- 作者列表："Parás-Bravo P","Paz-Zulueta M","Boixadera-Planas E","Fradejas-Sastre V","Palacios-Ceña D","Fernández-de-Las-Peñas C","Alonso-Blanco C
:The complexity of the diagnosis and treatment of cancer means that it is often associated with anxiety symptoms. The aim of our study was to further our understanding of the oncological process and the presence of anxiety symptoms, from a gender perspective. A cross-sectional study was performed, examining 402 medical records obtained by simple random sampling of oncology patients at a hospital in northern Spain from July 2012 to July 2014. Data collection took place between February and May 2015. Psychiatric and sociodemographic variables were gathered, as well as pain variables and information regarding the oncological process. The data analysis included a descriptive univariate analysis and a bivariate analysis, and a logistic regression model was performed. Our results suggest that women with cancer suffer more anxiety symptoms than men with cancer. Women with anxiety symptoms represented 76.5% of all patients with anxiety. The OR of suffering anxiety symptoms between women and men was 2.43 (95% CI 1.05-5.63) (p = 0.04). A greater incidence of anxiety symptoms was found in patients with cancer pain and oncological treatment with biological therapy. Our results suggest that the gender perspective is necessary in the management of mental health in patients with cancer. Nonetheless, further studies are necessary to confirm our findings.
: 癌症诊断和治疗的复杂性意味着它往往与焦虑症状有关。我们研究的目的是从性别角度进一步了解肿瘤过程和焦虑症状的存在。进行了一项横断面研究，检查了 2012年7月至 2014年7月西班牙北部一家医院通过简单随机抽样获得的 402 份肿瘤患者病历。数据收集在 2月至 2015年5月期间进行。收集了精神病学和社会人口学变量，以及疼痛变量和关于肿瘤过程的信息。数据分析包括描述性单变量分析和双变量分析，并进行 logistic 回归模型。我们的研究结果表明，女性癌症患者比男性癌症患者遭受更多的焦虑症状。有焦虑症状的女性占所有焦虑患者的 76.5%。女性和男性患焦虑症状的 OR 为 2.43 (95% CI 1.05-5.63) (p = 0.04)。在癌症疼痛和生物治疗的肿瘤治疗患者中发现焦虑症状的发生率更高。我们的研究结果表明，性别观点在癌症患者的精神卫生管理中是必要的。尽管如此，需要进一步的研究来证实我们的发现。
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.
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.
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.