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,psychede...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.展开更多
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....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.展开更多
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 pee...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.展开更多
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...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.展开更多
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. Ho...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.展开更多
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 le...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.展开更多
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）, s...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.展开更多
The blood-brain barrier （BBB） is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed mo...The blood-brain barrier （BBB） is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein I （DMP1）-proteoglycan （PG）, which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMPI-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 （S89） in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine （S89G）, which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that reg- ulated BBB formation, but also assigned a new function to DMP1-PG.展开更多
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 influe...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.展开更多
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 ...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 st...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.展开更多
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 numb...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.展开更多
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 different...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 NSClNPCs 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 NSCINPCs 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 NSCINPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Inter- estingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The ErkJMapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSCINPCs 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 NSCINPCs and their microenvironment in the context of the aging brain.展开更多
The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneit...The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in per- forming both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses （WGCNA）, we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neu- ronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.展开更多
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 ra...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.展开更多
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China(81271484,81471361,30900486,and 81371480)the National Basic Research Development Program(973 Program)of China(2012CB517904)the Nation Sponsored Study Abroad Program from China Scholarship Council(201506370095)
文摘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.
基金We thank Dr. Chunlin Qin （Bayler colleage of dentistry, Texas A＆M University） for providing us DMP1 antibody. This study was supported by China National Key Research and Development Program （2016YFA0100801 YS）, and the National Natural Science Foundation of China （Grant Nos. 8133030 YS and 31620103904 YS）, and grants： 2016YFC102705 YS 2014BAI04B07 WZL+1 种基金 81470715 YS TJ1504219036 WZL： 2017BR009 YS.
文摘The blood-brain barrier （BBB） is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein I （DMP1）-proteoglycan （PG）, which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMPI-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 （S89） in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine （S89G）, which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that reg- ulated BBB formation, but also assigned a new function to DMP1-PG.
基金National Key Basic Research Program from MOST, China (Nos. 2016YFA0100801 and 2014CB964602)the National Natural Science Foundation of China (Grant Nos. 81330030, 31620103904 and 81650110524)+1 种基金the National Institutes of Health (NIH5R21NS095184-02)the "RNAseq on Single Cell and beyond Core "in the Developme ntal Disabilities Research Center (NIH5U54HD087101-02) at University of California Los Angeles.
文摘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.
文摘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.
基金The research was supported by USAID Grant No.PCE-G-00-98-00036-00National Institutes of Health-Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH-(NICHD)1R01HD57646-01A1(CFDA#93.865),5R01HD057646-04“Increasing Animal Source Foods in Diets of HIV-infected Kenyan Women and Their Children”+2 种基金Center for HIV Identification,Prevention,and Treatment(CHIPTS)NIMH grant P30MH058107UCLA Center for AIDS Research(CFAR)grant 5P30AI028697,Core HBeef Checkoff,Heifer Project International,as well as internal support from Indiana University,UCLA,and Moi University.
文摘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.
文摘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.
基金This study is supported by the National Key research and development program(2016YFA 0100801)the Natural Science Foundation of China(31930044,31725012,31620103904)+2 种基金the Foundation of Shanghai Municipal Education Commission(2019-01-07-00-07-E00062)the Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)the Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)and ZJ Lab to Y.-C.Y.
文摘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.
文摘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.
基金This study was supported by China National Key Research and Development Program （2016YFA0100801 YS）, and the National Natural Science Foundation of China （Grant Nos. 8133030 YS and 31620103904 YS）, and grants： 2016YFC102705 YS 2014BAI04B07 WZL+1 种基金 81470715 YSTJ1504219036 WZL.
文摘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 NSClNPCs 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 NSCINPCs 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 NSCINPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Inter- estingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The ErkJMapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSCINPCs 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 NSCINPCs and their microenvironment in the context of the aging brain.
基金The online version of this article （doi：10.1007/s13238-016-0247-8） contains supplementary material, which is available to authorized users.This work was supported by the National Basic Research Program （973 Program） （No. 2012CB966303）, the National Natural Science Foundation of China （Grant Nos. 81330030, 91319309, and 31271371）, the Science and Technology Department of Yunnan Province （Grant 2012HA013）, the Yunnan Basic Research Projects （Grant 2014FC004）, and the Doctoral Tutor of Education Department of Shanghai, China （Grant 20130072110021 ）, grants from NASAD： BRN ＆ BEHV RES FND 23072, NIH R21：IR21NS095184-01 and finally, a fellowship from China Scholarship Council to X. -Y.C.
文摘The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming vari- ous neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in per- forming both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses （WGCNA）, we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neu- ronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.
基金supported by Ministry of Science and Technology of China(Grants 2017YFC1104001,2017YFC1104002,2020YFC2002804)National Natural Science Foundation of China(Grants 31900980,31970970,31730030,81941011,31971279,31771053,82030035,31900749)+5 种基金Beijing Science and Technology Program(Grant Z181100001818007)Natural Science Foundation of Beijing Municipality(Grant KZ201810025030,7222004)Priority of Shanghai Key Discipline of Medicine(Grant 2017ZZ02020)Foundation of Shanghai Municipal Education Commission(Grant 2019-01-07-00-07-E00055)the Key R&D Program of Jiangsu(Grant BE2020026)Fundamental Research Funds for Central Public Welfare Research Institutes(Grant 2022CZ-12).
文摘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.
