Substance use disorders(SUDs)impact an estimated 300 million people worldwide,significantly impairing both health and social functioning.These disorders are marked by an inability to regulate substance use,despite the...Substance use disorders(SUDs)impact an estimated 300 million people worldwide,significantly impairing both health and social functioning.These disorders are marked by an inability to regulate substance use,despite the harmful consequences.Addiction affects various neurotransmitter systems,including dopamine,serotonin,γ-aminobutyric acid(GABA),and glutamate,each of which plays a role in the reward,stress,and self-control pathways of the brain(Koob&Volkow,2016).While significant advances have been made in neuroscience,our understanding of how these neurotransmitter systems interact and contribute to addiction is still evolving.This knowledge gap represents a significant challenge in the formulation of effective treatments for SUDs.At present,the US Food and Drug Administration(FDA)has approved pharmacological treatments for alcohol,nicotine,and opioid use disorders(Vasiliu,2022);however,no such treatments have been authorized for SUDs in general,or specifically for stimulant use disorders,such as cocaine and methamphetamine addiction.Notably,the FDA has not approved any new drugs for SUD treatment in the past 40 years.展开更多
De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental disorders.Specifically,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding...De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental disorders.Specifically,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).展开更多
Background Previous studies have shown that educational attainment(EA),intelligence and income are key factors associated with mental disorders.However,the direct effects of each factor on major mental disorders are u...Background Previous studies have shown that educational attainment(EA),intelligence and income are key factors associated with mental disorders.However,the direct effects of each factor on major mental disorders are unclear.Aims We aimed to evaluate the overall and independent causal effects of the three psychosocial factors on common mental disorders.Methods Using genome-wide association study summary datasets,we performed Mendelian randomisation(MR)and multivariable MR(MVMR)analyses to assess potential associations between the 3 factors(EA,N=766345;household income,N=392422;intelligence,N=146808)and 13 common mental disorders,with sample sizes ranging from 9907 to 807553.Inverse-variance weighting was employed as the main method in the MR analysis.Results Our MR analysis showed that(1)higher EA was a protective factor for eight mental disorders but contributed to anorexia nervosa,obsessive-compulsive disorder(OCD),bipolar disorder(BD)and autism spectrum disorder(ASD);(2)higher intelligence was a protective factor for five mental disorders but a risk factor for OCD and ASD;(3)higher household income protected against 10 mental disorders but confers risk for anorexia nervosa.Our MVMR analysis showed that(1)higher EA was a direct protective factor for attention-deficit/hyperactivity disorder(ADHD)and insomnia but a direct risk factor for schizophrenia,BD and ASD;(2)higher intelligence was a direct protective factor for schizophrenia but a direct risk factor for major depressive disorder(MDD)and ASD;(3)higher income was a direct protective factor for seven mental disorders,including schizophrenia,BD,MDD,ASD,post-traumatic stress disorder,ADHD and anxiety disorder.Conclusions Our study reveals that education,intelligence and income intertwine with each other.For each factor,its independent effects on mental disorders present a more complex picture than its overall effects.展开更多
BACKGROUND Stroke is a common disabling disease,whether it is ischemic stroke or hemorrhagic stroke,both can result in neuronal damage,leading to various manifestations of neurological dysfunction.AIM To explore of th...BACKGROUND Stroke is a common disabling disease,whether it is ischemic stroke or hemorrhagic stroke,both can result in neuronal damage,leading to various manifestations of neurological dysfunction.AIM To explore of the application value of swallowing treatment device combined with swallowing rehabilitation training in the treatment of swallowing disorders after stroke.METHODS This study selected 86 patients with swallowing disorders after stroke admitted to our rehabilitation department from February 2022 to December 2023 as research subjects.They were divided into a control group(n=43)and an observation group(n=43)according to the treatment.The control group received swallowing rehabilitation training,while the observation group received swallowing treatment device in addition to the training.Both groups underwent continuous intervention for two courses of treatment.RESULTS The total effective rate in the observation group(93.02%)was higher than that in the control group(76.74%)(P=0.035).After intervention,the oral transit time,swallowing response time,pharyngeal transit time,and laryngeal closure time decreased in both groups compared to before intervention.In the observation group,the oral transit time,swallowing response time,and pharyngeal transit time were shorter than those in the control group after intervention.However,the laryngeal closure time after intervention in the observation group was compared with that in the control group(P=0.142).After intervention,average amplitude value and duration of the genioglossus muscle group during empty swallowing and swallowing 5 mL of water are reduced compared to before intervention in both groups.After intervention,the scores of the chin-tuck swallowing exercise and the Standardized Swallowing Assessment are both reduced compared to pre-intervention levels in both groups.However,the observation group scores lower than the control group after intervention.Additionally,the Functional Oral Intake Scale scores of both groups are increased after intervention compared to pre-intervention levels,with the observation group scoring higher than the control group after intervention(P<0.001).The cumulative incidence of complications in the observation group is 9.30%,which is lower than the 27.91%in the control group(P=0.027).CONCLUSION The combination of swallowing therapy equipment with swallowing rehabilitation training can improve the muscle movement level of the genioglossus muscle group,enhance swallowing function,and prevent the occurrence of swallowing-related complications after stroke.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyl...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.展开更多
BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during or...BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.展开更多
Neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental factors.A...Neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental factors.As a result,patients often experience a decline in mobility,sensation,memory,and cognition,which can ultimately lead to a fatal outcome.The global incidence of NDDs,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis(ALS),and multiple sclerosis,is increasing.展开更多
BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chroni...BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.展开更多
In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were ...In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were findings of a 21% increase in children who displayed behavioral and conduct problems from 2019 to 2020 [2]. Early detection of neuropsychiatric and neurodevelopmental disorders in children is critical for timely intervention and improved long-term outcomes. With early intervention, there is better aptitude to support healthy development and give proper treatment to attain a better quality of life. This paper explores studies aimed at enhancing the early detection of these disorders through the use of biomarkers with the aim of creating a bridge between the worlds of research and clinical practice. The disorders in this paper specifically discussed are Major Depressive Disorder, Bipolar Disorder, and Autism Spectrum Disorder. With this bridge, we can foster collaborations and encourage further advancement in the field of early detection and intervention.展开更多
People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the ...People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.展开更多
During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increase...During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.展开更多
Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-cal...Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was f...On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.展开更多
To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,...To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,2 and over 500000 adolescent SA are reported annually in the USA due to depression.3 Risk factors for SA include gender,hormone levels,family conflict and,particularly,negative cognitive styles such as rumination.展开更多
Background Addictive disorders have gained worldwide attention.The Chinese Association of Drug Abuse Prevention and Treatment,along with the consensus panel on digital therapeutics(DTx)for addictive disorders,has publ...Background Addictive disorders have gained worldwide attention.The Chinese Association of Drug Abuse Prevention and Treatment,along with the consensus panel on digital therapeutics(DTx)for addictive disorders,has published an expert consensus on DTx for addictive disorders.1 This consensus discusses and summarises the current research and application status of DTx for addictive disorders.It identifies its clinical value,application directions,research and development principles,and future prospects.As the consensus is published in Chinese,it may not be easily accessible to an international audience.To address this,we present here an overview of the expert consensus on DTx for addictive disorders in China.The recommendations from the consensus are summarised in table 1.展开更多
Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among ...Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among children and adolescents can help identify areas of success,stagnation and emerging threats,thereby facilitating effective improvement strategies.Aims To estimate the incidence and burden trends of anxiety disorders in children and adolescents from 1990 to 2019 in 204 countries and compare the incidence and disease burden in different countries.To examine the association between anxiety disorders and social indicators(healthcare access and quality of life).Methods Data were obtained from the Global Burden of Disease Study 2019.The age-standardised incidence rates(ASIRs)and disability-adjusted life years(DALYs)were reported to assess the burden of anxiety disorders,and the estimated annual percentage change was calculated to quantify the temporal trends.Pearson’s correlation was used to investigate country-level risk factors for incidence and DALYs.Results Globally,there were 932 million incident cases of anxiety disorders in children and adolescents,739.29 per 100000 ASIRs and 380.62 million DALYs in 2019.From 1990 to 2019,the estimated annual percentage change of incidence of anxiety disorders decreased by 2.2%.Significant variations were observed in the age-standardised burden rate and the changing trend of anxiety disorders among countries.Portugal reported the highest ASIR of anxiety disorders,while Mexico had the largest increase rate of ASIR.In 2019,Portugal reported the highest number of DALYs(1001.71 million),and India(212.09 million)reported the lowest number of DALYs.The burden of anxiety disorders was positively correlated with the average number of psychiatrists,psychologists and nurses in the mental health sector(per 100000),and quality of life and the correlation coefficients were 0.58,0.67,0.43 and 0.53,respectively.Conclusions The incidence and global burden of anxiety disorders in adolescents have continued to decrease over the past 30 years.However,the incidence and disease burden in developed countries are still increasing steadily.Policymakers should design and implement mental health strategies for adolescents based on their specific developmental status,as well as the cultural and regional characteristics of each country.展开更多
A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lew...A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).展开更多
Objective: To expose the problems and inherent limitations of neuroscience-based brain research on mental disorders. Method: Discussion of the theory underlying brain research on mental disorders, followed by a system...Objective: To expose the problems and inherent limitations of neuroscience-based brain research on mental disorders. Method: Discussion of the theory underlying brain research on mental disorders, followed by a systematic evaluation of typical studies. Results: The fundamental problem is that brain researchers fail to differentiate between biological mental disorders in which brain processes cause the disorder (notably schizophrenia, bipolar disorder, and melancholic depression) and learned mental disorders in which brain processes mediate but do not cause the disorder (which is the case with reactive depression, reactive anxiety, OCD, and PTSD). Researchers have been unsuccessful in identifying mechanisms in the brain that cause biological mental disorders, and will never be able to locate the innumerable specific neural connections that mediate learned mental disorders. Moreover, the author’s review of typical studies in this field shows that they have serious problems with theory, measurement, and data analysis, and that their findings cannot be trusted. Conclusions: Neuroscience-based brain research on mental disorders, unlike other neurological research, has been an expensive failure and it is not worth continuing.展开更多
Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a numb...Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.展开更多
基金supported by the National Science Foundation of China(T2350008,T2341003,22207103)STI2030-Major Projects(2021ZD0203000(2021ZD0203003))。
文摘Substance use disorders(SUDs)impact an estimated 300 million people worldwide,significantly impairing both health and social functioning.These disorders are marked by an inability to regulate substance use,despite the harmful consequences.Addiction affects various neurotransmitter systems,including dopamine,serotonin,γ-aminobutyric acid(GABA),and glutamate,each of which plays a role in the reward,stress,and self-control pathways of the brain(Koob&Volkow,2016).While significant advances have been made in neuroscience,our understanding of how these neurotransmitter systems interact and contribute to addiction is still evolving.This knowledge gap represents a significant challenge in the formulation of effective treatments for SUDs.At present,the US Food and Drug Administration(FDA)has approved pharmacological treatments for alcohol,nicotine,and opioid use disorders(Vasiliu,2022);however,no such treatments have been authorized for SUDs in general,or specifically for stimulant use disorders,such as cocaine and methamphetamine addiction.Notably,the FDA has not approved any new drugs for SUD treatment in the past 40 years.
基金supported by the German Research Foundation DFG grant GA 654/13-2 to OG。
文摘De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental disorders.Specifically,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).
基金Nanjing Medical Science and Technology Development Project(ZKX20027).
文摘Background Previous studies have shown that educational attainment(EA),intelligence and income are key factors associated with mental disorders.However,the direct effects of each factor on major mental disorders are unclear.Aims We aimed to evaluate the overall and independent causal effects of the three psychosocial factors on common mental disorders.Methods Using genome-wide association study summary datasets,we performed Mendelian randomisation(MR)and multivariable MR(MVMR)analyses to assess potential associations between the 3 factors(EA,N=766345;household income,N=392422;intelligence,N=146808)and 13 common mental disorders,with sample sizes ranging from 9907 to 807553.Inverse-variance weighting was employed as the main method in the MR analysis.Results Our MR analysis showed that(1)higher EA was a protective factor for eight mental disorders but contributed to anorexia nervosa,obsessive-compulsive disorder(OCD),bipolar disorder(BD)and autism spectrum disorder(ASD);(2)higher intelligence was a protective factor for five mental disorders but a risk factor for OCD and ASD;(3)higher household income protected against 10 mental disorders but confers risk for anorexia nervosa.Our MVMR analysis showed that(1)higher EA was a direct protective factor for attention-deficit/hyperactivity disorder(ADHD)and insomnia but a direct risk factor for schizophrenia,BD and ASD;(2)higher intelligence was a direct protective factor for schizophrenia but a direct risk factor for major depressive disorder(MDD)and ASD;(3)higher income was a direct protective factor for seven mental disorders,including schizophrenia,BD,MDD,ASD,post-traumatic stress disorder,ADHD and anxiety disorder.Conclusions Our study reveals that education,intelligence and income intertwine with each other.For each factor,its independent effects on mental disorders present a more complex picture than its overall effects.
文摘BACKGROUND Stroke is a common disabling disease,whether it is ischemic stroke or hemorrhagic stroke,both can result in neuronal damage,leading to various manifestations of neurological dysfunction.AIM To explore of the application value of swallowing treatment device combined with swallowing rehabilitation training in the treatment of swallowing disorders after stroke.METHODS This study selected 86 patients with swallowing disorders after stroke admitted to our rehabilitation department from February 2022 to December 2023 as research subjects.They were divided into a control group(n=43)and an observation group(n=43)according to the treatment.The control group received swallowing rehabilitation training,while the observation group received swallowing treatment device in addition to the training.Both groups underwent continuous intervention for two courses of treatment.RESULTS The total effective rate in the observation group(93.02%)was higher than that in the control group(76.74%)(P=0.035).After intervention,the oral transit time,swallowing response time,pharyngeal transit time,and laryngeal closure time decreased in both groups compared to before intervention.In the observation group,the oral transit time,swallowing response time,and pharyngeal transit time were shorter than those in the control group after intervention.However,the laryngeal closure time after intervention in the observation group was compared with that in the control group(P=0.142).After intervention,average amplitude value and duration of the genioglossus muscle group during empty swallowing and swallowing 5 mL of water are reduced compared to before intervention in both groups.After intervention,the scores of the chin-tuck swallowing exercise and the Standardized Swallowing Assessment are both reduced compared to pre-intervention levels in both groups.However,the observation group scores lower than the control group after intervention.Additionally,the Functional Oral Intake Scale scores of both groups are increased after intervention compared to pre-intervention levels,with the observation group scoring higher than the control group after intervention(P<0.001).The cumulative incidence of complications in the observation group is 9.30%,which is lower than the 27.91%in the control group(P=0.027).CONCLUSION The combination of swallowing therapy equipment with swallowing rehabilitation training can improve the muscle movement level of the genioglossus muscle group,enhance swallowing function,and prevent the occurrence of swallowing-related complications after stroke.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.
基金Natural Science Foundation of Jiangsu Province, No. SBK2021021787the Major Project of the Health Commission ofJiangsu Province, No. ZD2022025and the Key Project of the Nanjing Health Commission, No. ZKX20048.
文摘BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.
文摘Neurodegenerative diseases(NDDs)are a class of disorders characterized by the gradual loss or malfunction of specific cell populations in the nervous system,which can be triggered by genetic or environmental factors.As a result,patients often experience a decline in mobility,sensation,memory,and cognition,which can ultimately lead to a fatal outcome.The global incidence of NDDs,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis(ALS),and multiple sclerosis,is increasing.
文摘BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.
文摘In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were findings of a 21% increase in children who displayed behavioral and conduct problems from 2019 to 2020 [2]. Early detection of neuropsychiatric and neurodevelopmental disorders in children is critical for timely intervention and improved long-term outcomes. With early intervention, there is better aptitude to support healthy development and give proper treatment to attain a better quality of life. This paper explores studies aimed at enhancing the early detection of these disorders through the use of biomarkers with the aim of creating a bridge between the worlds of research and clinical practice. The disorders in this paper specifically discussed are Major Depressive Disorder, Bipolar Disorder, and Autism Spectrum Disorder. With this bridge, we can foster collaborations and encourage further advancement in the field of early detection and intervention.
文摘People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.For example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.
基金supported by the National Institute of Environmental Health Sciences(R21ES035492,R21ES035969)National Institutes of Child Health(R01HD090214)(to PA).
文摘During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.
文摘Acute myocardial infarction(MI)remains one of the leading causes of mortality and morbidity in the global communities.A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction,in particular following a major traumatic event such as MI.Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI,coronary catheterization,or cardiothoracic surgeries.In this review,we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression.We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors(SSRIs)and cognitive behavior and exercise therapies.We further envisage a possible role played by certain chemokines,e.g.,Chemokine(C-X-C motif)ligand 12(CXCL12)and Chemokine(C-C motif)ligand 2(CCL22),in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period.Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
文摘On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.
基金This study was supported by the Planning Program of the Health Committee of Ganzhou(2022-1-5)the Key R&D Program of Jiangxi Province(20202BBGL73106)grants from the National Science Foundation of China(81771435).
文摘To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,2 and over 500000 adolescent SA are reported annually in the USA due to depression.3 Risk factors for SA include gender,hormone levels,family conflict and,particularly,negative cognitive styles such as rumination.
基金supported by the National Key Research and Development Program of China(grant 2023YFC3304200).
文摘Background Addictive disorders have gained worldwide attention.The Chinese Association of Drug Abuse Prevention and Treatment,along with the consensus panel on digital therapeutics(DTx)for addictive disorders,has published an expert consensus on DTx for addictive disorders.1 This consensus discusses and summarises the current research and application status of DTx for addictive disorders.It identifies its clinical value,application directions,research and development principles,and future prospects.As the consensus is published in Chinese,it may not be easily accessible to an international audience.To address this,we present here an overview of the expert consensus on DTx for addictive disorders in China.The recommendations from the consensus are summarised in table 1.
基金This work was supported by the National Natural Science Foundation of China(82173636)the International Institute of Population Health,Peking University Health Science Center(Number:JKGL202302)the National Key Research and Development Plan Project(2022YFC3600904).The funders had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.
文摘Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among children and adolescents can help identify areas of success,stagnation and emerging threats,thereby facilitating effective improvement strategies.Aims To estimate the incidence and burden trends of anxiety disorders in children and adolescents from 1990 to 2019 in 204 countries and compare the incidence and disease burden in different countries.To examine the association between anxiety disorders and social indicators(healthcare access and quality of life).Methods Data were obtained from the Global Burden of Disease Study 2019.The age-standardised incidence rates(ASIRs)and disability-adjusted life years(DALYs)were reported to assess the burden of anxiety disorders,and the estimated annual percentage change was calculated to quantify the temporal trends.Pearson’s correlation was used to investigate country-level risk factors for incidence and DALYs.Results Globally,there were 932 million incident cases of anxiety disorders in children and adolescents,739.29 per 100000 ASIRs and 380.62 million DALYs in 2019.From 1990 to 2019,the estimated annual percentage change of incidence of anxiety disorders decreased by 2.2%.Significant variations were observed in the age-standardised burden rate and the changing trend of anxiety disorders among countries.Portugal reported the highest ASIR of anxiety disorders,while Mexico had the largest increase rate of ASIR.In 2019,Portugal reported the highest number of DALYs(1001.71 million),and India(212.09 million)reported the lowest number of DALYs.The burden of anxiety disorders was positively correlated with the average number of psychiatrists,psychologists and nurses in the mental health sector(per 100000),and quality of life and the correlation coefficients were 0.58,0.67,0.43 and 0.53,respectively.Conclusions The incidence and global burden of anxiety disorders in adolescents have continued to decrease over the past 30 years.However,the incidence and disease burden in developed countries are still increasing steadily.Policymakers should design and implement mental health strategies for adolescents based on their specific developmental status,as well as the cultural and regional characteristics of each country.
文摘A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).
文摘Objective: To expose the problems and inherent limitations of neuroscience-based brain research on mental disorders. Method: Discussion of the theory underlying brain research on mental disorders, followed by a systematic evaluation of typical studies. Results: The fundamental problem is that brain researchers fail to differentiate between biological mental disorders in which brain processes cause the disorder (notably schizophrenia, bipolar disorder, and melancholic depression) and learned mental disorders in which brain processes mediate but do not cause the disorder (which is the case with reactive depression, reactive anxiety, OCD, and PTSD). Researchers have been unsuccessful in identifying mechanisms in the brain that cause biological mental disorders, and will never be able to locate the innumerable specific neural connections that mediate learned mental disorders. Moreover, the author’s review of typical studies in this field shows that they have serious problems with theory, measurement, and data analysis, and that their findings cannot be trusted. Conclusions: Neuroscience-based brain research on mental disorders, unlike other neurological research, has been an expensive failure and it is not worth continuing.
文摘Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.