Faculty Bibliography

OBJECTIVE:We conducted a two-period (open-label and double-blind) pilot investigation of droxidopa, with and without carbidopa, for ADHD. METHOD/METHODS:Twenty adult ADHD patients received open-label droxidopa titrated from 200 to 600 mg 3 times per day (TID; Weeks 1-3), then open-label droxidopa plus carbidopa titrated from 25 or 50 mg TID (Weeks 4-6). In Weeks 7 to 8, patients were randomized to continued co-treatment or matching placebo substitution. RESULTS:Improvements in mean total Adult ADHD Investigator Symptom Report Scale (AISRS) scores were seen at Week 1 (p < .0001) and Week 3 (p < .0001). Improvements were maintained but not increased with carbidopa. Thirteen of 20 patients completed open-label treatment. In the double-blind period, mean total AISRS scores were similar between the co-treatment (n = 6) and placebo (n = 5) groups. No serious adverse events were reported. CONCLUSION/CONCLUSIONS:These preliminary findings indicate that droxidopa can improve adult ADHD symptoms. Further studies are warranted to examine the efficacy and safety of droxidopa in ADHD.

OBJECTIVES/OBJECTIVE:There is a need for brief and publicly-available assessments of attention deficit hyperactivity disorder (ADHD) easily administered in large-scale survey efforts monitoring symptoms among adolescents. The ADHD Self-Report Scale v1.1 (ASRS; Kessler et al., 2005) Screener, a six-item measure of ADHD symptoms, is a valid and reliable screening instrument for ADHD among adults. The current study provides initial evidence for the reliability and validity of the ASRS Screener among a community sample of U.S. adolescents. METHODS:Middle and high school students in grades 6 through 12 (N = 2,472) completed the ASRS Screener, along with the Strengths and Difficulties Questionnaire (SDQ; Goodman, 2001) and several questions about school functioning. RESULTS:The ASRS Screener demonstrated good internal consistency, with items captured by a single underlying latent variable, which was invariant across subsamples differing by gender. The ASRS Screener scores were associated with the SDQ subscale measuring hyperactivity/inattention (r = 0.58) and significantly less strongly associated with other SDQ subscale scores (r = -0.15-0.41). The ASRS Screener scores were also significantly associated with student-reported school functioning. CONCLUSION/CONCLUSIONS:Findings suggest directions for future research and provide preliminary support for use of the ASRS Screener as a brief tool for identifying symptoms of ADHD among adolescents.

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than controls, especially for orientation, as well as higher TIMO. In both ADHD and controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and controls with a mean accuracy of about 77%. Participants' self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.

BACKGROUND:Prefrontal-limbic circuits that form the neural architecture for emotion to influence behavior have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and represent a potentially important target of medication treatment that has not been substantively evaluated. This study tested the effect of the psychostimulant prodrug lisdexamfetamine dimesylate on amygdala activation and connectivity during the emotional bias of response execution and inhibition. METHODS:Twenty-five adults with ADHD were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task after 3 to 4 weeks of lisdexamfetamine treatment and 3 weeks off medication in a randomized, counterbalanced, hybrid crossover design. Drug, trial type, and face emotion (happy, sad, or neutral) were included as within-subjects factors in repeated measures analyses of activation and connectivity. RESULTS:Lisdexamfetamine was associated with increased right amygdala activation and reduced psychophysiological interactions with the orbital aspect of the left inferior frontal gyrus specifically for responses to sad faces compared with placebo, but there was no effect on the accuracy of response execution or inhibition. The relative gain in right amygdala activation in response to sad faces for lisdexamfetamine was correlated with a reduction in symptoms of ADHD. CONCLUSIONS:Treatment with lisdexamfetamine potentiates affective encoding in amygdala, purportedly via catecholaminergic mechanisms, but functionally disconnects the amygdala from inferior frontal regions that encode behavioral significance-resulting in reduced emotional bias of cognitive control. Pinpointing the neurophysiologic underpinnings of therapeutic improvement with lisdexamfetamine represents a first step in developing targeted approaches to treatment of ADHD.

OBJECTIVES: Assess agreement between self-ratings via the adult attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS)-v1.1 Symptom Checklist and clinician ratings via the adult ADHD Investigator Symptom Rating Scale (AISRS) expanded version using DSM-5 adult ADHD patients (referred sample) and ADHD controls (recruited from a primary care physician practice). METHODS: The ASRS v1.1 Symptom Checklist was administered to measure self-reported ADHD symptoms and impairment, the Adult ADHD Clinical Diagnostic Scale v1.2 was used to establish an adult ADHD diagnosis and the childhood and adult/current sections of the scale were used to provide scores to measure symptoms of childhood ADHD and recent symptoms of adult ADHD, the AISRS to measure ADHD current symptom severity. RESULTS: Participants (n = 299; range 18-58), of which 171 were ADHD+ and 128 ADHD-. ASRS and AISRS total scores and individual subsections examining inattention, hyperactivity, emotional dysfunction (EF), and emotional dyscontrol (EC) were all significantly correlated (Spearman's rho's = 0.78-0.89, ps < 0.01). Correlations remained significant when controlling for demographic factors and psychiatric conditions. CONCLUSIONS: The ASRS (self) and AISRS (clinician rated) scales have high agreement. This agreement extended not only the to the core 18 DSM symptoms, but also to the additional 13 symptoms that examine EC and EF.

Objectives: To examine the test-retest reliability of the DSM-IV Adult ADHD Self-Report Scale (ASRS) v1.1 Screener in adults without ADHD. Prior studies have not examined test-retest reliability of the Screener in non-ADHD controls. Methods: Subjects completed the Screener in a primary care physician (PCP) waiting room (T1); those who screened negative for ADHD (n = 104) (<4/6 significant Screener items) symptoms were further assessed on the phone (T2). T2 included phone administration of the full ASRS v1.1 Symptom Checklist (which contains the six items from the Screener). Spearman's correlations and intra-class correlation coefficients (ICCs) between T1 and T2 were calculated for the total Screener score and for each Screener item. McNemar-Bowker tests were conducted for the Screener total score and each item to check for significant changes from T1 to T2. Results: Screener T1 and T2 total scores were significantly correlated (Spearman's rho = 0.78, P < 0.0001), as were individual items. Correlations remained significant when controlling for a variety of demographic factors and psychiatric conditions. Confirming the significant Spearman correlations, ICCs for Screener total score and each item were also significant (ICC = 0.75, P < 0.0001). The McNemar-Bowker tests showed no significant differences for Screener total score and for the IA items; however, the H-I items were somewhat higher at T1 versus T2. Conclusions: The DSM-IV ASRS v1.1 Screener has high test-retest reliability in patients without ADHD.