Negative efficacy of antidepressants in pharmacotherapy of child and adolescent depression

Antidepressants are the main drugs used to treat depression,but they have not been shown to be effective in the treatment of child and adolescent depression.However,many adolescent depression treatment guidelines still recommend the use of antidepressants,especially specific serotonin re-uptake inhibitors.Previous studies have suggested that antidepressants have little therapeutic effect but many side effects,such as switching to mania,suicide,and non-suicidal self injury(NSSI),in the treatment of child and adolescent depression.In the process of developing guidelines,drug recommendations should not only focus on impro-ving symptoms,but they should also consider potential side effects.This review discusses the serious side effects of antidepressants,including switching to mania,suicide,and NSSI.

Depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite

The depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite still lacked in-depth insight.Therefore,the depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite was further systematically investigated with experiments and density functional theory(DFT)calculations.The X-ray photoelectric spectroscopy(XPS)results,DFT calculation results,and frontier molecular orbital analysis indicated that sulfite ions were difficult to be adsorbed on sphalerite surface,suggesting that sulfite ions achieved depression effects on sphalerite through other non-adsorption mechanisms.First,the oxygen content in the surface of sphalerite treated with sulfite ions in creased,which enhanced the hydrophilicity of the sphalerite and further increased the difference in hydrophilicity between sphalerite and galena.Then,sulfite ions were chelated with lead ions to form PbSO_(3)in solution.The hydrophilic PbSO_(3)was more easily adsorbed on sphalerite than galena.The interaction between sulfite ions and lead ions could effectively inhibit the activation of sphalerite.In addition the UV spectrum showed that after adding sulfite ions,the peak of perxanthate in the sphalerite treated xanthate solution was significantly stronger than that in the galena with xanthate solution,indicating that xanthate interacted more readily with sulfite ions and oxygen mo lecules within the sphalerite system,leading to the formation of perxanthate.However,sulfite ions hardly depressed the flotation of ga lena and could promote the flotation of galena to some extent.This study deepened the understanding of the depression mechanism o sulfite ions on sphalerite and Pb^(2+)activated sphalerite.

Gut-brain axis as a bridge in obesity and depression:Mechanistic exploration and therapeutic prospects

A recent study by Wang et al,published in the World Journal of Psychiatry,provided preventative and therapeutic strategies for the comorbidity of obesity and depression.The gut-brain axis,which acts as a two-way communication system between the gastrointestinal tract and the central nervous system,plays a pivotal role in the pathogenesis of these conditions.Evidence suggests that metabolic byproducts,such as short-chain fatty acids,lipopolysaccharide and bile acids,which are generated by the gut microbiota,along with neurotransmitters and inflammatory mediators within the gut-brain axis,modulate the host's metabolic processes,neuronal regulation,and immune responses through diverse mechanisms.The interaction between obesity and depression via the gut-brain axis involves disruptions in the gut microbiota balance,inflammatory immune responses,and alterations in the neuroendocrine system.Modulating the gut-brain axis,for example,through a ketogenic diet,the use of probiotics,and the supplementation of antioxidants,offers new remedial approaches for obesity and depression.Future research that explores the mechanisms of the gut-brain axis is needed to provide more evidence for clinical treatment.

Effect of esketamine on reducing postpartum pain and depression

In this editorial,we comment on a recent article by Chen et al,that addressed the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section.Poor management of postcesarean pain is associated with decreased maternal care for the baby,longer hospitalization,and higher risk of developing postpartum depression.Esketamine is a more potent S-enantiomer of ketamine which has shown promising analgesic and antidepressant properties for managing post-cesarean pain and depression in clinical studies.However,due to its potential adverse effects on the neurological and hemodynamic status of patients,it is recommended that its usage in low doses should be limited to cesarean candidates experiencing unbearable pain.Before any recommendation for routine perioperative use of esketamine,more standardized clinical trials are needed to strengthen our existing knowledge of its effectiveness in reducing postpartum pain and depression.

Clinical value of combining epirubicin with mindfulness intervention in patients with urinary system tumors and depression

BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is recommended by the European Association of Urology and can improve prognosis,its long-term use can cause toxic side effects,reduce treatment compliance,and increase psycho-logical burden.Therefore,an appropriate intervention mode is necessary.METHODS This was a retrospective study including 110 patients with urinary system tumors and depression admitted to Zhumadian Central Hospital between March 2021 and July 2023.Patients were divided into conventional(n=55)and joint inter-vention(n=55)groups.The conventional group received mitomycin and routine nursing,while the joint intervention group received EPI and mindfulness intervention.Both groups underwent three cycles of chemotherapy.Immune function(CD4+cells,CD8+cells,CD4+/CD8+ratio),tumor marker levels[urinary bladder cancer antigen(UBC),bladder tumor antigen(BTA)and nuclear matrix protein 22(NMP22)],quality of life questionnaire-core 30(QLQ-C30),17-item Hamilton depression scale(HAMD-17),and cancer-related fatigue[cancer fatigue scale(CFS)]were assessed.Adverse reactions and nursing satisfaction were recorded and evaluated.RESULTS Post-intervention,CD4+,CD8+,and CD4+/CD8+levels increased in both groups,with the joint intervention group showing more significant improvement(P<0.05).Tumor marker levels(NMP22,BTA,and UBC)were lower in the joint intervention group compared to the conventional group(P<0.05).The joint intervention group also showed a greater reduction in HAMD-17 scores(9.38±3.12 vs 15.45±4.86,P<0.05),higher QLQ-C30 scores,and lower CFS scores(both P<0.05).Additionally,the joint intervention group had a lower incidence of adverse reactions and higher nursing satisfaction(P<0.05).CONCLUSION EPI combined with mindfulness intervention significantly improved clinical outcomes in patients with urinary system tumors and depression and is worthy of clinical application.

Correlation between anxiety, depression, and social stress in young patients with thoracolumbar spine fractures

BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar fractures.This kind of fracture is easily combined with serious injuries to peripheral nerves and soft tissues,which causes paralysis of the lower limbs if there is no timely rehabilitation treatment.Young patients with thoracolumbar fractures find it difficult to recover after the operation,and they are prone to depression,low self-esteem,and other negative emotions.AIM To investigate the association between anxiety,depression,and social stress in young patients with thoracolumbar spine fractures and the effect on rehabilitation outcomes.METHODS This study retrospectively analyzed 100 patients admitted to the orthopedic department of Honghui Hospital,Xi’an Jiaotong University who underwent thoracolumbar spine fracture surgery from January 2022 to June 2023.The general data of the patients were assessed with the Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),life events scale,and social support rating scale(SSRS)to identify the correlation between anxiety,depression scores,and social stress and social support.The Japanese Orthopedic Association(JOA)was utilized to evaluate the rehabilitation outcomes of the patients and to analyze the effects of anxiety and depression scores on rehabilitation.RESULTS According to the scores of HAMD and HAMA in all patients,the prevalence of depression in patients was 39%(39/100),and the prevalence of anxiety was 49%(49/100).Patients were categorized into non-depression(n=61)and depression(n=39),non-anxiety(n=51),and anxiety(n=49)groups.Statistically significant differences in gender,occupation,Pittsburgh Sleep Quality Index(PSQI)score,and monthly family income were observed between the non-depression and depression groups(P<0.05).A significant difference in occupation and PSQI score was found between the non-anxiety and anxiety groups.Both depression(r=0.207,P=0.038)and anxiety scores(r=0.473,P<0.001)were significantly and positively correlated with negative life events.The difference in negative life event scores as well as SSRS total and item scores was statist-ically significant between patients in the non-depression and depression groups(P<0.05).The difference between the non-anxiety and anxiety groups was statistically significant(P<0.05)in the negative life event scores as well as the total SSRS scores.Additionally,JOA scores were significantly lower in both anxious and depressed patients.CONCLUSION Young patients with thoracolumbar fractures are prone to anxiety and depression.Patients’anxiety and depression are closely associated with social pressure,which reduces the life pressure of young patients with thoracolumbar fractures,enhances social support,and improves the psychology of anxiety and depression.,which affects patients’recovery.

Changes in Depression,Anxiety,and Stress Levels during a Religious Period:A Prospective Cohort Study

Objective:There is conflicting evidence suggesting an association between Ramadan and mental health.Aim:This study aims to assess changes in depression,anxiety,and stress levels during Ramadan among university students from Saudi Arabia and to measure the magnitude of change in these levels according to gender.Methods:This study is a prospective cohort study.Data was collected using a structured questionnaire that measured demographic data of the students,and levels of depression,anxiety,and stress utilizing the short form of the Depression Anxiety Stress Scales questionnaire(DASS 21).The assessments were performed starting from the month of Shaban(the month that precedes Ramadan),and the second wave of data collection was initiated beginning the second week of Ramadan until the end of the month.Differences in the proportion of students who are categorized as normal or having abnormal degrees of depression and anxiety between Shaban and Ramadan were tested using either the Chi-square test or Fisher’s exact test.Results:A total of 321 students completed the assessment during Shaban and Ramadan.More than half of the students were male(54.2%),with a mean age of 22.A statistically significant di7fference in levels of anxiety,depression,and stress between the assessment periods was detected(p<0.001).The proportion of students classified as normal increased during Ramadan across all measured conditions in comparison to during Shaban.The reduction in the number of students classified as having anxiety,depression,and stress between the assessment periods remained statistically significant across both genders.Nonetheless,degrees of change appear to be higher among male students than among female students.Conclusion:This study identified a reduction in levels of depression,anxiety,and stress among students during the month of Ramadan,as well as gender variation concerning levels of change.The results support the significance of considering social,religious,and spiritual aspects when designing interventions to address individuals’mental health.

Effect of insomnia on anxiety and depression:Mediation of cognitive failures and moderated mediation of neuroticism

BACKGROUND The coronavirus disease 2019 pandemic has had an ongoing impact on the public’s mental health that requires long-term attention.Exploring the relationship between mental health indicators would aid in identifying solutions to improve public mental health.AIM To investigate the prevalence of anxiety,depression,and insomnia and explore the relationship among neuroticism,cognitive failures,and mental health.METHODS A cross-sectional survey was conducted in December 2023 using an online platform to recruit adult participants.The neuroticism,subjective cognitive function,and mental health of the participants were assessed using the neuroticism subscale of the Chinese Big Five Personality Inventory Brief Version,cognitive failures questionnaire,generalized anxiety disorder-7,patient health questionnaire-9,and insomnia severity index.Pearson's correlation analysis,independent samples t-tests,one-way analysis of variance,and structural equation model were used to examine the relationship between mental health indicators.RESULTS A total of 1011 valid questionnaires were collected,of which 343 were completed by male(33.93%)respondents and 668 were completed by female(66.07%)respondents.The rates of anxiety,depression,and insomnia were 41.3%,44.6%,and 36.3%,respectively,most cases of which were mild.Among the mental health indicators,there were significant differences by age and between those with siblings and those who were only children.Neuroticism and cognitive failures were significantly positively correlated with mental health indicators.Further moderated mediation analysis showed that cognitive failures mediated the relationship between insomnia and anxiety and between insomnia and depression,with neuroticism moderating the first half of this pathway and the effect being greater in the low-neuroticism group.CONCLUSION Cognitive failures and neuroticism play important roles in mental health.Therefore,enhancing subjective cognitive function and regulating emotional stability may contribute to the improvement of mental health.

Overweight in mediating the association between depression and new-onset diabetes: A population-based research from Health and Retirement Study

BACKGROUND Several studies have suggested a close link between depression,overweight,and new-onset diabetes,particularly among middle-aged and older populations;however,the causal associations remain poorly understood.AIM To investigate the role of overweight in mediating the association between depression and new-onset diabetes in middle-aged and older populations.METHODS Data of 9426 individuals aged≥50 years from the 1998-2016 Health and Retirement Study database were analyzed.Weighted logistic regression was employed to obtain odds ratios(ORs)and 95%confidence intervals(95%CIs)for depression and new-onset diabetes in the middle-aged and older populations.Mediation analysis and the Sobel test were used to test the mediating effects of overweight between depression and the risk of new-onset diabetes.RESULTS New-onset diabetes was identified in 23.6%of the study population.Depression was significantly associated with new-onset diabetes(OR:1.18,95%CI:1.03-1.35,P value:0.014).Further adjustment for overweight attenuated the effect of depression on new-onset diabetes to 1.14(95%CI:1.00-1.30,P=0.053),with a significant mediating effect(P of Sobel test=0.003).The mediation analysis demonstrated that overweight accounted for 61%in depression for the risk of new-onset diabetes,with overweight having a partially mediating role in the depression-to-diabetes pathway.CONCLUSION New-onset diabetes was not necessarily a direct complication of depression;rather,depression led to behaviors that increase the risk of overweight and,consequently,new-onset diabetes.

Immune indicators and depression in adolescents:Associations with monocytes,lymphocytes,and direct bilirubin

BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.

Therapeutic potential of Carum carvi in depression,memory loss,and hippocampal sclerosis reversal in temporal lobe epilepsy

Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy with Hippocampal Sclerosis(TLE-HS)is the most drug-resistant form of epilepsy,and it also impacts physical,mental,and psychological well-being of patients.Carum carvi extract has demonstrated anti-convulsant,anti-depressant,and anxiolytic properties.This study was designed to investigate if Carum carvi extract can alleviate depression and memory loss symptoms in a TLE-HS animal model.Methods:Male Sprague Dawley rats were used to create a model of TLE-HS and Carum carvi extract treatment,along with appropriate controls,was used to test the efficacy of this herbal extract in reducing the symptoms of depression and memory loss.Results:Forced swim test showed that Carum carvi extract treated TLE-HS rats resulted in significant improvement of the symptoms of depression.However,novel object recognition test showed that memory improvement did not occur.Conclusion:Depression significantly impacts the quality of life in TLE-HS patients,and this study has shown that Carum carvi extract should be explored further as an adjuvant treatment for TLE-HS patients to improve their quality of life.

Depression levels of the general public increases during the COVID-19 pandemic in China:A web-based cross-sectional survey

BACKGROUND The coronavirus disease 2019(COVID-19)outbreak lasted several months,having started in December 2019.This study aimed to report the impacts of various factors on the depression levels of the general public and ascertain how emotional measures could be affected by psychosocial factors during the COVID-19 pandemic.AIM To investigate the depression levels of the general public in China during the COVID-19 pandemic.METHODS A total of 2001 self-reported questionnaires about Beck Depression Inventory(BDI)were collected on August 22,2022 via the website.Each questionnaire included four levels of depression and other demographic information.The BDI scores and incidences of different depression levels were compared between various groups of respondents.χ2 analysis and the two-tailed t-test were used to assess categorical and continuous data,respectively.Multiple linear regressions and logistic regressions were employed for correlation analysis.RESULTS The averaged BDI score in this study was higher than that for the non-epidemic periods,as reported in previous studies.Even higher BDI scores and incidences of moderate and severe depression were recorded for people who were quarantined for suspected COVID-19 infection,compared to the respondents who were not quarantined.The participants who did not take protective measures were associated with higher BDI scores than those who made efforts to keep themselves relatively safer.Similarly,the people who did not return to work had higher BDI scores compared to those managed to.A significant association existed between the depression levels of the subgroups and each of the factors,except gender and location of residence.However,quarantine was the most relative predictor for depression levels,followed by failure to take preventive measures and losing a partner,either through divorce or death.CONCLUSION Based on these data,psychological interventions for the various subpopulations in the general public can be implemented during and after the COVID-19 pandemic.Other countries can also use the data as a reference.

Improving the outcome in leukemia patients by controlling subthreshold depression and cancer-related fatigue

Patients with leukemia often suffer from the combined effects of cancer-related fatigue(CRF)and subthreshold depression,which mutually exacerbate each other in a vicious cycle.In this editorial,we comment on the article by Liu et al,published in the World Journal of Psychiatry.We further elucidate the profound impact of subthreshold depressive symptoms on the experience of CRF and complications in patients with leukemia.This editorial highlights the importance of early identification and treatment of subclinical depression,and advocates for a multidisciplinary and integrated treatment approach that includes social support,psychological interventions,and individualized treatment plans.Future research needs to explore the biological mechanisms underlying the interaction between the two to develop more effective prevention and treatment strategies.

Global trends of purinergic receptors and depression:A bibliometric analysis from 2003 to 2023

BACKGROUND Depression significantly threatens human health.Purinergic receptors are reported to be associated with depression.However,there is no bibliometric research in this field have been published.AIM To provide some reference for the further research in the field of purinergic receptors and depression utilizing bibliometric analysis.METHODS Relevant researches were retrieved from the Web of Science Core Collection database.The period of the search was from January 1,2003 to December 31,2023.The CiteSpace(6.2.R7)and VOSviewer(1.6.19)were applied to identify the main contributors of countries,authors,institutions,references and journals.Besides,we evaluate keywords to assess the hotspots and trends over the previous 2 decades.RESULTS Totally,247 articles were identified,showing an increasing trend over time.The most productive country,institution,and journal in this field are China,Harvard University,and Biological Psychiatry,respectively.Liang SD and Rodrigues,Ana Lucia S were the most prolific authors.Burnstock G ranked first among the cited authors.The cooperation among countries and disciplines is crucial.The P2X7 receptor provides promising prospects for treating depression and further studies are warranted to validate the scope and significance of depression therapeutic strategies.CONCLUSION This study provides an overview of the worldwide research status and future trends in purinergic receptors and depression.P2X7 receptor is considered an appropriate target for the treatment of depression,as well as neurological diseases.It is implied that based on purinergic system,the future prospects for interventions aimed at depression treatment are promising,showing the way for both augmentation strategies and new drug treatments in the context of the pharmacology of depression.

Addressing social function in the treatment of depression:A call for holistic approaches

This article discusses the importance of addressing social functioning impairment in patients with residual depressive symptoms,as highlighted in the study by Liao et al.The authors showed that social dysfunction persists in many patients despite symptom remission.This observation calls for a shift in depression treatment strategies,with an emphasis on integrating social functioning as a key treatment goal.This article suggests targeted interventions that focus on both symptomatic relief and the restoration of social function.

Activation of zona incerta gamma-aminobutyric acid-ergic neurons alleviates depression-like and anxiety-like behaviors induced by chronic restraint stress

BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.

Nursing interventions based on Snyder’s hope theory for depression following percutaneous coronary interventions:A clinical study

BACKGROUND Patients with depression following coronary heart disease often exhibit insufficient psychological resilience and self-care abilities;therefore,emphasis must be placed on nursing interventions.AIM To analyze the application value of problem-oriented education combined with nursing interventions based on the Snyder hope theory model in depressed patients after percutaneous coronary intervention(PCI).METHODS This study included 150 patients diagnosed with PCI postoperative depression because of coronary heart disease between February 2022 and February 2024.Participants were divided into two groups:A control group(n=75)receiving problem-oriented education and an observation group(n=75)receiving combined nursing interventions based on the Snyder hope theory model.Depression status,psychological resilience,self-care ability,and quality of life were compared between the two groups.RESULTS Before nursing interventions,there were no significant differences between the two groups(P>0.05).After the interventions,depression scores decreased while psychological resilience,self-care ability,and quality of life scores increased significantly in the observation group compared to that in the control group,with statistically significant differences noted(P<0.05).This combined approach can enhance psychological resilience,improve self-care abilities,and elevate the overall quality of life,warranting further promotion in clinical practice.CONCLUSION Combination of problem-oriented education and nursing interventions based on the Snyder hope theory model effectively alleviates depression in patients following PCI for coronary heart disease.

Hemispheric asymmetries and network dysfunctions in adolescent depression:A neuroimaging study using resting-state functional magnetic resonance imaging

BACKGROUND Currently,adolescent depression is one of the most significant public health concerns,markedly influencing emotional,cognitive,and social maturation.Despite advancements in distinguish the neurobiological substrates underlying depression,the intricate patterns of disrupted brain network connectivity in adolescents warrant further exploration.AIM To elucidate the neural correlates of adolescent depression by examining brain network connectivity using resting-state functional magnetic resonance imaging(rs-fMRI).METHODS The study cohort comprised 74 depressed adolescents and 59 healthy controls aged 12 to 17 years.Participants underwent rs-fMRI to evaluate functional connectivity within and across critical brain networks,including the visual,default mode network(DMN),dorsal attention,salience,somatomotor,and frontoparietal control networks.RESULTS Analyses revealed pronounced functional disparities within key neural circuits among adolescents with depression.The results demonstrated existence of hemispheric asymmetries characterized by enhanced activity in the left visual network,which contrasted the diminished activity in the right hemisphere.The DMN facilitated increased activity within the left prefrontal cortex and reduced engagement in the right hemisphere,implicating disrupted self-referential and emotional processing mechanisms.Additionally,an overactive right dorsal attention network and a hypoactive salience network were identified,underscoring significant abnormalities in attentional and emotional regulation in adolescent depression.CONCLUSION The findings from this study underscore distinct neural connectivity disruptions in adolescent depression,underscoring the critical role of specific neurobiological markers for precise early diagnosis of adolescent depression.The observed functional asymmetries and network-specific deviations elucidate the complex neurobiological architecture of adolescent depression,supporting the development of targeted therapeutic strategies.

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.