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Mindfulness-Based Stress Reduction for Parents Implementing Early Intervention for Autism: An RCT.

对实施自闭症早期干预的父母进行基于正念的减压: 一项 RCT。

  • 影响因子:5.00
  • DOI:10.1542/peds.2019-1895K
  • 作者列表:"Weitlauf AS","Broderick N","Stainbrook JA","Taylor JL","Herrington CG","Nicholson AG","Santulli M","Dykens EM","Juárez AP","Warren ZE
  • 发表时间:2020-04-01

BACKGROUND AND OBJECTIVES:Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up. METHODS:Participants included children (<36 months old) with autism spectrum disorder and caregivers. Participants were randomly assigned to P-ESDM only (n = 31) or P-ESDM plus MBSR (n = 30). Data were collected at baseline, midtreatment, the end of treatment, and 1, 3, and 6 months posttreatment. Multilevel models with discontinuous slopes were used to test for group differences in outcome changes over time. RESULTS:Both groups improved during active treatment in all subdomains of parent stress (β = -1.42, -1.25, -0.92; P < 0.001), depressive symptoms, and anxiety symptoms (β = -0.62 and -0.78, respectively; P < 0.05). Parents who received MBSR had greater improvements than those receiving P-ESDM only in parental distress and parent-child dysfunctional interactions (β = -1.91 and -1.38, respectively; P < 0.01). Groups differed in change in mindfulness during treatment (β = 3.15; P < .05), with P-ESDM plus MBSR increasing and P-ESDM declining. Treatment group did not significantly predict change in depressive symptoms, anxiety symptoms, or life satisfaction. Differences emerged on the basis of parent sex, child age, and child behavior problems. CONCLUSIONS:Results suggest that manualized, low-intensity stress-reduction strategies may have long-term impacts on parent stress. Limitations and future directions are described.


背景和目的: 护理系统强调父母对自闭症谱系障碍 (ASD) 儿童的干预。同时,多项研究记录了这些父母的心理困扰。这项试点纵向随机对照试验比较了父母实施的早期开始丹佛模型 (P-ESDM) 与父母的 P-ESDM 加基于正念的减压 (MBSR)。我们评估了积极治疗期间和随访时父母功能的变化。 方法: 参与者包括患有自闭症谱系障碍的儿童 (<36 个月) 和照顾者。参与者被随机分配到仅 P-ESDM (n = 31) 或 P-ESDM 加 MBSR (n = 30)。收集基线、治疗中期、治疗结束以及治疗后 1 、 3 和 6 个月的数据。使用具有不连续斜率的多水平模型检验结局随时间变化的组间差异。 结果: 两组在积极治疗期间在父母应激 (β = -1.42,-1.25,-0.92; P < 0.001) 的所有亚结构域均有改善,抑郁症状,和焦虑症状 (β 分别为-0.62 和-0.78; P <0.05)。接受 MBSR 的父母比仅接受 P-ESDM 的父母在父母困扰和亲子功能失调互动方面有更大的改善 (β 分别为-1.91 和-1.38; P <0.01)。组在治疗期间正念的变化存在差异 (β = 3.15; P <.05),P-ESDM 加 MBSR 增加,P-ESDM 下降。治疗组未显著预测抑郁症状、焦虑症状或生活满意度的变化。差异出现在父母性别、儿童年龄和儿童行为问题的基础上。 结论: 结果表明,手工化的低强度应激减轻策略可能对父母应激有长期影响。描述了局限性和未来方向。



来源期刊:Molecular psychiatry
作者列表:["Li C","Meng F","Garza JC","Liu J","Lei Y","Kirov SA","Guo M","Lu XY"]

METHODS::The adipocyte-derived hormone adiponectin has a broad spectrum of functions beyond metabolic control. We previously reported that adiponectin acts in the brain to regulate depression-related behaviors. However, its underlying neural substrates have not been identified. Here we show that adiponectin receptor 1 (AdipoR1) is expressed in the dorsal raphe nucleus (DRN) and colocalized with tryptophan hydroxylase 2 (TPH2), a marker of serotonin (5-HT) neurons. Selective deletion of AdipoR1 in 5-HT neurons induced anhedonia in male mice, as indicated by reduced female urine sniffing time and saccharin preference, and behavioral despair in female mice and enhanced stress-induced decrease in sucrose preference in both sexes. The expression levels of TPH2 were downregulated with a concurrent reduction of 5-HT-immunoreactivity in the DRN and its two major projection regions, the hippocampus and medial prefrontal cortex (mPFC), in male but not female mice lacking AdipoR1 in 5-HT neurons. In addition, serotonin transporter (SERT) expression was upregulated in both DRN projection fields of male mice but only in the mPFC of female mice. These changes presumably lead to decreased 5-HT synthesis and/or increased 5-HT reuptake, thereby reducing 5-HT transmission. The augmented behavioral responses to the selective serotonin reuptake inhibitor fluoxetine but not desipramine, a selective norepinephrine reuptake inhibitor, observed in conditional knockout male mice supports deficient 5-HT transmission underlying depression-related phenotypes. Our results indicate that adiponectin acts on 5-HT neurons through AdipoR1 receptors to regulate depression-related behaviors in a sex-dependent manner.

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作者列表:["Torretta S","Rampino A","Basso M","Pergola G","Di Carlo P","Shin JH","Kleinman JE","Hyde TM","Weinberger DR","Masellis R","Blasi G","Pennuto M","Bertolino A"]

METHODS::Multiple schizophrenia (SCZ) risk loci may be involved in gene co-regulation mechanisms, and analysis of coexpressed gene networks may help to clarify SCZ molecular basis. We have previously identified a dopamine D2 receptor (DRD2) coexpression module enriched for SCZ risk genes and associated with cognitive and neuroimaging phenotypes of SCZ, as well as with response to treatment with antipsychotics. Here we aimed to identify regulatory factors modulating this coexpression module and their relevance to SCZ. We performed motif enrichment analysis to identify transcription factor (TF) binding sites in human promoters of genes coexpressed with DRD2. Then, we measured transcript levels of a group of these genes in primary mouse cortical neurons in basal conditions and upon overexpression and knockdown of predicted TFs. Finally, we analyzed expression levels of these TFs in dorsolateral prefrontal cortex (DLPFC) of SCZ patients. Our in silico analysis revealed enrichment for NURR1 and ERR1 binding sites. In neuronal cultures, the expression of genes either relevant to SCZ risk (Drd2, Gatad2a, Slc28a1, Cnr1) or indexing coexpression in our module (Btg4, Chit1, Osr1, Gpld1) was significantly modified by gain and loss of Nurr1 and Err1. Postmortem DLPFC expression data analysis showed decreased expression levels of NURR1 and ERR1 in patients with SCZ. For NURR1 such decreased expression is associated with treatment with antipsychotics. Our results show that NURR1 and ERR1 modulate the transcription of DRD2 coexpression partners and support the hypothesis that NURR1 is involved in the response to SCZ treatment.SIGNIFICANCE STATEMENT In the present study, we provide in silico and experimental evidence for a role of the TFs NURR1 and ERR1 in modulating the expression pattern of genes coexpressed with DRD2 in human DLPFC. Notably, genetic variations in these genes is associated with SCZ risk and behavioral and neuroimaging phenotypes of the disease, as well as with response to treatment. Furthermore, this study presents novel findings on a possible interplay between D2 receptor-mediated dopamine signaling involved in treatment with antipsychotics and the transcriptional regulation mechanisms exerted by NURR1. Our results suggest that coexpression and co-regulation mechanisms may help to explain some of the complex biology of genetic associations with SCZ.

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作者列表:["Chadha R","Meador-Woodruff JH"]

METHODS::Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness may be associated with dysregulation of core intracellular processes such as signaling pathways that underlie the regulation and integration of these systems. The AKT-mTOR signaling cascade has been implicated in SZ by gene association, postmortem brain and animal studies. AKT and mTOR are serine/threonine kinases which play important roles in cell growth, proliferation, survival, and differentiation. Both AKT and mTOR require phosphorylation at specific sites for their complete activation. mTOR forms two functionally distinct multiprotein complexes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2). mTORC1 mediates ribosome biogenesis, protein translation, and autophagy, whereas mTORC2 contributes to actin dynamics. Altered protein synthesis and actin dynamics can lead to an abnormal neuronal morphology resulting in deficits in learning and memory. Currently, there is a lack of direct evidence to support the hypothesis of disrupted mTOR signaling in SZ, and we have addressed this by characterizing this signaling pathway in SZ brain. We found a reduction in AKT and mTOR protein expression and/or phosphorylation state in dorsolateral prefrontal cortex (DLPFC) from 22 pairs of SZ and matched comparison subjects. We also found reduced protein expression of GβL, a subunit protein common to both mTOR complexes. We further investigated mTOR complex-specific subunit composition and phosphorylation state, and found abnormal mTOR expression in both complexes in SZ DLPFC. These findings provide evidence that proteins associated with the AKT-mTOR signaling cascade are downregulated in SZ DLPFC.

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