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Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles. 具有各种抗焦虑、抗抑郁或促进认知特征的新型苯二氮卓类配体。
Pub Date : 2019-04-01 DOI: 10.1159/000496086
Thomas D Prevot, Guanguan Li, Aleksandra Vidojevic, Keith A Misquitta, Corey Fee, Anja Santrac, Daniel E Knutson, Michael Rajesh Stephen, Revathi Kodali, Nicolas M Zahn, Leggy A Arnold, Petra Scholze, Janet L Fisher, Bojan D Marković, Mounira Banasr, James M Cook, Miroslav Savic, Etienne Sibille

Altered gamma-aminobutyric acid (GABA) function is consistently reported in psychiatric disorders, normal aging, and neurodegenerative disorders and reduced function of GABA interneurons is associated with both mood and cognitive symptoms. Benzodiazepines (BZ) have broad anxiolytic, but also sedative, anticonvulsant and amnesic effects, due to nonspecific GABA-A receptor (GABAA-R) targeting. Varying the profile of activity of BZs at GABAA-Rs is predicted to uncover additional therapeutic potential. We synthesized four novel imidazobenzodiazepine (IBZD) amide ligands and tested them for positive allosteric modulation at multiple α-GABAA-R (α-positive allosteric modulators), pharmacokinetic properties, as well as anxiolytic and antidepressant activities in adult mice. Efficacy at reversing stress-induced or age-related working memory deficits was assessed using a spontaneous alternation task. Diazepam (DZP) was used as a control. Three ligands (GL-II-73, GL-II-74, and GL-II-75) demonstrated adequate brain penetration and showed predictive anxiolytic and antidepressant efficacies. GL-II-73 and GL-II-75 significantly reversed stress-induced and age-related working memory deficits. In contrast, DZP displayed anxiolytic but no antidepressant effects or effects on working memory. We demonstrate distinct profiles of anxiolytic, antidepressant, and/or pro-cognitive activities of newly designed IBZD amide ligands, suggesting novel therapeutic potential for IBZD derivatives in depression and aging.

γ -氨基丁酸(GABA)功能的改变在精神疾病、正常衰老和神经退行性疾病中一直有报道,GABA中间神经元功能的降低与情绪和认知症状有关。苯二氮卓类药物(BZ)由于非特异性gabaa - a受体(GABAA-R)靶向,具有广泛的抗焦虑,镇静,抗惊厥和遗忘作用。改变BZs在GABAA-Rs上的活性谱预计会发现额外的治疗潜力。合成了四种新型咪唑苯二氮卓(IBZD)酰胺配体,并对它们在α-GABAA-R (α-阳性变构调节剂)下的正变构调节、药代动力学特性、抗焦虑和抗抑郁活性进行了测试。使用自发交替任务评估逆转压力诱导或年龄相关的工作记忆缺陷的有效性。安定(DZP)作为对照。三种配体(GL-II-73、GL-II-74和GL-II-75)显示出足够的脑穿透性,并显示出预测的抗焦虑和抗抑郁功效。GL-II-73和GL-II-75显著逆转压力诱导和年龄相关的工作记忆缺陷。相比之下,DZP表现出抗焦虑作用,但没有抗抑郁作用或对工作记忆的影响。我们证明了新设计的IBZD酰胺配体具有不同的抗焦虑、抗抑郁和/或促认知活性,这表明IBZD衍生物在抑郁症和衰老方面具有新的治疗潜力。
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引用次数: 56
Transcriptional Changes following Cellular Knockdown of the Schizophrenia Risk Gene SETD1A Are Enriched for Common Variant Association with the Disorder. 精神分裂症风险基因SETD1A细胞敲低后的转录变化富集于与该疾病相关的常见变异。
Pub Date : 2019-04-01 Epub Date: 2019-03-25 DOI: 10.1159/000497181
Darren Cameron, Derek J Blake, Nicholas J Bray, Matthew J Hill

Loss of function mutations in SETD1A are the first experiment-wide significant findings to emerge from exome sequencing studies of schizophrenia. Although SETD1A is known to encode a histone methyltransferase, the consequences of reduced S ETD1A activity on gene expression in neural cells have, to date, been unknown. To explore transcriptional changes through which genetic perturbation of SETD1A could confer risk for schizophrenia, we have performed genome-wide gene expression profiling of a commonly used human neuroblastoma cell line in which SETD1A expression has been experimentally reduced using RNA interference (RNAi). We identified 1,031 gene expression changes that were significant in two separate RNAi conditions compared with control, including effects on genes of known neurodevelopmental importance such as DCX and DLX5. Genes that were differentially expressed following SETD1A knockdown were enriched for annotation to metabolic pathways, peptidase regulator activity and integrin-mediated regulation of cell adhesion. Moreover, differentially expressed genes were enriched for common variant association with schizophrenia, suggesting a degree of molecular convergence between this rare schizophrenia risk factor and susceptibility variants for the disorder operating more generally.

SETD1A的功能突变缺失是精神分裂症外显子组测序研究中出现的第一个实验范围内的重大发现。尽管已知SETD1A编码组蛋白甲基转移酶,但迄今为止,尚不清楚SETD1A活性降低对神经细胞中基因表达的影响。为了探索SETD1A基因扰动可能导致精神分裂症风险的转录变化,我们对一种常用的人类神经母细胞瘤细胞系进行了全基因组基因表达谱分析,在这种细胞系中,通过RNA干扰(RNAi)实验降低了SETD1A的表达。我们发现,与对照组相比,在两种不同的RNAi条件下,1031个基因表达发生了显著变化,包括对已知神经发育重要性基因(如DCX和DLX5)的影响。SETD1A敲低后差异表达的基因被富集,用于注释代谢途径、肽酶调节活性和整合素介导的细胞粘附调节。此外,与精神分裂症相关的常见变异富集了差异表达基因,这表明这种罕见的精神分裂症危险因素与更普遍的精神分裂症易感性变异之间存在一定程度的分子趋同。
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引用次数: 5
Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder. 精神分裂症和双相情感障碍中线粒体和核 DNA 之间的新型复杂相互作用。
Pub Date : 2019-03-01 Epub Date: 2019-02-05 DOI: 10.1159/000495658
Anton Schulmann, Euijung Ryu, Vanessa Goncalves, Brandi Rollins, Michael Christiansen, Mark A Frye, Joanna Biernacka, Marquis P Vawter

Mitochondrial dysfunction has been associated with schizophrenia (SZ) and bipolar disorder (BD). This review examines recent publications and novel associations between mitochondrial genes and SZ and BD. Associations of nuclear-encoded mitochondrial variants with SZ were found using gene- and pathway-based approaches. Two control region mitochondrial DNA (mtDNA) SNPs, T16519C and T195C, both showed an association with SZ and BD. A review of 4 studies of A15218G located in the cytochrome B oxidase gene (CYTB, SZ = 11,311, control = 35,735) shows a moderate association with SZ (p = 2.15E-03). Another mtDNA allele A12308G was nominally associated with psychosis in BD type I subjects and SZ. The first published study testing the epistatic interaction between nuclear-encoded and mitochondria-encoded genes demonstrated evidence for potential interactions between mtDNA and the nuclear genome for BD. A similar analysis for the risk of SZ revealed significant joint effects (34 nuclear-mitochondria SNP pairs with joint effect p ≤ 5E-07) and significant enrichment of projection neurons. The mitochondria-encoded gene CYTB was found in both the epistatic interactions for SZ and BD and the single SNP association of SZ. Future efforts considering population stratification and polygenic risk scores will test the role of mitochondrial variants in psychiatric disorders.

线粒体功能障碍与精神分裂症(SZ)和双相情感障碍(BD)有关。本综述探讨了线粒体基因与精神分裂症和躁狂症之间最新发表的文章和新的关联。通过基于基因和通路的方法发现了核编码线粒体变异与 SZ 的关联。两个控制区线粒体 DNA (mtDNA) SNPs(T16519C 和 T195C)均显示与 SZ 和 BD 有关。对位于细胞色素 B 氧化酶基因(CYTB,SZ = 11,311 例,对照 = 35,735 例)的 A15218G 的 4 项研究进行的回顾显示,该基因与 SZ 有中度关联(p = 2.15E-03)。另一个 mtDNA 等位基因 A12308G 名义上与 BD I 型受试者和 SZ 的精神病有关。首次发表的测试核编码基因与线粒体编码基因之间表观相互作用的研究显示,有证据表明 mtDNA 与核基因组之间存在潜在的 BD 相互作用。对 SZ 风险进行的类似分析显示了显著的联合效应(34 个核-线粒体 SNP 对的联合效应 p ≤ 5E-07)和投射神经元的显著富集。线粒体编码基因 CYTB 在 SZ 和 BD 的表观相互作用和 SZ 的单 SNP 关联中均有发现。考虑到人群分层和多基因风险评分,未来的研究工作将检验线粒体变异在精神疾病中的作用。
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引用次数: 0
Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia. 雄激素受体 CAG 三核苷酸重复长度和雷洛昔芬治疗与精神分裂症患者睾酮水平和感知压力的性别特异性关系
Pub Date : 2019-03-01 Epub Date: 2018-11-20 DOI: 10.1159/000495062
Samantha J Owens, Thomas W Weickert, Tertia D Purves-Tyson, Ellen Ji, Christopher White, Cherrie Galletly, Dennis Liu, Maryanne O'Donnell, Cynthia Shannon Weickert

Lower testosterone levels are associated with greater negative symptoms in men with schizophrenia. Testosterone signals via androgen receptor (AR). A functional variant in the AR gene (CAG trinucleotide repeat polymorphism) is associated with circulating testosterone and mood-related symptoms in healthy people. Raloxifene increases testosterone in healthy males and reduces symptom severity and improves cognition in schizophrenia; however, whether raloxifene increases testosterone in men with schizophrenia is unknown. We assessed the interaction of a functional AR gene variant and adjunctive raloxifene on peripheral testosterone and symptom severity in schizophrenia. Patients with schizophrenia (59 males and 38 females) participated in a randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene (120 mg/day). Healthy adults (46 males and 41 females) were used for baseline comparison. Baseline circulating testosterone was decreased in male patients compared to male controls and positively correlated with CAG repeat length in male controls and female patients. Male patients with short, compared to long, CAG repeat length had higher stress scores. Raloxifene treatment increased testosterone in male patients, but was unrelated to AR CAG repeat length, suggesting that raloxifene's effects may not depend on AR activity. Sex-specific alterations of the relationship between AR CAG repeat length and testosterone suggest that altered AR activity may impact perceived stress in men with schizophrenia.

睾酮水平较低与男性精神分裂症患者的阴性症状较重有关。睾酮通过雄激素受体(AR)发出信号。AR 基因的一个功能变异(CAG 三核苷酸重复多态性)与健康人的循环睾酮和情绪相关症状有关。雷洛昔芬可增加健康男性体内的睾酮,减轻精神分裂症患者的症状严重程度并改善其认知能力;然而,雷洛昔芬是否可增加精神分裂症男性患者体内的睾酮尚不清楚。我们评估了功能性 AR 基因变异和辅助性雷洛昔芬对精神分裂症患者外周睾酮和症状严重程度的相互作用。精神分裂症患者(59 名男性和 38 名女性)参加了一项随机、双盲、安慰剂对照、交叉试验,该试验采用的是雷洛昔芬辅助疗法(120 毫克/天)。健康成年人(46 名男性和 41 名女性)被用于基线对比。与男性对照组相比,男性患者的基线循环睾酮降低,男性对照组和女性患者的基线循环睾酮与 CAG 重复长度呈正相关。与长CAG重复序列相比,短CAG重复序列男性患者的压力评分更高。雷洛昔芬治疗可增加男性患者的睾酮,但与AR CAG重复长度无关,这表明雷洛昔芬的作用可能并不依赖于AR活性。AR CAG重复长度与睾酮之间关系的性别特异性改变表明,AR活性的改变可能会影响男性精神分裂症患者对压力的感知。
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引用次数: 0
Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches. 精神分裂症的表观遗传因素:机制和实验方法。
Pub Date : 2019-03-01 Epub Date: 2019-02-15 DOI: 10.1159/000495063
Melanie Föcking, Benjamin Doyle, Nayla Munawar, Eugene T Dillon, David Cotter, Gerard Cagney

Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in genomewide screens, suggesting a role for epigenetic effects. Rather, large numbers of weakly acting loci may cumulatively increase disease risk, including several mapping to epigenetic pathways. In this review, we discuss mechanisms of epigenetic regulation and evidence for an epigenetic contribution to disease phenotype. We further describe the range of experimental tools currently available to study epigenetic effects associated with the disease.

精神分裂症是一种慢性精神障碍,尽管经过了几十年的研究,人们对其仍知之甚少。许多因素已被发现导致发病,包括神经发育障碍、遗传风险和环境损害,但没有单一的根本原因出现。虽然来自双胞胎研究的证据表明有很强的遗传成分,但在全基因组筛选中发现的单个位点很少,这表明有表观遗传效应的作用。相反,大量的弱作用基因座可能会累积增加疾病风险,包括一些映射到表观遗传途径的基因座。在这篇综述中,我们讨论了表观遗传调控的机制和表观遗传对疾病表型贡献的证据。我们进一步描述了目前可用于研究与疾病相关的表观遗传效应的实验工具的范围。
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引用次数: 17
Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder. 自杀未遂及共病性物质使用障碍患者的脑基因表达模式
Pub Date : 2019-03-01 Epub Date: 2018-11-12 DOI: 10.1159/000493940
Brenda Cabrera, Nancy Monroy-Jaramillo, Gabriel Rodrigo Fries, Roberto Cuauhtemoc Mendoza-Morales, Fernando García-Dolores, Alejandra Mendoza-Larios, Carlos Diaz-Otañez, Consuelo Walss-Bass, David Colin Glahn, Patricia Ostrosky-Wegman, Cristobal Fresno, Humberto Nicolini

Background/aim: Although individuals with substance use disorder (SUD) are at high risk of committing suicide, most studies of postmortem gene expression exclude subjects with SUD due to the potential confounding effect of drugs in the transcriptome. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in suicides with SUD is crucial in the comprehension of the interaction between both pathologies.

Methods: We evaluated the gene expression profile in the dorsolateral prefrontal area of suicides and nonsuicides with and without SUD by microarrays.

Results: We identified 222 differentially expressed genes, predominately enriched in cell proliferation in the comparison between suicides with and without SUD. When comparing the transcriptome of suicides with SUD to nonsuicides with SUD, we identified 550 differentially expressed genes, mainly enriched in oxidative phosphorylation. Differentially expressed genes (1,417) between suicides and nonsuicides without SUD were detected. Most of them were related to mitochondrial function.

Conclusion: Interaction between suicide and SUD seems to influence the expression of genes involved in glial proliferation and glutamatergic neurotransmission. These results highlight, for the first time, that suicides with SUD have a gene expression profile distinct from that of subjects with only one of these disorders.

背景/目的:虽然物质使用障碍(SUD)患者有较高的自杀风险,但由于药物在转录组中的潜在混淆作用,大多数死后基因表达研究排除了SUD患者。因此,对SUD自杀的基因表达谱知之甚少。在患有SUD的自杀患者中识别改变的生物学过程对于理解两种病理之间的相互作用至关重要。方法:采用微阵列技术对有无SUD的自杀者和非自杀者前额叶背外侧区基因表达谱进行分析。结果:在合并和未合并SUD的自杀者中,我们鉴定出222个差异表达基因,主要富集于细胞增殖。通过比较自杀者合并SUD与非自杀者合并SUD的转录组,我们发现了550个差异表达基因,主要富集于氧化磷酸化。在自杀者和非自杀者之间检测到差异表达基因(1417个)。其中大部分与线粒体功能有关。结论:自杀与SUD的相互作用可能影响神经胶质增殖和谷氨酸能神经传递相关基因的表达。这些结果首次强调,患有SUD的自杀者与仅患有其中一种疾病的自杀者具有不同的基因表达谱。
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引用次数: 18
OMICS Approaches to Unravel the Complexity of Psychiatric Disorders: Impact on Biomarker Discovery. 揭示精神疾病复杂性的组学方法:对生物标志物发现的影响。
Pub Date : 2019-03-01 Epub Date: 2018-11-19 DOI: 10.1159/000495247
Daniel Martins-de-Souza
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引用次数: 1
X-Aptamer Technology Identifies C4A and ApoB in Blood as Potential Markers for Schizophrenia. x -适体技术鉴定血液中的C4A和ApoB是精神分裂症的潜在标志物。
Pub Date : 2019-03-01 Epub Date: 2018-10-10 DOI: 10.1159/000492331
Consuelo Walss-Bass, Ganesh L R Lokesh, Elena Dyukova, David G Gorenstein, David L Roberts, Dawn Velligan, David E Volk

The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech-nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients (n = 60) compared to controls (n = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that bound with high specificity to each target group. Based on this, we synthesized two unique X-aptamer sequences, and specific proteins pulled down from the patient and control groups by these X-aptamers were identified by mass spectrometry. We identified two protein biomarkers, complement component C4A and ApoB, upregulated in plasma samples from schizophrenia patients. ELISA validation suggested that the observed differences in C4 levels in patients are likely due to the presence of the illness itself, while ApoB may be a marker of antipsychotic-induced alterations. These studies highlight the utility of the X-aptamer technology in the identification of biomarkers for schizophrenia that will advance our understanding of the pathophysiological mechanisms of this disorder.

蛋白质组学作为基因组学方法的一个有希望的替代方法,正在迅速获得领域,以努力解开精神分裂症和其他精神疾病的复杂分子机制。x -适体技术已经成为一种新的蛋白质组学方法,用于高灵敏度分析,我们假设该技术将在精神分裂症患者(n = 60)的血浆样本中识别出与对照组(n = 20)相比独特的分子特征。利用x -适体珠的组合文库,我们开发了一种基于双色流式细胞仪的方法来鉴定对每个目标群体具有高特异性结合的特异性x -适体。在此基础上,我们合成了两个独特的x -适体序列,并通过质谱法鉴定了这些x -适体从患者和对照组中提取的特定蛋白质。我们发现了两种蛋白质生物标志物,补体成分C4A和ApoB,在精神分裂症患者的血浆样本中上调。ELISA验证表明,患者中观察到的C4水平差异可能是由于疾病本身的存在,而载脂蛋白b可能是抗精神病药物引起的改变的标志。这些研究突出了x适体技术在鉴定精神分裂症生物标志物方面的应用,这将促进我们对这种疾病的病理生理机制的理解。
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引用次数: 17
Ketamine's Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice. 氯胺酮对小鼠谷氨酸能和gaba能系统的影响:蛋白质组学和代谢组学研究。
Pub Date : 2019-03-01 Epub Date: 2018-11-15 DOI: 10.1159/000493425
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Christiana Labermaier, Giuseppina Maccarrone, Kathryn S Lilley, Marianne Mueller, Christoph W Turck

Ketamine, a noncompetitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect and is used for patients experiencing treatment-resistant depression. We carried out a time-dependent targeted mass spectrometry-based metabolomics profiling analysis combined with a quantitative based on in vivo 15N metabolic labeling proteome comparison of ketamine- and vehicle-treated mice. The metabolomics and proteomics datasets were used to further elucidate ketamine's mode of action on the gamma-aminobutyric acid (GABA)ergic and glutamatergic systems. In addition, myelin basic protein levels were analyzed by Western Blot. We found altered GABA, glutamate and glutamine metabolite levels and ratios as well as increased levels of putrescine and serine - 2 positive modulators of the NMDAR. In addition, GABA receptor (GABAR) protein levels were reduced, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit Gria2 protein levels were increased upon ketamine treatment. The significantly altered metabolite and protein levels further significantly correlated with the antidepressant-like behavior, which was assessed using the forced swim test. In conclusion and in line with previous research, our data indicate that ketamine impacts the AMPAR subunit Gria2 and results in decreased GABAergic inhibitory neurotransmission leading to increased excitatory neuronal activity.

氯胺酮是一种非竞争性、电压依赖性n -甲基-d -天冬氨酸受体(NMDAR)拮抗剂,已被证明具有快速的抗抑郁作用,可用于治疗难治抑郁症的患者。我们进行了一项基于时间依赖性靶向质谱的代谢组学分析,并结合了基于体内15N代谢标记的定量的氯胺酮处理和药物处理小鼠的蛋白质组比较。利用代谢组学和蛋白质组学数据集进一步阐明氯胺酮对γ -氨基丁酸(GABA)能和谷氨酸能系统的作用模式。Western Blot检测髓鞘碱性蛋白水平。我们发现GABA、谷氨酸和谷氨酰胺代谢物的水平和比例发生了变化,NMDAR的腐胺和丝氨酸- 2阳性调节剂的水平也有所增加。此外,经氯胺酮处理后,GABA受体(GABAR)蛋白水平降低,而α -氨基-3-羟基-5-甲基-4-异恶唑油酸受体(AMPAR)亚基Gria2蛋白水平升高。显著改变的代谢物和蛋白质水平进一步与抗抑郁样行为显著相关,这是通过强迫游泳测试来评估的。综上所述,与之前的研究一致,我们的数据表明氯胺酮影响AMPAR亚基Gria2,导致gaba能抑制性神经传递减少,导致兴奋性神经元活动增加。
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引用次数: 17
Exercise Reduces Salivary Morning Cortisol Levels in Patients with Depression. 运动可降低抑郁症患者早晨唾液皮质醇水平。
Pub Date : 2019-02-01 Epub Date: 2018-12-19 DOI: 10.1159/000494699
Md Shafiqur Rahman, Xuan Zhao, Jia Jia Liu, Enid Quintana Torres, Babylonia Tibert, Parvin Kumar, Viktor Kaldo, Nils Lindefors, Yvonne Forsell, Catharina Lavebratt

Purpose of the study: Cortisol hypersecretion plays a role in depression pathophysiology. Internet-based cognitive behavioural therapy (ICBT) and physical exercise (PE) are new treatment alternatives for depression, and their long-lasting effect on cortisol is unknown. We investigated cortisol level changes after 12 weeks of ICBT, PE or treatment as usual (TAU).

Procedures: The present pre-post repeated measure study analysed data derived from a randomised controlled trial evaluating the effects of 12 weeks' interventions of ICBT, PE and TAU in depressed primary care patients (Sweden 2011-2013) and aimed at prospectively evaluating the within-group effects of ICBT, PE and TAU on diurnal salivary cortisol levels in a small representative subsample (n = 56, 38 and 27, respectively).

Results: We found a marked flattening of the diurnal cortisol slope (p = 0.004) and a reduced cortisol level at awakening (p = 0.017) after 12 weeks of PE treatment. No apparent effects of ICBT or TAU interventions were seen on diurnal cortisol levels.

Conclusions and message: PE reduced the rate of cortisol level decline across the day in depressed adults. ICBT and TAU treatments had no detectable effects on diurnal cortisol levels. Larger samples are required for the detection and comparison of smaller effects of PE, ICBT and TAU on diurnal cortisol levels.

研究目的:皮质醇高分泌在抑郁症病理生理中起作用。基于互联网的认知行为疗法(ICBT)和体育锻炼(PE)是治疗抑郁症的新选择,它们对皮质醇的长期影响尚不清楚。我们研究了ICBT、PE或常规治疗(TAU) 12周后皮质醇水平的变化。本研究分析了来自一项随机对照试验的数据,该试验评估了ICBT、PE和TAU对抑郁症初级保健患者12周干预的效果(瑞典2011-2013),旨在前瞻性评估ICBT、PE和TAU对小代表性亚样本(n = 56、38和27)每日唾液皮质醇水平的组内影响。结果:我们发现在PE治疗12周后,皮质醇的日斜率明显变平(p = 0.004),觉醒时皮质醇水平降低(p = 0.017)。未观察到ICBT或TAU干预对日皮质醇水平的明显影响。结论和信息:PE降低了抑郁成年人全天皮质醇水平下降的速度。ICBT和TAU治疗对日皮质醇水平没有可检测到的影响。需要更大的样本来检测和比较PE、ICBT和TAU对日皮质醇水平的较小影响。
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引用次数: 5
期刊
Molecular Neuropsychiatry
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