Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients.     

Host‐associated genetic divergence and taxonomy in the Rhinusa pilosa Gyllenhal species complex: an integrative approach

A combined taxonomic, morphological, molecular and biological study revealed that stem‐galling weevils from the genus Rhinusa associated with toadflaxes from the genus Linaria (Plantaginaceae) are composed of three different species: Rhinusa pilosa, Rhinusa brondelii and Rhinusa rara sp.n. The authentic field host plants are respectively, Linaria vulgaris, Linaria purpurea and Linaria genistifolia/ Linaria dalmatica. These weevil species can be distinguished from each other by a few subtle morphological characteristics, mainly in the shape of the rostrum and of the integument. An analysis of the mitochondrial [cytochrome oxidase subunit II gene (COII) and 16S ribosomal RNA gene (16S)] and nuclear (elongation factor‐1α, EF‐1α) sequence data revealed high genetic divergence among these species. Uncorrected pairwise distances on mtCOII gene were 14.3% between R. pilosa and R. brondelii, 15.7% between R. pilosa and R. rara, while R. brondelii and R. rara were approximately 11% divergent from each other. Divergences obtained on 16S and nuclear EF‐1α genes were congruent. However, substantial intraspecific mitochondrial divergence was recorded for all studied populations of R. pilosa s.s. showing two mtDNA lineages, with estimated COII and 16S divergences of 4% and 1.6%, respectively. Nuclear pseudogenes (Numts) and Wolbachia influence, although recorded within both lineages, were excluded as possible causatives of the mtDNA divergence, while EF‐1α indicated absence of lineage sorting. Species from the R. pilosa complex are estimated to have diverged from each other approximately 7.2 million years ago (mya; late Miocene), while R. brondelii and R. rara diverged from each other about 4.7 mya (early Pliocene). This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:EEDD6248‐01DB‐4B4A‐B79D‐C5606393E3AA .