Pharmacological treatment of social anxiety disorder

Social anxiety disorder (social phobia) is a common and typically long-standing medical condition, characterized by an excessive fear of being observed or evaluated negatively in social or performance situations. Efficacious interventions in acute treatment include cognitive behavioural therapy and a range of medications including many antidepressants, some benzodiazepines and anticonvulsants, and the antipsychotic olanzapine. Most studies report no significant differences in overall efficacy or tolerability between active compounds. Responders to previous acute treatment benefit from continuing active medication for 6 months. Evidence of a dose-response relationship with antidepressant drugs is inconsistent, though only higher doses of pregabalin are efficacious. Switching between treatments with proven efficacy may be helpful. Augmentation of a selective serotonin reuptake inhibitor with buspirone or clonazepam can be beneficial. It is unlikely that combining pharmacotherapy with psychotherapy results in greater overall efficacy compared to either treatment given alone. Proof-of-concept and other preliminary studies suggest the efficacy of psychotherapy can be enhanced through prior administration of D-cycloserine, cannabidiol, or oxytocin. Copyright © 2013 S. Karger AG, Basel

DRD4 and DAT1 in ADHD: functional neurobiology to pharmacogenetics

Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of noncandidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches

A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability

Succinate-semialdehyde dehydrogenase (SSADH) deficiency is a rare cause of learning disability. We have investigated SSADH to assess its contribution to cognitive ability in the general population in both case-control- and family-based analyses. Sequence analysis of SSADH revealed four changes affecting the encoded protein, only one of which had a minor allele whose frequency is even moderately common. We genotyped this functional polymorphism in 197 high-IQ cases, 201 average-IQ controls and 196 parent high-IQ offspring trios. The minor allele was significantly less frequent in high-IQ cases and was significantly less frequently transmitted by parents to high-IQ subjects than chance expectation. A previous study has shown that the minor allele encodes a lower activity enzyme than the major allele. These data suggest that higher SSADH activity is associated with higher intelligence across the general population. The effect is small, with each allele having an effect size translating to about 1.5 IQ points

No association between apolipoprotein E polymorphisms and general cognitive ability in children

In this work we explored the hypothesis that variation in the gene encoding apolipoprotein E (ApoE) is a factor modifying general cognitive ability (g). A case control sample of 101 high g and 101 average g children was scored for ApoE genotypes and two variants in the transcriptional regulatory region of the gene (Th1/E47cs and -491 AT). No evidence of association between these polymorphisms and g was found. We conclude that variation at these loci is not a factor with a measurable impact on general cognitive ability in the healthy population

Evaluation of the efficacy of supplementing breeding calves with injectables copper

La hipocuprosis bovina es una de las principales enfermedades que afectan al ganado en pastoreo en argentina.Posee una clara incidencia geográfica, siendo la cuenca deprimida del Río del Salado donde adquiere mayor importancia. Durante la deficiencia se produce la alteración del funcionamiento de numerosas cupro-enzimas, fenómeno que se vincula con la aparición de los signos clínicos y subclínicos de la enfermedad. El objetivo del presente trabajo fue evaluar el valor terapéutico de un modelo de suplementación estratégica con cobre en terneros, consistente en una única suplementación al promediar los 4-5 meses de edad.Se estudiaron 3 grupos de 20 animales. El primero, bajo suplementación continua (control +), el segundo sin suplementación (control -), y finalmente el grupo en estudio, al cual se le aplicó una sola dosis en diciembre. Se realizaron 4 muestreos y en cada uno se analizó la cupremia, la ganancia diaria de peso y la evolución de los pesos.Los resultados obtenidos permitieron demostrar que una única dosis de Cu permitio mantener hasta 2 meses los niveles de normocupremia y evitaron una posterior hipocupremia severa. Las ganancias de peso no permitieron una diferenciación estadística, pero si marcaron una tendencia hacia una mayor ganancia de peso asociada con la suplementación.Fil: Mattioli, Guillermo Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Fazzio, Luis Emilio. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Cátedra de Clínica de Grandes Animales; ArgentinaFil: Rosa, D.E.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Picco, Sebastian Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; ArgentinaFil: Angelico, D.. Biogénesis Bagó. Investigación y Desarrollo ; ArgentinaFil: Turic, E.. Biogénesis Bagó. Investigación y Desarrollo; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Laboratorio de Nutrición Mineral, Cátedra de Fisiología; Argentin

Evaluation of the efficacy of supplementing breeding calves with injectables copper

La hipocuprosis bovina es una de las principales enfermedades que afectan al ganado en pastoreo en argentina.Posee una clara incidencia geográfica, siendo la cuenca deprimida del Río del Salado donde adquiere mayor importancia. Durante la deficiencia se produce la alteración del funcionamiento de numerosas cupro-enzimas, fenómeno que se vincula con la aparición de los signos clínicos y subclínicos de la enfermedad. El objetivo del presente trabajo fue evaluar el valor terapéutico de un modelo de suplementación estratégica con cobre en terneros, consistente en una única suplementación al promediar los 4-5 meses de edad.Se estudiaron 3 grupos de 20 animales. El primero, bajo suplementación continua (control +), el segundo sin suplementación (control -), y finalmente el grupo en estudio, al cual se le aplicó una sola dosis en diciembre. Se realizaron 4 muestreos y en cada uno se analizó la cupremia, la ganancia diaria de peso y la evolución de los pesos.Los resultados obtenidos permitieron demostrar que una única dosis de Cu permitio mantener hasta 2 meses los niveles de normocupremia y evitaron una posterior hipocupremia severa. Las ganancias de peso no permitieron una diferenciación estadística, pero si marcaron una tendencia hacia una mayor ganancia de peso asociada con la suplementación.Cattle hypocuprosis is one of the principal nutritional disorders that affeets pasture grazing cattle in Argentina. It possosses a definite geographical incidence, and acquires its highest importance in the Río Salado Depression basin. During the deficiency the functioning of numerous copper-enzymes become altered, a phenomena linked to the presentation of clinical and sub clinical signs of the disease. The objective of this study was the evaluation of a therapeutical model of strategic supplementation with Cu in breeding calves, consequent with a single supplementation when 4-5 months of age. Three groups of 20 animáis each were studied, the first on a continuous schedule (+ control); the second with no treatment (- control) and finally the study group which received a single dose in December. A total of 4 samples were made and in each cupremia valúes were assayed, as well as daily weight gain and the evolution of total weights. The results obtained demonstrated that the single Cu dose maíntained during up to 2 months the levels of normocupremia and avoided a later severe hypocuprosis. Weight gains did not allow a statistical difference but did mark a trend towards a higher weight gain with the supplementation.Instituto de Genética Veterinari

A simple method for analyzing microsatellite allele image patterns generated from DNA pools and its application to allelic association studies.

Allelic association studies provide the most powerful method for locating genes of small effect contributing to complex diseases and traits. However, in outbred populations, allelic association is usually maintained only over distances of <=1 cM. Therefore, systematic searches over large regions are costly. Here we present a method involving DNA pooling that can be used as a rapid preliminary screen for allelic association with the most common class of polymorphic markers, single-sequence repeats. Patient and control samples are pooled separately, and markers are typed in the two pools. By use of primers with fluorescent 5' ends, PCR products can be analyzed on an automated sequencing apparatus. Allele image patterns (AIPs) produced for the two groups are overlaid and differences in pattern area between pools computed. From this, a DeltaAIP statistic is calculated from the difference in areas between the two AIPs expressed as a fraction of the total shared and nonshared area. AIPs of a range of different-sized pools were generated by computer simulation for markers with a range of allele sizes and frequencies. DeltaAIPs from pools and chi2 values for individual genotypings were compared, with both simulated and real data from microsatellite markers. The results demonstrated a high correlation between DeltaAIP and chi2 values. DeltaAIP analysis of real microsatellite data indicated the feasibility of using this method in systematic searches for allelic association and generated a small number of false positives but few false negatives. We conclude that DeltaAIP analysis of DNA pools can be used effectively and efficiently as a rapid screen for allelic association in case-control studies