In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release f...In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.展开更多
To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive...To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.展开更多
Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of ...Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of NSSI in MDD remain elusive.Aims To review present evidence related to the potential mechanisms of NSSI in MDD.Methods According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines,articles for this systematic review were searched on Medline(through PubMed),Embase(through Elsevier),PsycINFO(through OVID)and Web of Science databases for English articles,as well as China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data,and the Chongqing VIP Chinese Science and Technology Periodical(VIP)Databases for Chinese articles published from the date of inception to 2 August 2022.Two researchers(BW,HZ)independently screened studies based on inclusion and exclusion criteria and assessed their quality.Results A total of 25157 studies were searched.Only 25 of them were ultimately included,containing 3336 subjects(1535 patients with MDD and NSSI,1403 patients with MDD without NSSI and 398 HCs).Included studies were divided into 6 categories:psychosocial factors(11 studies),neuroimaging(8 studies),stress and hypothalamic-pituitary-adrenal(HPA)axis(2 studies),pain perception(1 study),electroencephalogram(EEG)(2 studies)and epigenetics(1 study).Conclusions This systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors,aberrant brain functions and neurochemical metabolisms,HPA axis dysfunctions,abnormal pain perceptions and epigenetic alterations.展开更多
Introduction Nitrous oxide(N2O/laughing gas)has been used in medical practice as an inhalational anaesthetic and analgesic for more than 150 years.1 In the past decades,N2O exhibited increasing popularity among recrea...Introduction Nitrous oxide(N2O/laughing gas)has been used in medical practice as an inhalational anaesthetic and analgesic for more than 150 years.1 In the past decades,N2O exhibited increasing popularity among recreational drug users for its euphoric effects,potentially through its interaction with the endogenous opioid system.2 Recreational use of N2O emerged as the seventh most used drug globally in the past decade.3 The use of N2O can cause myelopathy,myocardial injury,anaemia,severe mood disorders,sensory and motor neuropathy,and psychotic symptoms.45 Prolonged N2O intake results in vitamin B12 deficiency and inhibits methionine synthetase,folate and DNA production,leading to plasma homocysteine(HCY)level elevation and bone marrow haematopoietic dysfunction.6 This study aimed to investigate the neurological symptoms of nitrous oxide use and then explore the relapse trajectory and risk factors for relapse.展开更多
Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA ...Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.展开更多
The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent f...The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.展开更多
The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain elusive.The presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some ...The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain elusive.The presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and communication.The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH.After 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal horn.Intrathecally administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns.The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro.In this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS.In this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.展开更多
Dear Editor,Pain is a common and complex clinical problem which affects 28%-50%of the general population and is responsible for large health-related costs.People with chronic pain often develop nociceptive sensitizati...Dear Editor,Pain is a common and complex clinical problem which affects 28%-50%of the general population and is responsible for large health-related costs.People with chronic pain often develop nociceptive sensitization,having mood and anxiety disorders as comorbidities.Sustained pain may alter the processing of affective information in the brain,thereby inducing anxio-depressive disorders.展开更多
Exposure therapy, an effective treatment for fear disorders, requires memory retrieval of previous horror experiences in controllable environment. However, it remains unknown whether previous fear memories have been u...Exposure therapy, an effective treatment for fear disorders, requires memory retrieval of previous horror experiences in controllable environment. However, it remains unknown whether previous fear memories have been updated [1] or inhibited [2] during the formation of new memories, as well as the underlying neural mechanisms involved (eg. the type of cells engaged in this process).展开更多
Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninv...Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice.Through the delivery of ultrasound energy to the ventral tegmental area,mice were aroused from an unconscious,anaesthetized state in this study,and this process was controlled by adjusting the ultrasound parameters.The mice in the sham group under isoflurane-induced,continuous,steady-state general anaesthesia did not regain their righting reflex.On insonation,the emergence time from inhaled isoflurane anaesthesia decreased(sham.13.63±0.53 min,ultrasound.1.5±0.19 min,p<0.001).Further,the induction time(sham.12.0±0.6 min,ultrasound.17.88±0.64 min,p<0.001)and the concentration for 50%of the maximal effect(EC50)of isoflurane(sham.0.6%,ultrasound.0.7%)increased.In addition,ultrasound stimulation reduced the recovery time in mice with traumatic brain injury(sham.30.38±1.9 min,ultrasound.7.38±1.02 min,p<0.01).This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.展开更多
Noninvasive brain stimulation includes repetitive transcranial magnetic stimulation(rTMS)and transcranial direct current stimulation(tDCS),and emerges as a prospective approach for addiction treatment in clinical prac...Noninvasive brain stimulation includes repetitive transcranial magnetic stimulation(rTMS)and transcranial direct current stimulation(tDCS),and emerges as a prospective approach for addiction treatment in clinical practices.The dorsolateral prefrontal cortex(DLPFC)is regarded as the most effective stimulation target,giving its important position in controlling cue-elicited drug craving and initiating drug abuse.In this paper,through literature searches(e.g.Pubmed,Google Scholar),34 studies(2003–2021)were identified examining the effect of rTMS,tDCS on cravings,and consumption of substance use disorders,including tobacco,alcohol,opioids,and stimulants.We summarize the main methods,designs,and effects of rTMS or tDCS that are delivered to the DLPFC on different types of addiction.We conclude that targeting DLPFC might be effective for all types of drug addiction.展开更多
基金supported by the National Natural Science Foundation of China,No.81971269 (to DP)the Science and Technology Commission of Shanghai,No.YDZX20213100001003 (to DP)。
文摘In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
基金This study was financially supported by the National Natural Science Foundation of China(81822017,82171493,52003021)the Lingang Laboratory(LG-QS-202203-10)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181715).
文摘To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.
基金This study was funded by Shanghai Science and Technology Committee(grant no.20ZR1448500,YDZX20213100001003,22YF1439100)the National Natural Science Foundation of China(grant no.82201678).
文摘Background Non-suicidal self-injury(NSSI)is a frequent and prominent phenomenon in major depressive disorder(MDD).Even though its prevalence and risk factors are relatively well understood,the potential mechanisms of NSSI in MDD remain elusive.Aims To review present evidence related to the potential mechanisms of NSSI in MDD.Methods According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines,articles for this systematic review were searched on Medline(through PubMed),Embase(through Elsevier),PsycINFO(through OVID)and Web of Science databases for English articles,as well as China National Knowledge Infrastructure(CNKI),SinoMed,Wanfang Data,and the Chongqing VIP Chinese Science and Technology Periodical(VIP)Databases for Chinese articles published from the date of inception to 2 August 2022.Two researchers(BW,HZ)independently screened studies based on inclusion and exclusion criteria and assessed their quality.Results A total of 25157 studies were searched.Only 25 of them were ultimately included,containing 3336 subjects(1535 patients with MDD and NSSI,1403 patients with MDD without NSSI and 398 HCs).Included studies were divided into 6 categories:psychosocial factors(11 studies),neuroimaging(8 studies),stress and hypothalamic-pituitary-adrenal(HPA)axis(2 studies),pain perception(1 study),electroencephalogram(EEG)(2 studies)and epigenetics(1 study).Conclusions This systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors,aberrant brain functions and neurochemical metabolisms,HPA axis dysfunctions,abnormal pain perceptions and epigenetic alterations.
基金National Natural Science Foundation of China grant(32241015,81822017)the Lingang Laboratory(LG-QS-202203-10)+1 种基金the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181715)the Shanghai Municipal Commission of Health(2022JC016).
文摘Introduction Nitrous oxide(N2O/laughing gas)has been used in medical practice as an inhalational anaesthetic and analgesic for more than 150 years.1 In the past decades,N2O exhibited increasing popularity among recreational drug users for its euphoric effects,potentially through its interaction with the endogenous opioid system.2 Recreational use of N2O emerged as the seventh most used drug globally in the past decade.3 The use of N2O can cause myelopathy,myocardial injury,anaemia,severe mood disorders,sensory and motor neuropathy,and psychotic symptoms.45 Prolonged N2O intake results in vitamin B12 deficiency and inhibits methionine synthetase,folate and DNA production,leading to plasma homocysteine(HCY)level elevation and bone marrow haematopoietic dysfunction.6 This study aimed to investigate the neurological symptoms of nitrous oxide use and then explore the relapse trajectory and risk factors for relapse.
基金National Natural Science Foundation of China (grant no. 3187110331671164).
文摘Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.
基金Science Foundation of Ministry of Education of China,No.FBB011469Hangzhou Municipal Natural Science Foundation, No.0737XP39Foundation of Hong Kong Special Administrative Region(RGC)
文摘The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.
基金the National Natural Science Foundation of China(82171486)Natural Science Foundation of Shanghai to T.X.(21ZR1448400)+2 种基金the Interdisciplinary Program of Shanghai Jiao Tong University to T.X.(YG2021ZD23)General Science Foundation of Shanghai Sixth People's Hospital to T.X.(YNMS202114)the Young Scholarship Program of the National Natural Science Foundation of China to Xiaqing Ma(82201366)and by Shanghai Sailing Program(21YF1434200).
文摘The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain elusive.The presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and communication.The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH.After 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal horn.Intrathecally administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns.The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro.In this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS.In this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.
基金supported by the National Natural Foundation of China(81571326 and 81501153)the Startup Funding of Shanghai Mental Health Center(2017-kyqd-01)+4 种基金Feixiang Personnel Training Program of Shanghai Mental Health Center(2018-FX-02)Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)Natural Science Research Projects in Anhui Universities(KJ2020A0218)Applied Medicine Research Project of Hefei Health Committee(Hwk2020zd0016,AHWJ2021a036)Funding of Key Research and Development Projects of Anhui Province(2022e07020002).
文摘Dear Editor,Pain is a common and complex clinical problem which affects 28%-50%of the general population and is responsible for large health-related costs.People with chronic pain often develop nociceptive sensitization,having mood and anxiety disorders as comorbidities.Sustained pain may alter the processing of affective information in the brain,thereby inducing anxio-depressive disorders.
文摘Exposure therapy, an effective treatment for fear disorders, requires memory retrieval of previous horror experiences in controllable environment. However, it remains unknown whether previous fear memories have been updated [1] or inhibited [2] during the formation of new memories, as well as the underlying neural mechanisms involved (eg. the type of cells engaged in this process).
基金supported by the National Natural Science Foundation of China(Grant No.11904380,No.81771430)Guangdong Grant“Key Technologies for Treatment of Brain Disorders”(No.2018B030332001,No.2018B030331001)+1 种基金Shenzhen Basic Science Research(JCYJ20200109105622824,JCYJ20200109110006136)Youth Innovation Promotion Association CAS(2018393,2020358).
文摘Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice.Through the delivery of ultrasound energy to the ventral tegmental area,mice were aroused from an unconscious,anaesthetized state in this study,and this process was controlled by adjusting the ultrasound parameters.The mice in the sham group under isoflurane-induced,continuous,steady-state general anaesthesia did not regain their righting reflex.On insonation,the emergence time from inhaled isoflurane anaesthesia decreased(sham.13.63±0.53 min,ultrasound.1.5±0.19 min,p<0.001).Further,the induction time(sham.12.0±0.6 min,ultrasound.17.88±0.64 min,p<0.001)and the concentration for 50%of the maximal effect(EC50)of isoflurane(sham.0.6%,ultrasound.0.7%)increased.In addition,ultrasound stimulation reduced the recovery time in mice with traumatic brain injury(sham.30.38±1.9 min,ultrasound.7.38±1.02 min,p<0.01).This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.
文摘Noninvasive brain stimulation includes repetitive transcranial magnetic stimulation(rTMS)and transcranial direct current stimulation(tDCS),and emerges as a prospective approach for addiction treatment in clinical practices.The dorsolateral prefrontal cortex(DLPFC)is regarded as the most effective stimulation target,giving its important position in controlling cue-elicited drug craving and initiating drug abuse.In this paper,through literature searches(e.g.Pubmed,Google Scholar),34 studies(2003–2021)were identified examining the effect of rTMS,tDCS on cravings,and consumption of substance use disorders,including tobacco,alcohol,opioids,and stimulants.We summarize the main methods,designs,and effects of rTMS or tDCS that are delivered to the DLPFC on different types of addiction.We conclude that targeting DLPFC might be effective for all types of drug addiction.
