Writing a wrong: Factors influencing the overprescription of antidepressants to youth.

Recently observed reductions in the use of antidepressant medication in youth come after a period that many have characterized as being marked by excessive reliance on such agents. The Food and Drug Administration advisory first issued in 2004 clearly influenced this change in clinical practice; however, other factors such as public and expert opinion, medicolegal considerations, and the behavior of pharmaceutical manufacturers also have had some effect. Some have speculated that a reduction in antidepressant use in youth is related to observed increases in suicide rates for this population. Although there has been an increase in the rate of adolescent suicide since 2003, such increases have also been seen in other age and demographic groups. The association between suicide rates and antidepressant use in adolescents or other groups is unclear, and is likely more correlational than causal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Bupropion on Depression Symptoms in a Smoking Cessation Clinical Trial.

Bupropion is an antidepressant shown to be efficacious for smoking cessation. This study examined the short- and long-term effects of bupropion (300 mg/day for 10 weeks) versus placebo on depression symptoms among 497 smokers attempting to quit in a randomized trial of bupropion plus behavioral counseling. Depression symptoms were assessed via the Center for Epidemiological Studies Depression Scale (L. Radloff, 1977) at baseline, end of treatment, and at 6-month follow-up. Baseline nicotine dependence level was assessed with the Fagerstrom Test for Nicotine Dependence (T. F. Heatherton, L. T. Kozlowski, R. C. Frecker, & K. O. Fagerstr?m, 1991). A regression model of depression symptoms demonstrated a significant interaction between nicotine dependence and treatment for the treatment phase and during follow-up. Depression symptoms did not mediate the effects of bupropion on abstinence at either time point. Highly nicotine-dependent smokers who receive bupropion are more likely to experience a decrease in depressive symptoms during active treatment but are also more likely to experience a rebound in depressive symptoms when bupropion is discontinued. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

准噶尔盆地玛湖凹陷二叠系烃源岩三环萜烷分布样式及影响因素

准噶尔盆地西北缘原油及烃源岩中生物标志物以高丰度的三环萜烷系列为典型特征,其分布样式的差异一直被当作研究本区原油成因类型及油-源对比的典型指标。通过对烃源岩样品的系统地球化学分析,认为本区风城组源岩（P₁f）主要以三环萜烷（C₂₀,C₂₁,C₂₃）呈“上升型”为特征,泥质岩类与碳酸盐岩类相比C₂₄,C₂₅三环萜烷含量较高;下乌尔禾组（P₂w）源岩和佳木河组（P₁j）源岩样品三环萜均呈“下降型”分布特征。通过对源岩镜下进行观察和加水热模拟实验等方法,分别探讨了沉积环境与母质类型、成熟度及排烃作用对三环萜分布样式的影响,认为P₁f和P₂w源岩中三环萜烷的分布主要受控于沉积环境和母质类型的原生差异。P₁f源岩有机质多源于本地沉积的藻类及细菌,沉积环境属于蒸发、还原的咸化湖沉积;P₂w源岩中外来有机质含量相对较多,沉积环境属于淡水还原环境。P₁j源岩整体热演化程度较高,有机质炭化作用强烈;埋藏成熟演化在有机质处于成熟-高熟阶段内对三环萜烷分布样式影响不大,若达到过熟阶段则会造成低碳数三环萜烷（C₂₀,C₂₁）含量增加;排烃作用对三环萜烷影响相对较小,不改变其分布样式。     

珠江口盆地珠三坳陷不同沉积环境下烃源岩和原油中长链三环萜烷、二环倍半萜烷分布特征及地球化学意义

应用长链三环萜烷、二环倍半萜烷系列标志化合物,对珠江口盆地珠三坳陷文昌A、B凹陷3类重要烃源岩及相关原油的沉积环境和油源进行了研究。结果显示,3类烃源岩及相关原油中萜烷分布特征差异明显,这种差异性主要受控于烃源岩的沉积环境及有机质输入类型,表现在：①文昌B凹陷文昌组中深湖相烃源岩及相关原油中,长链三环萜烷以C₂₁为主峰碳,C₂₀—C₂₁—C₂₃呈山峰型分布,二环倍半萜烷高含8β(H)?升补身烷,含很低的重排补身烷和补身烷,揭示其有机质输入以低等水生生物为主,形成于偏还原的沉积环境;②文昌B凹陷文昌组浅湖相烃源岩及相关原油中,代表沉积环境和有机质输入类型的指标分布形态和相对含量具有双重特征,其母源兼有湖相低等水生生物及陆源高等植物输入贡献,形成于弱氧化—氧化的沉积环境;③文昌A凹陷恩平组浅湖相烃源岩及相关原油中,长链三环萜烷以C₂₀为主峰碳,峰形呈快速下降型,二环倍半萜烷高含重排补身烷,而含较低的8β(H)?升补身烷和补身烷,揭示其有机质输入以陆源高等植物为主,形成于偏氧化—氧化的沉积环境。     

Recent developments in the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD).

In comparison to other mental health disorders in pediatric populations, there seems to be compelling evidence-based support for both the efficacy of stimulant medication for children and adolescents with attention deficit/hyperactivity disorder (ADHD) and associated symptoms. Tricyclic antidepressants provide an alternative when stimulants are found to be ineffective or associated with too many adverse effects, particularly for children who have comorbid conditions including anxiety and depression. Finally, the alpha-adrenergic agents, although not approved for the management of ADHD, have been widely employed clinically, particularly for the treatment of impulsivity, overactivity, and aggression. Behavior therapy has been demonstrated to be effective for many of the functional impairments associated with ADHD. Research efforts are needed to examine these therapies either alone or in combination on the long-term outcome of children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates

Conformational changes are fundamental events in the transport mechanism. The serotonin transporter (SERT) catalyzes reuptake of the neurotransmitter serotonin after its release by serotonergic neurons and is the molecular target for antidepressant drugs and psychostimulants. Despite significant progress in characterizing the structure–function relationship of SERT, its conformational mechanism has not been fully understood. We present here a cell-based method for determining conformational changes in SERT with its fluorescent substrates by fluorescence imaging analysis. This method fluorometrically measures accessibility of strategically positioned cysteine residues in the substrate permeation pathway to calculate the rate constants of reactivity with MTS reagents in live or permeabilized cells. We validated this method by investigating ligand and ion-induced conformational changes in both the extracellular and cytoplasmic pathways of SERT. Furthermore, we applied this method for examining the influence of Cl⁻ binding and vilazodone inhibition on SERT conformation. Our results showed that Cl⁻ ion, in the presence of Na⁺, facilitates the conformational conversion from outward to inward open states, and that vilazodone binding stabilizes SERT in an outward open and inward-closed conformation. The present work provided insights into the conformational mechanism of SERT and also indicated that the cell-based fluorometric method is robust, straightforward to perform, and potentially applicable to any monoamine transporters in exploring the transport mechanism and mechanism of action of therapeutic agents for the treatment of several psychiatric disorders.     

Agomelatine,Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study

This determination of the mitochondrial effect of pharmacologically different antidepressants (agomelatine, ketamine and vortioxetine) was evaluated and quantified in vitro in pig brain-isolated mitochondria. We measured the activity of mitochondrial complexes, citrate synthase, malate dehydrogenase and monoamine oxidase, and the mitochondrial respiratory rate. Total hydrogen peroxide production and ATP production were assayed. The most potent inhibitor of all mitochondrial complexes and complex I-linked respiration was vortioxetine. Agomelatine and ketamine inhibited only complex IV activity. None of the drugs affected complex II-linked respiration, citrate synthase or malate dehydrogenase activity. Hydrogen peroxide production was mildly increased by agomelatine, which might contribute to increased oxidative damage and adverse effects at high drug concentrations. Vortioxetine significantly reduced hydrogen peroxide concentrations, which might suggest antioxidant mechanism activation. All tested antidepressants were partial MAO-A inhibitors, which might contribute to their antidepressant effect. We observed vortioxetine-induced MAO-B inhibition, which might be linked to decreased hydrogen peroxide formation and contribute to its procognitive and neuroprotective effects. Mitochondrial dysfunction could be linked to the adverse effects of vortioxetine, as vortioxetine is the most potent inhibitor of mitochondrial complexes and complex I-linked respiration. Clarifying the molecular interaction between drugs and mitochondria is important to fully understand their mechanism of action and the connection between their mechanisms and their therapeutic and/or adverse effects.     

Synthesis and field testing of 4,6,6-lineatin,the aggregation pheromone ofTrypodendron lineatum (Coleoptera: Scolytidae)

Authentic 4,6,6-lineatin (3,3,7-trimethyl-2,9-dioxatricyclo-[3.3.1.0^4,7]nonane) (I) was produced in low yield via three synthetic pathways. In field tests, microgram amounts of the product from all three syntheses attracted large numbers ofTrypodendron lineatum of both sexes. These results confirm that 4,6,6-lineatin (I) is a population aggregation pheromone forT. lineatum.Research supported by National Science Foundation (U.S.A), Grant PCM4-13643, National Research Council (Canada), Co-op Grant A0243 and Operating Grants A3881 and A3785, and a Canadian Forestry Service Science Subvention Grant.     

三环嘌呤类衍生物合成的研究

以无环鸟苷为原料,经过环化反应、酯化反应和烷基化反应,合成了2种新型三环嘌呤类衍生物。每一步反应的中间产物和最终产物都经过质谱、元素分析、核磁氢谱等手段进行检测,并确定了所得化合物即为目标产物。