常用失眠动物模型及其睡眠结构特征研究进展

失眠症是最为常见的睡眠障碍,以入睡和睡眠维持困难及日间功能障碍为主要表现。失眠症的病理生理研究和镇静催眠药物的非临床评价需以适当的动物模型为基础。本文以模型动物睡眠结构为重点,从心理应激、特殊睡眠环境和药物模型3个方面归纳常用失眠模型。现有失眠动物模型存在一定的局限性,在镇静催眠药物研究中应当灵活选择多种造模方法,以用更接近失眠临床表现的动物模型评价药物作用。     

慢性应激大鼠模型的应用与改进

1．为什么要建立慢性应激大鼠模型？慢性应激大鼠模型是用一些不可预知的损害性应激造成的大鼠模型。现代社会中，慢性应激是许多疾病的基本发病因素，应激诱发的疾病日益增加，如高血压病，肿瘤，心血管疾病及情感性疾病等。该模型一定程度上模拟了社会生活节奏加快，竞争激烈的现状。抑郁症是复杂的心境障碍性疾病，是常见的应激诱发疾病。抑郁症主要表现为兴趣丧失，疲乏无力，睡眠障碍，情绪低落，语言减少，精神、运动迟缓，有自杀倾向。为临床多发病，占人口的5％～7％左右，在西方国家发病率约为9％-18％，据WHO预测，2020年抑郁症将可能由第四位致残致死上升为第二位。未预知的慢性应激模型模拟抑郁症发病的环境诱因，其行为改变与内源性抑郁症症状相似，是最为接近临床抑郁症的模型，具有较高科研价值。     

失眠机制及药物治疗

随着工业化进程的加快,社会竞争日益加剧、工作压力、人口老龄化等原因,全球三分之一的人有睡眠问题,5%的人依靠药物维持着低质量的睡眠。临床使用的苯二氮卓艹类药物虽能增加睡眠量,但改变了睡眠脑电活动的生理模式,副作用多且易耐受。新型镇静催眠药主要包括:非苯二氮卓艹类、褪黑素受体激动剂、抗组胺药和食欲肽受体拮抗剂。这些药物起效快、疗效明显、"宿睡作用"少、耐受性及依赖性较低,已逐渐成为治疗失眠的主要手段。生理性睡眠调节异常是失眠的重要原因。由于缺乏失眠动物模型,限制了治疗药物开发。近年来,我们从生理性睡眠调节机制出发,探索能模拟人病理生理学特征的失眠动物模型,建立了紧张应激型、内稳态失衡型、生物钟紊乱型、神经网络功能异常、第一晚效应等失眠动物模型,用于镇静催眠药的筛选。中药是祖国医学的精华之一,但由于疗效观察多凭主观问卷,缺乏客观标准,加上中药成分复杂、作用机制不明、缺乏可靠的质控标准、使用不便等原因,限制其广泛应用和推广。我们利用高度自动化睡眠记录与解析平台,突破制约中药临床前疗效评价的瓶颈,运用现代药理学及睡眠神经生物学等研究手段,对可能具有镇静催眠效应的传统中药进行筛选和再评价,找出具有较强生理性睡眠调节作用的有效单体;利用基因敲除动物及各种失眠动物模型,结合神经化学、分子生物学、药理学等方法,从基因到行为研究这些有效单体的作用机制。结果发现,厚朴酚、厚朴酚、西红花素、西红花醛和白芍苷等能增加睡眠量,缩短睡眠潜伏期。脑电能谱分析显示,这些成分诱导的睡眠与生理性睡眠相似,提示这些成分可能适用于临床失眠症的治疗。     

军事演习中官兵睡眠状况与应激性失眠交叉滞后分析

目的了解某装甲部队军事演习期间官兵睡眠状况,并分析睡眠与应激性失眠的相关性,为有针对性开展心理干预提供理论依据。方法随机整群抽样选取某装甲部队官兵400名,于演习前1个月(首测)及演习期间(后测),采用匹兹堡睡眠质量指数量表(PSQI)及福特应激失眠反应测试(FIRST)进行调查,并分析其相关性。结果睡眠质量指数后测较首测在总分、主观睡眠质量、入睡时间、睡眠时间、睡眠效率、睡眠障碍和日间功能障碍因子评分上存在显著性差异(P<0.05或P<0.01);交叉滞后相关分析表明,应激失眠反应(首测)能显著正向预测睡眠质量指数(后测)(P<0.01),睡眠质量指数(前测)对应激失眠反应(后测)无显著预测意义(P>0.05)。结论军事演习应激因素对官兵睡眠状况影响大,需要进行心理干预。官兵应激失眠反应对军事演习期间官兵睡眠状况具有较好的预测作用。     

海马miR-182在慢性应激抑郁模型大鼠中的变化

目的:探索miRNA与抑郁症的关系,为揭示应激诱导的抑郁症发生机制和开发新型抗抑郁症药物奠定基础。方法:建立慢性不可预见性轻度应激(Chronic unpredictable mild stress,CUMS)抑郁症动物模型,运用miRNA二代测序、miRNA差异表达分析、荧光定量PCR(q PCR)等方法检测抑郁模型动物miRNA表达谱的变化。结果:(1)大鼠经历5周连续的不可预见性应激,通过检测糖水偏好、体重增加、自发活动减少等指标表明大鼠形成抑郁样行为。利用Solexa测序技术对大鼠海马miRNA表达谱进行分析,结果发现与对照组比较,抑郁模型组变化幅度超过两倍的miRNAs有:miR-1224上调,miR-1249、miR-182、miR-183、miR-204下调。(2)对于差异表达的miRNA进行靶基因分析发现,miR-182所调控的脑源性营养因子(brain derived neurotrophic factor,BDNF)、CLOCK、胰岛素样生长因子1型受体(insulin-like growth factor 1 receptor,IGF1R)、cAMP反应元件结合蛋白1(c AMP-response element binding protein 1,CREB1)与抑郁症的病因具有密切的联系。用定量PCR对慢性应激模型大鼠和对照组大鼠海马三个亚区miR-182的表达量进行分析发现,海马齿状回(dentate gyrus,DG)miR-182下调程度最为显著。CA1(cornuammonis 1)区和CA3(cornuammonis 3)区miR-182出现下调倾向,但无统计学差异。结论:大鼠海马DG区miR-182可能参与调控了慢性应激所致大鼠抑郁样行为的形成。     

复方柴金解郁片对抑郁症失眠大鼠脑内GABA受体表达的影响

目的探究复方柴金解郁片对抑郁症失眠大鼠脑内GABA受体表达的影响。方法SD大鼠随机分为空白组、模型组、阳性药(盐酸文拉法辛13.5 mg·kg^-1+地西泮0.9 mg·kg^-1)组、复方柴金解郁片高(10.8 g·kg^-1)、中(5.4 g·kg^-1)、低(2.7 g·kg^-1)剂量组。除空白组外,各组均采用慢性不可预见性轻度应激联合慢性睡眠剥夺的方法制作抑郁症失眠大鼠模型。旷场实验和糖水偏好实验检测大鼠抑郁样行为;翻正反射检测睡眠行为;ELISA检测海马和下丘脑Glu和GABA含量;qRT-PCR和Western blot检测GAD67、GABA AR、GABA BR mRNA及蛋白表达。结果与模型组相比,各复方柴金解郁片给药组活动次数和糖水偏嗜度增加;睡眠潜伏期缩短,睡眠时间延长,入睡率增加;Glu含量减少、GABA含量增加;GAD67、GABA AR、GABA BR的蛋白及基因表达增加。结论复方柴金解郁片具有良好的抗抑郁症失眠功效,其机制可能与增加脑内GABA受体表达有关。     

慢性应激和脂多糖构建昆明种小鼠抑郁症动物模型

目的 利用慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)联合脂多糖(lipopolysaccharide,LPS)构建稳定的抑郁症动物模型.方法 雄性昆明种小鼠48只分为正常对照组、LPS 组(LPS 0.2 mg·kg-1,i.p.)、CUMS 组(CUMS+生...     

Cdk5/p35参与了慢性应激诱导的大鼠抑郁样行为

背景:对抑郁症发生机制的研究表明,抑郁症患者表现为海马以及其他脑边缘结构的体积减少和细胞丢失,抗抑郁剂可显著促进抑郁模型动物海马神经元发生,提示神经可塑性机制涉及了抑郁症的发生过程。周期素依赖性蛋白激酶-5(Cdk5)及其活性调节蛋白p35是保持成熟神经系统内边缘系统,尤其是海马中神经元具有潜在可塑性的关键激酶。Cdk5在中枢神经系统发育过程中起着至关重要的作用,主要与神经元迁移、轴突生长和神经递质释放有关,还参与细胞骨架形成、轴突导向、膜转运、突触功能和多巴胺信号转导等多种神经功能调控。然而,在某些病理性因素作用下,Cdk5激酶活性异常升高会引起神经元的过度死亡,导致一些神经退行性疾病的发生。Cdk5在调节神经元的生存方面发挥着重要的作用,那么在抑郁症损伤的海马神经元中,Cdk5是否也参与了神经元的生存过程,从而介导了抑郁症的发生尚未见到报道。目的:本研究将基于抑郁症神经可塑性的研究基础,探讨Cdk5/p35在抑郁症模型大鼠抑郁样行为中的作用,以期进一步阐明抑郁症发生的神经生物学机制,并为临床发现新的治疗抑郁症的有效手段奠定理论基础。方法:采用连续21d的慢性不可预见性的中等强度应激抑郁模型(CMS),以动物的体重变化、蔗糖水偏爱(sucrosep reference)和自发活动能力为指标,考察抑郁模型动物行为学变化;通过测定Cdk5特定底物-组蛋白H1被磷酸化的程度检测大鼠海马部位Cdk5激酶活性,用Westernblot的方法检测p35蛋白的表达;同时在应激过程中,采用微量注射的方法,分别在海马齿状回(DG),CA1及CA3亚区给予Cdk5激酶抑制剂(butyrolactone),观察抑制不同脑区Cdk5激酶对抑郁症模型动物体重,糖水偏爱、自发活动性等抑郁样行为的影响。此外,在慢性应激的同时,连续给予抗抑郁药venlafaxine和mirtazapine,考察抗抑郁剂的治疗作用对海马p35蛋白表达水平的影响。结果:慢性应激大鼠海马部位Cdk5激酶活性显著升高;Western blot结果表明应激大鼠海马DG区胞膜组分p35蛋白的表达水平明显上调,而胞浆p35蛋白表达水平显著降低;相关性分析结果表明海马Cdk5激酶活性与胞膜p35蛋白的表达水平呈明显正相关,而与胞浆p35蛋白的表达水平呈明显负相关;大鼠体重增加值,糖水偏爱与海马胞膜p35蛋白的表达水平呈显著负相关。上述结果表明海马Cdk5激酶活性升高参与了慢性应激诱导的大鼠抑郁样行为。行为学检测结果表明,海马DG区微注射Cdk5激酶抑制剂butyrolactone(50,100ng)可显著逆转慢性应激引起的大鼠抑郁样行为,而在CA1和CA3区微注射butyrolactone(100ng)则对大鼠的抑郁样行为没有明显影响,说明抑制Cdk5激酶活性改善大鼠抑郁样行为具有脑区特异性。在慢性应激实验中发现连续给予抗抑郁药venlafaxine(40mg·kg-1)和mirtazapine(20mg·kg-1)可明显降低DG区胞膜p35蛋白的表达水平,促进p35蛋白由胞膜转运至胞浆,而抗精神病药aripiprazole(5mg.kg-1)对慢性应激引起的DG区胞膜p35蛋白表达增加没有明显影响,说明降低胞膜p35蛋白的表达水平,抑制Cdk5激酶活性是抗抑郁药物特异性的。结论:本研究通过一系列实验证实了Cdk5/p35在慢性应激大鼠抑郁样行为中的作用,抑制Cdk5活性可有效逆转动物的抑郁样行为,抗抑郁剂在发挥治疗作用的同时可抑制Cdk5激酶的异常激活。因此,本研究结果为抑郁症的神经生物学机制研究和临床抗抑郁治疗药物研究开发提供了新的思路。     

盐酸舍曲林联合阿戈美拉汀治疗抑郁症伴失眠的效果以及对血清氧化应激因子水平的影响

目的观察盐酸舍曲林联合阿戈美拉汀治疗抑郁症伴失眠的效果,以及对血清超氧化物歧化酶(SOD)和丙二醛(MDA)水平的影响。方法筛选抑郁症伴失眠患者98例,按随机数字表法分为对照组和观察组,各49例。对照组给予盐酸舍曲林片50 mg,po,qd;观察组在对照组基础上给予阿戈美拉汀片(起始剂量为25 mg·d^-1,po;2周后若疗效欠佳则加量至50 mg·d^-1)。2组患者均连续治疗6周。比较2组患者汉密尔顿抑郁量表(HAMD)-17评分、抑郁自评量表(SDS)评分、匹茨堡睡眠质量指数(PSQI)评分、临床疗效以及血清SOD和MDA水平,并记录2组不良反应发生情况。结果治疗6周后,观察组患者HAMD-17、SDS和PSQI指标(入睡时间、睡眠效率、睡眠时间、睡眠障碍和日间功能)评分均明显低于对照组(P<0.01);观察组总有效率明显高于对照组(95.59%vs 79.59%,P<0.05);观察组患者血清MDA水平明显低于对照组,SOD显著高于对照组(P<0.01)。2组患者不良反应发生率差异无统计学意义(P>0.05)。结论盐酸舍曲林联合阿戈美拉汀治疗抑郁症伴失眠,可明显改善患者的抑郁和失眠症状,提高临床疗效,改善氧化应激水平可能是其疗效途径之一,且安全性好。     

失眠患者睡眠结构及睡眠纺锤波的异常改变

目的 本研究旨在探索失眠患者与健康受试者睡眠纺锤波的差异，以及睡眠纺锤波与失眠严重程度及日间疲劳程度的关系。方法 纳入33名失眠患者和28名健康受试者，采集一般人口学资料并进行两晚的多导睡眠监测。对多导睡眠监测数据进行睡眠及相关信号的分析，并根据睡眠纺锤波持续时间以及振幅进行特征选取，随后分析失眠及日间嗜睡疲劳症状与睡眠纺锤波的相关性。结果 失眠患者慢波睡眠时间显著低于健康受试者(P<0.001),失眠患者入睡后的觉醒总时间高于健康受试者(P<0.001),失眠患者的纺锤波数量显著低于健康受试者(P=0.002)。失眠严重程度与睡眠纺锤波的数量(r=-0.35,P<0.001)、时长(r=-0.62,P<0.001)和密度(r=-0.56,P<0.001)均呈显著负相关，日间嗜睡及疲劳程度也与睡眠纺锤波的时长和密度显著负相关(P<0.01)。结论 研究结果证实了失眠患者睡眠结构的异常改变，表明睡眠纺锤波与失眠严重程度、日间嗜睡及疲劳症状显著相关。     

Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences

Rationale  

A complex relationship exists among stressful situations, body's reaction to stress, and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-α) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Sesamol, a phenolic derivative with a methylenedioxy group, is a potent inhibitor of cytokine production as well as an antioxidant.     

新的失眠动物模型研究概述

近年来用多种方法在小鼠与大鼠成功地建立了若干新的失眠动物模型。现简要介绍几个新的失眠动物模型的制作方法及其在药物研究中的应用,这些模型是小鼠慢性重复接触乙醇蒸汽后撤离法睡眠障碍模型、大鼠水面栅格法睡眠干扰模型、大鼠睡眠相位延迟综合征模型、大鼠平台法睡眠剥夺狂躁模型。评价指标有:测定脑电图和肌电图分析睡眠结构(快速眼动睡眠和非快速眼动睡眠)、睡眠时间、睡眠潜伏期与觉醒时间等。     

Effects of neuronal and inducible NOS inhibitor 1-[2-(trifluoromethyl) phenyl] imidazole (TRIM) in unpredictable chronic mild stress procedure in mice

Nitric oxide is an intracellular messenger which is involved in several functions and pathologies such as depression, anxiety, learning and memory. In many studies nitric oxide synthase inhibitors (NOSI) were shown to possess antidepressant-like effects in animal models of depression. The aim of this study is to investigate the effects of a selective neuronal and inducible nitric oxide synthase inhibitor TRIM (30 mg/kg/day, 35 days) in mice subjected to unpredictable chronic mild stress and then compare it's effect with a conventional selective serotonin reuptake inhibitor fluoxetine (15 mg/kg/day, 35 days). Stressed vehicle animals showed a significant disturbed coat state when compared with nonstressed animals and this effect was reversed by TRIM or fluoxetine. Both TRIM and fluoxetine prevented the stress-induced deficit in the grooming behaviour in the splash test. TRIM and fluoxetine also significantly decreased the attack frequency when compared to the stressed control group in the resident-intruder test. These results support the assumption that NOS inhibitors can be a new class of antidepressant drugs possibly acting on neuronal NOS.     

Circadian rhythms and depression: human psychopathology and animal models

Most organisms (including humans) developed daily rhythms in almost every aspect of their body. It is not surprising that rhythms are also related to affect in health and disease. In the present review we present data that demonstrate the evidence for significant interactions between circadian rhythms and affect from both human studies and animal models research. A number of lines of evidence obtained from human and from animal models research clearly demonstrate relationships between depression and circadian rhythms including (1) daily patterns of depression; (2) seasonal affective disorder; (3) connections between circadian clock genes and depression; (4) relationship between sleep disorders and depression; (5) the antidepressant effect of sleep deprivation; (6) the antidepressant effect of bright light exposure; and (7) the effects of antidepressant drugs on sleep and circadian rhythms. The integration of data suggests that the relationships between the circadian system and depression are well established but the underlying biology of the interactions is far from being understood. We suggest that an important factor hindering research into the underlying mechanisms is the lack of good animal models and we propose that additional efforts in that area should be made. One step in that direction could be the attempt to develop models utilizing diurnal animals which might have a better homology to humans with regard to their circadian rhythms. This article is part of a Special Issue entitled 'Anxiety and Depression'.     

Systemic amitriptyline administration does not prevent the increased thermal response induced by paradoxical sleep deprivation

Sleep deprivation has been associated with hyperalgesia in humans and in animal models. The tricyclic antidepressant amitriptyline is used as an analgesic drug in patients and in animal models of chronic pain, including that associated with spinal nerve injury. Pain hypersensitivity following paradoxical sleep deprivation (PSD) and that following peripheral nerve injury seem to share common spinal mechanisms. Accordingly, we evaluated the effects of amitriptyline (acutely and chronically administered) on the increased thermal response observed in PSD rats (72 or 96 h). Rats were evaluated for thermal sensitivity using a hot plate (52 °C or 46 °C) at 1 or 24 h after the last administration of the drug. Following the hot plate test, motor behavior was analyzed in an open field arena for a period of 5 min. Paw withdrawal latency response to temperatures of 46 °C and 52 °C was significantly lower in PSD and in 24-hour post-PSD rats than in controls and it was not modified by amitriptyline (3, 10 and 30 mg/kg). Analgesic effects and reduced motor behavior were only observed in control groups. Overall, these findings indicate that a period of PSD can influence pain modulatory mechanisms, and that amitriptyline action is insufficient to reduce PSD-enhanced thermal sensitivity.     

Sustained stress-induced changes in mice as a model for chronic depression

Rationale  

Major depression is a chronic disabling disorder, often preceded by stress. Despite emerging clinical interest in mechanisms perpetuating episodes of depression and/or establishing increased vulnerability for relapse, little attention has been paid to address these aspects in experimental models. Here, we studied the long-term neuroadaptive effects of chronic mild stress (CMS) as well as the effectiveness of a course of an antidepressant treatment.     

Pharmacotherapy of insomnia

Introduction: Insomnia is one of the most prevalent sleep disorders in developed countries, being surpassed only by chronic sleep deprivation. Patients with insomnia tend to have an altered quality of life, impaired daytime functioning and an increased risk of work accidents and motor vehicle crashes. Insomnia is commonly associated with chronic medical conditions, metabolic illnesses and mental disorders (such as depression and anxiety), with which there is a dual, reciprocal relationship.

Areas covered: This paper focuses on current pharmacotherapy options for the treatment of insomnia, particularly benzodiazepine receptor agonists, which nowadays represent the mainstay of hypnotic therapy. The melatonin receptor antagonist, ramelteon, is reviewed (an alternative for some patients with only sleep-onset difficulty), as are sedating antidepressants, which are commonly used ‘off-label’ to treat insomnia, despite limited efficacy data and potential significant safety concerns. Orexin (OX) antagonists are also discussed, especially those that block OX2 or both OX1 and OX2 receptors, as these are the most promising new agents for the treatment of insomnia, with encouraging results in preliminary clinical trials.

Expert opinion: Research to evaluate and formulate treatments for insomnia is often complicated by the fact that insomnia is usually of multifactorial etiology. Understanding the molecular and receptor mechanisms involved in promoting sleep in varied disorders could provide future approaches in new drug development. In the long term, more randomized controlled trials are needed to assess both short-term and long-term effects of these medications and their efficacy in comorbid diseases that affect sleep quality or quantity.     

The sleep-improving effects of doxepin are paralleled by a normalized plasma cortisol secretion in primary insomnia

Rationale In primary care, sedating antidepressants are often used for treating insomnia, although their underlying sleep-promoting mechanisms are only incompletely understood. Since enhanced evening and nocturnal plasma cortisol levels are supposed to maintain insomniac sleep complaints, a functional link between sleep and cortisol secretion in the mode of action of antidepressants in insomnia might be suspected.Objectives We therefore investigated the effects of the tricyclic antidepressant doxepin on nocturnal sleep and plasma cortisol concentration in ten patients (age 41.3±9.5 years) with chronic primary insomnia between 1700 hours and 0800 hours.Methods Single infusions of placebo and 25 mg doxepin were applied following a double-blind, randomized cross-over design. Afterward, all patients received 25 mg doxepin p.o. for 3 weeks in an open-study design.Results Both doxepin application forms improved sleep significantly and reduced mean cortisol levels from 9.0±1.7 µg/l (single placebo i.v.) to 7.5±1.6 µg/l (single doxepin i.v.) or 7.6±2.0 µg/l (subchronic doxepin p.o.). The duration of the quiescent period of the cortisol rhythm was significantly prolonged following both doxepin administrations compared with placebo.Conclusions The results implicate that the sleep-improving effects of doxepin are mediated at least in part by a normalization of hypothalamic–pituitary–adrenal axis functions. Although in some patients rebound insomnia and specific side effects must be considered, our findings give a further rationale for the use of antidepressants in the treatment of primary insomnia.     

Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact and approaches to management

Subjective reports of sleep disturbance indicate that 70-91% of patients with post-traumatic stress disorder (PTSD) have difficulty falling or staying asleep. Nightmares are reported by 19-71% of patients, depending on the severity of their PTSD and their exposure to physical aggression. Objective measures of sleep disturbance are inconsistent, with some studies that used these measures indicating poor sleep and others finding no differences compared with non-PTSD controls. Future research in this area may benefit from examining measures of instability in the microstructure of sleep. Additionally, recent findings suggest that sleep disordered breathing (SDB) and sleep movement disorders are more common in patients with PTSD than in the general population and that these disorders may contribute to the brief awakenings, insomnia and daytime fatigue in patients with PTSD. Overall, sleep problems have an impact on the development and symptom severity of PTSD and on the quality of life and functioning of patients. In terms of treatments, SSRIs are commonly used to treat PTSD, and evidence suggests that they have a small but significant positive effect on sleep disruption. Studies of serotonin-potentiating non-SSRIs suggest that nefazodone and trazodone lead to significant reductions in insomnia and nightmares, whereas cyproheptadine may exacerbate sleep problems in patients with PTSD. Prazosin, a centrally acting alpha1-adrenoceptor antagonist, has led to large reductions in nightmares and insomnia in small studies of patients with PTSD. Augmentation of SSRIs with olanzapine, an atypical antipsychotic, may be effective for treatment-resistant nightmares and insomnia, although adverse effects can be significant. Additional medications, including zolpidem, buspirone, gabapentin and mirtazapine, have been found to improve sleep in patients with PTSD. Large randomised, placebo-controlled trials are needed to confirm the above findings. In contrast, evidence suggests that benzodiazepines, TCAs and MAOIs are not useful for the treatment of PTSD-related sleep disorders, and their adverse effect profiles make further studies unlikely. Cognitive behavioural interventions for sleep disruption in patients with PTSD include strategies targeting insomnia and imagery rehearsal therapy (IRT) for nightmares. One large randomised controlled trial of group IRT demonstrated significant reductions in nightmares and insomnia. Similarly, uncontrolled studies combining IRT and insomnia strategies have demonstrated good outcomes. Uncontrolled studies of continuous positive airway pressure for SDB in patients with PTSD show that this treatment led to significant decreases in nightmares, insomnia and PTSD symptoms. Controlled studies are needed to confirm these promising findings.