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 ( Trial registration EudraCT Number: 2014-003080-38, date of registration: 14 July 2014. Keywords: Glutamate, Memantine, Obsessive-compulsive disorder, Autism, Pilot trial, Psychopharmacology, Child and adolescent psychiatry
Bipolar disorder is associated with cognitive impairment. High homocysteine levels seem to have a negative impact on cognition in the elderly. The aim of the present study was to investigate the ...potential relationship of elevated homocysteine levels and cognitive impairment in bipolar patients.
Cognitive functioning of DSM-IV bipolar disorder patients who were euthymic (Hamilton Rating Scale for Depression score < or = 5 and Young Mania Rating Scale score < or = 5) and healthy controls was assessed with the revised Wechsler Adult Intelligence Scale Information Subtest, the Wechsler Adult Intelligence Scale III Letter-Number Sequencing Subtest, the Trail Making Test, and the Repeatable Battery for the Assessment of Neuropsychological Status Form A to examine premorbid IQ, information processing speed, working memory, verbal learning, visuospatial/constructional abilities, delayed memory, and executive functions. Total homocysteine plasma concentration was measured by using high-performance liquid chromatography. Multivariate analyses of variance and multiple regression analyses were conducted to examine group differences and possible associations between cognitive functioning and homocysteine level. The study was conducted from 2002 through 2006.
Seventy-five euthymic bipolar patients and 42 healthy controls participated in the study. Patients performed significantly worse than controls in all cognitive domains tested (Pillai Spur: F = 3.32, p = .038) except premorbid IQ (p = .068). The mean +/- SD homocysteine levels were 10.2 +/- 3.2 microM/L for patients and 8.9 +/- 2.8 microM/L for controls (p = .036). Stepwise regression analyses revealed a significant and independent association of homocysteine levels with verbal learning (p = .002), delayed memory (p = .030), and executive function (p = .011) in the patient group. About 11% of the variance was explained by only the homocysteine level.
Elevated homocysteine levels may have a negative impact on verbal learning, delayed memory, and executive function in euthymic bipolar patients, but further studies are warranted.
Objective: To compare the safety and efficacy of atomoxetine, a selective inhibitor of the norepinephrine transporter, versus placebo in Attention-Deficit/Hyperactivity Disorder (ADHD) patients with ...comorbid Oppositional Defiant Disorder (ODD).
Methods: A subset analysis of 98 children from two identical, multi-site, double-blind, randomized, placebo-controlled trials involving 9 weeks of treatment with atomoxetine or placebo was conducted. Patients met DSM-IV ADHD criteria. ODD was diagnosed with the Diagnostic Interview for Children and Adolescents-IV (DICA-IV; Reich, Welner, & Herjanic, 1997). ADHD severity was assessed with the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHD-RS-IV-Parent:Inv; DuPaul, Power, Anastopoulos, & Reid, 1998); the short version of the Conners’ Parent Rating Scales-Revised (CPRS-R:S; Conners, 2000); and the Clinical Global Impressions of ADHD Severity (CGI-ADHD-S; Guy, 1976). Clinical response was defined as a ≥ 25% reduction in ADHD-RS-IV-Parent:Inv total score.
Results: ADHD-RS-IV-Parent:Inv, CGI-ADHD-S, and three CPRS-R:S subscale scores improved markedly with atomoxetine treatment. However, a decrease in the CPRS-R:S Oppositional subscore for atomoxetine-treated patients was not significantly greater than scores for placebo-treated patients. Clinical response rates were 65.4% in the atomoxetine group, and 36.4% in the placebo group (p = .007).
Conclusion: Atomoxetine was effective for the treatment of ADHD in patients with comorbid ODD. It did not significantly reduce the severity of ODD symptoms, and was well tolerated by the patients.
We present a search for neutral Higgs bosons varphi decaying into bb, produced in association with b quarks in pp collisions. This process could be observable in supersymmetric models with high ...values of tan beta . The event sample corresponds to 2.6 fb super(-1) of integrated luminosity collected with the CDF II detector at the Fermilab Tevatron collider. We search for an enhancement in the mass of the two leading jets in events with three jets identified as coming from b quarks using a displaced vertex algorithm. A data-driven procedure is used to estimate the dijet mass spectrum of the nonresonant multijet background. The contributions of backgrounds and a possible Higgs boson signal are determined by a two-dimensional fit of the data, using the dijet mass together with an additional variable which is sensitive to the flavor composition of the three tagged jets. We set mass-dependent limits on sigma(pp arrow right varphib) x Bernoulli(varphi arrow right bb) which are applicable for a narrow scalar particle varphi produced in association with b quarks. We also set limits on tan beta in supersymmetric Higgs models including the effects of the Higgs boson width.
Enigmatic phylogeny of skuas (Aves: Stercorariidae) Cohen, B. L.; Baker, A. J.; Blechschmidt, K. ...
Proceedings of the Royal Society. B, Biological sciences,
02/1997, Letnik:
264, Številka:
1379
Journal Article
Recenzirano
Odprti dostop
Multiple sources of evidence show that the skuas (Aves: Stercorariidae) are a monophyletic group, closely related to gulls (Laridae). On morphological and behavioural evidence the Stercorariidae are ...divided into two widely divergent genera, Catharacta and Stercorarius, consistent with observed levels of nuclear and mitochondrial gene divergence. Catharacta skuas are large-bodied and with one exception breed in the Southern Hemisphere. Stercorarius skuas (Otherwise known as jaegers) are smaller bodied and breed exclusively in the Northern Hemisphere. Evidence from both mitochondrial and nuclear genomes and from ectoparasitic lice (Insecta: Phthiraptera) shows that the Pomarine skua, S. pomarinus, which has been recognized as being somewhat intermediate in certain morphological and behavioural characteristics, is much more closely related to species in the genus Catharacta, especially to the Northern Hemisphere-breeding Great skua, C. skua, than it is to the other two Stercorarius skuas, the Arctic skua, S. parasiticus and the Longtailed skua, S. longicaudus. Three possible explanations that might account for this discordant aspect of skua phylogeny are explored. These involve (i) the segregation of ancestral polymorphism, (ii) convergent evolution of morphology and behaviour or (iii) inter-generic hybridization. The available evidence from both nuclear and mitochondrial genomes does not exclude any of these hypotheses. Thus, resolution of this enigma of skua phylogeny awaits further work.
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