Dasotraline in ADHD: novel or me too drug?

INTRODUCTION: A 'holy grail' of treatment options for attention-deficit hyperactivity disorder (ADHD) has been an agent with low abuse potential and peak-trough clinical effects, providing sustained therapeutic benefits throughout the day. One such agent, dasotraline, a dopamine and norepinephrine reuptake inhibitor agent, was recently reviewed by the FDA. Areas covered: The authors completed a timely drug review using a PubMed literature search using words 'Dasotraline, ADHD' 'stimulant, abuse' 'atomoxetine, ADHD.' FDA fact sheets of available medications were reviewed for comparison of safety and tolerability data. The authors reviewed preclinical, efficacy, and safety trials of dasotraline in ADHD: two phase 1, one phase 2, and several phase 3 trials have established efficacy in reducing ADHD symptoms. Expert opinion: Due to its stable plasma concentrations with once-daily dosing, dasotraline could have sustained treatment benefits for ADHD, with low abuse potential and a stable therapeutic response over a 24-h period.

Reading related white matter structures in adolescents are influenced more by dysregulation of emotion than behavior.

Mood disorders and behavioral are broad psychiatric diagnostic categories that have different symptoms and neurobiological mechanisms, but share some neurocognitive similarities, one of which is an elevated risk for reading deficit. Our aim was to determine the influence of mood versus behavioral dysregulation on reading ability and neural correlates supporting these skills in youth, using diffusion tensor imaging in 11- to 17-year-old children and youths with mood disorders or behavioral disorders and age-matched healthy controls. The three groups differed only in phonological processing and passage comprehension. Youth with mood disorders scored higher on the phonological test but had lower comprehension scores than children with behavioral disorders and controls; control participants scored the highest. Correlations between fractional anisotropy and phonological processing in the left Arcuate Fasciculus showed a significant difference between groups and were strongest in behavioral disorders, intermediate in mood disorders, and lowest in controls. Correlations between these measures in the left Inferior Longitudinal Fasciculus were significantly greater than in controls for mood but not for behavioral disorders. Youth with mood disorders share a deficit in the executive-limbic pathway (Arcuate Fasciculus) with behavioral-disordered youth, suggesting reduced capacity for engaging frontal regions for phonological processing or passage comprehension tasks and increased reliance on the ventral tract (e.g., the Inferior Longitudinal Fasciculus). The low passage comprehension scores in mood disorder may result from engaging the left hemisphere. Neural pathways for reading differ mainly in executive-limbic circuitry. This new insight may aid clinicians in providing appropriate intervention for each disorder.

Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?

INTRODUCTION: High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points. METHODS: A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels. RESULTS: Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas. CONCLUSIONS: The combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.

Convergence Insufficiency Treatment Trial - Attention and Reading Trial (CITT-ART): Design and Methods.

OBJECTIVE: To describe the design and methodology of the Convergence Insufficiency Treatment Trial: Attention and Reading Trial (CITT-ART), the first randomized clinical trial evaluating the effect of vision therapy on reading and attention in school-age children with symptomatic convergence insufficiency (CI). METHODS: CITT-ART is a multicenter, placebo-controlled, randomized clinical trial of 324 children ages 9 to 14 years in grades 3 to 8 with symptomatic CI. Participants are randomized to 16 weeks of office-based vergence/accommodative therapy (OBVAT) or placebo therapy (OBPT), both supplemented with home therapy. The primary outcome measure is the change in the Wechsler Individual Achievement Test-Version 3 (WIAT-III) reading comprehension subtest score. Secondary outcome measures are changes in attention as measured by the Strengths and Weaknesses of Attention (SWAN) as reported by parents and teachers, tests of binocular visual function, and other measures of reading and attention. The long-term effects of treatment are assessed 1 year after treatment completion. All analyses will test the null hypothesis of no difference in outcomes between the two treatment groups. The study is entering its second year of recruitment. The final results will contribute to a better understanding of the relationship between the treatment of symptomatic CI and its effect on reading and attention. CONCLUSION: The study will provide an evidence base to help parents, eye professionals, educators, and other health care providers make informed decisions as they care for children with CI and reading and attention problems. Results may also generate additional hypothesis and guide the development of other scientific investigations of the relationships between visual disorders and other developmental disorders in children.

The 24-month course of manic symptoms in children.

OBJECTIVES: The Longitudinal Assessment of Manic Symptoms (LAMS) study was designed to investigate phenomenology and establish predictors of functional outcomes in children with elevated manic symptoms. The purpose of this series of analyses was to determine whether the participants demonstrated different trajectories of parent-reported manic and biphasic symptoms over the first 24 months of follow-up and to describe the clinical characteristics of the trajectories. METHODS: The 707 participants were initially aged 6-12 years and ascertained from outpatient clinics associated with the four university-affiliated LAMS sites. There were 621 children whose parents/guardians' ratings scored ≥ 12 on the Parent General Behavior Inventory-10-item Mania Form (PGBI-10M) and a matched random sample of 86 children whose parents/guardians' ratings scored ≤ 11 on the PGBI-10M. Participants were seen every six months after the baseline and their parents completed the PGBI-10M at each visit. RESULTS: For the whole sample, manic symptoms decreased over 24 months (linear effect B = -1.15, standard error = 0.32, t = -3.66, p < 0.001). Growth mixture modeling revealed four unique trajectories of manic symptoms. Approximately 85% of the cohort belonged to two classes in which manic symptoms decreased. The remaining ~15% formed two classes (high and rising and unstable) characterized by the highest rates of diagnostic conversion to a bipolar disorder (all p-values < 0.001). CONCLUSIONS: Outcomes are not uniform among children with symptoms of mania or at high risk for mania. A substantial minority of clinically referred children shows unstable or steadily increasing manic symptoms, and these patterns have distinct clinical correlates.