Chronic morphine exposure and its abstinence alters dendritic spine morphology and upregulates Shank1

Exposure to chronic drugs of abuse has been reported to produce significant changes in postsynaptic protein profile, dendritic spine morphology and synaptic transmission. In the present study we demonstrate alterations in dendritic spine morphology in the frontal cortex and nucleus accumbens of mice following chronic morphine treatment as well as during abstinence for two months. Such alterations were accompanied with significant upregulation of the postsynaptic protein Shank1 in synaptosomal enriched fractions. mRNA levels of Shank1 was also markedly increased during morphine treatment and during withdrawal. Studies of the different postsynaptic proteins at the protein and mRNA levels showed significant alterations in the morphine treated groups compared to that of saline treated controls. Taken together, these observations suggest that Shank1 may have an important role in the regulation of spine morphology induced by chronic morphine leading to addiction.     

Aquaporin-4 water channels and synaptic plasticity in the hippocampus

Aquaporin-4 (AQP4) is the major water channel expressed in the central nervous system (CNS) and is primarily expressed in glial cells. Many studies have shown that AQP4 regulates the response of the CNS to insults or injury, but far less is known about the potential for AQP4 to influence synaptic plasticity or behavior. Recent studies have examined long-term potentiation (LTP), long-term depression (LTD), and behavior in AQP4 knockout (KO) and wild-type mice to gain more insight into its potential role. The results showed a selective effect of AQP4 deletion on LTP of the Schaffer collateral pathway in hippocampus using an LTP induction protocol that simulates pyramidal cell firing during theta oscillations (theta-burst stimulation; TBS). However, LTP produced by a different induction protocol was unaffected. There was also a defect in LTD after low frequency stimulation (LFS) in AQP4 KO mice. Interestingly, some slices from AQP4 KO mice exhibited LTD after TBS instead of LTP, or LTP following LFS instead of LTD. These data suggest that AQP4 and astrocytes influence the polarity of long-term synaptic plasticity (potentiation or depression). These potentially powerful roles expand the influence of AQP4 and astrocytes beyond the original suggestions related to regulation of extracellular potassium and water balance. Remarkably, AQP4 KO mice did not show deficits in basal transmission, suggesting specificity for long-term synaptic plasticity. The mechanism appears to be related to neurotrophins and specifically brain-derived neurotrophic factor (BDNF) because pharmacological blockade of neurotrophin trk receptors or scavenging ligands such as BDNF restored plasticity. The in vitro studies predicted effects in vivo of AQP4 deletion because AQP4 KO mice performed worse using a task that requires memory for the location of objects (object placement). However, performance on other hippocampal-dependent tasks was spared. The results suggest an unanticipated and selective role of AQP4 in synaptic plasticity and spatial memory, and underscore the growing appreciation of the role of glial cells in functions typically attributed to neurons. Implications for epilepsy are discussed because of the previous evidence that AQP4 influences seizures, and the role of synaptic plasticity in epileptogenesis.     

Assessing the cryptic invasion of a domestic conspecific: American mink in their native range

Control of invasions is facilitated by their early detection, but this may be difficult when invasions are cryptic due to similarity between invaders and native species. Domesticated conspecifics offer an interesting example of cryptic invasions because they have the ability to hybridize with their native counterparts, and can thus facilitate the introgression of maladaptive genes. We assessed the cryptic invasion of escaped domestic American mink (Neovison vison) within their native range. Feral mink are a known alien invader in many parts of the world, but invasion of their native range is not well understood. We genetically profiled 233 captive domestic mink from different farms in Ontario, Canada and 299 free‐ranging mink from Ontario, and used assignments tests to ascertain genetic ancestries of free‐ranging animals. We found that 18% of free‐ranging mink were either escaped domestic animals or hybrids, and a tree regression showed that these domestic genotypes were most likely to occur south of a latitude of 43.13°N, within the distribution of mink farms in Ontario. Thus, domestic mink appear not to have established populations in Ontario in locations without fur farms. We suspect that maladaptation of domestic mink and outbreeding depression of hybrid and introgressed mink have limited their spread. Mink farm density and proximity to mink farms were not important predictors of domestic genotypes but rather, certain mink farms appeared to be important sources of escaped domestic animals. Our results show that not all mink farms are equal with respect to biosecurity, and thus that the spread of domestic genotypes can be mitigated by improved biosecurity.     

Incest versus abstinence: reproductive trade‐offs between mate limitation and progeny fitness in a self‐incompatible invasive plant

Plant mating systems represent an evolutionary and ecological trade‐off between reproductive assurance through selfing and maximizing progeny fitness through outbreeding. However, many plants with sporophytic self‐incompatibility systems exhibit dominance interactions at the S‐locus that allow biparental inbreeding, thereby facilitating mating between individuals that share alleles at the S‐locus. We investigated this trade‐off by estimating mate availability and biparental inbreeding depression in wild radish from five different populations across Australia. We found dominance interactions among S‐alleles increased mate availability relative to estimates based on individuals that did not share S‐alleles. Twelve of the sixteen fitness variables were significantly reduced by inbreeding. For all the three life‐history phases evaluated, self‐fertilized offspring suffered a greater than 50% reduction in fitness, while full‐sib and half‐sib offspring suffered a less than 50% reduction in fitness. Theory indicates that fitness costs greater than 50% can result in an evolutionary trajectory toward a stable state of self‐incompatibility (SI). This study suggests that dominance interactions at the S‐locus provide a possible third stable state between SI and SC where biparental inbreeding increases mate availability with relatively minor fitness costs. This strategy allows weeds to establish in new environments while maintaining a functional SI system.     

Use of standardised patients in the evaluation of a residency mood disorders curriculum: a brief report

Background and objectives The purpose of this paper is to describe the use of resident performance on an observed structured clinical examination (OSCE) as a tool to refine a mood disorders curriculum, and to disseminate a mood disorders OSCE for use in other residency settings.Methods A depression-focused OSCE and a direct observation evaluation tool were developed and implemented. A total of 24 first-year family medicine residents (PGY1) participated in the OSCE, and their performance was used to direct changes in a mood disorders curriculum.Results Residents performed well on general interview behaviours, and 67% were able to uncover depression in a patient presenting with headaches. Less than 50% of the residents asked about suicidal ideation and recreational drug use. Curriculum was added that addressed the latter deficiencies.Conclusions Tracking of resident performance on specific behaviours during OSCE sessions can be used for curriculum evaluation purposes. The mood disorders curriculum in additional family medicine residency programmes can now be evaluated using our depression-focused OSCE and Clinical Performance Checklist.     

不同电针方法对慢性应激抑郁模型大鼠下丘脑TRH表达的影响

目的:研究分析两种不同电针方法对慢性应激抑郁模型大鼠(CUMS)下丘脑中促甲状腺激素释放激素(TRH)表达的影响。方法:选取60只健康雄性SPF级SD大鼠编号后采用随机数字表法分为对照组(正常喂养)、模型组(仅建立CUMS模型,不予治疗)、观察组A(建立CUMS模型后,脉冲电针治疗)、观察组B(建立CUMS模型后,音乐电针治疗)、氟西汀组(建立CUMS模型后,氟西汀治疗)各12只,对除对照组之外的其他各组大鼠进行1只/笼的孤养结合方式建造CUMS模型,利用开野实验观察各组大鼠行为学改变,采用实时荧光定量(PCR)法测定各组大鼠下丘脑组织中TRH m RNA的表达,采用免疫组化法测定TRH蛋白的表达。结果:在刺激21 d后,模型组大鼠的水平运动次数、垂直运动次数显著的低于对照组、实验组A、实验组B、氟西汀组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的水平运动次数、垂直运动次数显著低于对照组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的水平运动次数、垂直运动次数差异无统计学意义(P0.05);模型组大鼠的下丘脑TRH m RNA、TRH蛋白水平低于对照组、实验组A、实验组B、氟西汀组,且差异均具有统计学意义(P0.05),实验组A、实验组B、氟西汀组大鼠的大鼠的下丘脑TRH m RNA、TRH蛋白水平显著低于对照组,且差异均具有统计学意义(P0.05);实验组A、实验组B、氟西汀组大鼠的大鼠的下丘脑TRH m RNA、TRH蛋白水平差异无统计学意义(P0.05)。结论:CUMS大鼠下丘脑中促甲状腺激素释放激素表达水平降低,脉冲电针与音乐电针能有效逆转这一现象,效果相当。     

Understanding the burnout experience: recent research and its implications for psychiatry

The experience of burnout has been the focus of much research during the past few decades. Measures have been developed, as have various theoretical models, and research studies from many countries have contributed to a better understanding of the causes and consequences of this occupationally‐specific dysphoria. The majority of this work has focused on human service occupations, and particularly health care. Research on the burnout experience for psychiatrists mirrors much of the broader literature, in terms of both sources and outcomes of burnout. But it has also identified some of the unique stressors that mental health professionals face when they are dealing with especially difficult or violent clients. Current issues of particular relevance for psychiatry include the links between burnout and mental illness, the attempts to redefine burnout as simply exhaustion, and the relative dearth of evaluative research on potential interventions to treat and/or prevent burnout. Given that the treatment goal for burnout is usually to enable people to return to their job, and to be successful in their work, psychiatry could make an important contribution by identifying the treatment strategies that would be most effective in achieving that goal.     

The effectiveness of the peer-delivered Thinking Healthy PLUS (THPP+) Program for maternal depression and child socioemotional development in Pakistan: study protocol for a randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.

Trial registration

THPP-P ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02111915","term_id":"NCT02111915"}}NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02658994","term_id":"NCT02658994"}}NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1530-y) contains supplementary material, which is available to authorized users.     

The Protective Association between Pet Ownership and Depression among Street-involved Youth: A Cross-sectional Study

Street-involved youth represent a particularly vulnerable subsection of the homeless population and are at increased risk of health problems, substance abuse, and depression. Qualitative research has demon- strated that animal companions help homeless youth cope with loneliness, are motivators for positive change, such as decreasing drug or alcohol use, provide unconditional love without judgement, and improve youths’ sense of health. To quantitatively investigate the association between depression and pet ownership among street-involved youth, a cross-sectional study was per- formed with a convenience sample of 189 street-involved youths who were surveyed in four cities in Ontario, Canada, 89 of whom were pet owners and 100 of whom were not. Logistic regression modelling found pet ownership to be negatively associated with depression in the study population (controlling for gender, regular use of drugs, and time since youth left home), with the odds of being depressed three times greater for youths who did not own pets. While pet ownership among street-involved youth has many liabilities, includ- ing impairing youths’ ability to access shelter, services, and housing and employment opportunities, companion animals may offer both physical and psychosocial benefits that youth have difficult attaining. This finding highlights the importance of increased awareness among youth service providers of the potential impacts of pet ownership for street-involved youth.     

新型抗抑郁药物分子靶标研究进展

抑郁症是一种严重的精神障碍疾病,其发病机制复杂。近年来随着对抑郁症发病机制的深入研究,发现了一些基于非单胺递质的 新型抗抑郁药物分子靶标。综述N -甲基-D-天冬氨酸（NMDA）受体、促肾上腺皮质激素释放因子（CRF）受体、阿片受体、γ-氨基丁 酸B(GABAB) 受体、乙酰胆碱受体等抗抑郁药物作用的新靶标及其相应分子机制研究进展,为开发高效、安全的抗抑郁症新药提供参考。