Glutamatergic medication in the treatment of obsessive compulsive disorder (OCD) and autism spectrum disorder (ASD) - study protocol for a randomised controlled trial

BACKGROUND: Compulsivity is a cross-disorder trait underlying phenotypically distinct psychiatric disorders that emerge in childhood or adolescence. Despite the effectiveness of serotonergic compounds in the treatment of obsessive-compulsive disorder, treatment-resistant symptoms remaining in 40 to 60 % of patients present a pressing clinical problem. There are currently no medications that effectively treat the core impairments of autism spectrum disorder. There is an urgent need for the development of conceptually novel pharmacological strategies. Agents targeting glutamate neurotransmission, such as memantine, represent promising candidates. This proof-of-concept clinical study will allow pilot-testing of memantine for both clinical effectiveness and tolerability/safety. Memantine is an N-methyl-D-aspartate receptor antagonist, approved for the treatment of Alzheimer's dementia in a number of countries. METHODS/DESIGN: This 12-week study has an add-on, randomised, double-blind, placebo-controlled design of treatment with memantine, including an up-titration phase (forced flexible dose design, 5-15 mg/day), in patients aged 6-17 years and 9 months with obsessive-compulsive disorder or autism spectrum disorder. It is planned to include patients with obsessive-compulsive disorder (N = 50) or autism spectrum disorder (N = 50) across four centres in three European countries. Patients will be randomly assigned to memantine or placebo in a 1:1 ratio. Primary objectives are the investigation of the effectiveness of memantine in paediatric patients for improving symptoms of compulsivity (primary outcome measure: total score on the Children's Yale-Brown Obsessive-Compulsive Scale) and to explore its tolerability and safety. Secondary objectives are to explore the effects of memantine at the level of structure, function and biochemistry of the fronto-striatal circuits, and to collect blood for genetic analyses and biomarkers. Tertiary objectives are to explore the role of new candidate genes and pathways for compulsivity by linking genes to clinical phenotypes, response to treatment, neurocognitive test performance, and key structural and functional neuroimaging measures of the fronto-striatal circuits and to explore biomarkers/proteomics for compulsivity traits. DISCUSSION: This study is part of the large, translational project TACTICS ( http://www.tactics-project.eu/ ) that is funded by the European Union and investigates the neural, genetic and molecular factors involved in the pathogenesis of compulsivity. Its results will provide clinically relevant solid information on potential new mechanisms and medication treatment in obsessive-compulsive and autism spectrum disorders. TRIAL REGISTRATION: EudraCT Number: 2014-003080-38 , date of registration: 14 July 2014

Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate

Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score

Welche Hör- und Sprachbefunde verbergen sich hinter der Verdachtsdiagnose AVS?

Hintergrund: Die Häufigkeit und Symptomzusammensetzung von Kindern mit dem Verdacht auf eine auditive Verarbeitungsstörung sind nach wie vor unklar.Material und Methoden: In der vorliegenden Arbeit wurden 106 Kinder (5-14 Jahre) mit der Überweisungsdiagnose "auditive Verarbeitungsstörung" (AVS) nach den Vorgaben der aktuellen Leitlinie untersucht. Pathologien im Sinne umschriebener Entwicklungsstörungen des Sprechens und der Sprache, tiefgreifende Entwicklungsstörungen wie Autismusspektrumstörungen oder hyperkinetische Störungen sowie eine unterdurchschnittliche Intelligenz wurden vor Beginn der Testung ausgeschlossen.Ergebnisse: Signifikant auffällige Testergebnisse zeigten sich der Häufigkeit nach vor allem in den Teilbereichen dichotische Signalverarbeitung (36,4%), Lautdifferenzierung (34,9%), phonologische Verarbeitung und Bewusstheit (22,8%) sowie der auditiven Merkspanne und Gedächtnis (22,6%). Defizite in den Teilleistungsgebieten auditive Reizfilterung (10,0%), Sprach- und Grammatikverständnis (7,4%), lautgetreues Schreiben (5,2%) und Wortschatzdefizit/Wortfindungsstörung (1,1%) waren demgegenüber deutlich seltener. Auffällig im Sinne der für die Diagnose AVS geforderten Testergebnisse waren 33 der untersuchten 106 Kinder (31,1%).Diskussion: Bei 87,7% der Kinder im Gesamtkollektiv wurden Reste einer Sprachentwicklungsstörung gesehen, bei 54,7% wurde eine Legasthenie diagnostiziert. Zwei Drittel (66,6%) der 33 mit AVS diagnostizierten Kinder hatten Defizite in der phonologische Verarbeitung/Bewusstheit sowie der auditiven Merkspanne/Gedächtnis, etwa die Hälfte hatte Probleme mit der Lautdifferenzierung (54,5%) und der beidohrigen Signalverarbeitung (48,5%).Fazit: Somit überwiegen bei einem Großteil der Kinder mit V.a. AVS sprachsystematische Probleme, die entsprechend aufzuarbeiten sind

California sea lions interfere with striped marlin hunting behaviour in multi-species predator aggregations

Hansen MJ, Kurvers RHJM, Licht M, et al. California sea lions interfere with striped marlin hunting behaviour in multi-species predator aggregations. Philosophical Transactions of the Royal Society of London, Series B : Biological Sciences. 2023;378(1878): 20220103.The open ocean offers a suite of ecological conditions promoting the occurrence of multi-species predator aggregations. These mixed predator aggregations typically hunt large groups of relatively small and highly cohesive prey. However, the mechanisms and functions of these mixed predator aggregations are largely unknown. Even basic knowledge of whether the predator species' interactions are mutualistic, commensal or parasitic is typically missing. Moreover, recordings of attack and capture rates of marine multi-species predator aggregations, which are critical in understanding how and why these interactions have evolved, are almost completely non-existent owing to logistical challenges. Using underwater video, we quantified the attack and capture rates of two high-trophic level marine predators, California sea lions (Zalophus californianus) and striped marlin (Kajikia audax) attacking schools of fishes in the Southern California Current System, offshore the Baja California Peninsula. Recording over 5000 individual attacks across 13 fish schools, which varied in species, size and predator composition, we found that sea lions kleptoparasitized striped marlin hunts and reduced the frequency of marlin attacks and captures via interference competition. We discuss our results in the context of the phenotypic differences between the predator species and implications for a better understanding of multi-species predator aggregations. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'