Therapeutic role of psilocybin and 3,4-methylenedioxymethamphetamine in trauma:A literature review

With the Food and Drug Administration designation in 2017 of 3,4-methylenedioxymethamphetamine(MDMA)as a breakthrough therapy in post-traumatic stress disorder and psilocybin in treatment-resistant depression,psychedelic drugs have continued to garner the attention of researchers and clinicians for their promise of unmatched,rapid improvement in a multitude of psychiatric conditions.Classic psychedelic drugs including psilocybin,lysergic acid diethylamide,and ayahuasca,as well as non-classic drugs such as MDMA and ketamine,are currently being investigated for a potential therapeutic role in trauma,depressive disorders,and other psychopathologies.However,psilocybin and MDMA each have a functional profile well-suited for integration with psychotherapy.The present review focuses on psilocybin and MDMA in psychedelic-assisted therapy(PAT),as these studies compose most of the literature pool.In this review,we discuss the current and future uses of psychedelic drugs,with an emphasis on the role of MDMA and psilocybin in PAT in the setting of trauma and related comorbidities on the efficacy of psychedelic drugs across multiple psychiatric disorders.The article concludes with thoughts for future research,such as incorporating wearables and standardization of symptom scales,therapy styles,and assessment of adverse drug reactions.

Use of technology and social media in dementia care:Current and future directions

As the population across the globe continues to dramatically increase,the prevalence of cognitive impairment and dementia will inevitably increase as well,placing increasing burden on families and health care systems.Technological advancements over the past decade provide potential benefit in not only relieving caregiver burden of caring for a loved one with dementia,but also enables individuals with dementia to age in place.Technological devices have served to improve functioning,tracking and mobility.Similarly,smartphones,tablets and the ubiquitous world wide web have facilitated the dissemination of health information to previously hard to reach populations largely through use of various social media platforms.In this review,we discuss the current and future uses of technology via devices and social media to promote healthy aging in individuals with dementia,and also limitations and challenges to consider in the future.

Impact of social isolation on behavioral health in elderly: Systematic review

AIM: To examine and compare the effects of subjective and objective social isolation on behavioral health in elderly adults.METHODS: A systematic search of Pub Med was performed for original research articles from peerreviewed journals examining one of the following topics: "Social isolation and sleep disturbance", "social isolation and depression", or "social isolation and fatigue in older adults". Studies were selected following the criteria established based on the aim of this review. Data were extracted from the articles by two independent reviewers. Due to the heterogeneity in study designs and outcome measures of the included studies, qualitative and narrative analyses were conducted.RESULTS: The set criteria were used to select a total of 16 studies for the review. Of the 16, 13 were crosssectional studies. The characteristics of study populations were identified as follows. A total of 12 studies randomly selected subjects irrespective of pre-existing health conditions. Consequently, an unspecified number of the study subjects had chronic diseases in the studies compared. In addition, cultural and ethnic backgrounds of studies in this review were diverse, and included subjects living in North America, South America, Asia, Europe, and Oceania. Both subjective and objective types of social isolation increased behavioral symptoms, such as sleep disturbance, depressive symptoms, and fatigue in older adults. Furthermore, a few recent studies reported stronger effects of subjective social isolation than objective social isolation on sleep disturbance and depressive symptoms.CONCLUSION: Social isolation affects behavioral health in older adults. Compared to the objective social isolation, subjective social isolation contributes more significantly to sleep disturbance and depression.

Emerging wearable technology applications in gastroenterology:A review of the literature

The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity,sleep quality,pain,and even gut activity.The past decade has seen the emergence of wearable devices including Fitbit,Apple Watch,AbStats,and ingestible sensors.In this review,we discuss current and future devices designed to measure sweat biomarkers,steps taken,sleep efficiency,gastric electrical activity,stomach pH,and intestinal contents.We also summarize several clinical studies to better understand wearable devices so that we may assess their potential benefit in improving healthcare while also weighing the challenges that must be addressed.

Culturally sanctioned suicide:Euthanasia,seppuku,and terrorist martyrdom

Suicide is one of the greatest concerns in psychiatric practice, with considerable efforts devoted to prevention. The psychiatric view of suicide tends to equate it with depression or other forms of mental illness. However, some forms of suicide occur independently of mental illness and within a framework of cultural sanctioning such that they aren't regarded as suicide at all. Despitepersistent taboos against suicide, euthanasia and physician-assisted suicide in the context of terminal illness is increasingly accepted as a way to preserve autonomy and dignity in the West. Seppuku, the ancient samurai ritual of suicide by self-stabbing, was long considered an honorable act of self-resolve such that despite the removal of cultural sanctioning, the rate of suicide in Japan remains high with suicide masquerading as seppuku still carried out both there and abroad. Suicide as an act of murder and terrorism is a practice currently popular with Islamic militants who regard it as martyrdom in the context of war. The absence of mental illness and the presence of cultural sanctioning do not mean that suicide should not be prevented. Culturally sanctioned suicide must be understood in terms of the specific motivations that underlie the choice of death over life. Efforts to prevent culturally sanctioned suicide must focus on alternatives to achieve similar ends and must ultimately be implemented within cultures to remove the sanctioning of self-destructive acts.

Social media and schizophrenia:An update on clinical applications

Social media has redesigned the landscape of human interaction,and data obtained through these platforms are promising for schizophrenia diagnosis and management.Recent research shows mounting evidence that machine learning analysis of social media content is capable of not only differentiating schizophrenia patients from healthy controls,but also predicting conversion to psychosis and symptom exacerbations.Novel platforms such as Horyzons show promise for improving social functioning and providing timely access to therapeutic resources.Social media is also a considerable means to assess and lessen the stigma surrounding schizophrenia.Herein,the relevant literature pertaining to social media and its clinical applications in schizophrenia over the past five years are summarized,followed by a discussion centered on user feedback to highlight future directions.Social media provides valuable contributions to a multifaceted digital phenotype that may improve schizophrenia care in the near future.

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

Schizophrenia is a severe mental disorder characterized by impaired perception,delusions,thought disorder,abnormal emotion regulation,altered motor function,and impaired drive. The default mode network(DMN),since it was first proposed in 2001,has become a central research theme in neuropsychiatric disorders,including schizophrenia. In this review,first we define the DMN and describe its functional activity,functional and anatomical connectivity,heritability,and inverse correlation with the task positive network. Second,we review empirical studies of the anatomical and functional DMN,and anti-correlation between DMN and the task positive network in schizophrenia. Finally,we review preliminary evidence about the relationship between antipsychotic medications and regulation of the DMN,review the role of DMN as a treatment biomarker for this disease,and consider the DMN effects of individualized therapies for schizophrenia.

Glycosylation of dentin matrix protein 1 is a novel key element for astrocyte maturation and BBB integrity

血大脑障碍(BBB ) 是在 endothelial 房间和星形细胞之间形成的一条紧密的边界，它在循环把大脑与大多数病原体以及神经毒素分开并且保护。然而，详细说明了涉及 BBB 的形成的分子的播放器完全不被知道。牙质矩阵蛋白质 1 (DMP1 )-proteoglycan (PG ) 被知道涉及骨头和牙质的矿化作用，也与未知功能包括大脑在软纸巾被表示。在现在的学习，我们报导 DMP1-PG 在大脑星形细胞被表示并且在 BBB 充实单位。DMP1 的唯一的 glycosylation 地点在在鼠标的蛋白质的 N 终端域是 serine89 (S89 ) 。有 DMP1 的变异的老鼠削尖把 S89 改变到 glycine (S89G ) 的变化，它蛋白质的完全根除的 glycosylation，表明的严重 BBB 混乱。DMP1 变异的鼠标的另一个品种，缺乏 DMP1 的 C 终端域，表明了正常 BBB 功能。S89G-DMP1 星形细胞的极性被破坏，房间房间粘附被松开。通过一组分析，我们发现 DMP1 glycosylation 极其在 vitro 并且在 vivo 为星形细胞成熟被要求。S89G-DMP1 变异的星形细胞没能表示 aquaporin 4 并且减少了 laminin 和 ZO1 表示，它导致了 BBB 的混乱。有趣地，在 nestin 倡导者驾驶的老鼠大脑的野类型的 DMP1-PG 的 overexpression 在野类型层次以外提高了 laminin 和 ZO1 表示并且能有效地抵抗的静脉内的导致甘露糖醇的 BBB 可逆的洞。一起拿，我们的学习不仅揭示了一个新奇元素，即， DMP1-PG，调整了 BBB 形成，而且把新功能分到 DMP1-PG。

Unbiased transcriptomic analyses reveal distinet effects of immune deficiency in CNS function with and without injury

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Tattoos as a window to the psyche:How talking about skin art can inform psychiatric practice

Tattooing the skin as a means of personal expression is a ritualized practice that has been around for centuries across many different cultures.Accordingly,the symbolic meaning of tattoos has evolved over time and is highly individualized,from both the internal perspective of the wearer and the external perspective of an observer.Within modern Western societies through the 1970 s,tattoos represented a cultural taboo,typically associated with those outside of the mainstream such as soldiers,incarcerated criminals,gang members,and others belonging to marginalized and counter-cultural groups.This paper aims to review the more recent epidemiology of tattoos in Western culture in order to establish that tattooing has become a mainstream phenomenon.We then review psychological and psychiatric aspects of tattoos,with a goal of revising outmoded stigmas about tattooing and helping clinicians working with tattooed patients to facilitate an exploration of the personal meaning of skin art and self-identity.We suggest that as a kind of augmentation of the physical exam,looking at and talking to patients about their tattoos can provide a valuable window into the psyche,informing clinical practice.

Effects of biscuit-type feeding supplementation on the neurocognitive outcomes of HIV-affected school-age children:a randomized,double-blind,controlled intervention trial in Kenya

Objective:To determine if meat or soy protein dietary supplementation will enhance the neuro-cognitive performance of HIV-affected children at-risk of malnutrition and food insecurity.Methods:A randomized,double-blind,controlled intervention trial evaluated the effect of nu-tritional supplementation on the neurocognitive outcomes of 49 HIV-affected school-age children in western Kenya.The intervention consisted in providing the mother,target child,and siblings with one of three isocaloric biscuit-type supplements-soy,wheat,or beef-on 5 days per week for 18 months.Neurocognitive outcomes of the target children were assessed by a battery of eight measures and followed up longitudinally for up to 24 months.Results:Mixed effects modeling demonstrated significant differences in the rates of increase over time among all three groups(F test degrees of freedom of 2,P<0.05)for Raven’s progressive matrices performance,but not for verbal meaning,arithmetic,digit span backward,forward,and total,embedded figure test,and Beery visual-motor integration scores.Conclusion:HIV-affected school-age children provided with soy protein supplementation showed greater improvement in nonverbal cognitive(fluid intelligence)performance compared with peers who received isocaloric beef or wheat biscuits.Soy nutrients may have an enhancing effect on neurocognitive skills in HIV-affected school-age children.

自闭症患儿反语理解力的神经学基础:韵律和语境的作用

While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.

Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2

Rett syndrome(RTT)is a progressive neurodevelop-mental disorder,mainly caused by mutations in MeCP2 and currently with no cure.We report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine density.Moreover,RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain features.Knockdown of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons,which appeared to retain partial function.Strikingly,consistent deficits in nuclear size,dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived neurons.Both neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2,strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the mutant.Our findings thus reveal stable neuronal maturation deficits and unexpectedly,graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency,which is informative for future therapeutic development.

Hypocretin(orexin) pathology in Alzheimer's disease

Alzheimer's disease(AD) is a growing health problem. It has enormous public health impact. Sleep problems show an early component of this disease. Hypocretin hasa major function in sleep-wake cycle. The total number of hypocretin neurons in the normal humans ranges from 51000-83000, located exclusively in the hypothalamus. Deficiency in hypocretins neurotransmission results in narcolepsy, Parkinson's disease, and other neurological and psychological disorders. Cerebrospinal fluid(CSF) hypocretin levels were directly related with t-tau protein amount in AD. Increased hypocretin CSF in AD suggest that hypocretin is involved in the mechanism of AD pathology.

星形胶质细胞之间的接触和生长因子信号传导的正反馈回路对星形胶质细胞成熟的调节

星形胶质细胞对于中枢神经系统的发育和功能至关重要。在大脑发育过程中,未成熟的星形胶质细胞会发生形态、分子、细胞和功能的变化以至成熟。尽管已经广泛研究了调节中枢神经系统中其他主要细胞类型(如神经元和少突胶质细胞)成熟过程的机制,但对于控制星形胶质细胞成熟的细胞和分子机制知之甚少。本研究确定了星形胶质细胞成熟的分子标志物,并建立了研究星形胶质细胞成熟机制的离体检验方法。离体条件下,成熟的星形胶质细胞表现出与在体星形胶质细胞相似的分子变化及类似的多种分子亚型。使用该系统,我们发现星形胶质细胞之间的接触强烈促进星形胶质细胞的成熟。此外,来自小胶质细胞、少突胶质细胞前体细胞或内皮细胞的分泌信号影响星形胶质细胞的一小部分基因,但不会持续改变星形胶质细胞的成熟。为了确定星形胶质细胞成熟的分子机制,我们用影响肿瘤相关基因功能的分子处理了成熟中的星形胶质细胞。我们发现肝素结合表皮生长因子样生长因子(HBEGF)和表皮生长因子受体(EGFR)信号通路的正反馈回路调节星形胶质细胞的成熟。此外,HBEGF、EGFR和肿瘤蛋白53(TP53)影响一些基因的表达,这些基因对纤毛发育,昼夜节律和突触功能至关重要。这些结果揭示了星形胶质细胞成熟的细胞和分子机制,对理解胶质母细胞瘤具有重要意义。

Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive “big-data” processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.

Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation

哺乳动物的大脑是异构的，包含形成各种各样的神经电路，感觉，运动，思维，和情感通过产生的触处的十亿个神经原和万亿。大脑的细胞的异质使学习神经电路配线的分子的逻辑困难，修剪，直到最近， transcriptome 与分辨率使基因译码规章的单个房间分析的激活，和粘性联网可能的内在的上述的电路性质。这里，我们在在文化在单个人的神经原上执行 electrophysiological 和整个染色体的 transcriptome 分析报导成功。用加权的基因 Coexpression 网络分析(WGCNA ) ，我们鉴别基因簇高度相关， neuronal 成熟由 electrophysiological 特征判定了。在涉及 ubiquitination 和 mitochondrial 功能的 neuronal 成熟和基因之间的一个紧密的连接被揭示。而且，我们识别了候选人基因的一张表，它能潜在地为 neuronal 成熟用作 biomarkers。联合 electrophysiological 记录和单个房间 transcriptome 分析将在未来用作强大的工具为神经电路功能揭开分子的逻辑。

Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar

Spinal cord injury(SCI)is a severe damage usually leading to limb dysesthesia,motor dysfunction,and other physiological disability.We have previously shown that NT3-chitosan could trigger an acute SCI repairment in rats and non-human primates.Due to the negative effect of inhibitory molecules in glial scar on axonal regeneration,however,the role of NT3-chitosan in the treatment of chronic SCI remains unclear.Compared with the fresh wound of acute SCI,how to handle the lesion core and glial scars is a major issue related to chronic-SCI repair.Here we report,in a chronic complete SCI rat model,establishment of magnetic resonancediffusion tensor imaging(MR-DTI)methods to monitor spatial and temporal changes of the lesion area,which matched well with anatomical analyses.Clearance of the lesion core via suction of cystic tissues and trimming of solid scar tissues before introducing NT3-chitosan using either a rigid tubular scaffold or a soft gel form led to robust neural regeneration,which interconnected the severed ascending and descending axons and accompanied with electrophysiological and motor functional recovery.In contrast,cystic tissue extraction without scar trimming followed by NT3-chitosan injection,resulted in little,if any regeneration.Taken together,after lesion core clearance,NT3-chitosan can be used to enable chronic-SCI repair and MR-DTI-based mapping of lesion area and monitoring of ongoing regeneration can potentially be implemented in clinical studies for subacute/chronic-SCI repair.