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Abstract Background Substance use disorders (SUDs) and mental health disorders (MHDs) are significant public health challenges with far-reaching consequences on individuals and society. Dual diagnosis, the coexistence of SUDs and MHDs, poses unique complexities and impacts treatment outcomes. A research landscape analysis was conducted to explore the growth, active countries, and active journals in this field, identify research hotspots, and emerging research topics. Method A systematic research landscape analysis was conducted using Scopus to retrieve articles on dual diagnosis of SUDs and MHDs. Inclusion and exclusion criteria were applied to focus on research articles published in English up to December 2022. Data were processed and mapped using VOSviewer to visualize research trends. Results A total of 935 research articles were found. The number of research articles on has been increasing steadily since the mid-1990s, with a peak of publications between 2003 and 2012, followed by a fluctuating steady state from 2013 to 2022. The United States contributed the most articles (62.5%), followed by Canada (9.4%). The Journal of Dual Diagnosis, Journal of Substance Abuse Treatment, and Mental Health and Substance Use Dual Diagnosis were the top active journals in the field. Key research hotspots include the comorbidity of SUDs and MHDs, treatment interventions, quality of life and functioning, epidemiology, and the implications of comorbidity. Emerging research topics include neurobiological and psychosocial aspects, environmental and sociocultural factors, innovative interventions, special populations, and public health implications. Conclusions The research landscape analysis provides valuable insights into dual diagnosis research trends, active countries, journals, and emerging topics. Integrated approaches, evidence-based interventions, and targeted policies are crucial for addressing the complex interplay between substance use and mental health disorders and improving patient outcomes.

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) has recently gained relevance in treating different psychiatric disorders. Limited evidence suggests that the beneficial effects of rTMS on psychopathology could be at least partly mediated through changes in inflammatory response. This systematic review summarizes the literature on whether rTMS can modulate inflammatory markers and thus positively influence the course of psychiatric illnesses. Materials and methods A systematic review of rTMS and inflammatory markers in psychiatric diseases was conducted according to PRISMA guidelines. Information on the association between rTMS treatment response and changes of inflammatory markers was extracted. The quality of the studies was assessed using the National Heart, Lung, and Blood Institute for human studies and the Systematic Review Center for Laboratory Animal Experimentation for animal studies. Results This review includes 17 studies (2 animal and 15 human studies) on the relationship between rTMS treatment response and changes of inflammatory markers. Positive changes in microglial activity and anti-inflammatory effects were associated with behavioral improvement in animal models of depression. However, these findings have not been consistently replicated in human studies focusing on treatment-resistant depression. While several studies reported rTMS-induced alterations in peripheral inflammatory markers, only two could demonstrate their association to clinical treatment response. Notably, most studies showed poor or moderate quality in the bias assessment. Conclusions While certain human studies suggest an association between rTMS-induced anti-inflammatory effects and improvement in psychopathology, heterogeneity, and underpowered analyses constrain the generalizability of these results. The discrepancy between animal and human findings highlights the need for larger, standardized human studies. Trial registration (PROSPERO Registration: CRD42023492732).

Abstract This study examined whether maternal depression is related to Early Childhood Developmental (ECD) delay among children by quantifying the mediating contribution of responsive caregiving. We used data from 1235 children (Children’s mean age = 50.4 months; 582 girls, 653 boys, 93.9% were Han), selected through convenience sampling, in 2021. 4.7% of children had ECD delay, 34.3% of mothers had depression. Children with depressed mothers were less likely to receive responsive caregiving (OR 4.35, 95% CI 2.60–7.27), and those who did not receive responsive caregiving were more likely to experience ECD delay (OR 3.89, 95% CI 1.89–8.02). Responsive caregiving partly mediated the relationship between maternal depression and ECD. Early intervention for children with depressed mothers is worthy of further investigation.

Abstract Background Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. Methods Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5–84 years), year (1990–2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. Results In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from −0.54% (−0.61%, −0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. Conclusions Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Abstract Background The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties. Methods Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure. Results Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%. Conclusions Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.

Abstract Background In the available literature, levels of BDNF and CRP have been reported to correlate with suicide in depressive patients but there are inconsistencies in the results. We aimed to evaluate and compare BDNF and CRP concentrations in MDD patients with(MDD + SA) and without suicide attempts (MDD-SA) and healthy controls. Methods 30 (MDD + SA) patients, 30 (MDD-SA) patients, and 26 healthy controls were enrolled in the study. Age, sex, and BMI of patients were recorded. Blood sample was obtained for measurement of BDNF and CRP. Smoking and drug history, family history of suicide, and history of self-harm were also documented. Data were analyzed with SPSS version 22 and R version 4.1.1. Results 86 patients in three groups were evaluated (mean age: 28.45 ± 9.27 years, 56.71% female). Baseline and demographic parameters except for self-harm (40%, 3.3%, and 0% for MDD + SA, MDD-SA, and healthy controls, respectively, p = 0.001) did not differ between groups. CRP level was not significantly different between groups. BDNF showed a significant difference between groups (17.35, 16.45, and 19.43 for three groups, respectively, p

Abstract Background The presence of depression related to an increased risk of all-cause and cardiovascular disease (CVD) mortality has been reported. However, studies conducted on certain specific depressive symptoms are scarce. Our purpose was to assess the effect of both depressive symptoms scores and certain specific depressive symptoms on all-cause and CVD mortality. Methods In the present cohort study, all participants, aged 18 years or older, were enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Depressive symptoms score was assessed using the validated 9-item Patient Health Questionnaire Depression Scale (PHQ-9), which ranges from 0 to 27, with a PHQ-9 score ≥ 10 diagnosed as depression. The outcome events were all-cause and CVD mortality, which were followed up from 2005 to 2014. The associations of both depressive symptoms score and certain specific depressive symptoms with all-cause and CVD mortality were examined by weighted multivariable proportional hazards models. Results A total of 26,028 participants aged ≥ 18 years were included in the statistical analysis, including 12,813 (49.2%) males and 13,215 (50.8%) females, with a mean (SD) age of 47.34 (18.86) years. During the 9.32 (3.20) years of mean (SD) follow-up, 3261 deaths were recorded, of which 826 were cardiovascular deaths. All-cause mortality was 16.87/1000 person-years in subjects with depression. In terms of CVD mortality, these figures were 4.53/1000 person-years. In the full model (model 3), elevated depressive symptoms scores were independently associated with an increased risk of all-cause mortality (Highest depression symptom score group: adjusted hazard ratio, 1.63; 95% CI 1.44–1.85) and CVD mortality (Highest depression symptom score group: adjusted hazard ratio, 1.73; 95% CI 1.34–2.24). All 9 specific depressive symptoms that make up the PHQ-9 were related to an increased risk of all-cause mortality. However, only 3 symptoms, including trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation, were no significantly associated with an increased risk of CVD mortality. Conclusions The elevated depressive symptoms scores were strongly associated with an increased risk of all-cause and CVD mortality in US adults. Furthermore, all 9 specific depressive symptoms were associated with high all-cause mortality. However, trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation might not increase the risk of CVD mortality.

Abstract Background and Objectives The aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25). Methods The 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S). Results The safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin. Conclusions In adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin. Clinicaltrials.gov identifiers D1050234, D1050302.

Abstract General Practitioners (GPs) play a key role in the early detection and management of depression and in preventing suicide risk. They are often the first healthcare professionals that people in crisis contact. However, their effectiveness can be limited by several barriers, including the lack of specific training and appropriate tools. The EAAD-Best project aims to fill these gaps through its iFightDepression tool, an online tool designed to support patients, psychologists, psychiatrists, and GPs in managing depression and preventing suicide. This article examines the implementation of the iFightDepression platform in Italy, assessing its impact on the empowerment of GPs in the fight against depression. Through a qualitative and quantitative analysis of the data collected by the project, the ‘unmet need’ of GPs’ in Italy regarding their specific training in mental health is highlighted. The response of 2,068 Italian GPs in just 7 months after the start of the iFD project is an expression of GPs’ engagement to work against depression and for suicide risk prevention.

Abstract Purpose This study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance on methylphenidate (MPH) over a three-year period. Methods A total of 517 ADHD children aged 6–14 years were included. Baseline assessments included the identification of EEG-ab, ADHD inattentive subtype (ADHD-I), comorbid epilepsy, the use of antiepileptic drugs (AEDs) and the use of MPH. At the 3-year follow-up, assessments included the presence of EEG-ab, maintenance on MPH, AED usage, SZ risk in cases with EEG-epileptiform abnormalities (EEG-epi-ab), compared with control ADHD cases without EEG-epi-ab matched for age and gender. Results EEG-ab were identified in 273 (52.8%) cases. No statistically significant differences were observed between the EEG-ab and EEG-non-ab groups in terms of age, gender, ADHD-I type or initial use of MPH. EEG non-epileptiform abnormalities (EEG-non-epi-ab) were found in 234 out of 478 (49%) cases without EEG-epi-ab. Notably, EEG-non-epi-ab occurred more frequently in the group of 39 cases with EEG-epi-ab (30/39 (76.9%) vs. 9/39, (21.3%), a subset selected for 3-year follow-up. At 3-year-follow-up no statistically significant difference was found in maintenance on MPH in ADHD cases with and without EEG-epi-ab. Nobody of ADHD cases without comorbid epilepsy or with comorbid epilepsy with achieved SZ freedom developed new SZ. Only 3 children with drug resistant epilepsy experienced SZs, without increase in SZ frequency. The disappearance rate of EEG-epi-ab was higher than that EEG-non-epi-ab (71.8% vs. 33.3%). Conclusions Children with and without EEG-ab exhibited similar patterns of MPH use (initial use, positive response, and maintenance on MPH). The presence of comorbid epilepsy and EEG-ab, with or without EEG-epi-ab, was not associated with an increased risk of SZ despite the use of MPH.

Abstract Background Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine. Methods This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring. Results We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25–1.50), bipolar disorder (1.35, 1.06–1.71), and depressive disorder (1.33, 1.21–1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks. Conclusions Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.

Abstract Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD.

Abstract Background Depression is a highly heterogeneous disorder, often resulting in suboptimal response and remission rates. This underscores the need for more nuanced clinical characterization of patients to tailor individualized treatment plans. Emerging evidence highlights the critical role of cognitive and emotional dysfunction in major depression, prompting the exploration of novel therapeutic interventions that target these specific symptom domains. Main text Vortioxetine, a multimodal antidepressant, enhances serotonergic activity while also modulating several other neurotransmitter systems involved in depressive symptoms such as emotional blunting, anhedonia, and cognitive dysfunction. Numerous randomized, placebo-controlled trials have demonstrated vortioxetine’s efficacy and safety in treating depression, particularly in specific subgroups of depressed patients, including those with cognitive deficits and comorbid anxiety symptoms or disorders. Although not randomized or placebo-controlled, studies have also shown vortioxetine’s efficacy in depressed patients with emotional blunting or anhedonia. Vortioxetine’s ability to effectively treat a range of depressive symptoms, including anhedonia, emotional blunting, anxiety, and cognitive dysfunction, provides an individualized treatment solution for depressed individuals suffering from these symptoms. The purpose of this paper is to identify clinical profiles of patients who may benefit from vortioxetine, with the goal of optimizing therapeutic outcomes. Conclusion Vortioxetine has been shown to be effective for patients with depression and symptoms such as anhedonia, emotional blunting, anxiety, and cognitive dysfunction. Tailoring treatment plans to individual needs and personalizing treatment choices based on the specific symptoms presented by depressed patients improve treatment outcomes.

Abstract Background Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. Objectives Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. Methods 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach’s coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. Result CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach ‘s of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. Conclusion Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial.

Abstract Background Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. Methods Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. Results The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P

Abstract Purpose Formal coercion in psychiatry is widely studied yet much less is known about pressures patients may experience, partly because of the very few measures available. The goal of this study was to validate the P-PSY35 (Pressures in Psychiatry Scale) and provide a paper-and-pencil and a computerised adaptive test (CAT) to measure pressures experienced by patients in psychiatry. Methods The P-PSY35 items were developed with users. Patients were evaluated during psychiatric hospitalisation or through an online survey. Mokken scale analysis and Item response theory (IRT) were used to select and estimate the items parameters. A Monte-Carlo simulation was performed to evaluate the number of items needed to transform the paper-and-pencil test into a reliable psychometric CAT. Results A total of 274 patients were assessed. The P-PSY35 demonstrated good internal validity, internal consistency, convergent and divergent validity. The P-PSY35 could be substantially shortened while maintaining excellent reliability using the CAT procedure. Conclusion The P-PSY35 was developed in collaboration with users. It is a psychometrically rigorous tool designed to measure experienced pressures in French-language. The development and successful validation of the P-PSY35 represent a welcome step towards implementing and evaluating programs aimed at reducing negative consequences of coercion.

Abstract Background While depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown. Methods Sixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants. Results The result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately. Conclusions Cortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness.

Abstract Background Patients with mood disorders usually require repeated and prolonged hospitalization, resulting in a heavy burden on healthcare resources. This study aims to identify variables associated with length of stay(LOS) of repeatedly hospitalized patients with mood disorders and to provide information for optimizing psychiatry management and healthcare resource allocation. Methods Electronic medical records (EMRs) of repeatedly hospitalized patients with mood disorders from January 2010 to December 2018 were collected and retrospectively analyzed. Chi-square and t-test were adopted to investigate the differences in characteristics between the two groups of short LOS and long LOS. Generalized estimating equation (GEE) was conducted to investigate potential factors influencing LOS. Results A total of 2,009 repeatedly hospitalized patients with mood disorders were enrolled, of which 797 (39.7%) had a long LOS and 1,212 (60.3%) had a short LOS. Adverse effects of treatment, continuous clinical manifestation, chronic onset type, suicide attempt, comorbidity and use of antidepressants were positively associated with long LOS among all repeatedly hospitalized patients with mood disorders (P

Abstract Introduction Bipolar disorder (BD) is a chronic psychiatric disorder that combines hypomania or mania and depression. The study aims to investigate the research areas associated with cognitive function in bipolar disorder and identify current research hotspots and frontier areas in this field. Methodology Publications related to cognitive function in BD from 2012 to 2022 were searched on the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and Scimago Graphica were used to conduct this bibliometric analysis. Results A total of 989 articles on cognitive function in BD were included in this review. These articles were mainly from the United States, China, Canada, Spain and the United Kingdom. Our results showed that the journal “Journal of Affective Disorders” published the most articles. Apart from “Biploar disorder” and “cognitive function”, the terms “Schizophrenia”, “Meta analysis”, “Rating scale” were also the most frequently used keywords. The research on cognitive function in bipolar disorder primarily focused on the following aspects: subgroup, individual, validation and pathophysiology. Conclusions The current concerns and hotspots in the filed are: “neurocognitive impairment”, “subgroup”, “1st degree relative”, “mania”, “individual” and “validation”. Future research is likely to focus on the following four themes: “Studies of the bipolar disorder and cognitive subgroups”, “intra-individual variability”, “Validation of cognitive function tool” and “Combined with pathology or other fields”.

Abstract Introduction There is substantial evidence that people with mental illness have higher mortality rates than the general population. However, most of the studies were from Western countries, and it is not clear whether this finding also applies to Arab countries like Qatar. Objectives We aimed to explore whether mortality in patients with mental illness in Qatar, is different from those without. Methods We conducted a retrospective cohort study, including all Qatari nationals deceased in 2017 and 2018, using the list of registered deaths from Hamad Medical Corporation (HMC) Mortuary. We divided the cohort of deceased people into two groups: with and without mental illness. For each of the groups, we collected the age at death, the reported cause of death as well as sociodemographic and clinical data. Results There were 602 registered deaths in 2017 and 589 deaths in 2018. The prevalence of mental illness was 20.4%. Compared to subjects without mental illness, subjects with mental illness surprisingly had higher age at death (median ± IQR = 76.5 ± 22.1 years vs. 62.7 ± 32.9 years; p

Abstract Background Hikikomori (HK) is characterized by self-isolation and social refusal, being more likely also associated with affective disorders, including depression. This case–control study primarily aimed at identifying (if any) predominant affective temperaments are associated with HK in depressed versus not-depressed individuals. Secondary objectives comprise assessing which other psychopathological dimensions (e.g., boredom, anxiety) are associated with the HK specifier in depressed individuals. Methods From the larger SWATCH study, 687 Italian young people were screened for depression, as measured by 9 items-Patient Health Questionnaire (PHQ-9) and HK-like social withdrawal, through the Hikikomori Questionnaire-25 (HQ-25). All subjects were administered a brief-Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M), the 7 items-Generalized Anxiety Disorder (GAD-7) and the Multidimensional State Boredom Scale (MSBS). Results Males reported significantly higher scores at HQ-25 total score than females (p = 0.026). In the total sample, HK social withdrawal is positively predicted by MSBS low arousal, disengagement, depressive levels, depressive and irritable affective temperaments, while negatively by anxiety (F(6, 680) = 82.336, p

Abstract Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

Abstract Background Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. Methods Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran’s Q test, the MR–Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. Results According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001–1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914–0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010–0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567–0.912; P = 0.006). Conclusion The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Abstract Background Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. Methods This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5–20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. Results Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). Conclusion Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. Trial Registration NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Abstract Introduction A change of therapy from one to another antipsychotic medication is currently the main challenge of therapy. This study aimed to assess the prevalence of antipsychotic medication switches and determinants among patients with schizophrenia in Northwest Ethiopia. Methods Multi-center hospital-based cross-sectional study was conducted at five Comprehensive Specialized Hospitals found in Northwest Ethiopia from April 30, 2021, to August 30, 2021. Data were extracted from both patients’ medical charts and interviews. Data were entered into Epi-data software version 3.5.1 and exported to SPSS version 25.0 for analysis. A multivariable logistic regression model was fitted to identify factors associated with medication regimen switch. The level of significance of the study was kept at a p-value of 0.05 with a 95% confidence interval. Result A total of 414 patients are involved in the study, and 188 (45.5%) of patients switched antipsychotics within one year. The unavailability of the medication is the commonest reason for switching. Being male [AOR = 2.581, 95% CI (1.463, 4.552)], having relapse [AOR = 2.341,95% CI (1.169,4.687)], history of hospitalization in the past year [AOR = 3.00,95% CI (1.478,5.715)] and taking typical antipsychotics [AOR = 3.340, CI (1.76, 6.00)] had a significant association with antipsychotics switching. Conclusions and recommendations There is a high prevalence of antipsychotic switches among schizophrenia patients. Prescribers need to be careful while dosing, selecting, and switching antipsychotics, hence may help reduce discontinuation and unnecessary switch and thus achieve optimal clinical management.

Abstract Purpose The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. Materials and methods An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. Results PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. Conclusion The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

Abstract Introduction Weight gain in the months/years after diagnosis/treatment of severe enduring mental illness (SMI) is a major predictor of future diabetes, dysmetabolic profile and increased risk of cardiometabolic diseases. There is limited data on the longer-term profile of weight change in people with a history of SMI and how this may differ between individuals. We here report a retrospective study on weight change over the 5 years following an SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community, with particular focus on comparing non-affective psychosis (NAP) vs affective psychosis (AP) diagnoses. Methods We undertook an anonymised search in the Greater Manchester Care Record (GMCR). We reviewed the health records of anyone who had been diagnosed for the first time with first episode psychosis, schizophrenia, schizoaffective disorder, delusional disorder (non-affective psychosis = NAP) or affective psychosis (AP). We analysed body mass index (BMI) change in the 5-year period following the first prescription of antipsychotic medication. All individuals had taken an antipsychotic agent for at least 3 months. The 5-year follow-up point was anywhere between 2003 and 2023. Results We identified 9125 people with the diagnoses above. NAP (n = 5618; 37.3% female) mean age 49.9 years; AP (n = 4131; 60.5% female) mean age 48.7 years. 27.0% of NAP were of non-White ethnicity vs 17.8% of AP individuals. A higher proportion of people diagnosed with NAP were in the highest quintile of social disadvantage 52.4% vs 39.5% for AP. There were no significant differences in baseline BMI profile. In a subsample with HbA1c data (n = 2103), mean HbA1c was higher in NAP at baseline (40.4 mmol/mol in NAP vs 36.7 mmol/mol for AP). At 5-year follow-up, there was similarity in both the overall % of individuals in the obese ≥ 30 kg/m2 category (39.8% NAP vs 39.7% AP), and % progressing from a normal healthy BMI transitioned to obese/overweight BMI (53.6% of NAP vs 55.6% with AP). 43.7% of those NAP with normal BMI remained at a healthy BMI vs 42.7% with AP. At 5-year follow-up for NAP, 83.1% of those with BMI ≥ 30 kg/m2 stayed in this category vs 81.5% of AP. Conclusion The results of this real-world longitudinal cohort study suggest that the changes in BMI with treatment of non-affective psychosis vs bipolar disorder are not significantly different, while 43% maintain a healthy weight in the first 5 years following antipsychotic prescription.

Abstract Background More and more studies have confirmed that the heredity plays an important role in mental disorders, especially microRNA. The objective of this research was to explore the level of miR-15a-5p in patients with schizophrenia (SZ), and to evaluate the feasibility of this miRNA as a diagnostic marker of SZ. Methods The serum level of miR-15a-5p in patients with SZ and healthy people was detected by RT-qPCR. ROC curve was established to evaluate the clinical diagnostic significance of miR-15a-5p in SZ. Pearson correlation coefficient was used to evaluate the correlation between miR-15a-5p level and PANSS score. Logistic regression was used to assess the risk factors of SZ. A rat model of SZ was established, and the effects of miR-15a-5p on the behavior of SZ rats were observed through water maze test and open field test. Results The serum level of miR-15a-5p in patients with SZ was significantly increased, and ROC analysis revealed that miR-15a-5p had clinical diagnostic value in SZ. High level of miR-15a-5p was positively correlated with the positive symptom, negative symptom and general psychopathology subscore of patients. Logistic regression results showed that miR-15a-5p was a risk factor affecting the occurrence of SZ. Animal studies showed that the serum level of miR-15a-5p was elevated in the SZ rats, and inhibiting the expression of miR-15a-5p has a positive effect on improving the cognitive function and anxiety behavior of SZ rats. Conclusions Serum miR-15a-5p is a risk factor for SZ, which is of great significance for the diagnosis of SZ.

Abstract Background Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens. Methods The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model. Results Four predictors were selected from 38 variables by the univariate analysis (p

Abstract Background People are more likely to fall victim to depression during adolescence since it is a period of rapid biopsychosocial transformation. Despite this, most depression research has concentrated on clinical issues, and evaluating depressive symptoms in teenagers is not as widespread. This study used item response theory (IRT) to examine the psychometric properties of the Patient Health Report scale (PHQ-9) in Chinese adolescents. Meanwhile, item function difference tests were used to check whether there were differences in depression symptoms in this group based on education and gender. Methods In this research, the PHQ-9 was employed as a measurement tool, and 5958 valid data points were obtained from 12 secondary schools in China (M age = 13.484; SD age = 1.627; range 11–19 years; 52.17% boys). Results IRT shows that all items of the PHQ-9 satisfy monotonicity, unidimensionality and local independence and that they have good psychometric properties. Furthermore, DIF analysis revealed gender and educational disparities in adolescent depressive symptoms. Conclusion The study indicates that the PHQ-9 possesses favourable psychometric properties for use in Chinese adolescents. As a result, it serves as a valuable tool for effectively screening depressive symptoms in adolescents. It provides a foundation for prioritizing the development of secondary school students' physical and mental health.

Abstract Major depressive disorder (MDD) is predicted to become the second most common cause of disability in the near future. Exposure to glyphosate (Gly)-based herbicides has been linked to the onset of MDD. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the potential molecular mechanisms of MDD induced by Gly using network toxicology approach. The MDD dataset GSE76826 from the Gene Expression Omnibus database was referenced to identify differentially expressed genes (DEGs) in peripheral blood leukocytes of MDD patients and controls. The potential intersection targets of Gly-induced MDD were screened by network toxicology. The intersection targets were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and to construct protein–protein interaction networks. The binding potentials of hub targets with Gly were validated by molecular docking. In total, 1216 DEGs associated with Gly-induced MDD were identified. Subsequent network pharmacology further refined the search to 43 targets. GO and KEGG enrichment analyses revealed multiple signaling pathways involved in GLY-induced MDD. Six potential core targets (CD40, FOXO3, FOS, IL6, TP53, and VEGFA) were identified. Finally, molecular docking demonstrated that Gly exhibited strong binding affinity to the core targets. The results of this study identified potential molecular mechanisms underlying Gly induced MDD and provided new insights for prevention and treatment.

Abstract Facing suicide risk is probably the most difficult task for clinicians when dealing with patients in crisis. It requires professional, intellectual, and emotional efforts. Suicide risk assessment can sometimes be distressing for clinicians, and such a state may favour the avoidance of an in-depth exploration of suicidal thoughts and behaviour. Patients often feel subjected to interpersonal assessments with little opportunity to explore their perspectives. The "One size fits all" approach tends to create distance and paradoxically contributes to an increase in the risk of suicide. Traditional clinical factors may be of limited value if a shared understanding of the patient’s suicide risk is missed. To understand the suicidal mind, it is necessary to take the point of view of the subject in crisis. In this essay, the “operational model of mental pain as a main ingredient of suicide” provided by Edwin Shneidman is overviewed with the aim of a better empathic understanding of patients’ sufferance. With a phenomenological approach, the suicidal crisis appears as a complex, pervasive state rather than as a symptom of a mental disorder, as the new paradigm also suggests. In this regard, the "mentalistic" aspects of suicide propose a broader insight into the suicidal scenario far beyond the diagnosis of psychiatric disorders. In this article, the perspective of individuals who deem their mental pain to be intolerable is described to make sense of their ambivalence between the wish to die and the wish to live that can prevail if relief is provided.

Abstract Background It is known worldwide that stigma towards mental illness exists. Studies on stigma perceived by patients with mental illness have shown decreased quality of life and a negative impact on work, school and social life. The aim of this study was to estimate the prevalence of perceived stigma among respondents who had been diagnosed with a mental illness during the past 12 months, its association with socio-demographic variables and its effect on work and social roles limitations among Saudis. Methods The Saudi National Mental Health Survey (SNMHS) data were used for the analysis. The SNMHS is a nationally representative survey that was conducted using face-to -face interviews with Saudi individuals (age 15–65) in their households. Respondents were diagnosed (N = 639) with mental disorders based on a well-validated questionnaire—the Composite International Diagnostic Interview (CIDI) 3.0. Two dimensions from CIDI assessed perceived stigma: embarrassment and perceived discrimination. Results The prevalence of perceived stigma was 27.8% among mentally ill respondents. Stigma was lower among respondents who didn’t seek any type of treatment than those who sought treatment OR = 0.28 (95% CI 0.084–0.935, P = 0.03). Respondents who reported perceived stigma had more work role limitations (OR = 1.1 95% CI 1.01–0.10 P 0.006) and social limitations (OR = 1.3 95% CI 0.99–1.62 P 0.05) than respondents who didn’t report stigma. Conclusion Perceived stigma is experienced by mentally ill individuals and it negatively affects their work and social roles. Awareness programs to remove stigma and educate the public are needed to be established by policymakers and healthcare providers in Saudi Arabia.

Abstract Background Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings. Methods This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019. Results A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce. Conclusions In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.

Abstract Background Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019). Methods Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence. Results Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705–1.706)) and 2019 (RR: 1.602 (1.619–1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910–1.915)) was observed in the age group of 10–14. Relative sex difference had a significant positive relationship with SDI (standardized β = 0.267, P

Abstract Background Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a ‘forgotten drug’ and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common “misconceptions” and “stereotypes” associated with lithium treatment; we also provide a list of “good reasons” for using lithium in ordinary clinical practice to overcome those false myths. Main text A narrative search of the available literature has been performed entering the following keywords: “bipolar disorder”, “lithium”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding”. The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients’ groups suffering from bipolar disorder; (3) Drug–drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. Conclusions In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Abstract Background Major depressive disorder (MDD) is a major and common cause of suicide. The purpose of this article is to report the clinical characteristics and patterns of co-morbid suicidal behavior (SB) in first hospitalized and drug-naïve MDD patients. Methods A total of 345 patients with first hospitalization and drug-naïve MDD with SB were included in this study, while 183 patients without SB were included as a control group. We collected socio-demographic, general clinical data and common biochemical indicators of all participants and assessed their clinical symptoms. Results Compared to patients without SB, MDD with SB had more severe clinical symptoms and worse metabolic indicators. Duration of disease, depressive symptom scores, and thyroid stimulating hormone (TSH) levels was risk factors for SB and its number. Conclusions MDD patients with SB suffered more severe clinical symptoms and worse metabolic indicators, and risk factors for SB in this population were identified, which may provide beneficial insight and reference for clinical prevention and intervention of SB in MDD patients.

Abstract The digital transformation has made its way into many areas of society, including medicine. While AI-based systems are widespread in medical disciplines, their use in psychiatry is progressing more slowly. However, they promise to revolutionize psychiatric practice in terms of prevention options, diagnostics, or even therapy. Psychiatry is in the midst of this digital transformation, so the question is no longer “whether” to use technology, but “how” we can use it to achieve goals of progress or improvement. The aim of this article is to argue that this revolution brings not only new opportunities but also new ethical challenges for psychiatry, especially with regard to safety, responsibility, autonomy, or transparency. As an example, the relationship between doctor and patient in psychiatry will be addressed, in which digitization is also leading to ethically relevant changes. Ethical reflection on the use of AI systems offers the opportunity to accompany these changes carefully in order to take advantage of the benefits that this change brings. The focus should therefore always be on balancing what is technically possible with what is ethically necessary.

Abstract Background The purpose of the present review was to summarize the main literature contribution on the relationship between borderline personality disorder (BPD) and early psychosis. While retracing the historical path of the term “borderline”, specific attention was paid to psychotic and psychotic-like symptoms in BPD. Its relationship with At Risk Mental State was evaluated, as well. Methods This search was conducted on PUBMED/MEDLINE and PsycInfo, looking for “Borderline personality disorder, First Episode Psychosis, Early Psychosis, Ultra-High Risk AND/OR Clinical High Risk” for psychosis. Results Eight pertinent papers were identified on this topic. Their main findings were then discussed. The term “borderline” has undergone different changes in meaning and use, despite always referring to states considered on the fence between neurosis and psychosis. However, considering the history of psychopathology and its relationship with diagnostic manuals, little attention has been given to its psychotic features. Being those symptoms highly burdensome, this neglect has often led to misdiagnosis and under-treatment. Conclusions Psychotic symptoms in BPD can be severe and distressing. Nonetheless they can be easily neglected, and when found they challenge clinicians in defining a differential diagnosis to distinguish between BPD and Psychosis Spectrum Disorders. Given specific needs and interventions for these different conditions, a dimensional, rather than categorical, approach should be considered, as well as specific care pathways and monitoring should be advised.

Abstract Background There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses. Methods We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4–15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions—Improvement (CGI-I) was a secondary endpoint. Results Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (− 12.5 ± 3.18 [mean ± SE]) vs. placebo (− 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65). Conclusion Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27–0419-6116. ClinicalTrials.Gov registration ID is NCT06058962, last update posted 2023–09-28.

Abstract Background Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation. Methods We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent. Results Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications. Conclusions Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.

Abstract Background Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. Methods A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues’ responses. Stata 16.1 software was used for the analyses. Results Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. Conclusions This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients.

Abstract Background Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. Methods In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. Results We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. Conclusions While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

Abstract Objective To evaluate the clinical efficacy and safety of Agomelatine in improving symptoms in patients with major depressive disorder (MDD), providing more scientific evidence for the treatment of depression, and offering more effective therapeutic options for patients. Methods A total of 180 MDD patients in acute phase from 10 psychiatric hospitals of Grade three in Zhejiang Province were enrolled in this 12-week study with the competitive and consecutive pattern, and they were randomized into two different groups treated with flexible-dosage antidepressants of selective serotonin reuptake inhibitors (SSRI) or agomelatine, respectively. The subjects were evaluated with psychological scales of HAMD-17, HAMA, SHAPS for anhedonia, MFI-20 for fatigue, PQSI for sleep quality and MEQ for disturbances in chronobiologic rhythms at baseline, 2, 4, 8 and 12-weekend points, and TESS was used for side-effect. The results were analyzed with repeated measurement analysis of variance. Results The two groups each had 90 participants, and there were no significant differences at baseline. The scores of various assessment scales showed statistically significant time main effects during the visits (P

Abstract Background There is a conceptual overlap between negative and depressive symptoms, requiring further exploration to advance the understanding of negative symptoms. The aim of this study was to examine psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression, and to explore the relationship between the negative and affective symptoms domains. Methods Fifty-one patients with a depressive episode were included and interviewed with the CAINS and the Brief Psychiatric Rating Scale—Expanded (BPRS-E). Self-reported depressive symptoms were collected with the Montgomery-Asberg Depression Rating Scale (MADRS-S). Inter-rater agreement, internal consistency and validity measures were examined, as were correlations between negative and affective symptoms. Results The intraclass correlation for the CAINS motivation and pleasure subscale (CAINS-MAP) was 0.98 (95% CI 0.96–0.99) and that for the expressional subscale (CAINS-EXP) was 0.81 (95% CI 0.67–0.89). Cronbach’s alpha was 0.71 (95% CI 0.57–0.82) for the CAINS-MAP and 0.86 (95% CI 0.79–0.92) for the CAINS-EXP. The correlation with the negative symptoms subscale of the BPRS-E was 0.35 (p = 0.011, blinded/different raters) or 0.55 (p

Abstract Background The COVID-19 pandemic emerged as an expected source of stress and anxiety as the healthcare workers had to work for long hours in close contact with infected patients, thus increasing the probability of medical errors and threatening the patients’ safety. This study aims to measure the levels of depressive symptoms, anxiety symptoms, and stress among Syrian healthcare workers and their quality of life during the COVID-19 pandemic. Methods A cross-sectional study was conducted in six central hospitals in Damascus, Syria. Data were collected from 1 to 30 June—2021. The Depression Anxiety Stress Scale—21 (DASS-21) was used to evaluate depression, anxiety, and stress among healthcare workers. Quality of life was assessed using the EUROHIS-QOL 8-item index. Results A total of 700 participants were included in this study. 61.6% (n = 431) were males and 38.4% (n = 269) were females. Younger ages (18–29 years old) were significantly associated with higher levels of depression and stress (p

Abstract Objective Schizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia. Methods The study was case–control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy–Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed. Results There were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724–rs 2228611 was complete linkage disequilibrium, and rs 1569686–rs 2424908, rs 2424932–rs 1569696 and rs 2424932–rs 2424908 were strongly linkage disequilibrium. Conclusion The polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic was reported to have increased depression among university students which was associated with impairments in their campus lives. This study examined changes in depressive states among Japanese university students during the COVID-19 pandemic. Methods A secondary data analysis from a factorial randomized controlled trial involving smartphone-based cognitive-behavioral therapy was performed. Six cohorts (N = 1626) underwent an 8-week intervention during the spring or autumn of 2019–2021, with a 9-month follow-up. We evaluated participants’ depressive states weekly using the Patient Health Questionnaire-9 (PHQ-9) during the intervention, with monthly evaluations thereafter. The follow-up periods included Japan’s four states of emergency (SOEs) to control COVID-19. Hypothesizing that SOEs caused a sudden worsening of depressive states, Study 1 compared the cohorts’ PHQ-9 scores, and Study 2 employed time series analysis with a mixed-effects model to estimate identified changes in PHQ-9 scores. Results Although no changes in depressive states were observed in relation to the SOEs, Study 1 identified sudden increases in PHQ-9 scores at the 28-week evaluation point, which corresponded to the beginning of the new academic year for the three autumn cohorts. In contrast, the three spring cohorts did not exhibit similar changes. Study 2 showed that, for all three autumn cohorts (n = 522), the 0.60-point change was significant (95% CI 0.42–0.78; p

Abstract Background In Kalhbaum's first characterization of catatonia, the emotional symptoms, such as decreased or restricted expression of feelings and emotions, which is described as blunted affect, are related to the motor symptoms. In later years, the affective domain was excluded from the concept of catatonia and was not included among the diagnostic criteria in the various Diagnostic Statistical Manual (DSM) versions. In recent times, some authors have proposed the proposition of reevaluating the notion of catatonia through the reintroduction of the affective domain. The objective of this study was to examine the correlation between catatonic-like behavior (CLB), such as emotional withdrawal, blunted affect, and psychomotor slowing, and inflammatory markers, namely the neutrophil/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR), in individuals diagnosed with schizophrenia. Method A sample of 25 patients with schizophrenia (10 females, 15 males) was recruited, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of emotional withdrawal, blunted affect, and psychomotor slowing. Findings: The correlation analysis (Spearman ρ) revealed a robust direct association between blunted affect and psychomotor slowing (ρ = 0.79, P = 0.001), and a significant direct correlation between CLB (emotional withdrawal, ρ = 0.51, P = 0.05; blunted affect ρ = 0.58, P = 0.05; motor retardation, ρ = 0.56, P = 0.05) and LMR (ρ = 0.53, P = 0.05). In addition, patients with a duration of illness (DOI) older than five years had a higher presence of CLB and a higher LMR than patients with a more recent diagnosis of the disease. Likely, patients with positive symptoms and in the prodromal and active stages of the disease have a different immune profile than patients in the residual stage and with a predominance of negative symptoms. Conclusions Psychomotor slowing and blunted affect are two significantly related features, representing the two-faced Janus of immobility. Furthermore, aggregating them in CLB is more predominant the longer the duration of schizophrenia and is associated with different a specific pattern of immune activation.

Abstract Background Blonanserin (BNS) had been undergoing post-market surveillance (PMS) since September 2018. Using the surveillance data, we did this analysis to assess the safety and effectiveness of different doses of BNS to explore a sufficient dose range of BNS in Chinese patients with schizophrenia (SZ). Methods A 12-week, prospective, observational, single-arm, multicenter, open-label PMS was conducted. In this analysis, we divided the patients from PMS into low, medium to high, and high dose groups based on the dose of BNS they received, with medium to high dose group being the focus. The Brief Psychiatric Rating Scale (BPRS) scores at week 2 or 4, 6 or 8, and 12 were calculated to evaluate the effectiveness of BNS in improving psychiatric symptoms. The safety of BNS was reported as the incidence of adverse drug reactions. Results 364 patients were included in the medium to high dose group, of which 321 completed the surveillance, with a dropout rate of 11.8%. The mean daily dose was 15.1 ± 1.92 mg. The BPRS total score was 50.1 ± 11.95 at baseline and decreased to 26.6 ± 7.43 at 12 weeks (P