Social causation or social selection? The longitudinal interrelationship between poverty and depressive symptoms in China.
- 作者列表："Jin Y","Zhu D","He P
RATIONALE:To our knowledge, no prior studies have investigated these bidirectional pathways between poverty and depressive symptoms to identify potential mechanisms. OBJECTIVE:This study aimed to investigate the interrelationship between poverty and depressive symptoms by examining two causal theories: social causation, which claims that the condition of poverty causes mental health disorders, and social selection, which suggests that those with poor mental health are more likely to drift into poverty. METHOD:We obtained data from 17,250 adults aged 45 years or above from the China Health and Retirement Longitudinal Studies, first conducted in 2011-2012. Participants were tracked for 4 years, with baseline measurements taken as well as two 2-year follow-up visits. Structural equation models were used to examine the pathways in two directions at baseline, 2-year follow-up and 4-year follow-up. RESULTS:We found significant total effects and indirect effects of poverty on depressive symptoms at baseline, which were mediated through deterioration of household living conditions, decrease in social participation, and decline in life satisfaction. In the opposite direction, depressive symptoms directly led individuals to drift into poverty at baseline and at follow-up. CONCLUSIONS:This study suggested that social causation and social selection may operate concurrently. Proactive interventions, especially ones focusing on modifiable protective factors that our findings identified as mediators in the link between poverty and depression, are urgently needed to break the vicious cycle of poverty and depression and create a virtuous cycle of increasing returns.
理由: 据我们所知，之前没有研究调查贫困和抑郁症状之间的这些双向途径来确定潜在的机制。 目的: 本研究旨在通过检验两种因果理论来探讨贫困和抑郁症状之间的相互关系: 社会因果关系，声称贫困状况导致精神卫生障碍，以及社会选择, 这表明那些有贫穷精神卫生的人更容易陷入贫困。 方法: 我们从 17,250-2011 首次进行的中国健康和退休纵向研究中获得了 2012 名 45 岁或以上成年人的数据。对参与者进行了 4 年的跟踪，进行了基线测量以及两次 2 年的随访。使用结构方程模型在基线、 2 年随访和 4 年随访时检查两个方向的通路。 结果: 我们发现基线时贫困对抑郁症状有显著的总效应和间接效应，这些效应是通过家庭生活条件恶化、社会参与减少和生活满意度下降来介导的。相反的方向是，抑郁症状直接导致个体在基线和随访时陷入贫困。 结论: 本研究提示社会因果关系和社会选择可能同时运作。积极的干预措施，特别是那些关注我们的发现被确定为贫困和抑郁之间联系的调解人的可改变的保护因素, 迫切需要打破贫困和抑郁的恶性循环，创造回返增加的良性循环。
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.