Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

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.

Cognition and movement in neurodegenerative disorders:a dynamic duo

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.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Disorder effects in NbTiN superconducting resonators

Disordered superconducting materials like NbTiN possess a high kinetic inductance fraction and an adjustable critical temperature, making them a good choice for low-temperature detectors. Their energy gap(D), critical temperature(T_(c)),and quasiparticle density of states(QDOS) distribution, however, deviate from the classical BCS theory due to the disorder effects. The Usadel equation, which takes account of elastic scattering, non-elastic scattering, and electro–phonon coupling,can be applied to explain and describe these deviations. This paper presents numerical simulations of the disorder effects based on the Usadel equation to investigate their effects on the △, Tc, QDOS distribution, and complex conductivity of the NbTiN film. Furthermore, NbTiN superconducting resonators with coplanar waveguide(CPW) structures are fabricated and characterized at different temperatures to validate our numerical simulations. The pair-breaking parameter α and the critical temperature in the pure state T_(c)^(P) of our NbTiN film are determined from the experimental results and numerical simulations. This study has significant implications for the development of low-temperature detectors made of disordered superconducting materials.

Food intolerance and the few-foods(or oligoantigenic)diet in children with attention-deficit hyperactivity disorder

The hypothesis that some children with attention-deficit hyperactivity disorder(ADHD)may show sensitivity or allergic reactions to various food items has led to the development of the the few-foods(or oligoantigenic)diet.The rationale of the diet is to eliminate certain foods from the diet in order to exclude potential allergens contained either naturally in food or in artificial ingredients with allergenic properties.The oligoantigenic diet attempts to identify individual foods to which a person might be sensitive.First,ADHD symptoms are monitored while multiple foods are excluded from the diet.Subsequently,if symptoms remit,foods are re-introduced,while observing the individual for the return of symptoms.An advantage of the oligoantigenic diet is that it can be tailored to the individual.A growing body of evidence suggests that behavioral symptoms of subgroups of children with ADHD may benefit from the elimination of certain foods.The effect sizes of an oligoantigenic diet regarding improvement of ADHD symptoms have been found to be medium to large.Available evidence suggests that the investigation of the role of food hypersensitivities in ADHD is a promising avenue worthy of further exploration.Further large-scale,randomized controlled studies including assessment of long-term outcome are therefore warranted.

Risk factors for postpartum posttraumatic stress disorder after emergency admission

BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency admission.METHODS:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.RESULTS:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,P<0.001),and cervical dilation(OR=3.203;95%CI:1.670–6.141,P=0.039)as independent risk factors for postpartum PTSD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTSD.CONCLUSION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.

Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

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.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Mediating effect of resilience on the relationship between rumination and suicide attempts in Chinese adolescents with mood disorders

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.

MicroRNAs as potential biomarkers for diagnosis of attention deficit hyperactivity disorder

Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.

Exploring the influences of education,intelligence and income on mental disorders

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.

Thirty-year trends of anxiety disorders among adolescents based on the 2019 Global Burden of Disease Study

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.

Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders-a Mendelian randomization study

Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.

K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

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).

Biomarker bust:meta-analyses reveal unreliability of neuronal extracellular vesicles for diagnosing parkinsonian disorders

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).

COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors

BACKGROUND Recently,a growing number of adolescents have been afflicted with mental disorders,with annual morbidity rates on the rise.This trend has been exacerbated by the global coronavirus disease 2019(COVID-19)pandemic,leading to a surge in suicide and self-harm rates among this demographic.AIM To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder(BD),along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents.METHODS A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians.Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders,international classification of diseases-11,and the National institute of mental health research domain criteria.Statistical analyses were performed using SPSS 26.0 software,with significance set at P<0.05.RESULTS A cohort of 171 adolescents diagnosed with BD between January 1,2018,and December 31,2022,was included in the analysis.The gender distribution was 2.8:1(female to male),with ages ranging from 11 to 18 years old.Major factors contributing to adolescent BDs included familial influences,academic stress,genetic predisposition and exposure to school-related violence.Notably,a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic.Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress,thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents.CONCLUSION The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD.This study underscores the urgent need for societal,familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention,diagnosis and treatment of adolescent BDs.