Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic facto...Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.展开更多
Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that ther...Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms:(1) conventional risk factors that actually are compensatory behaviors, attempts at selfhelp through the use of agents and foods; and(2) the effects of chronic stress.展开更多
The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented...The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD.The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new,data-driven,machine learning method to model psychiatric illness,namely nomothetic network psychiatry(NNP).This review discusses many false dogmas including:MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions;mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances;DSM/ICD are the gold standards to make the MDD/BD diagnosis;severity of illness should be measured using rating scales;clinical remission should be defined using threshold values on rating scale scores;existing diagnostic BD boundaries are too restrictive;and mood disorder spectra are the rule.In contrast,our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders;the DSM/ICD taxonomies are counterproductive;a shared core,namely the reoccurrence of illness(ROI),underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors;mood disorders should be ROI-defined;ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders;severity of illness and treatment response should be delineated using the NNP-derived causome,pathway,ROI and integrated phenome scores;and MDD and BD are the same illness.展开更多
BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation(TMS)both in neurological and psychiatric fields.After Food and Drug Administration approval of TMS for the therapy of treatment-resis...BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation(TMS)both in neurological and psychiatric fields.After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression,TMS has been widely used in the context of mood disorders(MD).However,growing reports regarding the possibility of developing hypomanic/manic switch(HMS)have generated concern regarding its use in MDs.AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD.METHODS We led our research on PubMed,Scopus and Web of Science on March 22,2020,in accordance to the PRISMA guidelines for systematic review.Only double blind/single blind studies,written in English and focused on the TMS treatment of MD,were included.A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software.The assessment of Risk of Bias was done using Cochrane risk of bias tool.This protocol was registered on PROSPERO with the CRD42020175811 code.RESULTS Twenty-five studies were included in our meta-analysis:Twenty-one double blind randomized controlled trials(RCT)and four single blind-RCT(no.of subjects involved in active stimulation=576;no.of subjects involved in sham protocol=487).The most frequently treated pathology was major depressive episode/major depressive disorder,followed by resistant depression,bipolar depression and other MD.The majority of the studies used a repetitive TMS protocol,and the left dorsolateral prefrontal cortex was the main target area.Side effects were reported in eight studies and HMS(described as greater energy,insomnia,irritability,anxiety,suicidal attempt)in four studies.When comparing active TMS vs sham treatment,the risk of developing HMS was not significantly different between conditions.CONCLUSION Applying the most usual protocols and the appropriate precautionary measures,TMS seems not to be related to HMS development.展开更多
OBJECTIVE:To evaluate the clinical effectiveness of Shumian capsule(舒眠胶囊)in improving the symptoms of insomnia,anxiety,depression,and other symptoms of convalescent patients of COVID-19.METHODS:Totally 200 patient...OBJECTIVE:To evaluate the clinical effectiveness of Shumian capsule(舒眠胶囊)in improving the symptoms of insomnia,anxiety,depression,and other symptoms of convalescent patients of COVID-19.METHODS:Totally 200 patients were collected and randomly divided into experiment group(n=100)and control group(n=100).The control group was treated with Shumian capsule simulator,and the experiment group was treated with Shumian capsule.The improvement of TCM symptom score,the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed,and the clinical effect was evaluated.RESULTS:One week after treatment,the scores of anxiety symptoms in the experiment group were significantly different from those in the control group(P<0.05),but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group(P>0.05).There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).After 2 weeks of treatment,the scores of insomnia,anxiety,depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group(P<0.05).There was no significant difference in the disappearance rate of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).There were no significant differences in heart rate,respiration,systolic blood pressure and diastolic blood pressure between the experiment group and the control group(P>0.05).CONCLUSION:Shumian capsule can significantly improve the symptoms of insomnia,anxiety and depression in COVID-19’s convalescent patients with sleep and mood disorders.展开更多
Recent research on autoimmune disorders suggests additional links between systemic and central nervous system(CNS)pathophysiology,among which the identification of antibody-induced limbic encephalitis provided the str...Recent research on autoimmune disorders suggests additional links between systemic and central nervous system(CNS)pathophysiology,among which the identification of antibody-induced limbic encephalitis provided the strongest evidence for the potential involvement of autoimmunity in the pathogenesis of severe mood and psychotic symptoms.In these illnesses,psychiatric symptoms predominate in the initial phase of the disorder in up to 70%of the cases,and they often lead patients to early psychiatric evaluation.For this reason,it is very important to increase the limited knowledge among psychiatrists about these autoimmune neuropsychiatric diseases,which can mimic psychiatric syndromes,in particular,those typically presented in severe mood disorders and schizophrenia.On the other hand,similarities in clinical presentation suggest that neuroinflammation and systemic immune dysregulation may play a role in the pathophysiology of severe mood and psychotic disorders.A complex interaction between periphery and immune cells of the CNS may result in cellular damage through mechanisms involving excitotoxicity,oxidative stress,and mitochondrial dysfunction.These pathways are possibly shared between comorbid medical disorders and severe mood and psychotic disorders and may reflect common underlying vulnerability.展开更多
Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known f...Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.展开更多
Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chr...Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.展开更多
BACKGROUND Bipolar disorder(BD)is a severe psychiatric disorder characterized by mood swings.Psychosocial interventions,such as psychoeducation,play an essential role in promoting social rehabilitation and improving p...BACKGROUND Bipolar disorder(BD)is a severe psychiatric disorder characterized by mood swings.Psychosocial interventions,such as psychoeducation,play an essential role in promoting social rehabilitation and improving pharmacological treatment.AIM To investigate the role of psychoeducation in BD.METHODS A systematic review of original studies regarding psychoeducation interventions in patients with BD and their relatives was developed.A systematic literature search was performed using the Medline,Scopus,and Lilacs databases.No review articles or qualitative studies were included in the analysis.There were no date restriction criteria,and studies published up to April 2021 were included.RESULTS A total of forty-seven studies were selected for this review.Thirty-eight studies included patients,and nine included family members.Psychoeducation of patients and family members was associated with a lower number of new mood episodes and a reduction in number and length of stay of hospitalizations.Psychoeducational interventions with patients are associated with improved adherence to drug treatment.The strategies studied in patients and family members do not interfere with the severity of symptoms of mania or depression or with the patient's quality of life or functionality.Psychoeducational interventions with family members do not alter patients'adherence to pharmacotherapy.CONCLUSION Psychoeducation as an adjunct strategy to pharmacotherapy in the treatment of BD leads to a reduction in the frequency of new mood episodes,length of hospital stay and adherence to drug therapy.展开更多
Available evidence points to a possible role of the renin-angiotensin system(RAS)in the pathophysiology of mood disorders and suicide.We carried out a critical analysis of literature data regarding this role,with a fo...Available evidence points to a possible role of the renin-angiotensin system(RAS)in the pathophysiology of mood disorders and suicide.We carried out a critical analysis of literature data regarding this role,with a focus on the proposed association between RAS dysfunction and suicidal behavior.Epidemiological,genetic,and biochemical findings are described,and the pathophysiological hypothesis aiming at explaining the possible relationship between RAS and suicide are discussed.Available findings do support the involvement of the RAS in the neurobiology of suicide,although the exact mechanisms underlying this involvement are still unknown.展开更多
The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better...The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better understand the etiology of psychiatric disorders.One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation.While some epigenetic modifications(such as DNA methylation)are well known and studied,the roles of others have been investigated much less.DNA hydroxymethylation is a rarely studied epigenetic modification,which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity.In contrast to DNA methylation,DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression.Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders,the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment,which both influence the development of psychiatric disorders,and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.展开更多
OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 p...OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19.Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization.The patients received either Xiaoyao capsule(experimental group)or a placebo Xiaoyao capsule(control group)for 2 weeks.The improvements in the Traditional Chinese Medicine(TCM)syndrome scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep were compared between the two groups.RESULTS:The TCM syndrome pattern scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment(P>0.05).CONCLUSIONS:Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.展开更多
Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifical...Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifically focusing on those seeking assistance due to suicide attempts (TS) versus CLP requests for other reasons (non-TS) between the years 2010 and 2020. Additionally, we aim to assess factors associated with suicide attempts. Method: This retrospective controlled study involves a thorough examination of medical records encompassing 3913 patients who received CLP services at the Hospital de Base (HB) and the Children and Maternity Hospital (HCM) of São José do Rio Preto Medical School Foundation (Funfarme) from June 2010 to June 2020. The patient cohort is categorized into two groups: those with requests for SA (n = 677) and those with requests for other reasons. Results: In the SA group, as opposed to the non SA group, statistically significant differences were observed for gender (predominantly female), employment status (employed), marital status (single), and age (younger). Notably, a higher prevalence of psychiatric antecedents (88.7%, n = 555 vs. 73.6% n = 2018) was found in the SA group, indicating a significant association. The frequency of SA requests remained stable over the years. Among the SA group, mood disorders were the most prevalent (39%, n = 372), followed by disorders related to substance use (21.2%, n = 202), and personality disorders (16%, n = 152). A history of previous suicide attempts emerged as a crucial factor for the recurrence of SA (p-value ≤ 0.001). Exogenous intoxication emerged as the most frequently employed method in attempts (79.6%, n = 539), particularly prevalent among patients diagnosed with mood disorders (41%, n = 314). A significant association was observed between the method of attempt and the nosological psychiatric diagnosis (χ<sup>2</sup> = 42.277;p ≤ 0.001). Regarding outcomes, the majority of patients were referred for outpatient follow-up (23%, n = 336) in specialized mental health services or at the Primary Healthcare Unit, highlighting the general hospital’s pivotal role in integrating patients into the broader healthcare network. Conclusion: Variables such as gender (female), age group (young adults), and psychiatric history exhibited stronger associations with suicide attempts compared to the group assisted by CLP for other reasons. Furthermore, a noteworthy correlation between the method employed and the psychiatric diagnosis was identified.展开更多
Psychiatry remains in a permanent state of crisis,which fragmented psychiatry from the field of medicine.The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness includin...Psychiatry remains in a permanent state of crisis,which fragmented psychiatry from the field of medicine.The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic,biological,molecular,pan-omics,precision,cognitive and phenomenological psychiatry,folk psychology,mind-brain dualism,descriptive psychopathology,and postpsychiatry.The current“gold standard”Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach.Therefore,it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches.The aim of this paper is to explain the new nomothetic network psychiatry(NNP)approach,which uses machine learning methods to build data-driven causal models of mental illness by assembling risk-resilience,adverse outcome pathways(AOP),cognitome,brainome,staging,symptomatome,and phenomenome latent scores in a causal model.The latter may be trained,tested and validated with Partial Least Squares analysis.This approach not only allows to compute pathway-phenotypes or biosignatures,but also to construct reliable and replicable nomothetic networks,which are,therefore,generalizable as disease models.After integrating the validated feature vectors into a well-fitting nomothetic network,clustering analysis may be applied on the latent variable scores of the R/R,AOP,cognitome,brainome,and phenome latent vectors.This pattern recognition method may expose new(transdiagnostic)classes of patients which if cross-validated in independent samples may constitute new(transdiagnostic)nosological categories.展开更多
The versatility of glutamate as the brain’s foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge.Years of research have continued to uncover glutamate’s...The versatility of glutamate as the brain’s foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge.Years of research have continued to uncover glutamate’s effects and roles in several neurological and neuropsychiatric disorders,including depression.It had been considered that a deeper understanding of the roles of glutamate in depression might open a new door to understanding the pathological basis of the disorder,improve the approach to patient management,and lead to the development of newer drugs that may benefit more patients.This review examines our current understanding of the roles of endogenous and exogenous sources of glutamate and the glutamatergic system in the aetiology,progression and management of depression.It also examines the relationships that link the gut-brain axis,glutamate and depression;as it emphasizes how the gut-brain axis could impact depression pathogenesis and management via changes in glutamate homeostasis.Finally,we consider what the likely future of glutamate-based therapies and glutamate-based therapeutic manipulations in depression are,and if with them,we are now on the final chapter of understanding the neurochemical milieu of depressive disorders.展开更多
A number of studies have assessed the influence of depression on the risk of cardiovascular disease. A growing literature indicates a link between depression and cerebrovascular events, although the direction of this ...A number of studies have assessed the influence of depression on the risk of cardiovascular disease. A growing literature indicates a link between depression and cerebrovascular events, although the direction of this association remains unclear. Numerous data have emerged suggesting an association between depressive symptoms and subsequent risk of stroke, thus leading to the hypothesis that a direct causality between depression and stroke exists. Notwithstanding, how depression may act as a risk factor for stroke is still unclear. Depression might be linked to stroke via neuroendocrine and inflammation effects, through correlation with major comorbidities such as hypertensionand diabetes or by intervention of lifestyle behavioral mediators. Finally, antidepressant medications have recently drawn attention for a possible association with increased risk of stroke, although such findings remain uncertain. Depression has been also established as an important consequence after stroke, exerting a significant adverse impact on the course of motor recovery, social functioning and, overall, on quality of life. Post stroke depression occurs in nearly one third of stroke cases, but the exact mechanism leading to depression after stroke is still incompletely understood. In this article, we will review contemporary epidemiologic studies, discuss potential mechanisms and specific aspects of the complex relation between depression and stroke.展开更多
AIM: To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. METHODS: Fourteen remitted participants with a history of major depression and f...AIM: To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. METHODS: Fourteen remitted participants with a history of major depression and fourteen closely matched healthy control participants took part in the study. We used two psychiatric interviews(Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and one self-report scale(Beck Depression Inventory) to assess remission. Healthy control participants were interviewed by an experienced psychiatrist to exclude those who showed any current or lifetime psychiatric or neurological disorders. To explore psychosocialand cognitive-interpersonal underpinnings of potential vulnerability markers of depression, early life stress, coping styles and alexithymia were also assessed. We induced pleasant and unpleasant emotional states using congruent combinations of music and human emotional faces to investigate neural and behavioral correlates of emotional experiences; neutral stimuli were used as a control condition. Brain responses were recorded using functional magnetic resonance imaging. Behavioral responses of pleasantness, arousal, joy and fear were measured via button-press inside the resonance imaging scanner. RESULTS: The mean age of the sample was 54.9(± 11.3) years. There were no differences between remitted depressed(RD)(n = 14; 9 females and 5 males) and healthy participants(n = 14; 8 females and 6 males) regarding age, current degree of depression, early life stress, coping styles and alexithymia. On a neural level, RD participants showed reduced activations in the pregenual anterior cingulate cortex(pg ACC) in response to pleasant [parameter estimates:-0.78 vs 0.32; t(26) =-3.41, P < 0.05] and unpleasant [parameter estimates:-0.88 vs 0.56; t(26)=-4.02, P < 0.05] emotional stimuli. Linear regression analysis revealed that pg ACC activity was modulated by early life stress [β =-0.48; R2 = 0.23, F(1,27) = 7.83, P < 0.01] and taskoriented coping style [β = 0.63; R2 = 0.37, F(1,27) = 16.91, P < 0.001]. Trait anxiety modulated hippocampal responses to unpleasant stimuli [β = 0.62; R2= 0.38, F(1,27) = 15.95, P < 0.001]. Interestingly, in their reported experiences of pleasantness, arousal, happiness and fear in response to pleasant, unpleasant and neutral stimuli, RD participants did not differ significantly from healthy control participants. Adding trait anxiety or alexithymia as a covariate did not change the results.CONCLUSION: The present study indicates that, in euthymic individuals, depression history alters neural correlates, but not the subjective dimension of pleasant and unpleasant emotional experiences.展开更多
BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in T...BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.展开更多
Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential n...Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential non-pharmacological therapies have been studied in the last years,including the use of mesenchymal stem cell therapies to treat depression.These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients.Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its antiinflammatory and neurotrophic properties.However,some clinical trials involving treatment of depression with stem cells are in progress,but with no published results.These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.展开更多
基金Supported by National Natural Science Foundation of China,No. 82071347 and No. 81771354 (to Dai RP)
文摘Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.
文摘Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms:(1) conventional risk factors that actually are compensatory behaviors, attempts at selfhelp through the use of agents and foods; and(2) the effects of chronic stress.
基金Supported by the Ratchadapiseksompotch Funds,Faculty of Medicine,Chulalongkorn University,RA61/050.
文摘The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD.The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new,data-driven,machine learning method to model psychiatric illness,namely nomothetic network psychiatry(NNP).This review discusses many false dogmas including:MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions;mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances;DSM/ICD are the gold standards to make the MDD/BD diagnosis;severity of illness should be measured using rating scales;clinical remission should be defined using threshold values on rating scale scores;existing diagnostic BD boundaries are too restrictive;and mood disorder spectra are the rule.In contrast,our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders;the DSM/ICD taxonomies are counterproductive;a shared core,namely the reoccurrence of illness(ROI),underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors;mood disorders should be ROI-defined;ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders;severity of illness and treatment response should be delineated using the NNP-derived causome,pathway,ROI and integrated phenome scores;and MDD and BD are the same illness.
文摘BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation(TMS)both in neurological and psychiatric fields.After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression,TMS has been widely used in the context of mood disorders(MD).However,growing reports regarding the possibility of developing hypomanic/manic switch(HMS)have generated concern regarding its use in MDs.AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD.METHODS We led our research on PubMed,Scopus and Web of Science on March 22,2020,in accordance to the PRISMA guidelines for systematic review.Only double blind/single blind studies,written in English and focused on the TMS treatment of MD,were included.A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software.The assessment of Risk of Bias was done using Cochrane risk of bias tool.This protocol was registered on PROSPERO with the CRD42020175811 code.RESULTS Twenty-five studies were included in our meta-analysis:Twenty-one double blind randomized controlled trials(RCT)and four single blind-RCT(no.of subjects involved in active stimulation=576;no.of subjects involved in sham protocol=487).The most frequently treated pathology was major depressive episode/major depressive disorder,followed by resistant depression,bipolar depression and other MD.The majority of the studies used a repetitive TMS protocol,and the left dorsolateral prefrontal cortex was the main target area.Side effects were reported in eight studies and HMS(described as greater energy,insomnia,irritability,anxiety,suicidal attempt)in four studies.When comparing active TMS vs sham treatment,the risk of developing HMS was not significantly different between conditions.CONCLUSION Applying the most usual protocols and the appropriate precautionary measures,TMS seems not to be related to HMS development.
基金Supported by State Administration of Traditional Chinese Medicine COVID-19 Traditional Chinese Medicine Emergency Project(the fifth batch):Study on TCM Screening for Recovery from COVID-19(No.2020ZYLCYJ08)。
文摘OBJECTIVE:To evaluate the clinical effectiveness of Shumian capsule(舒眠胶囊)in improving the symptoms of insomnia,anxiety,depression,and other symptoms of convalescent patients of COVID-19.METHODS:Totally 200 patients were collected and randomly divided into experiment group(n=100)and control group(n=100).The control group was treated with Shumian capsule simulator,and the experiment group was treated with Shumian capsule.The improvement of TCM symptom score,the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed,and the clinical effect was evaluated.RESULTS:One week after treatment,the scores of anxiety symptoms in the experiment group were significantly different from those in the control group(P<0.05),but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group(P>0.05).There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).After 2 weeks of treatment,the scores of insomnia,anxiety,depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group(P<0.05).There was no significant difference in the disappearance rate of insomnia,anxiety and depression between the experiment group and the control group(P>0.05).There were no significant differences in heart rate,respiration,systolic blood pressure and diastolic blood pressure between the experiment group and the control group(P>0.05).CONCLUSION:Shumian capsule can significantly improve the symptoms of insomnia,anxiety and depression in COVID-19’s convalescent patients with sleep and mood disorders.
文摘Recent research on autoimmune disorders suggests additional links between systemic and central nervous system(CNS)pathophysiology,among which the identification of antibody-induced limbic encephalitis provided the strongest evidence for the potential involvement of autoimmunity in the pathogenesis of severe mood and psychotic symptoms.In these illnesses,psychiatric symptoms predominate in the initial phase of the disorder in up to 70%of the cases,and they often lead patients to early psychiatric evaluation.For this reason,it is very important to increase the limited knowledge among psychiatrists about these autoimmune neuropsychiatric diseases,which can mimic psychiatric syndromes,in particular,those typically presented in severe mood disorders and schizophrenia.On the other hand,similarities in clinical presentation suggest that neuroinflammation and systemic immune dysregulation may play a role in the pathophysiology of severe mood and psychotic disorders.A complex interaction between periphery and immune cells of the CNS may result in cellular damage through mechanisms involving excitotoxicity,oxidative stress,and mitochondrial dysfunction.These pathways are possibly shared between comorbid medical disorders and severe mood and psychotic disorders and may reflect common underlying vulnerability.
文摘Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.
基金supported by Shanxi“1331 Project”Key Subjects Construction,No.1331KSC(to JSQ)Science Research Start-up Fund for Doctors of Shanxi Province,No.SD2011(to TL)Science Research Start-Up Fund for Doctors of Shanxi Medical University,No.XD2017(to TL)。
文摘Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.
文摘BACKGROUND Bipolar disorder(BD)is a severe psychiatric disorder characterized by mood swings.Psychosocial interventions,such as psychoeducation,play an essential role in promoting social rehabilitation and improving pharmacological treatment.AIM To investigate the role of psychoeducation in BD.METHODS A systematic review of original studies regarding psychoeducation interventions in patients with BD and their relatives was developed.A systematic literature search was performed using the Medline,Scopus,and Lilacs databases.No review articles or qualitative studies were included in the analysis.There were no date restriction criteria,and studies published up to April 2021 were included.RESULTS A total of forty-seven studies were selected for this review.Thirty-eight studies included patients,and nine included family members.Psychoeducation of patients and family members was associated with a lower number of new mood episodes and a reduction in number and length of stay of hospitalizations.Psychoeducational interventions with patients are associated with improved adherence to drug treatment.The strategies studied in patients and family members do not interfere with the severity of symptoms of mania or depression or with the patient's quality of life or functionality.Psychoeducational interventions with family members do not alter patients'adherence to pharmacotherapy.CONCLUSION Psychoeducation as an adjunct strategy to pharmacotherapy in the treatment of BD leads to a reduction in the frequency of new mood episodes,length of hospital stay and adherence to drug therapy.
文摘Available evidence points to a possible role of the renin-angiotensin system(RAS)in the pathophysiology of mood disorders and suicide.We carried out a critical analysis of literature data regarding this role,with a focus on the proposed association between RAS dysfunction and suicidal behavior.Epidemiological,genetic,and biochemical findings are described,and the pathophysiological hypothesis aiming at explaining the possible relationship between RAS and suicide are discussed.Available findings do support the involvement of the RAS in the neurobiology of suicide,although the exact mechanisms underlying this involvement are still unknown.
基金Supported by Slovenian Research Agency,Young Researcher Grant toŠalamon Arčan I,No.P1-0390,J3-4533,Z3-2653.
文摘The global burden of psychopathologies appears to be underestimated,since the global psychiatric disorder burden is exceeding other medical burdens.To be able to address this problem more effectively,we need to better understand the etiology of psychiatric disorders.One of the hallmarks of psychiatric disorders appears to be epigenetic dysregulation.While some epigenetic modifications(such as DNA methylation)are well known and studied,the roles of others have been investigated much less.DNA hydroxymethylation is a rarely studied epigenetic modification,which as well as being an intermediate stage in the DNA demethylation cycle is also an independent steady cell state involved in neurodevelopment and plasticity.In contrast to DNA methylation,DNA hydroxymethylation appears to be related to an increase in gene expression and subsequent protein expression.Although no particular gene or genetic locus can be at this point linked to changes in DNA hydroxymethylation in psychiatric disorders,the epigenetic marks present good potential for biomarker identification because the epigenetic landscape is a result of the interplay between genes and environment,which both influence the development of psychiatric disorders,and because hydoxymethylation changes are particularly enriched in the brain and in synapse-related genes.
文摘OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19.Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization.The patients received either Xiaoyao capsule(experimental group)or a placebo Xiaoyao capsule(control group)for 2 weeks.The improvements in the Traditional Chinese Medicine(TCM)syndrome scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep were compared between the two groups.RESULTS:The TCM syndrome pattern scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment(P>0.05).CONCLUSIONS:Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.
文摘Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifically focusing on those seeking assistance due to suicide attempts (TS) versus CLP requests for other reasons (non-TS) between the years 2010 and 2020. Additionally, we aim to assess factors associated with suicide attempts. Method: This retrospective controlled study involves a thorough examination of medical records encompassing 3913 patients who received CLP services at the Hospital de Base (HB) and the Children and Maternity Hospital (HCM) of São José do Rio Preto Medical School Foundation (Funfarme) from June 2010 to June 2020. The patient cohort is categorized into two groups: those with requests for SA (n = 677) and those with requests for other reasons. Results: In the SA group, as opposed to the non SA group, statistically significant differences were observed for gender (predominantly female), employment status (employed), marital status (single), and age (younger). Notably, a higher prevalence of psychiatric antecedents (88.7%, n = 555 vs. 73.6% n = 2018) was found in the SA group, indicating a significant association. The frequency of SA requests remained stable over the years. Among the SA group, mood disorders were the most prevalent (39%, n = 372), followed by disorders related to substance use (21.2%, n = 202), and personality disorders (16%, n = 152). A history of previous suicide attempts emerged as a crucial factor for the recurrence of SA (p-value ≤ 0.001). Exogenous intoxication emerged as the most frequently employed method in attempts (79.6%, n = 539), particularly prevalent among patients diagnosed with mood disorders (41%, n = 314). A significant association was observed between the method of attempt and the nosological psychiatric diagnosis (χ<sup>2</sup> = 42.277;p ≤ 0.001). Regarding outcomes, the majority of patients were referred for outpatient follow-up (23%, n = 336) in specialized mental health services or at the Primary Healthcare Unit, highlighting the general hospital’s pivotal role in integrating patients into the broader healthcare network. Conclusion: Variables such as gender (female), age group (young adults), and psychiatric history exhibited stronger associations with suicide attempts compared to the group assisted by CLP for other reasons. Furthermore, a noteworthy correlation between the method employed and the psychiatric diagnosis was identified.
文摘Psychiatry remains in a permanent state of crisis,which fragmented psychiatry from the field of medicine.The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic,biological,molecular,pan-omics,precision,cognitive and phenomenological psychiatry,folk psychology,mind-brain dualism,descriptive psychopathology,and postpsychiatry.The current“gold standard”Diagnostic and Statistical Manual of Mental Disorders/International Classification of Diseases taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach.Therefore,it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches.The aim of this paper is to explain the new nomothetic network psychiatry(NNP)approach,which uses machine learning methods to build data-driven causal models of mental illness by assembling risk-resilience,adverse outcome pathways(AOP),cognitome,brainome,staging,symptomatome,and phenomenome latent scores in a causal model.The latter may be trained,tested and validated with Partial Least Squares analysis.This approach not only allows to compute pathway-phenotypes or biosignatures,but also to construct reliable and replicable nomothetic networks,which are,therefore,generalizable as disease models.After integrating the validated feature vectors into a well-fitting nomothetic network,clustering analysis may be applied on the latent variable scores of the R/R,AOP,cognitome,brainome,and phenome latent vectors.This pattern recognition method may expose new(transdiagnostic)classes of patients which if cross-validated in independent samples may constitute new(transdiagnostic)nosological categories.
文摘The versatility of glutamate as the brain’s foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge.Years of research have continued to uncover glutamate’s effects and roles in several neurological and neuropsychiatric disorders,including depression.It had been considered that a deeper understanding of the roles of glutamate in depression might open a new door to understanding the pathological basis of the disorder,improve the approach to patient management,and lead to the development of newer drugs that may benefit more patients.This review examines our current understanding of the roles of endogenous and exogenous sources of glutamate and the glutamatergic system in the aetiology,progression and management of depression.It also examines the relationships that link the gut-brain axis,glutamate and depression;as it emphasizes how the gut-brain axis could impact depression pathogenesis and management via changes in glutamate homeostasis.Finally,we consider what the likely future of glutamate-based therapies and glutamate-based therapeutic manipulations in depression are,and if with them,we are now on the final chapter of understanding the neurochemical milieu of depressive disorders.
文摘A number of studies have assessed the influence of depression on the risk of cardiovascular disease. A growing literature indicates a link between depression and cerebrovascular events, although the direction of this association remains unclear. Numerous data have emerged suggesting an association between depressive symptoms and subsequent risk of stroke, thus leading to the hypothesis that a direct causality between depression and stroke exists. Notwithstanding, how depression may act as a risk factor for stroke is still unclear. Depression might be linked to stroke via neuroendocrine and inflammation effects, through correlation with major comorbidities such as hypertensionand diabetes or by intervention of lifestyle behavioral mediators. Finally, antidepressant medications have recently drawn attention for a possible association with increased risk of stroke, although such findings remain uncertain. Depression has been also established as an important consequence after stroke, exerting a significant adverse impact on the course of motor recovery, social functioning and, overall, on quality of life. Post stroke depression occurs in nearly one third of stroke cases, but the exact mechanism leading to depression after stroke is still incompletely understood. In this article, we will review contemporary epidemiologic studies, discuss potential mechanisms and specific aspects of the complex relation between depression and stroke.
基金Supported by German Research Foundation(Cluster of Excellence"Languages of Emotion",EXC302 and KFO247)
文摘AIM: To investigate neural and behavioral correlates of emotional experiences as potential vulnerability markers in remitted depression. METHODS: Fourteen remitted participants with a history of major depression and fourteen closely matched healthy control participants took part in the study. We used two psychiatric interviews(Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and one self-report scale(Beck Depression Inventory) to assess remission. Healthy control participants were interviewed by an experienced psychiatrist to exclude those who showed any current or lifetime psychiatric or neurological disorders. To explore psychosocialand cognitive-interpersonal underpinnings of potential vulnerability markers of depression, early life stress, coping styles and alexithymia were also assessed. We induced pleasant and unpleasant emotional states using congruent combinations of music and human emotional faces to investigate neural and behavioral correlates of emotional experiences; neutral stimuli were used as a control condition. Brain responses were recorded using functional magnetic resonance imaging. Behavioral responses of pleasantness, arousal, joy and fear were measured via button-press inside the resonance imaging scanner. RESULTS: The mean age of the sample was 54.9(± 11.3) years. There were no differences between remitted depressed(RD)(n = 14; 9 females and 5 males) and healthy participants(n = 14; 8 females and 6 males) regarding age, current degree of depression, early life stress, coping styles and alexithymia. On a neural level, RD participants showed reduced activations in the pregenual anterior cingulate cortex(pg ACC) in response to pleasant [parameter estimates:-0.78 vs 0.32; t(26) =-3.41, P < 0.05] and unpleasant [parameter estimates:-0.88 vs 0.56; t(26)=-4.02, P < 0.05] emotional stimuli. Linear regression analysis revealed that pg ACC activity was modulated by early life stress [β =-0.48; R2 = 0.23, F(1,27) = 7.83, P < 0.01] and taskoriented coping style [β = 0.63; R2 = 0.37, F(1,27) = 16.91, P < 0.001]. Trait anxiety modulated hippocampal responses to unpleasant stimuli [β = 0.62; R2= 0.38, F(1,27) = 15.95, P < 0.001]. Interestingly, in their reported experiences of pleasantness, arousal, happiness and fear in response to pleasant, unpleasant and neutral stimuli, RD participants did not differ significantly from healthy control participants. Adding trait anxiety or alexithymia as a covariate did not change the results.CONCLUSION: The present study indicates that, in euthymic individuals, depression history alters neural correlates, but not the subjective dimension of pleasant and unpleasant emotional experiences.
基金Supported by Ratchadapisek Research Funds,Faculty of Medicine,Chulalongkorn University,No.RA60/042(to BK),and No.RA61/050(to MM).
文摘BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and psychosis.Aberrations in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric conditions.AIM To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in TLE.METHODS We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal controls.The areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for MTS.Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(P<0.0001)and psychopathology(P<0.0001),which were both mediated by lowered CMPAase activity,while arylesterase activity was not significant.The severity of TLE was significantly associated with psychopathology scores.Furthermore,PON1 CMPAase activity was inversely associated with Mini Mental State Examination score.CONCLUSION The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase activity.Total PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity.PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.
基金Supported by Conselho Nacional de Desenvolvimento Cientifico-CNPq.
文摘Although efforts have been made to improve the pharmacological treatment of depression,approximately one-third of patients with depression do not respond to conventional therapy using antidepressants.Other potential non-pharmacological therapies have been studied in the last years,including the use of mesenchymal stem cell therapies to treat depression.These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients.Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its antiinflammatory and neurotrophic properties.However,some clinical trials involving treatment of depression with stem cells are in progress,but with no published results.These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.
