A randomized, double-blind, placebo-controlled trial to assess the efficacy of topiramate in the treatment of post-traumatic stress disorder

<p>Abstract</p> <p>Background</p> <p>Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD.</p> <p>Methods and design</p> <p>Seventy-two adult outpatients with DSM-IV-diagnosed PTSD will be recruited from the violence program of Federal University of São Paulo Hospital (UNIFESP). After informed consent, screening, and a one week period of wash out, subjects will be randomized to either placebo or topiramate for 12 weeks. The primary efficacy endpoint will be the change in the Clinician-administered PTSD scale (CAPS) total score from baseline to the final visit at 12 weeks.</p> <p>Discussion</p> <p>The development of treatments for PTSD is challenging due to the complexity of the symptoms and psychiatric comorbidities. The selective serotonin reuptake inhibitors (SSRIs) are the mainstream treatment for PTSD, but many patients do not have a satisfactory response to antidepressants. Although there are limited clinical studies available to assess the efficacy of topiramate for PTSD, the findings of prior trials suggest this anticonvulsant may be promising in the management of these patients.</p> <p>Trial Registration</p> <p>NCT 00725920</p

Problems of multi-species organisms: endosymbionts to holobionts

The organism is one of the fundamental concepts of biology and has been at the center of many discussions about biological individuality, yet what exactly it is can be confusing. The definition that we find generally useful is that an organism is a unit in which all the subunits have evolved to be highly cooperative, with very little conflict. We focus on how often organisms evolve from two or more formerly independent organisms. Two canonical transitions of this type—replicators clustered in cells and endosymbiotic organelles within host cells—demonstrate the reality of this kind of evolutionary transition and suggest conditions that can favor it. These conditions include co-transmission of the partners across generations and rules that strongly regulate and limit conflict, such as a fair meiosis. Recently, much attention has been given to associations of animals with microbes involved in their nutrition. These range from tight endosymbiotic associations like those between aphids and Buchnera bacteria, to the complex communities in animal intestines. Here, starting with a reflection about identity through time (which we call “Theseus’s fish”), we consider the distinctions between these kinds of animal–bacteria interactions and describe the criteria by which a few can be considered jointly organismal but most cannot

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk.

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.Neuropsychopharmacology advance online publication, 16 July 2014; doi:10.1038/npp.2014.137

Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a heightened noradrenergic response

O exercício físico no tratamento da depressão em idosos: revisão sistemática Physical exercise in the treatment of depression in the elderly: a systematic review

OBJETIVOS: Revisar a literatura quanto (I) ao possível efeito protetor do exercício físico sobre a incidência de depressão e (II) à eficácia do exercício físico como intervenção no tratamento da depressão. MÉTODO: Revisão sistemática de artigos em inglês e português nas bases ISI, PubMed, SciELO e LILACS de janeiro de 1993 a maio de 2006, utilizando conjuntamente os termos "depressão", "idosos" e "exercício". Artigos que avaliaram o efeito do exercício em idosos com doenças clínicas ou que utilizaram escalas para depressão somente para um diagnóstico inicial foram excluídos. RESULTADOS: Do total de 155 artigos, 22 atenderam aos critérios de inclusão, e oito foram acrescentados com busca manual. Os artigos de corte transversal (n = 8) utilizaram somente questionários de auto-avaliação para medir os níveis de atividade física. Os artigos longitudinais (n = 22) utilizaram também pedômetro digital, consumo direto de oxigênio e o exercício físico como intervenção metodológica. Os estudos que atenderam ao objetivo I apontaram para uma relação inversamente proporcional entre atividade física e alterações nos níveis de depressão. Os trabalhos que utilizaram o exercício como intervenção terapêutica na depressão encontraram resultados divergentes e apontaram para a interferência de fatores fisiológicos e psicológicos nessa relação. CONCLUSÃO: O papel do exercício e da atividade física no tratamento da depressão direciona-se para duas vertentes: a depressão promove redução da prática de atividades físicas; a atividade física pode ser um coadjuvante na prevenção e no tratamento da depressão no idoso.<br>OBJECTIVES: To review the literature on the (I) possible protective effect of physical activity on the incidence of depression, and (II) on the efficacy of physical exercise as a therapeutic intervention in depression. METHODS: Systematic review of ISI, PubMed, LILACS and SciELO articles in English and Portuguese from January 1993 to May 2005 using the keywords "depression," "elderly," and "exercise." Articles assessing the effect of physical exercise in the elderly with clinical diseases or that used depression scales only for initial diagnosis were excluded. RESULTS: We found 155 articles, 22 of which met the inclusion criteria. Other eight studies were included after a manual search. Cross-sectional studies (n = 8) used only self-evaluation questionnaires to measure the levels of physical activity. Longitudinal studies (n = 22) also used digital pedometer, direct measurements of oxygen consumption and physical exercise as methodological intervention. The studies meeting the first objective pointed to an inverse relationship between physical activity and changes in levels of depression. The studies that used physical activity as a therapeutic intervention in depression found divergent results and pointed to the interference of physiological and psychological factors on this relation. CONCLUSION: There are two aspects involved in the role of physical activity and exercise in the treatment of depression. Depression decreases the practice of physical activities; physical activity may be useful in the treatment and prevention of depression in the elderly