Association between apathy and caregiver burden in patients with amyotrophic lateral sclerosis: a cross-sectional study.

OBJECTIVES: To investigate the relationship among patients' apathy, cognitive impairment, depression, anxiety, and caregiver burden in amyotrophic lateral sclerosis (ALS). DESIGN: A cross-sectional study design was used. SETTING: The study was conducted at a tertiary hospital in Wuhan, Hubei, China. PARTICIPANTS: A total of 109 patients with ALS and their caregivers were included. OUTCOME MEASURES: Patients with ALS were screened using the Edinburgh Cognitive and Behavioural Screen, Beck Depression Inventory-II, Generalised Anxiety Disorder-7 and Apathy Scale to assess their cognition, depression, anxiety and apathy, respectively. The primary caregivers completed the Zarit Burden Interview. The association between apathy, cognitive impairment, depression, anxiety and caregiver burden was analysed using logistic regression. Mediation models were employed to investigate the mediating effect of patients' apathy on the relationship between depression/anxiety and caregiver burden. RESULTS: Patients in the high caregiver burden group exhibited significantly higher levels of depression, anxiety and apathy compared with those in the low caregiver burden group (p<0.05). There was a positive association observed between caregiver burden and disease course (rs=0.198, p<0.05), depression (rs=0.189, p<0.05), anxiety (rs=0.257, p<0.05) and apathy (rs=0.388, p<0.05). There was a negative association between caregiver burden and the Revised ALS Functional Rating Scale (rs=-0.275, p<0.05). Apathy was an independent risk factor for higher caregiver burden (OR 1.121, 95% CI 1.041 to 1.206, p<0.05). Apathy fully mediated the relationship between depression and caregiver burden (ß=0.35, 95% CI 0.16 to 0.54, p<0.05) while partially mediating the relationship between anxiety and caregiver burden (ß=0.34, 95% CI 0.16 to 0.52, p<0.05). CONCLUSIONS: Apathy, depression and anxiety exerted a detrimental impact on caregiver burden in individuals with ALS. Apathy played a mediating role in the relationship between depression and caregiver burden and between anxiety and caregiver burden. These findings underscore the importance of identifying apathy and developing interventions for its management within the context of ALS.

Mental disorders in adults from Ribeirão Preto, Brazil: a cross-sectional analysis of two birth cohorts.

BACKGROUND: In Brazil, the prevalence of mental disorders is heterogeneous, with most studies conducted in large cities with high population density. This study aimed to assess the prevalence of mental disorders and psychiatric comorbidities among young adults (22-23 years old) and adults (37-38 years old) from Ribeirão Preto, a city located in the Northeast of the São Paulo state, with approximately 700,000 inhabitants, and to explore associations with sociodemographic variables, suicide risk, and health service usage. Second, we aimed to evaluate the performance of the Self-Report Questionnaire (SRQ-20) as a screening tool for mental disorders to be applied to the local population. METHODS: Participants from the 1978/1979 and 1994 Ribeirão Preto birth cohorts were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the SRQ-20 at mean ages of 22-23, and 37-38 years, respectively. RESULTS: Our sample comprised 1,769 individuals from the 1978/1979 cohort and 1,037 from the 1994 cohort. The prevalence of mental disorders ranged from 28.6% (1978/79) to 31% (1994), with frequent comorbid diagnoses (42.7% and 43.3%, respectively). Men and women had a similar prevalence of mental disorders in the younger cohort, while women had a higher prevalence in the older cohort. Low educational attainment was associated with higher rates of diagnosis. In both cohorts, alcohol and other psychoactive substance use was higher among those with a psychiatric diagnosis. Although those with a psychiatric diagnosis were less satisfied with their own health, only one-fifth had seen a mental health professional in the previous year. A psychiatric diagnosis increased the suicide risk by 5.6 to 9.1 times. Regarding the SRQ-20, the best cutoff points were 5/6 for men and 7/8 for women, with satisfactory performance. CONCLUSIONS: The prevalence and comorbidity of mental disorders were high in both cohorts and comparable to those in larger Brazilian cities. However, few individuals with a diagnosis had sought specialized care. These data suggest that the mental health gap is still significant in Brazil.

Suicide warning signs of self-identification in patients with mood disorders: a qualitative analysis based on safety planning.

Introduction: Warning signs serve as proximal indicators of suicide risk, making early recognition imperative for effective prevention strategies. This study aimed to explore self-identified suicide warning signs among Chinese patients with mood disorders based on safety planning framework. Methods: Researchers collaborated with patients to develop a safety plan and compiled warning signs based on it. Word frequency and network analysis were conducted to identify key warning signs. Directed content analysis categorized these signs into cognitive, emotional, behavioral, or physiological themes according to the suicide mode theory. Additionally, we examined potential variations in reported warning signs among participants with different demographic characteristics, including age, gender, and history of suicide attempts. Results: "Low mood" and "crying" emerged as prominent warning signs, with "social withdrawal" closely following. Patients commonly reported emotional themes during suicidal crises, often experiencing two to three themes simultaneously, primarily focusing on emotional, behavioral, and physiological themes. Males exhibited a higher proportion of concurrently reporting three sign themes compared to females (P < 0.05), while no difference was observed in warning signs among patients with other demographic traits. Discussion: This study offers a nuanced understanding of warning signs among mood disorder patients in China. The findings underscore the necessity for comprehensive suicide risk management strategies, emphasizing interventions targeting emotional regulation and social support. These insights provide valuable information for enhancing suicide prevention and intervention efforts.

Glymphatic System and Psychiatric Disorders: A Rapid Comprehensive Scoping Review.

BACKGROUND: Since discovering the glymphatic system, there has been a looming interest in exploring its relationship with psychiatric disorders. Recently, increasing evidence suggests an involvement of the glymphatic system in the pathophysiology of psychiatric disorders. However, clear data are still lacking. In this context, this rapid comprehensive PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) scoping review aims to identify and analyze current evidence about the relation between the glymphatic system and psychiatric disorders. METHODS: We conducted a comprehensive review of the literature and then proceeded to discuss the findings narratively. Tables were then constructed and articles were sorted according to authors, year, title, location of study, sample size, psychiatric disorder, the aim of the study, principal findings, implications. RESULTS: Twenty papers were identified as eligible, among which 2 articles on Schizophrenia, 1 on Autism Spectrum Disorders, 2 on Depression, 1 on Depression and Trauma-related Disorders, 1 on Depression and Anxiety, 2 on Anxiety and Sleep Disorders, 8 on Sleep Disorders, 2 on Alcohol use disorder and 1 on Cocaine Use Disorder. CONCLUSION: This review suggests a correlation between the glymphatic system and several psychiatric disorders: Schizophrenia, Depression, Anxiety Disorders, Sleep Disorders, Alcohol Use Disorder, Cocaine Use Disorder, Trauma-Related Disorders, and Autism Spectrum Disorders. Impairment of the glymphatic system could play a role in Trauma-Related Disorders, Alcohol Use Disorders, Cocaine Use Disorders, Sleep Disorders, Depression, and Autism Spectrum Disorders. It is important to implement research on this topic and adopt standardized markers and radio diagnostic tools.

High rates of mood disorders in patients with chronic idiopathic eosinopenia.

Background: Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods: This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results: Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions: CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

Magnesium (Mg2+): Essential Mineral for Neuronal Health: From Cellular Biochemistry to Cognitive Health and Behavior Regulation.

Magnesium (Mg2+) is a crucial mineral involved in numerous cellular processes critical for neuronal health and function. This review explores the multifaceted roles of Mg2+, from its biochemical interactions at the cellular level to its impact on cognitive health and behavioral regulation. Mg2+ acts as a cofactor for over 300 enzymatic reactions, including those involved in ATP synthesis, nucleic acid stability, and neurotransmitter release. It regulates ion channels, modulates synaptic plasticity, and maintains the structural integrity of cell membranes, which are essential for proper neuronal signaling and synaptic transmission. Recent studies have highlighted the significance of Mg2+ in neuroprotection, showing its ability to attenuate oxidative stress, reduce inflammation, and mitigate excitotoxicity, thereby safeguarding neuronal health. Furthermore, Mg2+ deficiency has been linked to a range of neuropsychiatric disorders, including depression, anxiety, and cognitive decline. Supplementation with Mg2+, particularly in the form of bioavailable compounds such as Magnesium-L-Threonate (MgLT), Magnesium-Acetyl-Taurate (MgAT), and other Magnesium salts, has shown some promising results in enhancing synaptic density, improving memory function, and alleviating symptoms of mental health disorders. This review highlights significant current findings on the cellular mechanisms by which Mg2+ exerts its neuroprotective effects and evaluates clinical and preclinical evidence supporting its therapeutic potential. By elucidating the comprehensive role of Mg2+ in neuronal health, this review aims to underscore the importance of maintaining optimal Mg2+ levels for cognitive function and behavioral regulation, advocating for further research into Mg2+ supplementation as a viable intervention for neuropsychiatric and neurodegenerative conditions.

Benzodiazepine use for anxiety disorders is associated with increased long-term risk of mood and substance use disorders: A large-scale retrospective cohort study.

Background: Benzodiazepines (BZDs) are widely prescribed for anxiety disorders. However, the long-term implications on mental health remain uncertain, especially the potential association between chronic BZD use and subsequent diagnosis of mood and substance use disorders (SUDs). Method: We conducted a 5-year retrospective cohort study by analyzing the TriNetX database, a real-time electronic medical record network. The study population was defined as patients aged 18-65 with anxiety disorders (ICD-10-CM: F40-F48). We employed propensity score matching to pair a BZD-exposed cohort (≥12 BZD prescriptions) with a BZD-unexposed control cohort. The outcomes were defined as depressive disorders, bipolar disorders, and SUDs. We employed Kaplan-Meier analyses to assess the survival probability over five years following diagnosis and BZD exposure; log-rank test to obtain the hazard ratio (HR) with 95 % confidence interval (CI). Results: We identified and matched 76,137 patients in the study and control cohorts. Compared to the control cohort, the BZD-exposed group exhibited significantly higher risks of being diagnosed with depressive disorders (HR, 2.64; 95 % CI, 2.59-2.68), bipolar disorders (HR, 4.39; 95 % CI, 4.15-4.64), overall substance use disorders (HR, 3.00; 95 % CI, 2.92-3.08), alcohol use disorder (HR, 3.38; 95 % CI, 3.20-3.57), stimulant use disorder (HR, 3.24; 95 % CI, 2.95, 3.55), cannabis use disorder (HR, 2.93; 95 % CI, 2.75-3.11), inhalant use disorder (HR, 4.14; 95 % CI, 3.38-5.06), and nicotine use disorder (HR, 2.72; 95 % CI, 2.63-2.81). Conclusion: Our findings demonstrate a concerning association between BZD use and an increased risk of being diagnosed with various mood disorders and SUDs.

Evaluation of Catatonia with Different Assessment Scales in Psychiatry and Neurology. / Psikiyatri ve Nörolojide Katatoninin Farkli Ölçeklerle Degerlendirilmesi.

OBJECTIVE: Catatonia is a syndrome that can be missed in clinical settings. Diagnosis of catatonia is important because the condition can be reversible and is associated with severe complications. This study aims to screen patients with catatonia admitted to a university hospital's psychiatry and neurology services, examine their characteristics, and compare the coverage of different catatonia scales. METHOD: During a consecutive 20 months study period, the Turkish adaptations of the Bush-Francis Catatonia Rating and the KANNER scales were administered in psychiatry and neurology inpatient units and patients on the waiting list for psychiatric hospitalization. The participants were also evaluated with DSM-5 criteria. In addition, the sociodemographic and clinical characteristics of the patients in the psychiatric group were compared. RESULTS: A total of 214 patients were evaluated. Twenty-eight (13.1%) screened positive for catatonia, and 23 (82.1%) were diagnosed with catatonia according to DSM-5 criteria. KANNER and Bush- Francis identified the same patients as having catatonia. In addition to schizophrenia and mood disorders; neurodevelopmental disorder, encephalitis, postpartum psychosis, obsessive-compulsive disorder, delirium, cerebrovascular disease, functional neurological symptom disorder have also been found to be associated with catatonia. The most common complication was urinary tract infection. Life-threatening complications were also observed. CONCLUSION: Overlooking catatonia may have dire consequences. Adhering solely to the DSM-5 criteria may miss some patients with catatonia. Widely and efficiently using standardized catatonia scales can improve detection capacity and enhance the management of morbidity and mortality.

Use of virtual reality in bipolar disorder: a systematic review.

Virtual reality (VR) is a technology that allows to interact with recreated digital environments and situations with enhanced realism. VR has shown good acceptability and promise in different mental health conditions. No systematic review has evaluated the use of VR in Bipolar Disorder (BD). This PRISMA-compliant systematic review searched PubMed and Web of Science databases (PROSPERO: CRD42023467737) to identify studies conducted in individuals with BD in which VR was used. Results were systematically synthesized around four categories (cognitive and functional evaluation, clinical assessment, response to VR and safety/acceptability). Eleven studies were included (267 individuals, mean age = 36.6 years, 60.7% females). Six studies using VR to carry out a cognitive evaluation detected impairments in neuropsychological performance and delayed reaction times. VR was used to assess emotional regulation. No differences in well-being between VR-based and physical calm rooms were found. A VR-based stress management program reduced subjective stress, depression, and anxiety levels. VR-based cognitive remediation improved cognition, depressive symptoms, and emotional awareness. 48.7% of the individuals with BD considered VR-based cognitive remediation 'excellent', whereas 28.2% considered it 'great'. 87.2% of individuals did not report any side effects. 81.8% of studies received a global quality rating of moderate. Emerging data point towards a promising use of VR in BD as an acceptable assessment/intervention tool. However, multiple unstudied domains as comorbidity, relapse and prodromal symptoms should be investigated. Research on children and adolescents is also recommended. Further research and replication of findings are required to disentangle which VR-interventions for which populations and outcomes are effective.

The Emerging Role of Neurosteroids: Novel Drugs Brexanalone, Sepranolone, Zuranolone, and Ganaxolone in Mood and Neurological Disorders.

This review investigates the potential of neurosteroids, including brexanolone, zuranolone, sepranolone, and ganaxalone, as therapeutic agents for a range of mood and neurological disorders. Notably, these disorders encompass postpartum depression, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), epilepsy, and Alzheimer's disease. Brexanolone and zuranolone have emerged as frontrunners in the treatment of postpartum depression, offering rapid relief from debilitating symptoms. Their mechanism of action involves modulation of the gamma-aminobutyric acid (GABA) system, which plays a pivotal role in mood regulation. Clinical trials have demonstrated their efficacy, heralding a potential breakthrough in addressing this often-overlooked condition. In the context of PTSD and MDD, neurosteroids have demonstrated significant promise. Their positive allosteric modulation of GABA-A receptors translates into improved mood stabilization and reduced symptoms. This novel approach represents a departure from conventional treatments and could offer newfound hope for individuals grappling with these disorders. Beyond mood disorders, neurosteroids, especially ganaxalone, exhibit potential in the realm of epilepsy management. Ganaxalone's capacity to control seizures is attributed to its GABAergic activity, which helps restore the delicate balance of neurotransmission in epileptic brains. Moreover, neurosteroids have revealed neuroprotective properties in Alzheimer's disease models. By influencing the GABAergic system, they mitigate excitotoxicity, a hallmark of Alzheimer's pathology. This neuroprotection opens a novel avenue for slowing neurodegeneration, although further research and clinical validation are essential. In conclusion, this review underscores the substantial therapeutic promise of neurosteroids in mood and neurological disorders. Their modulation of the GABA system emerges as a central mechanism of action, emphasizing the importance of GABAergic signaling in these conditions. The path forward entails continued investigation and clinical trials to fully unlock the potential of neurosteroids, offering hope for enhanced treatments in these challenging clinical domains.

Clinical experience with parenteral trazodone in mood disorders: A literature review. / Doswiadczenia kliniczne z trazodonem stosowanym droga pozajelitowa w zaburzeniach nastroju: przeglad literatury.

Trazodone is a serotonin antagonist/reuptake inhibitor, approved for treating major depressive disorder (MDD). Oral formulations are widely studied and marketed in several countries worldwide while there is little evidence to support use of parenteral formulation. Our narrative review summarizes pharmacological properties and clinical data concerning use of parenteral trazodone in mood disorders. PubMed and Web of Science were used to identify the most relevant literature. The main evidence concerns four studies evaluating efficacy in major depressive disorder and indicates that trazodone was well tolerated and effective. Off-label use in agitation associated with bipolar disorder is also reported in three studies, although prescription of concomitant treatment, as a confounding factor, may have influenced outcome measures. The limited available evidence supports parenteral trazodone use in major depressive disorder and suggests that trazodone is a suitable option in patients at high risk of treatment-emergent mania (TEM).

Trends in Electroconvulsive Therapy Utilization in South Korea: Health Insurance Review Data From 2008 to 2018.

OBJECTIVE: The study aimed to analyze and clinically correlate 10-year trends in the demographic characteristics of patients receiving electroconvulsive therapy (ECT) to provide an overview of ECT utilization in South Korea. METHODS: Using health insurance claims data from 2008 to 2018 retrieved from Health Insurance Review and Assessment Service database in South Korea, we identified individuals undergoing ECT based on procedural codes. Descriptive analysis evaluated baseline clinical characteristics, and trend analysis used a linear regression model. RESULTS: The prevalence of ECT increased by 240.49% (0.405/105 inhabitants in 2008 to 0.974/105 inhabitants in 2018). The increasing trend was more pronounced in younger and older patients. The proportion of women consistently exceeded that of men. A rise in the proportion of patients with affective disorders, and a decrease in the proportion of psychotic disorders was observed. More antidepressants and atypical antipsychotics were prescribed to patients undergoing ECT. The proportion of ECT sessions conducted in large hospital inpatient settings also decreased during the observation period. Despite increasing global trends, ECT prevalence in South Korea remains significantly lower than worldwide rates. CONCLUSION: This study demonstrated an increasing trend of ECT across a wide range of population demographics and in more accessible settings. The comparatively low prevalence of ECT in Korea compared to other countries might be attributed to insufficient mental health literacy and the stigma associated with ECT. Given the elevated suicide rates in Korea, more extensive adoption of ECT appears imperative.

Dysfunctional Alpha Modulation as a Mechanism of Working Memory Impairment in Serious Mental Illness.

BACKGROUND: People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on two potential mechanisms: first, poor attentional engagement should be associated with elevated levels of pre-stimulus alpha-band activity within the EEG, whereas impaired working memory encoding should be associated with reduced post-stimulus alpha suppression. METHODS: We collected EEG data from 68 people with schizophrenia, 43 people with bipolar disorder with a history of psychosis, and 53 people with major depressive disorder, as well as 90 healthy comparison subjects (HCS), while they completed a spatial working memory task. We quantified attention lapsing, memory precision, and memory capacity from the behavioral responses, and we quantified alpha using both traditional wavelet analysis as well as a novel approach for isolating oscillatory alpha power from aperiodic elements of the EEG signal. RESULTS: We found that (1) greater pre-stimulus alpha power estimated using traditional wavelet analysis predicted behavioral errors; (2) post-stimulus alpha suppression was reduced in the patient groups; and (3) reduced suppression was associated with lower likelihood of memory storage. However, we also observed that pre-stimulus alpha was larger among HCS compared to patients, and single-trial analyses showed that it was the aperiodic elements of the pre-stimulus EEG-not oscillatory alpha-that predicted behavioral errors. DISCUSSION: These results suggest that working memory impairments in serious mental illness primarily reflect an impairment in the post-stimulus encoding processes rather than reduced attentional engagement prior to stimulus onset.

VIVALDI ASCOT and Ethnography Study: protocol for a mixed-methods longitudinal study to evaluate the impact of COVID-19 and other respiratory infection outbreaks on care home residents' quality of life and psychosocial well-being.

INTRODUCTION: Older adults in care homes experienced some of the highest rates of mortality from SARS-CoV-2 globally and were subjected to strict and lengthy non-pharmaceutical interventions, which severely impacted their daily lives. The VIVALDI ASCOT and Ethnography Study aims to assess the impact of respiratory outbreaks on care home residents' quality of life, psychological well-being, loneliness, functional ability and use of space. This study is linked to the VIVALDI-CT, a randomised controlled trial of staff's asymptomatic testing and sickness payment support in care homes (ISRCTN13296529). METHODS AND ANALYSIS: This is a mixed-methods, longitudinal study of care home residents (65+) in Southeast England. Group 1-exposed includes residents from care homes with a recent COVID-19 or other respiratory infection outbreak. Group 2-non-exposed includes residents from care homes without a recent outbreak. The study has two components: (a) a mixed-methods longitudinal face-to-face interviews with 100 residents (n=50 from group 1 and n=50 from group 2) to assess the impact of outbreaks on residents' quality of life, psychological well-being, loneliness, functional ability and use of space at time 1 (study baseline) and time 2 (at 3-4 weeks after the first visit); (b) ethnographic observations in communal spaces of up to 10 care homes to understand how outbreaks and related restrictions to the use of space and social activities impact residents' well-being. The study will interview only care home residents who have the mental capacity to consent. Data will be compared and integrated to gain a more comprehensive understanding of the impact of outbreaks on residents' quality of life and well-being. ETHICS AND DISSEMINATION: The VIVALDI ASCOT and Ethnography Study obtained ethical approval from the Health Research Authority (HRA) Social Care REC (24/IEC08/0001). Only residents with the capacity to consent will be included in the study. Findings will be published in scientific journals.

Prevalence, determinants and care-seeking behaviour for anxiety and depression in Nepalese population: a secondary analysis of data from Nepal Demographic and Health Survey 2022.

OBJECTIVE: To determine the prevalence and factors associated with anxiety and depression and the care-seeking behaviour among Nepalese population. DESIGN AND SETTINGS: Secondary analysis of the data from nationally representative Nepal Demographic and Health Survey 2022. PARTICIPANTS: Analysed data of 12 355 participants (7442 females and 4913 males) aged 15-49 years. OUTCOME MEASURES: Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder Assessment (GAD-7) tools, respectively. STATISTICAL ANALYSIS: We performed weighted analysis to account for the complex survey design. We presented categorical variables as frequency, per cent and 95% confidence interval (CI), whereas numerical variables were presented as median, inter-quartile range (IQR) and 95% CI. We performed univariate and multivariable logistic regression to determine factors associated with anxiety and depression, and results were presented as crude OR (COR), adjusted OR (AOR) and their 95% CI. RESULTS: The prevalence of depression and anxiety were 4.0% (95% CI 3.5 to 4.5) and 17.7% (95% CI 16.5 to 18.9), respectively. Divorced or separated participants were found to have higher odds of developing anxiety (AOR 2.40, 95% CI 1.74 to 3.31) and depression (AOR 3.16, 95% CI 1.84 to 5.42). Among ethnic groups, Janajati had lower odds of developing anxiety (AOR 0.77, 95% CI 0.65 to 0.92) and depression (AOR 0.67, 95% CI 0.49 to 0.93) compared with Brahmin/Chhetri. Regarding disability, participants with some difficulty had higher odds of developing anxiety (AOR 1.81, 95% CI 1.56 to 2.10) and depression (AOR 1.94, 95% CI 1.51 to 2.49), and those with a lot of difficulty had higher odds of anxiety (AOR 2.09, 95% CI 1.48 to 2.96) and depression (AOR 2.04, 95% CI 1.06 to 3.90) compared with those without any disability. Among those who had symptoms of anxiety or depression, only 32.9% (95% CI 30.4 to 34.4) sought help for the conditions. CONCLUSIONS: Marital status and disability status were positively associated with anxiety and depression, whereas Janajati ethnicity had relatively lower odds of experiencing anxiety and depression. It is essential to develop interventions and policies targeting females and divorced individuals to help reduce the burden of anxiety and depression in Nepal.

Stress and the gut-brain axis: an inflammatory perspective.

The gut-brain axis (GBA) plays a dominant role in maintaining homeostasis as well as contributes to mental health maintenance. The pathways that underpin the axis expand from macroscopic interactions with the nervous system, to the molecular signals that include microbial metabolites, tight junction protein expression, or cytokines released during inflammation. The dysfunctional GBA has been repeatedly linked to the occurrence of anxiety- and depressive-like behaviors development. The importance of the inflammatory aspects of the altered GBA has recently been highlighted in the literature. Here we summarize current reports on GBA signaling which involves the immune response within the intestinal and blood-brain barrier (BBB). We also emphasize the effect of stress response on altering barriers' permeability, and the therapeutic potential of microbiota restoration by probiotic administration or microbiota transplantation, based on the latest animal studies. Most research performed on various stress models showed an association between anxiety- and depressive-like behaviors, dysbiosis of gut microbiota, and disruption of intestinal permeability with simultaneous changes in BBB integrity. It could be postulated that under stress conditions impaired communication across BBB may therefore represent a significant mechanism allowing the gut microbiota to affect brain functions.

Beneficial and harmful effects of tricyclic antidepressants for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis.

QUESTION: Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder. STUDY SELECTION AND ANALYSIS: We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or 'active placebo' for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17. FINDINGS: We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference -3.77 HDRS-17 points; 95% CI -5.91 to -1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference. CONCLUSIONS: The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence. PROSPERO REGISTRATION NUMBER: CRD42021226161.

The sensitivity of the Mini-Mental State Examination to detect objective cognitive side-effects induced by electroconvulsive therapy, results from the Dutch ECT Consortium.

BACKGROUND: Monitoring cognitive side-effects following electroconvulsive therapy (ECT) is crucial for balancing side-effects and clinical effectiveness. Unfortunately, evidence-based guidelines on cognitive testing following ECT are lacking. A frequently used test in global ECT practice is the Mini Mental State Examination (MMSE). We examined the change of the MMSE and its performance in identifying a decline in predefined neuropsychological measures sensitive to ECT-induced cognitive changes: verbal recall and verbal fluency. METHODS: The mean MMSE scores pre- and one week post-ECT were compared using a Wilcoxon signed-rank test. The Reliable Change Index was calculated for all cognitive measures to indicate whether an individual's change score from pre- to post-ECT is considered statistically significant. The sensitivity and specificity of the MMSE were calculated. RESULTS: 426 patients with depression from five sites were included from the Dutch ECT Consortium. The mean MMSE increased significantly from 26.2 (SD=3.9) pre-ECT to 26.8 (SD=3.8) post-ECT (p=0.002). 36 patients (8.5%) showed a significant decline in MMSE score post-ECT. The sensitivity of the MMSE in identifying patients who experienced a significant decline in verbal recall or verbal fluency ranged from 3.6% to 11.1%. The specificity of the MMSE in identifying patients who did not experience a significant decline in verbal recall or verbal fluency ranged from 95.6% to 96.6%. CONCLUSIONS: Given the very low sensitivity of the MMSE, we propose reconsidering the prominence of the MMSE in ECT practice and cognitive monitoring guidelines, advocating for a more comprehensive approach to assess ECT-induced cognitive changes.

Heart Rate Variability as a Potential Predictor of Response to Intranasal Esketamine in Patients with Treatment-Resistant Depression: A Preliminary Report.

Background: Esketamine has received approval as a nasal spray (ESK-NS) for treatment-resistant depression (TRD) and evidence from real-world investigations has confirmed the effectiveness of ESK-NS, albeit with interindividual differences in response. Heart rate variability (HRV), defined as the fluctuation in time interval between consecutive heartbeats, can be used to measure autonomic dysfunction in psychiatric disorders and its role has been investigated in diagnosis and prognosis of depression. Methods: This preliminary report aims to evaluate HRV parameters and their association with treatment outcome in 18 patients (55.6% males, 55.6 ± 9.39 years old) with TRD treated with a target dose of ESK-NS for one month (mean dose: 80.9 ± 9.05 mg). The Beck Depression Inventory (BDI) and a 3 min resting electrocardiogram were used to assess changes in depressive symptoms and HRV measurements before and after treatment. Results: Responders (n = 8, 44.5%; based on ≥30% BDI scores reduction) displayed lower HRV values than non-responders at baseline (p = 0.019), which increased at one month (p = 0.038). Receiver-Operating Characteristic (ROC) curves obtained from a logistic regression displayed a discriminative potential for baseline HRV in our sample (AUC = 0.844). Conclusions: These preliminary observations suggest a mutual interaction between esketamine and HRV, especially in relation to treatment response. Further studies are required to investigate electrophysiological profiles among predictors of response to ESK-NS and allow for personalized intervention strategies in TRD that still represent a public health concern.

Prevalence and Risk by Age and Sex of Sleep Dysregulation and Depressive Episodes in Bipolar and Depressive Disorders in a Community Survey in Sardinia, Italy.

Background/Objectives: Sleep disturbances often accompany mood disorders and persistent insomnia after mood symptoms have resolved may be a marker of poor outcome. The association between sleep symptoms and mood disorders seems to change with age and sex. This study aims to assess the frequency of depressive episodes and sleep disorders in the general population through an agile screening questionnaire and to evaluate the association of depressive episodes and sleep symptoms by sex and age categories. Methods: 774 women and 728 men from Sardinia aged > 16 years old were enrolled. The Patient Health Questionnaire (PHQ-9) was administered through a computer-assisted telephonic interview. Results: The frequency of depressive episodes was double in women (10.6% vs. 4.4%; p < 0.0001), with the highest values in women > 75 yo (17.4%). The frequency of sleep dysregulation was double in women (18.7% vs. 9.6%; p < 0.0001), with the highest values in women > 75 yo (35.9%) and the lowest in the group of men > 75 yo. The group of young males showed the lowest frequency of depressive episodes (1.4%) and a frequency of sleep dysregulation (9.1%) similar to that of the other groups of age and sex. Sleep dysregulation without depressive episodes presented a higher distribution in the elderly, both in males (20.7%) and in females (18.5%). No significative differences were found across sex and age groups in the distribution of depressive episodes without sleep dysregulation. Conclusions: The use of an agile screener such as PHQ9 in the general population and/or in populations at risk can be a valuable tool in finding those individuals in whom sleep dysregulation may represent an early warning signal, one that may be thoroughly evaluated to identify and treat possible sleep disorders early.