Translational developmental psychiatry最新文献

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FCAP 2015 FCAP 2015

Translational developmental psychiatry

Pub Date : 2015-01-01 DOI: 10.3402/tdp.v3.29697

引用次数: 0

Manualized social skills group training for children and adolescents with higher functioning autism spectrum disorder: protocol of a naturalistic multicenter, randomized controlled trial 高功能自闭症谱系障碍儿童和青少年的手工社交技能小组训练:一项自然多中心随机对照试验方案

Translational developmental psychiatry

Pub Date : 2015-01-01 DOI: 10.3402/tdp.v3.29825

Nora Choque Olsson, K. Tammimies, S. Bölte

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction, and the presence of stereotyped, repetitive and restricted behavior, interests, and activities. Despite prior studies showing moderate efficacy of social skills group training (SSGT) for children and adolescents with ASD, its effectiveness remains unclear. To investigate the efficacy and effectiveness of SSGT, we have initiated a large randomized controlled multicenter trial of the manualized SSGT program ‘KONTAKT’ in N=288 children and adolescents with high functioning ASD and psychiatric comorbidities (attention deficit hyperactivity disorder, anxiety, and depression) recruited from 14 clinical units. Based on stratification for age group (children vs. adolescents) and lengths of intervention (short vs. long), the participants are randomly assigned to SSGT KONTAKT training (n=144) or to treatment as usual (n=144). Outcomes are assessed by blinded teachers and unblinded parents on the Social Responsiveness Scale (primary outcomes), participant's self-reports, and clinician ratings using well-established instruments for adaptive skills, general psychopathology, and experienced stress (secondary outcomes). We expect that participants receiving SSGT KONTAKT will show improved social responsiveness and everyday functioning, decreased general symptom severity, and perceived stress compared to standard care. Moreover, we predict that participant characteristics such as genetic predisposition, age, IQ, sex, verbal skills, and comorbidity moderate treatment effects.

自闭症谱系障碍(ASD)是一种终身的神经发育障碍，其特征是社会沟通和互动障碍，以及刻板、重复和限制的行为、兴趣和活动的存在。尽管先前的研究显示社会技能小组训练(SSGT)对患有自闭症的儿童和青少年有中等疗效，但其有效性尚不清楚。为了研究SSGT的疗效和有效性，我们启动了一项大型随机对照多中心试验，在14个临床单位中招募了288名患有高功能ASD和精神共病(注意缺陷多动障碍、焦虑和抑郁)的儿童和青少年进行了人工SSGT项目“KONTAKT”。根据年龄组(儿童与青少年)和干预时间(短与长)的分层，参与者被随机分配到SSGT KONTAKT培训组(n=144)或正常治疗组(n=144)。结果由盲法教师和非盲法家长对社会反应量表(主要结果)、参与者的自我报告和临床医生使用成熟的适应技能、一般精神病理学和经历压力(次要结果)的评分进行评估。与标准治疗相比，我们期望接受SSGT KONTAKT的参与者表现出更好的社会反应和日常功能，降低一般症状严重程度和感知压力。此外，我们预测参与者的遗传易感性、年龄、智商、性别、语言技能和共病等特征会影响治疗效果。

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引用次数: 10

A neuroconstructivistic research strategy to study the underlying causes of dyslexia 一种研究阅读障碍潜在原因的神经建构主义研究策略

Translational developmental psychiatry

Pub Date : 2014-01-01 DOI: 10.3402/tdp.v2.21684

M. Trautmann

The present article suggests an extended neuroconstructivistic research strategy for assessing the causes of dyslexia. Instead of following one line of argumentation, such as the influence of auditory perception on the development of phonological awareness, a systematic facet model is suggested to identify the development of singular, bi-, and cross-modal perception, attention, and higher cognition in dyslexia over time. In addition, such a study should also include etiological measures such as genetic and family risk factors. This developmental approach is necessary to suggest a pragmatic concept for investigating all processing types of dyslexia under several methodological aspects.

本文提出了一种扩展的神经建构主义研究策略来评估阅读障碍的原因。不同于单一的论证，如听觉感知对语音意识发展的影响，我们建议采用一个系统的方面模型来识别阅读障碍患者的单、双、跨模态感知、注意力和高级认知的发展。此外，这样的研究还应包括病因学措施，如遗传和家庭危险因素。这种发展的方法是必要的，以提出一个实用的概念，以研究在几个方法学方面的所有处理类型的阅读障碍。

引用次数: 4

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight 抗精神病药物结果的遗传学及其对临床医生的影响:成为焦点

Translational developmental psychiatry

Pub Date : 2014-01-01 DOI: 10.3402/tdp.v2.24663

Amtul H. Changasi, T. Shams, Jennie G Pouget, D. Müller

Background and purpose Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals’ responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip® CYP450 Test and more recently the DMET™ Plus Panel, the Genecept™ Assay, the Genomas HILOmet PhyzioType™ System, and the GeneSight® Test.

背景和目的抗精神病药物(APs)是治疗精神分裂症和其他精神障碍的主要方法。不幸的是，由于AP治疗结果的个体间差异很大，通常需要长时间的试错方法来找到最佳药物和剂量。文献已经显示了大量的证据表明遗传成分在个体对ap的反应。药物遗传学研究分析了特定的遗传标记及其与APs症状改善和副作用发生的关系。本研究旨在通过预测检测优化AP药物治疗，实现个体化用药。本综述将重点介绍APs药物遗传学中最一致的发现，并将更新读者的临床意义。这将包括基因变异如何调节AP药物水平、副作用和治疗症状改善(即反应)。一些有希望的发现表明，除了5 -羟色胺受体基因变异外，多巴胺受体基因变异也与反应和常见副作用有关。值得注意的是，与反应相比，副作用的遗传效应似乎特别高。一个例子是抗精神病药物引起的体重增加，其中瘦素，HTR2C，特别是黑素皮质素-4受体(MC4R)基因与儿童和青少年的体重增加有关。与迟发性运动障碍和粒细胞缺乏症相关的基因也得到了一致的发现。然而，最具临床相关性的发现与药物代谢相关的基因有关，如CYP2D6和CYP2C19基因，这些基因已被纳入首批基因检测试剂盒，如Amplichip®CYP450测试和最近的DMET™Plus Panel, Genecept™Assay, Genomas HILOmet PhyzioType™系统和GeneSight®测试。

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引用次数: 9

Corrigendum: Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight 勘误:抗精神病药物结果的遗传学及其对临床医生的影响:成为焦点

Translational developmental psychiatry

Pub Date : 2014-01-01 DOI: 10.3402/tdp.v2.25715

引用次数: 0

Treatment experiences of males with an eating disorder: a systematic review of qualitative studies 男性饮食失调的治疗经验:质性研究的系统回顾

Translational developmental psychiatry

Pub Date : 2014-01-01 DOI: 10.3402/tdp.v2.25552

Priyanka Thapliyal, P. Hay

Research has commonly examined eating disorders (EDs) predominantly in female groups. However, males are a large minority of people with EDs. In view of this, the present paper aimed to investigate and review the experience of treatment and recovery for males with an ED. We carried out a systematic search for qualitative articles focusing on the experiences of treatment and found only four papers which met inclusion criteria. Key themes identified across studies were 1) delays in seeking treatment, 2) clinical features distinctive to males such as drive for muscularity, 3) feminine and other aspects of treatment services, and 4) lack of consensus in views about relevance of sex in treatment. More studies are needed to explore male pathways through treatment and both impediments, but also facilitators, of successful engagement in and response to treatment.

研究表明，饮食失调(EDs)主要发生在女性群体中。然而，男性在ed患者中占少数。鉴于此，本文旨在调查和回顾男性ED的治疗和康复经验。我们对关注治疗经验的定性文章进行了系统检索，发现只有4篇论文符合纳入标准。所有研究确定的关键主题是:1)寻求治疗的延迟;2)男性特有的临床特征，如对肌肉的渴望;3)治疗服务的女性化和其他方面;4)在治疗中性别相关性的观点上缺乏共识。需要更多的研究来探索男性通过治疗的途径，以及成功参与治疗和对治疗作出反应的障碍和促进因素。

引用次数: 40

Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge. 血清素转运体基因型调节应激时 HPA 轴的输出：应激、地塞米松试验和促肾上腺皮质激素挑战的影响。

Translational developmental psychiatry

Pub Date : 2013-09-09 DOI: 10.3402/tdp.v1i0.21130

Andrea N Sorenson, Erin C Sullivan, Sally P Mendoza, John P Capitanio, J Dee Higley

Background: Studies show that the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in depression. Some studies suggest that variation in the serotonin transporter genotype (hereafter 5HTT) modulates both risk for depression and psychopathological HPA axis responsiveness. Rhesus monkeys are well suited to model such relationships. Rhesus macaque models of human psychopathology have assessed the effect of the serotonin transporter (rh5HTT) on levels of cortisol in stressed subjects. These studies show that that under conditions of stress, heterozygous females (Ls) reared under adversity exhibit high levels of cortisol. Studies have not to our knowledge, however, assessed the potential additive effect on the cortisol response in a number of macaque subjects homozygous for the serotonin transporter short allele (ss). Moreover, little is known about the level of the central or peripheral nervous system at which the 5HTT genotype acts to modulate the cortisol response.

Methods: This study assesses a relatively large number of subjects homozygous and heterozygous for the rh5HTT short and long alleles (a) during stress; (b) following a dexamethasone suppression test; and (c) following an adrenocorticotropic hormone (ACTH) challenge. Subjects included 190 infant rhesus macaques (Macaca mulatta - 84 males and 106 females; 118 LL, 60 Ls, and 12 ss subjects), obtaining two blood plasma samples during the stress of separation from their mothers. Then on the following day, we obtained a blood sample following a dexamethasone test, and later that day we obtained a blood sample after an ACTH challenge test. Subjects ranged in age between 90 and 128 days, with a mean age of 107 days.

Results: Subjects homozygous for the short allele had significantly higher levels of cortisol across all test conditions, when compared to those homozygous for the long allele, or those heterozygous with Ls alleles. Subsequent analyses showed a high correlation between individual cortisol levels across the three different tests.

Conclusions: These data suggest that subjects homozygous for the short allele are more likely to show dysregulated cortisol levels in response to stress. Given the correlation in individual responses of the HPA axis across the different tests, our data suggest that the effect of the 5HTT genotype shows some commonality in its regulation of stress, feedback, and ACTH-stimulated cortisol output. Our data suggest that under conditions of stress, the serotonin transporter may modulate HPA axis psychopathology.

背景：研究表明，抑郁症患者的下丘脑-垂体-肾上腺（HPA）轴功能失调。一些研究表明，5-羟色胺转运体基因型（以下简称 5HTT）的变异可调节抑郁症风险和精神病理 HPA 轴反应性。猕猴非常适合模拟这种关系。人类精神病理学的猕猴模型评估了血清素转运体（rh5HTT）对受试者皮质醇水平的影响。这些研究表明，在压力条件下，逆境饲养的杂合子雌猴（Ls）表现出较高的皮质醇水平。然而，据我们所知，还没有研究评估了一些同源血清素转运体短等位基因（ss）的猕猴对皮质醇反应的潜在叠加效应。此外，人们对 5HTT 基因型调节皮质醇反应的中枢或外周神经系统水平知之甚少：本研究对相对较多的 rh5HTT 短等位基因和长等位基因同卵和异卵受试者进行了评估：(a) 应激时；(b) 地塞米松抑制试验后；(c) 促肾上腺皮质激素（ACTH）挑战后。受试者包括 190 只猕猴幼崽（猕猴：84 只雄性，106 只雌性；118 只 LL 受试者，60 只 Ls 受试者，12 只 SS 受试者），在与母亲分离的应激状态下采集两份血浆样本。第二天，我们在地塞米松试验后采集了一份血样，随后又在促肾上腺皮质激素挑战试验后采集了一份血样。受试者的年龄在 90 到 128 天之间，平均年龄为 107 天：结果：与长等位基因的同卵受试者或Ls等位基因的异卵受试者相比，短等位基因的同卵受试者在所有测试条件下的皮质醇水平都明显较高。随后的分析表明，在三种不同的测试中，个体皮质醇水平之间存在高度相关性：这些数据表明，短等位基因的同卵受试者更有可能对压力表现出失调的皮质醇水平。考虑到不同测试中 HPA 轴个体反应的相关性，我们的数据表明，5HTT 基因型对压力、反馈和 ACTH 刺激皮质醇输出的调节作用具有一定的共性。我们的数据表明，在压力条件下，血清素转运体可能会调节 HPA 轴的精神病理学。

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引用次数: 0

Differential Effects of Tryptophan Challenge on Mood and Coping with Stress in Subjects with Genetic (5-HTTLPR) or Chronic Stress-Induced Brain 5-HT Vulnerabilities 色氨酸挑战对遗传性(5-HTTLPR)或慢性应激性脑5-羟色胺脆弱性受试者情绪和应激应对的差异影响

Translational developmental psychiatry

Pub Date : 2013-01-01 DOI: 10.3402/TDP.V1I0.19055

R. Markus

Background Brain serotonin (5-HT) dysfunction is a relevant pathophysiological factor contributing to stress proneness and hence to stress-related affective disturbances. Susceptibility to 5-HT dyfunction, 5-HT vulnerability, is not only promoted by cognitive proneness (frequent stress perceptions and experiences) but also by genetic vulnerabilities. A commonly recognized 5-HT vulnerable genotype involves a polymorphism in the 5-HT transporter-linked promoter region (5-HTTLPR). This region encodes the 5-HT transporter protein (5-HTT), controls 5-HT reuptake and function, and is the target mechanism for antidepressant drugs. The short-allele (S) variant 5-HTTLPR is associated with lower 5-HTT mRNA concentrations than the long-allele (L) variant and is thought to promote 5-HT vulnerability for the negative affective effects of stress. Brain 5-HT vulnerabilities are often explored by tryptophan depletion (ATD). This intervention reduces brain 5-HT by lowering the plasma dietary amino acid tryptophan, the precursor of 5-HT, which competes with other large neutral amino acids (TRP/LNAA ratio) for uptake into the brain. Yet, because 5-HT vulnerable subjects may exhibit enhanced post-synaptic sensitization, as a compensatory response to reduced 5-HT availability and/or lower pre-synaptic 5HTT expression, they may be particularly susceptible for the beneficial effects of tryptophan challenge. Data showing that cognitive and/or genetically 5-HT vulnerable subjects are indeed less affected by the negative effects of acute stress exposure following dietary tryptophan augmentation will be presented.

脑5-羟色胺(5-HT)功能障碍是导致应激倾向和应激相关情感障碍的相关病理生理因素。对5-羟色胺功能障碍的易感性，即5-羟色胺易感性，不仅由认知倾向(频繁的应激感知和经历)促进，也由遗传脆弱性促进。常见的5-HT易感基因型涉及5-HT转运体连接启动子区域(5-HTTLPR)的多态性。该区域编码5-羟色胺转运蛋白(5-HTT)，控制5-羟色胺的再摄取和功能，是抗抑郁药物的靶机制。短等位基因(S)变体5-HTTLPR比长等位基因(L)变体具有更低的5-HTT mRNA浓度，并且被认为促进了5-HT对应激的负面影响的易感性。脑5-HT脆弱性通常通过色氨酸耗竭(ATD)来探索。这种干预通过降低血浆膳食氨基酸色氨酸(5-羟色胺的前体)来降低脑5-羟色胺，色氨酸与其他大的中性氨基酸(TRP/LNAA比率)竞争，以进入大脑。然而，由于5-HT易感受试者可能表现出增强的突触后敏化，作为对5-HT可用性降低和/或突触前5HTT表达降低的代偿反应，他们可能特别容易受到色氨酸挑战的有益影响。数据显示，认知和/或基因上的5-羟色胺易感受试者确实较少受到急性应激暴露后饮食色氨酸增加的负面影响。

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引用次数: 1

The Use of Acute Tryptophan Depletion in Children and Adolescents 急性色氨酸耗竭在儿童和青少年中的应用

Translational developmental psychiatry

Pub Date : 2013-01-01 DOI: 10.3402/TDP.V1I0.18393

F. Zepf

The neurotransmitter serotonin (5-HT) plays an important role in many neuropsychiatric disorders, in particular affective disorders, eating disorders and disorders related to problems in processing emotions. Different methods have been applied in previous studies on adults to investigate central nervous serotonergic neurotransmission. Acute tryptophan depletion (ATD) is a neurodietary method to reduce central nervous serotonin synthesis in humans for a short period by decreasing the availability of the amino acid tryptophan, TRP, the physiological precursor to 5-HT. Uptake of endogenous TRP into the central nervous system is decreased by a reduced transport of TRP over the blood–brain barrier as TRP competes with other amino acids administered to the subjects within an amino acid beverage lacking TRP after an overnight fast. According to previous studies, frequent side effects of using ATD in adults are vomiting and nausea, thus limiting its use. Here, we present a modified ATD protocol that was adapted for use in children and adolescents, with the administration of an amino acid beverage adapted to the body weight of the subjects. Underlying principles of this ATD modification termed Moja-De and first research findings based on this ATD formulation will be presented and discussed.

神经递质5-羟色胺(5-HT)在许多神经精神疾病中起着重要作用，特别是情感障碍、饮食障碍和与情绪处理问题相关的障碍。在以往的成人研究中，已经采用了不同的方法来研究中枢神经5 -羟色胺能神经传递。急性色氨酸耗散(ATD)是一种神经饮食方法，通过减少5-羟色胺的生理前体色氨酸(TRP)的可用性，在短时间内减少人体中枢神经5-羟色胺的合成。内源性TRP进入中枢神经系统的吸收减少了，因为TRP通过血脑屏障的运输减少了，因为在禁食一夜后，在缺乏TRP的氨基酸饮料中，TRP与给予受试者的其他氨基酸竞争。根据以往的研究，成人使用ATD的常见副作用是呕吐和恶心，因此限制了其使用。在这里，我们提出了一个修改后的ATD方案，适用于儿童和青少年，并给予适应受试者体重的氨基酸饮料。本文将介绍和讨论这种被称为Moja-De的ATD改性的基本原理，以及基于这种ATD配方的首次研究成果。

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引用次数: 4

Placental tryptophan metabolism as a potential novel pathway for the developmental origins of mental diseases 胎盘色氨酸代谢作为精神疾病发育起源的潜在新途径

Translational developmental psychiatry

Pub Date : 2013-01-01 DOI: 10.3402/tdp.v1i0.20593

N. Goeden, J. Velásquez, A. Bonnin

Dysfunction of brain serotonin (5-HT) signaling contributes to the pathophysiology of several psychiatric disorders. However, before 5-HT acts as a neurotransmitter/neuromodulator in the adult brain, increasing evidence suggests that it plays crucial roles in the modulation of essential neurodevelopmental processes. It was recently demonstrated that the placenta synthesizes 5-HT from maternally derived tryptophan during pregnancy. Therefore, genetic and environmental perturbations that affect placental tryptophan metabolism could alter neurodevelopmental processes in the developing embryo, and contribute to the developmental origin of psychiatric disorders. Here we discuss how disruptions of the placental tryptophan metabolic pathway may lead to abnormal brain development and function in adult life.

脑5-羟色胺(5-HT)信号的功能障碍与几种精神疾病的病理生理有关。然而，在5-HT在成人大脑中作为神经递质/神经调节剂之前，越来越多的证据表明它在基本神经发育过程的调节中起着至关重要的作用。最近的研究表明，胎盘在怀孕期间从母体来源的色氨酸合成5-羟色胺。因此，影响胎盘色氨酸代谢的遗传和环境扰动可能改变胚胎发育中的神经发育过程，并有助于精神疾病的发育起源。在这里，我们讨论胎盘色氨酸代谢途径的中断如何导致成人生活中大脑发育和功能异常。

引用次数: 14

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