceptors, and Ca(2+) channels), the authors find that several of the dopamine receptor (DRD) antagonists significantly enhance GDIS, whereas DRD agonists profoundly inhibit GDIS. Subsequent siRNA studies in the same cell line indicate that knockdown of DRD2 enhanced GDIS. Furthermore, selective DRD2 antagonists and agonists also enhance or suppress, respectively, GDIS in isolated rat islets. The data support that the approach described here offers a rapid and effective way for target identification and validation.

OBJECTIVE: The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic "crossover" among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system. METHOD: A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period. RESULTS: Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa. CONCLUSIONS: These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema.

The study investigated whether the P600/SPS component is sensitive to the richness of semantic content in sentences. ERPs were recorded while 30 native Swedish speakers read sentences, of which half were syntactically correct and half contained a syntactic violation. Both kinds of sentences came in one of three types of descending semantic completeness: semantically coherent sentences, sentences which were incoherent due to violations of selectional restrictions, or sentences of pseudo words, hence void of lexical content. In the semantically coherent sentences a P600/SPS was found for the syntactic violation. A less salient positivity was found for the violation in the semantically incoherent sentences. No P600/SPS was found for the syntactic violation in the pseudo word sentences and no LAN component in any sentence type. The results are interpreted as supporting the hypothesis that the P600/SPS component reflects a semantically based reanalysis process.