Efficacy of light therapy for perinatal depression: a review

ABSTRACT: Perinatal depression is an important public health problem affecting 10-20% of childbearing women. Perinatal depression is associated with significant morbidity, and has enormous consequences for the well-being of the mother and child. Treatment of depression during the perinatal period poses a complex problem for both mother and clinician, as antidepressant treatment strategies must consider the welfare of both mother and child during pregnancy and lactation. Bright light therapy may be an attractive treatment for perinatal depression because it is low cost, home-based, and has a much lower side effect profile than pharmacotherapy. The antidepressant effects of bright light are well established, and there are several rationales for expecting that bright light might also be efficacious for perinatal depression. This review describes these rationales, summarizes the available evidence on the efficacy of bright light therapy for perinatal depression, and discusses future directions for investigation of bright light therapy as a treatment for perinatal depression.     

THE GENETIC INTERPRETATION OF INBREEDING DEPRESSION AND OUTBREEDING DEPRESSION

Inbreeding with close relatives and outbreeding with members of distant populations can both result in deleterious shifts in the means of fitness-related characters, most likely for very different reasons. Such processes often occur simultaneously and have important implications for the evolution of mating systems, dispersal strategies, and speciation. They are also relevant to the design of breeding strategies for captive populations of endangered species. A general expression is presented for the expected phenotype of an individual under the joint influence of inbreeding and crossbreeding. This expression is a simple function of the inbreeding coefficient, of source and hybridity indices of crossbreeding, and of specific forms of gene action. Application of the model may be of use in identifying the mechanistic bases for a number of evolutionary phenomena such as the shift from outbreeding enhancement to outbreeding depression that occurs with population divergence.     

Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects

Objective: To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity. Research Methods and Procedures: Four randomized, double‐blind, multicenter trials compared ecopipam (n = 1667) and placebo (n = 1118) in obese subjects including type 2 diabetic subjects. Subjects received oral ecopipam 10, 30, or 100 mg daily for 12 weeks (Phase 2) or 50 or 100 mg daily for 52 weeks (Phase 3) combined with a weight loss program. Primary efficacy variables were the proportion of subjects with ≥5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3). Results: In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved ≥5% weight loss after 12 weeks (p < 0.01). In the Phase 3 studies, ecopipam 100 mg produced a 3.1% to 4.3% greater weight loss than placebo at 52 weeks. More subjects administered ecopipam vs. placebo achieved a 5% to 10% or >10% weight loss in two non‐diabetic phase 3 trials. Ecopipam‐treated subjects also maintained more weight loss compared with placebo subjects at 52 weeks. Phase 3 studies were discontinued because of unexpected psychiatric adverse events (ecopipam 31% vs. placebo 15%), including depression, anxiety, and suicidal ideation. Discussion: Ecopipam was effective for achieving and maintaining weight loss in obese subjects, including type 2 diabetic subjects; however, the adverse effects on mood observed in the Phase 3 studies exclude its projected use in weight management.     

Nutritional Interventions in Depression and Perinatal Depression

Depression is the leading cause of mental disability worldwide. Women who are depressed during pregnancy are at a higher risk for preterm delivery, preeclampsia, birth difficulties, and postpartum depression. The treatment of depression in conventional medicine has focused on physiological factors that lead to impaired neurotransmitter function and treatments to improve neurotransmitter function. Pharmaceutical substances pose risks for pregnant and lactating women, and lower risk options are preferred. Micronutrients, including certain B vitamins, folate, and docosahexaenoic acid (DHA), play a role in the synthesis and absorption of neurotransmitters. Experimental studies suggest that supplementation with specific micronutrients may alleviate depressive symptoms and improve birth outcomes in patients with perinatal depression. Alternative treatments for depression, including nutritional supplements, are an important treatment option for depressive symptoms while limiting potential side effects and treatment costs. This article explores the biological basis of perinatal depression and reviews the potential benefits of non-pharmacological interventions.     

Between a rock and a hard place: evaluating the relative risks of inbreeding and outbreeding for conservation and management

As populations become increasingly fragmented, managers are often faced with the dilemma that intentional hybridization might save a population from inbreeding depression but it might also induce outbreeding depression. While empirical evidence for inbreeding depression is vastly greater than that for outbreeding depression, the available data suggest that risks of outbreeding, particularly in the second generation, are on par with the risks of inbreeding. Predicting the relative risks in any particular situation is complicated by variation among taxa, characters being measured, level of divergence between hybridizing populations, mating history, environmental conditions and the potential for inbreeding and outbreeding effects to be occurring simultaneously. Further work on consequences of interpopulation hybridization is sorely needed with particular emphasis on the taxonomic scope, the duration of fitness problems and the joint effects of inbreeding and outbreeding. Meanwhile, managers can minimize the risks of both inbreeding and outbreeding by using intentional hybridization only for populations clearly suffering from inbreeding depression, maximizing the genetic and adaptive similarity between populations, and testing the effects of hybridization for at least two generations whenever possible.     

Research advances in geriatric depression

Technical advances have facilitated the exploration of factors related to geriatric depression and have helped generate novel biological and psychosocial treatment approaches. This review summarizes the main advancements in epidemiology, clinical presentation and course, genetics, and other areas of biological research. Treatment interventions outlined in this paper include electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation, deep brain stimulatn, depression prophylaxis, multidisciplinary approaches to depression treatment, and psychotherapy. Forms of psychotherapy for geriatric depression summarized include interpersonal psychotherapy, supportive psychotherapy, cognitive-behavioral therapy, problem-solving therapy, and ecosystem-focused therapy. Neuroimaging techniques based on magnetic resonance imaging are discussed briefly, including volumetric brain studies, diffusion tensor imaging, fractional anisotropy, fiber tractography, magnetization transfer imaging, and blood-oxygenation-level-dependent functional magnetic resonance imaging. Finally, treatment effectiveness is addressed in a discussion of new models to improve access to and quality of care offered in the community.     

布拉酵母联合舍曲林治疗产后抑郁症的疗效观察

目的探讨布拉酵母菌联合舍曲林对产后抑郁症(PPD)的临床疗效及安全性。方法选择2016年1月至2018年12月我院104例PPD患者为研究对象。入选患者随机分为观察组和对照组各52例,两组患者均给予舍曲林50 mg/次,1次/d,口服。观察组患者同时联用布拉酵母0.5 g/次,2次/d,口服,8周为一疗程。治疗前后检测患者孕酮及雌二醇水平,并于治疗前及治疗第4周、第8周时采用汉密顿抑郁量表(HAMD)评价患者治疗结果、临床疗效及安全性。结果治疗后,两组患者HAMD评分与治疗前比较均降低(t=8.162,P0.001;t=17.916,P0.001;t=16.995,P0.001;t=28.683,P0.001),且观察组患者降低幅度大于对照组(t=7.741,P0.001;t=13.073,P0.001)。观察组患者临床总有效率(90.38%)明显高于对照组(69.23%)。治疗后观察组患者孕酮水平低于对照组,雌二醇水平高于对照组,差异均有统计学意义(t=10.774,P0.001;t=7.239,P0.001)。两组母婴无明显不良反应。结论布拉酵母联合舍曲林对产后抑郁症的临床疗效明显,安全性高,值得临床推广。     

Parental relatedness and major histocompatibility effects on early embryo survivorship in Atlantic salmon

Salmon have provided key insights into the relative influence of natural and sexual selection on major histocompatibility complex (MHC) variation. Natural selection on salmon MHC genes has been demonstrated in pathogen studies, and there is evidence of MHC-based mate choice (sexual selection). We tested whether parental MHC genes affect survivorship of juvenile Atlantic salmon (Salmo salar) by quantifying the influence of parental genome-wide relatedness and MHC genotype on survivorship to the swim-up stage. Thirteen microsatellite loci were used to estimate the influence of genome-wide relatedness between parents on offspring survivorship and MHC genotypes were determined by sequencing part of the class IIβ gene. Our results revealed no significant relationship between early offspring survivorship and genome-wide relatedness, predicted MHC heterozygosity, or MHC allelic similarity. Overall, our data are consistent with the contention that excess MHC heterozygosity in Atlantic salmon juveniles is due to sexual selection as well as differential survival of offspring due to MHC genotype.     

When does depression become a disorder? Using recurrence rates to evaluate the validity of proposed changes in major depression diagnostic thresholds

High community prevalence estimates of DSM‐defined major depressive disorder (MDD) have led to proposals to raise MDD's diagnostic threshold to more validly distinguish pathology from normal‐range distress. However, such proposals lack empirical validation. We used MDD recurrence rates in the longitudinal 2‐wave Epidemiologic Catchment Area Study to test the predictive validity of three proposals to narrow MDD diagnosis: a) excluding “uncomplicated” episodes (i.e., episodes that last no longer than 2 months and do not include suicidal ideation, psychotic ideation, psychomotor retardation, or feelings of worthlessness); b) excluding mild episodes (i.e., episodes with only five to six symptoms); and c) excluding nonmelancholic episodes. For each proposal, we used lifetime MDD diagnoses at wave 1 to distinguish the group proposed for exclusion, other MDD, and those with no MDD history. We then compared these groups’ 1‐year MDD rates at wave 2. A proposal was considered strongly supported if at wave 2 the excluded group's MDD rate was not only significantly lower than the rate for other MDD but also not significantly greater than the no‐MDD‐history group. Results indicated that all three excluded groups had significantly lower recurrence rates than other MDD (uncomplicated vs. complicated, 3.4% vs. 14.6%; mild vs. severe, 9.6% vs. 20.7%; nonmelancholic vs. melancholic, 10.6% vs. 19.2%, respectively). However, only uncomplicated MDD's recurrence rate was also not significantly greater than the MDD occurrence rate for the no‐MDD‐history group (3.4% vs. 1.7%, respectively). This low recurrence rate resulted from an interaction between uncomplicated duration and symptom criteria. Multiple‐episode uncomplicated MDD did not entail significantly elevated recurrence over single‐episode cases (3.7% vs. 3.0%, respectively). Uncomplicated MDD's general‐distress symptoms, transient duration, and lack of elevated recurrence suggest it may generally represent nonpathologic intense sadness that should be addressed in treatment guidelines and considered for exclusion from MDD diagnosis to increase the validity of the MDD/normal sadness boundary.     

Depressing synapse as a detector of frequency change

In this article we discuss the short-term synaptic depression using a mathematical model. We derive the model of synaptic depression caused by the depletion of synaptic vesicles for the case of infinitely short stimulation time and show that the analytical formulas for the postsynaptic potential (PSP) and kinetic functions take simple closed form. A solution in this form allows an analysis of the characteristics of depression as a function of the models parameters and the derivation of analytic formulas for measures of short time synaptic depression commonly used in experimental studies. Those formulas are used to validate the model by fitting it to two types of synapses described in the literature. Given the fitted parameters we discuss the behavior of the synapse in situations involving frequency change. We also indicate a possible role of depressing synapses in information processing as not only a filter of high frequency input but as a detector of the return from high frequency stimulation to the stimulation within frequency band specific for a given synapse.     

Admixture between native and invasive populations may increase invasiveness of Mimulus guttatus

Self-fertilization and admixture of genotypes from different populations can have major fitness consequences in native species. However, few studies have addressed their potential roles in invasive species. Here, we used plants of Mimulus guttatus from seven native North American, three invasive Scottish and four invasive New Zealand populations to address this. We created seeds from self-fertilization, within-population outcrossing, between-population outcrossing within the same range, and outcrossing between the native and invasive ranges. A greenhouse experiment showed that native and invasive plants of M. guttatus suffered to similar degrees from inbreeding depression, in terms of asexual reproduction and biomass production. After outcrossing with plants from other populations, M. guttatus benefited from heterosis, in terms of asexual and sexual reproduction, and biomass production, particularly when plants from native and invasive populations were crossed. This suggests that, when novel genotypes of M. guttatus from the native North American range will be introduced to the invasive ranges, subsequent outcrossing with M. guttatus plants that are already there might further boost invasiveness of this species.     

Heterosis is common and inbreeding depression absent in natural populations of Arabidopsis thaliana

The importance of genetic drift in shaping patterns of adaptive genetic variation in nature is poorly known. Genetic drift should drive partially recessive deleterious mutations to high frequency, and inter‐population crosses may therefore exhibit heterosis (increased fitness relative to intra‐population crosses). Low genetic diversity and greater genetic distance between populations should increase the magnitude of heterosis. Moreover, drift and selection should remove strongly deleterious recessive alleles from individual populations, resulting in reduced inbreeding depression. To estimate heterosis, we crossed 90 independent line pairs of Arabidopsis thaliana from 15 pairs of natural populations sampled across Fennoscandia and crossed an additional 41 line pairs from a subset of four of these populations to estimate inbreeding depression. We measured lifetime fitness of crosses relative to parents in a large outdoor common garden (8,448 plants in total) in central Sweden. To examine the effects of genetic diversity and genetic distance on heterosis, we genotyped parental lines for 869 SNPs. Overall, genetic variation within populations was low (median expected heterozygosity = 0.02), and genetic differentiation was high (median F_ST = 0.82). Crosses between 10 of 15 population pairs exhibited significant heterosis, with magnitudes of heterosis as high as 117%. We found no significant inbreeding depression, suggesting that the observed heterosis is due to fixation of mildly deleterious alleles within populations. Widespread and substantial heterosis indicates an important role for drift in shaping genetic variation, but there was no significant relationship between fitness of crosses relative to parents and genetic diversity or genetic distance between populations.     

Unexpected positive and negative effects of continuing inbreeding in one of the world's most inbred wild animals

Inbreeding depression, the reduced fitness of offspring of related individuals, is a central theme in evolutionary biology. Inbreeding effects are influenced by the genetic makeup of a population, which is driven by any history of genetic bottlenecks and genetic drift. The Chatham Island black robin represents a case of extreme inbreeding following two severe population bottlenecks. We tested whether inbreeding measured by a 20‐year pedigree predicted variation in fitness among individuals, despite the high mean level of inbreeding and low genetic diversity in this species. We found that paternal and maternal inbreeding reduced fledgling survival and individual inbreeding reduced juvenile survival, indicating that inbreeding depression affects even this highly inbred population. Close inbreeding also reduced survival for fledglings with less‐inbred mothers, but unexpectedly improved survival for fledglings with highly inbred mothers. This counterintuitive interaction could not be explained by various potentially confounding variables. We propose a genetic mechanism, whereby a highly inbred chick with a highly inbred parent inherits a “proven” genotype and thus experiences a fitness advantage, which could explain the interaction. The positive and negative effects we found emphasize that continuing inbreeding can have important effects on individual fitness, even in populations that are already highly inbred.     

Investigating the genetic load of an emblematic invasive species: the case of the invasive harlequin ladybird Harmonia axyridis

Introduction events can lead to admixture between genetically differentiated populations and bottlenecks in population size. These processes can alter the adaptive potential of invasive species by shaping genetic variation, but more importantly, they can also directly affect mean population fitness either increasing it or decreasing it. Which outcome is observed depends on the structure of the genetic load of the species. The ladybird Harmonia axyridis is a good example of invasive species where introduced populations have gone through admixture and bottleneck events. We used laboratory experiments to manipulate the relatedness among H. axyridis parental individuals to assess the possibility for heterosis or outbreeding depression in F₁ generation offspring for two traits related to fitness (lifetime performance and generation time). We found that inter‐populations crosses had no major impact on the lifetime performance of the offspring produced by individuals from either native or invasive populations. Significant outbreeding depression was observed only for crosses between native populations for generation time. The absence of observed heterosis is indicative of a low occurrence of fixed deleterious mutations within both the native and invasive populations of H. axyridis. The observed deterioration of fitness in native inter‐population crosses most likely results from genetic incompatibilities between native genomic backgrounds. We discuss the implications of these results for the structure of genetic load in H. axyridis in the light of the available information regarding the introduction history of this species.     

Depression case management by practice nurses in primary care: an audit

Introduction Depression is a common and debilitating condition. A body of evidence exists about improving depression outcomes in primary care, using collaborative care models. Such approaches, however, have not been routinely adopted within general practice settings. In this paper we outline the results of an audit of an enhanced care initiative that trained practice nurses to deliver such approaches.Method An audit of symptom outcome and satisfaction was conducted in depression case-management clinics run by practice nurses. Results were then benchmarked against appropriate randomised trial data. The cost of practice nurse time devoted to the delivery of the service was estimated by multiplying time by unit cost.Results A mean change of 9.07 (standard deviation (SD) 6.67, 95% confidence interval (CI) 7.93-10.22, P < 0.001) points on the Patient Health Questionnaire (PHQ9) score was observed in those who were using/had used the service. Clinical change demonstrated a shift from moderate-to-severe to mild depression. The results reflect the changes seen in randomised controlled trial data from similar interventions in similar samples, and are superior to expected treatment as usual outcomes. Overall, respondents were 'very satisfied' with the service on offer. The mean cost of practice nurse time was estimated at ￡45 per patient.Discussion While acknowledging the limitations of audit data, practice nurses in general practice appear to be able to offer effective and acceptable case management to patients experiencing depression.     

产后抑郁发病因素的综合研究

目的：研究产后抑郁可能的心理社会因素,为提高围产保健水平提供一些理论与实践的依据。方法：自拟一般资料调查表等4种表格收集有关的心理,社会,环境因素及产科因素;用Edinburgh(EPDS)抑郁量表分≥10分为界,筛查产后抑郁,共298例完成了产后第3天评定,127例完成了产后第42天的评定,测定38名产妇临产前与产后72小时的雌二醇,孕酮及催乳素水平。结果：产后抑郁的发病率为23．15％,家庭支持等社会心理因素以及雌二醇的变化幅度和产后抑郁密切相关,结论：产后抑郁的发生具有一定的心理,社会与生物学因素,妊娠,分娩与产褥期良好的社会,家庭支持是减少产后抑郁障碍的有力措施。     

Rates of depression among men attending high-HIV-caseload general practices in Australia

This paper compares rates of current depression among men attending high-HIV-caseload general practices in New South Wales and South Australia. Current depression was assessed by the treating general practitioner (GP), using the nine-item Patient Health Questionnaire (PHQ-9), and by patient self-reporting. The study found that GPs, the PHQ-9 screening tool and patients were equally likely to identify current depression. High rates of depression were observed among the men attending general practice, with the highest rates among men with HIV and men who did not identify as either heterosexual or homosexual.     

Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women

Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11-0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders.     

交配距离与父本数量对野慈姑有性繁殖的影响

植物的有性繁殖是生活史和进化的核心, 母本及环境对繁殖的影响固然重要, 父本的贡献亦不容忽视。父本来源与多样性对坐果结籽和后代质量的影响明显, 但由于不同物种或种群的繁殖特点和进化历程, 往往也会呈现其独特性。该研究旨在探究挺水植物野慈姑(Sagittaria trifolia)是否存在自交或远交衰退, 以及父本数量对其繁殖和后代表现的影响。通过人工控制授粉, 设置自交、近距离异交(<50 km)、远距离异交(＞200 km) 3种交配距离以及单、双两类父本数量, 共计5种授粉处理, 观测野慈姑坐果概率、单果种子数量、种子面积、萌发率(2018和2019年)、幼苗芽长(2018和2019年)共7项指标。结果显示: 不同距离的交配对野慈姑的坐果概率、单果种子数量、种子面积、萌发率、幼苗芽长没有显著影响, 野慈姑未出现明显的自交衰退或远交衰退现象。父本数量的增加对野慈姑的结实数量(坐果概率、单果种子数量、种子面积)无影响, 但结实质量方面, 双父本处理的种子萌发率略高于单父本处理。综上所述, 交配距离与父本数量对野慈姑的繁殖表现影响较小, 这可能与其频繁的自交历史、远距离的基因扩散以及高度相似的水生环境有关; 同时, 该研究基于20余个自然种群的基因型, 研究结果也表明了野慈姑物种水平有性繁殖的优异和稳定性。     

The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms

The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination, to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan. All areas of neuroscience, from genes to behaviour, molecules to mind, and experimental to clinical, are actively engaged in attempts at elucidating the pathophysiology of depression and the mechanisms underlying the efficacy of antidepressant treatments. This first of two special issues of Philosophical Transactions B seeks to provide an overview of current developments in the field, with an emphasis on cellular and molecular mechanisms, and how their unravelling opens new perspectives for future research.