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Background: The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels., Methods: We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder., Results: Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one., Conclusions: In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.

Background: Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. Methods: A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1–2 months after completing a 6–8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. Results: Five themes were identified in the qualitative data: (1) 'Encouraging entry and supporting exit' (e.g. recognising and managing participants' varied motives and expectations, including around weight loss and symptom alleviation); (2) 'Challenging but potentially transformational,' which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) 'Intervention facilitators,' including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) 'Intervention barriers' (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) 'The wider context' (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. Conclusion: We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. Trial registration: Study registration number: ISRCTN61613198 (02/03/22). [ABSTRACT FROM AUTHOR]

Background: Klotho and neurotrophic factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF), have been shown to play a role in cognitive functions. However, these molecules have not been investigated in bipolar disorder simultaneously to assess the interactions among them and their relationships with cognitive functions. This study investigated the relationships among cognitive function, klotho, and neurotrophic factors in patients with bipolar disorder in the remission period. Methods: Male, bipolar disorder (BD) patients (patient group, n = 48) in the remission period and healthy volunteers (control group, n = 48) were included in the study. The Stroop test and Wechsler Memory Scale–Visual Production Subtest were applied, and the serum levels of Klotho, BDNF, GDNF, and NGF were measured with an ELISA reader. Results: The klotho protein levels (0.12 ± 0.15 and 0.17 ± 0.16) and NGF levels (34.36 ± 41.99 and 48.54 ± 41.06) in the patient group were significantly lower than those in the control group (Z = -3.071, p = 0.002 and Z = -2.217, p = 0.027, respectively). In the patient group, there was a positive correlation between the klotho and NGF levels (p = 0.003, rs = 0.413), and a negative correlation was detected between the NGF and GDNF levels (p = 0.013, rs = -0.355). Klotho and NGF were predictors of Weshler 40-min test results (adjusted R2 = 0.467), and Klotho and BDNF were predictors of Stroop test colour word reading time (adjusted R2 = 0.391) with other variables. Conclusion: In BD patients, klotho, BDNF, GDNF and NGF are associated with cognitive functions and exhibit different characteristics from those of the control group. Nevertheless, the differences related to these molecules seem to be associated with a regulatory system rather than merely an increase or decrease in serum levels. [ABSTRACT FROM AUTHOR]

Objective: In recent years, there has been a rapid increase in reports upon social-cognition impairments in bipolar disorder. This study aimed to compare the characteristics of social cognition domains in bipolar I (BD I) and II (BD II) based on the findings to date. Methods: A systematic literature search was conducted on Web of Science and PubMed from inception to 28 August 2024. Studies with all-age-group of ICD-10, DSM-IV, DSM-IV-TR, or DSM-5 defined BD (I or II) either in a remitted or symptomatic state were included. The risk of bias was measured using the Newcastle–Ottawa Scale, and the quality of the sources was evaluated using GRADE criteria. Results of the studies were measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach. Results: A total of 20 studies were included, covering three core domains of social cognition (theory of mind (ToM), emotion processing and attributions). There was no significant difference in ToM between BD I and BD II and in emotion processing between non-psychotic patients with BD I and BD II, and history of psychosis negatively predicted performance on emotion processing. Furthermore, BD II performed worse than BD I in attributions, with a low to moderate summary effect size. Conclusions: BD I and BD II performed similarly on ToM and emotional processing, but BD II had more impaired attributions. Future studies are encouraged to control for the influence of clinical features, to use more neuroscientific techniques, and to explore on other domains of social cognition in bipolar subtypes. [ABSTRACT FROM AUTHOR]

Objective: Autism spectrum disorder (ASD) is characterized by high rates of comorbidity with other mental disorders, including anxiety disorders and obsessive–compulsive disorder. Beyond a mere concept of comorbidity, recent literature is speculating the existence of a neurodevelopmental nature of such mental disorders. The aim of the study is to investigate the distribution of social-phobic, obsessive–compulsive and panic-agoraphobic traits within a sample of individuals with ASD, social anxiety disorder (SAD), obsessive–compulsive disorder (OCD) and panic disorder (PD). Methods: 40 participants with ASD, 40 with SAD, 40 with OCD, 40 with PD and 50 HC were assessed with the Social Anxiety Spectrum—Short Version (SHY-SV) questionnaire, the Obsessive—Compulsive Spectrum—Short Version (OBS-SV) questionnaire and the Panic Agoraphobic Spectrum—Short Version (PAS-SV) questionnaire. Statistical analyses included Kruskal–Wallis test and Chi-square test. Results: When analyzing SHY-SV scores, the SAD group obtained the highest scores, with individuals with ASD following closely, significantly surpassing the scores of the remaining diagnostic groups. In the examination of OBS-SV questionnaire scores, individuals with ASD once again secured the second-highest scores, trailing only the OCD group. These scores were notably higher than those of both the PD group and healthy controls. In the analysis of PAS-SV scores, the ASD group once again achieved the highest scores after the PD individuals, although this time the difference was not statistically significant compared to the other diagnostic groups. Discussion: These findings highlight the central role of the autism spectrum in SAD and OCD diagnoses. They provide support for the hypotheses of a neurodevelopmental basis for social anxiety and OCD, contributing to the growing body of evidence supporting a dimensional and interconnected view of mental health conditions. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii (T. gondii) is the most successful obligate protozoan that can infect warm-blooded vertebrate hosts. Some researchers suggest that the presence of Toxoplasma cysts in the brain can lead to mental disorders. Bipolar disorder (BD) is one of the serious neuropsychiatric disorders. Several studies have shown a high seroprevalence of T. gondii in bipolar patients. Therefore, this study aims to determine the prevalence of this infection in patients with BD. Methods: In this case-control study, anti-Toxoplasma immunoglobulin (Ig) G and IgM antibodies were measured in serum samples from 115 patients with BD and 115 subjects without this disorder from the general population using commercially available enzyme-linked immunosorbent assay. Demographic characteristics of the patient and control groups, information about T. gondii infection and BD, and their potential risk factors were analyzed. We utilized the Mann-Whitney U test for continuous variables, the chi-square test for categorical data, and multivariate logistic regression to assess T. gondii infection and BD, with significance set at P < 0.05. Results: Twenty-eight (24.34%) of 115 patients with BD and 10 (8.7%) of 115 controls had anti-T. gondii IgG antibodies. IgM antibodies against T. gondii were not reported to be positive in any participants. Furthermore, there was a statistically significant difference in the results [odds ratio (OR) = 2.89: 95% confidence interval (CI) = 1.08–7.73. P = 0.03]. Within the study population, various factors were identified as significant risk factors for BD: sex (OR 8.10, 95% CI 3.16–20.75), age 20–50 (OR 5.11, 95% CI 1.81–14.45), age over 50 (OR 19.54, 95% CI 4.02–94.89), education level (OR 0.24, 95% CI 0.09–0.60), working status (non-employment, OR 4.12, 95% CI 1.65–10.30), and income (middle, OR 0.29, 95% CI 0.10–0.89; high, OR 0.12, 95% CI 0.01–0.77), all with P-values less than 0.05. In addition, in the group of patients, there was no statistically significant relationship between T. gondii infection with the type of bipolar disease (P = 0.93), the severity of the disease (P = 0.61), and the history of suicide attempts (P = 0.63). Conclusion: This study showed that toxoplasmosis is a risk factor for BD and increases the chance of developing BD. However, more studies with a larger sample size are recommended to clarify the development pathways of this disorder and provide new strategies for the prevention and treatment of this disease. Clinical trial: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Past research has highlighted that bipolar I disorder is associated with significant changes in brain structure and function. Notably, the manifestation and progression of bipolar I disorder have been known to differ between males and females. However, the relationship between sex-related differences and bipolar I disorder diagnosis affecting these changes was not fully understood. This study aimed to investigate the sex-by-diagnosis interactions concerning the structural and functional features of the brain in individuals with bipolar I disorder. Methods: Both structural and functional MRI data were obtained from 105 individuals with bipolar I disorder (36 males and 69 females) and 210 healthy controls (72 males and 138 females). Voxel-wise analyses of gray matter volume and functional connectivity were conducted using a general linear regression model. This model included age, sex, diagnosis, and a sex-by-diagnosis interaction as predictors to explore potential sex-related differences in the brain features of participants with bipolar I disorder. Results: The gray matter volume analysis revealed significant sex-by-diagnosis interactions in six brain regions: the left caudate (p < 0.001), left thalamus (p < 0.001), right caudate (p = 0.003), right thalamus (p < 0.001), left anterior cingulate gyrus (p = 0.022), and left middle/posterior cingulate gyrus (p = 0.015). Using these regions as seeds, we detected a significant sex-by-diagnosis interaction in the functional connectivity alteration between the left thalamus and right angular gyrus (p = 0.019). Conclusions: Our findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants. These results hint at potential sex-related differences in the pathophysiology of the limbic system in bipolar I disorder, which may have significant implications for understanding the underlying mechanisms in bipolar I disorder. Our findings could contribute to developing more personalized treatment approaches for individuals with bipolar I disorder. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic and the associated measures have had a significant impact on millions of individuals and families worldwide. Although cross-sectional studies have demonstrated the considerable burden placed on families during the pandemic, trends over different phases of the pandemic including later stages and using population-based samples is scarce. Objective: In this study, we aimed to assess trends in family functioning across four population-based surveys between December 2020 and March 2023 using a repeated cross-sectional design. The surveys were conducted using a similar sampling strategy and measures. We included individuals residing in a household with at least one minor below the age of 16. Results: The most notable changes across surveys over time were related to quality of life. While 54.3% of respondents reported a decline in quality of life during the winter of 20/21 compared to pre-pandemic levels, this was observed in only 22.6% of participants during the spring of 23. The proportion of respondents who indicated a deterioration in their relations with their children also decreased during the pandemic. While 9.9% of respondents reported a deterioration in their relationship with their children during the winter of 20/21 in comparison to the initial phase of the pandemic, this was reported by only 5.2% in the spring 23. The relationship with one's partner and health status exhibited minimal fluctuations. Mental health problems were associated with a decline in quality of life, health status and relationships with children and partners compared to pre-pandemic levels at all time points. Moreover, lower income levels were associated with poorer relationship quality with the partner in the most recent wave. Conclusions: Our findings demonstrate significant improvements in family functioning since the onset of the pandemic, indicating that individuals and families in our sample were generally adapting well. However, a subgroup of the population still reports suboptimal family functioning compared to before the pandemic. Psychosocial care and social policy support for families are needed. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is a chronic, disabling mental illness with a high disease burden and is often comorbid with metabolic syndrome (MetS). The aim of this study was to determine the prevalence of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and to explore predictive factors affecting the development and severity of MetS. Methods: A total of 274 patients with SCZ who met the inclusion criteria were enrolled in this study, and their demographic data and general clinical information were collected. Concurrently, patients were assessed for psychopathology, illness severity, and antipsychotic drug–related adverse effects. Results: The prevalence of MetS in the target population was 35.77%, and the MetS subtype of abdominal obesity + high triglycerides + low level of high-density lipoprotein cholesterol accounted for the majority of patients in the MetS subgroup. Binary logistic regression showed that body mass index (BMI), uric acid (UA), thyroid-stimulating hormone, and QT-c interval could significantly and positively predict the development of MetS. Multiple linear regression showed that olanzapine concentration, BMI, and UA could significantly and positively predict higher MetS scores. Conclusion: This study reports the clinical patterns of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and identifies the correlations influencing the development and severity of MetS. These findings could potentially be applied toward the prevention of and intervention in MetS. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM). Methods: A total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups. Results: Analysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group. Conclusions: The present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature. [ABSTRACT FROM AUTHOR]

Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services., Methods/design: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers' patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrollment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms' severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in 'real-world' clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction.

Background: Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. Methods: The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. Results: In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. Conclusions: Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The diaphragm, the main muscle involved in respiration and one of those responsible for maintaining life, is still little explored in terms of its morphology in wild animals. There are few studies on the anatomy of Eira barbara, a carnivorous mustelid that is a victim of the urbanization process. In order to contribute to the conservation of the species, we described the topography and morphology of the diaphragm, which may be involved in injuries caused by the impacts of human activities. Results: We studied five specimens of Eira barbara, whose diaphragmatic muscle had a dorsal insertion on the 14th thoracic vertebra, laterally between the 8th and 13th intercostal space (EIC) and ventrally on the 8th EIC, with attachment to the xiphoid process. Consisting of three muscle regions (lumbar, costal and sternal), the diaphragm in Eira barbara showed radially arranged bundles, with the right costal muscle being slimmer than the left; the left pillar wider than the right and between them were the aortic and esophageal hiatuses. The Y-shaped tendinous center housed the foramen of the vena cava bordering the right costal region. In the most dorsal portion of the diaphragm, between the costal regions and the diaphragmatic pillar, we found two triangular-shaped regions devoid of muscle. Conclusions: Our findings, when compared with the current literature, indicate that the location and positioning of the diaphragm are independent of the physical conformation of the species, and that the right costal region, as well as the triangular areas devoid of musculature, may be fragile points for herniation in cases of Eira barbara being run over. [ABSTRACT FROM AUTHOR]

People living with mental illness experience poorer oral health outcomes compared to the general population, yet little is known about their oral health knowledge, attitudes, and practices. The aim of this mixed-methods systematic review was to synthesise evidence regarding oral health knowledge, attitudes, and practices of people living with mental illness to inform preventative strategies and interventions. Database searches were conducted in PubMed, MEDLINE, PsycINFO, CINAHL, ProQuest, and Scopus with no limitations placed on the year of study. All studies available in the English language, that explored the oral health knowledge, attitudes, and/or practices of people with a mental illness were included. Articles were excluded if they primarily pertained to intellectual disability, behavioural and psychological symptoms of dementia, drug and alcohol or substance use, or eating disorders. A thematic synthesis was undertaken of 36 studies (26 high-moderate quality), resulting in 3 themes and 9 sub-themes. Study participants ranged from n = 7 to n = 1095 and aged between 15–83 years with most having a diagnosis of schizophrenia, schizoaffective, or bipolar affective disorder. People diagnosed with a mental illness were found to have limited oral health knowledge, particularly regarding the effects of psychotropic medication. Various barriers to oral health care were identified, including high dental costs, the negative impact of mental illness, dental fears, lack of priority, and poor communication with dental and health care providers. Study participants often displayed a reduced frequency of tooth brushing and dental visits. The findings highlight the potential for mental health care providers, oral health and dental professionals, mental health consumers, and carers to work together more closely to improve oral health outcomes for people with mental illness. The systematic review protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO), (registration ID CRD42022352122). [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis (AHN) is affected by multiple factors, such as enriched environment, exercise, ageing, and neurodegenerative disorders. Neurodegenerative disorders can impair AHN, leading to progressive neuronal loss and cognitive decline. Compelling evidence suggests that individuals engaged in regular exercise exhibit higher production of proteins that are essential for AHN and memory. Interestingly, specific molecules that mediate the effects of exercise have shown effectiveness in promoting AHN and cognition in different transgenic animal models. Despite these advancements, the precise mechanisms by which exercise mimetics induce AHN remain partially understood. Recently, some novel exercise molecules have been tested and the underlying mechanisms have been proposed, involving intercommunications between multiple organs such as muscle-brain crosstalk, liver-brain crosstalk, and gut-brain crosstalk. In this review, we will discuss the current evidence regarding the effects and potential mechanisms of exercise mimetics on AHN and cognition in various neurological disorders. Opportunities, challenges, and future directions in this research field are also discussed. [ABSTRACT FROM AUTHOR]

Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. Methods: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. Results: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. Conclusion: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long. Key points: • The mean duration of depression before ECT was 8.8 months. • The duration before ECT for Bipolar Disorder (vs Major Depressive Disorder) is shorter. • The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. • Focusing on the first-line indications for using ECT, only a previous response reduces the duration of depression before ECT. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE. Methods: This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences. Results: Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05). Conclusion: PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients. [ABSTRACT FROM AUTHOR]

Background: Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT4) in a cohort of healthy individuals (N = 254) and, for 5-HT4, in a cohort of unmedicated patients with depression (N = 90). To do so, we quantified SLC6A4/TPH2 methylation using bisulfite pyrosequencing and estimated brain 5-HT4 and 5-HTT levels using positron emission tomography. In addition, we explored the association between SLC6A4 and TPH2 methylation and measures of early life and recent stress, depressive and anxiety symptoms on 297 healthy individuals. Results: We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity. Conclusions: We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms. [ABSTRACT FROM AUTHOR]

Background: Relatives of patients with bipolar disorder (BD) often experience emotional burden with stress and depressive symptoms that again increase the likelihood of destabilization and relapses in the patient. The effects of group-based psychoeducation have not been investigated in large-scale real-world settings. We are currently conducting a large-scale real-world randomized controlled parallel group trial (RCT) to test whether group-based psychoeducation for 200 relatives to patients with BD improves mood instability and other critical outcomes in relatives and the corresponding patients with BD. Methods: The trial is designed as a two-arm, parallel-group randomized trial with a balanced randomization 1:1 to either group-based psychoeducation or a waiting list for approximately 4 months and subsequent group-based psychoeducation. The primary outcome measure is mood instability calculated based on daily smartphone-based mood self-assessments. Other relevant outcomes are measured, including patients' reported outcomes, assessing self-assessed burden, self-efficacy, and knowledge about BD. Discussion: This protocol describes our currently ongoing randomized controlled trial (RCT) that aims at investigating group-based psychoeducation as an intervention for relatives of individuals diagnosed with bipolar disorder (BD). The study is the first large-scale real-world RCT to focus on a relatively short intervention of psychoeducation (6 sessions of 2 h each) in a large group of relatives (approximately 30 participants per group). With this focus, we wish to test an intervention that is feasible to implement in real-life psychiatric settings with limited budgets and time. It is also the first study to use mood instability in relatives as the primary outcome measure and to investigate whether mood instability and other affective symptoms in patients and relatives covary. It could be considered as limitations, that the trial is not blinded and does not include long-term follow-up. Trial registration: ClinicalTrials.gov NCT06176001. Registered on 2023–12-19. The study is approved by the data agency (P-2021–809). The project was allowed to be initiated without permission from the Scientific Ethical Committees for the Capital Region, because it according to section 1, paragraph 4 of the Committee Act was not defined as a health scientific intervention study (case number 21063013). [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. Methods: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). Results: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. Conclusions: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates. Methods: The present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms. Results: The prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13–2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32–0.88, P = 0.014) and 1.48 (1.04–2.10, P = 0.030), respectively. Conclusions: A U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this randomized controlled trial (RCT) is to establish the effectiveness of time-restricted eating (TRE) compared with the Mediterranean diet for people with bipolar disorder (BD) who have symptoms of sleep disorders or circadian rhythm sleep–wake disruption. This work builds on the growing evidence that TRE has benefits for improving circadian rhythms. TRE and Mediterranean diet guidance will be offered remotely using self-help materials and an app, with coaching support. Methods: This study is an international RCT to compare the effectiveness of TRE and the Mediterranean diet. Three hundred participants will be recruited primarily via social media. Main inclusion criteria are: receiving treatment for a diagnosis of BD I or II (confirmed via DIAMOND structured diagnostic interview), endorsement of sleep or circadian problems, self-reported eating window of ≥ 12 h, and no current mood episode, acute suicidality, eating disorder, psychosis, alcohol or substance use disorder, or other health conditions that would interfere with or limit the safety of following the dietary guidance. Participants will be asked to complete baseline daily food logging for two weeks and then will be randomly allocated to follow TRE or the Mediterranean diet for 8 weeks, during which time, they will continue to complete daily food logging. Intervention content will be delivered via an app. Symptom severity interviews will be conducted at baseline; mid-intervention (4 weeks after the intervention begins); end of intervention; and at 6, 9, and 15 months post-baseline by phone or videoconference. Self-rated symptom severity and quality of life data will be gathered at those timepoints, as well as at 16 weeks post baseline. To provide a more refined index of whether TRE successfully decreases emotional lability and improves sleep, participants will be asked to complete a sleep diary (core CSD) each morning and complete six mood assessments per day for eight days at baseline and again at mid-intervention. Discussion: The planned research will provide novel and important information on whether TRE is more beneficial than the Mediterranean diet for reducing mood symptoms and improving quality of life in individuals with BD who also experience sleep or circadian problems. Trial registration: ClinicalTrials.gov ID NCT06188754. [ABSTRACT FROM AUTHOR]

Background: Emotional urgency, defined as a trait concept of emotion-based impulsivity, is at least moderately associated with general psychopathology. However, its clinical significance and associations with clinically relevant features of bipolar disorder remain unclear. This scoping review aims address this gap by determining the extent of evidence in this niche scope of study. Methods: Evidence of between-group differences of positive and negative urgency, its associations with mood severity, and all peripheral associations related to illness and psychosocial outcomes were synthesized based on PRISMA checklists and guidelines for scoping reviews (PRISMA-ScR). Design: Electronic databases were searched for articles published between January 2001 and January 2024. A total of 1013 entries were gathered, and a total of 10 articles were included in the final selection after the removal of duplicates and ineligible articles. Results: Differences in urgency scores between bipolar disorder and healthy controls were large (Cohen's d ranged from 1.77 to 2.20). Negative urgency was at least moderately associated with overall trauma, emotional abuse, neglect, suicide ideation, neuroticism, and irritable/cyclothymic temperament, whereas positive urgency was at least moderately associated with various aspects of aggression and quality of life. Positive but not negative urgency was associated with quality of life in bipolar disorder. Conclusion: Large between-group differences found for emotional urgency in bipolar disorder imply large clinical significance. Emotional urgency was associated with worse clinical features and outcomes. Given the high clinical heterogeneity of the disorder, emotional urgency may be an important phenotype indicative of greater disorder severity. [ABSTRACT FROM AUTHOR]

Background: Older critically ill patients experience rapid muscle loss during stay in an intensive care unit (ICU) due to physiological stress and increased catabolism. This may lead to increased ICU length of stay, delayed weaning from ventilation and persistent functional limitations. We hypothesized that with optimal nutrition and early physical therapy acting in synergism, we can reduce muscle mass loss and improve functional outcomes. Methods: This was a prospective, single blinded randomized, controlled single-center pilot study to compare the lean muscle mass (measured at bilateral quadriceps femoris using ultrasound) of older ICU patients at 4 time points over 14 days between the control and intervention groups. The control group received standard weight-based empiric feeding and standard ICU physiotherapy. The intervention group received indirect calorimetry directed feeding adjusted daily and 60 min per day of cycle ergometry. 21 patients were recruited and randomized with 11 patients in the control arm and 10 patients in the intervention arm. Secondary outcome measures included ICU and hospital mortality, length of stay, functional assessments of mobility and assessment of strength. Results: Median age was 64 in the control group and 66 in the intervention group. Median calories achieved was 24.5 kcal/kg per day in the control group and 23.3 kcal/kg per day in the intervention group. Cycle ergometry was applied to patients in the intervention group for a median of 60 min a day and a patient had a median of 8.5 sessions in 14 days. Muscle mass decreased by a median of 4.7cm2 in the right quadriceps femoris in the control group and 1.8cm2 in the intervention group (p = 0.19), while the left quadriceps femoris decreased by 1.9cm2 in the control group and 0.1cm2 in the intervention group (p = 0.51). Conclusion: In this pilot study, we found a trend towards decrease muscle loss in bilateral quadriceps femoris with our combined interventions. However, it did not reach statistical significance likely due to small number of patients recruited in the study. However, we conclude that the intervention is feasible and potentially beneficial and may warrant a larger scale study to achieve statistical significance. Trial Registration: This study was registered on Clinicaltrials.gov on 30th May 2018 with identifier NCT03540732. [ABSTRACT FROM AUTHOR]

Background: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. Method: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. Result: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. Conclusion: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. Methods: This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. Results: Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). Conclusions: This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk. [ABSTRACT FROM AUTHOR]

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 < 0.001, R2 = 0.421). By selecting only depressed sample, HQ-25 is positively predicted by MSBS total score, low arousal and depressive affective temperament, while negatively by MSBS high arousal (F(4, 383) = 48.544, p < 0.001, R2 = 0.336). The logistic regression model found that the likelihood of developing depression with the HK specifier is significantly predicted by depressive and cyclothymic affective temperaments. Conclusions: These preliminary findings could help in clinically characterizing the relationship between specific affective temperamental profiles among individuals with depression with/without HK specifier, in order to provide a more tailored and personalized therapeutic approach. Our Italian study should be extensively replicated in larger, longitudinal and multicentric pan-European studies, by specifically assessing the impact of these findings on depression clinical course, prognosis and treatment outcomes. [ABSTRACT FROM AUTHOR]

Necrosis of the femoral head is the main complication in femoral neck fracture patients with triangle cannulated screw fixation. Instant postoperative fixation instability is a main reason for the higher risk of femoral head necrosis. Biomechanical studies have shown that cross screw fixation can effectively optimize fixation stability in patients with proximal humerus fractures and pedicle screw fixation, but whether this method can also effectively optimize the fixation stability of femoral neck fractures and reduce the corresponding risk of femoral head necrosis has yet to be identified. In this study, a retrospective review of imaging data in femoral neck fracture patients was performed. The cross angle between the femoral neck and the caudal cannulated screw was reported; if the angle between the screw and the transverse plane increased, it was recorded as positive; otherwise, it was recorded as negative. Angle values and their corresponding absolute values were compared in patients with and without femoral head necrosis. Regression analysis identified potential risk factors for femoral head necrosis. Moreover, the biomechanical effect of the screw–femoral neck angle on fixation stability was also verified by numerical mechanical simulations. Clinical review presented significantly larger positive angle values in patients with femoral head necrosis, which was also proven to be an independent risk factor for this complication. Moreover, fixation stability progressively deteriorated with increasing angle between the caudal screw and the transverse plane. Therefore, increasing the angle between the caudal screw and the transverse plane may aggravate the risk of femoral head necrosis by deteriorating the fixation stability in patients with femoral neck fracture. [ABSTRACT FROM AUTHOR]

Objective: Personality, emotions, and olfaction exhibit partial anatomical overlap in the limbic system structure, establishing potential mechanisms between personality, affective disorders, and olfactory-related aspects. Thus, this study aims to investigate the associations among the Big Five personality traits, alexithymia, anxiety symptoms, and odor awareness. Methods: A total of 863 college participants were recruited for this study. All participants completed the Chinese Big Five Personality Inventory-15, the Odor Awareness Scale (OAS), the Toronto Alexithymia Scale-20, and the Generalized Anxiety Disorder Screener-7. Structural equation modeling was employed to examine the hypothesized mediated model. Results: The findings revealed the majority of significant intercorrelations among the dimensions of the Big Five personality traits, alexithymia, anxiety symptoms, and OAS (|r| = 0.072–0.567, p < 0.05). Alexithymia and anxiety symptoms exhibited a serial mediation effect between neuroticism and OAS (95%CI[0.001, 0.014]), conscientiousness and OAS (95%CI[-0.008, -0.001]), and extraversion and OAS (95%CI[-0.006, -0.001]). Anxiety symptoms mediated the relationship between agreeableness and OAS (95%CI[-0.023, -0.001]) and between openness and OAS (95%CI [0.004, 0.024]). Conclusion: The mediating roles of alexithymia and anxiety symptoms between the Big Five personality traits and odor awareness support the idea of a certain level of association among personality, emotions, and olfaction, with the underlying role of the limbic system structure. This enhances our understanding of personality, emotions, and olfaction and provides insights for future intervention measures for affective disorders and olfactory dysfunctions. [ABSTRACT FROM AUTHOR]

Background: Melancholic depression (MD) is one of the most prevalent and severe subtypes of major depressive disorder (MDD). Previous studies have revealed inconsistent results regarding alterations in grey matter volume (GMV) of the hippocampus and amygdala of MD patients, possibly due to overlooking the complexity of their internal structure. The hippocampus and amygdala consist of multiple and functionally distinct subregions, and these subregions may play different roles in MD. This study aims to investigate the volumetric alterations of each subregion of the hippocampus and amygdala in patients with MD and non-melancholic depression (NMD). Methods: A total of 146 drug-naïve, first-episode MDD patients (72 with MD and 74 with NMD) and 81 gender-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent magnetic resonance imaging (MRI) scans. The subregional segmentation of hippocampus and amygdala was performed using the FreeSurfer 6.0 software. The multivariate analysis of covariance (MANCOVA) was used to detect GMV differences of the hippocampal and amygdala subregions between three groups. Partial correlation analysis was conducted to explore the relationship between hippocampus or amygdala subfields and clinical characteristics in the MD group. Age, gender, years of education and intracranial volume (ICV) were included as covariates in both MANCOVA and partial correlation analyses. Results: Patients with MD exhibited a significantly lower GMV of the right hippocampal tail compared to HCs, which was uncorrelated with clinical characteristics of MD. No significant differences were observed among the three groups in overall and subregional GMV of amygdala. Conclusions: Our findings suggest that specific hippocampal subregions in MD patients are more susceptible to volumetric alterations than the entire hippocampus. The reduced right hippocampal tail may underlie the unique neuropathology of MD. Future longitudinal studies are required to better investigate the associations between reduced right hippocampal tail and the onset and progression of MD. [ABSTRACT FROM AUTHOR]

Background: It has been reported that the way we breathe (whether through the nose or mouth) can influence many aspects of our health and to some extent, sport performance. The purpose of this study was to evaluate the acute effects of different breathing regimens on muscular endurance and physiological variables. Methods: A randomized experiment to verify the acute effect of different breathing regimens (NN– inhaling and exhaling through the nose; NM– inhaling through the nose, exhaling through the mouth; MM– inhaling and exhaling through the mouth) on the muscular endurance performance was conducted. 107 physically active college students (68 males, 39 females) performed repeated bench press testing protocol (repetitions to failure (RTF) with 60% of body weight for males (BP60), respectively 40% of body weight for females (BP40)) with various breathing regimens (NN, NM, MM) in random order. Heart rate (HR), blood oxygen saturation (SpO2) and perceived exertion by Borg scale (RPE) were measured as well. A short questionnaire, given after the testing protocol and observation during familiarization, was used to detect each subject's normal breathing approach during resistance training. Results: In both genders, no significant differences in RTF, RPE and SpO2 were found. No individual case of deviation of arterial oxygen saturation outside the physiological norm was recorded. ​​In the male group, significantly lower HR values were found during the NN trials, compared to during the NM (p = 0.033) and MM (p = 0.047) trials with no significant differences in females. The HR differences in the males demonstrated a small effect size (NN < NM, d = 0.32; NN < MM, d = 0.30). Questionnaire results suggest that 80% of our participants use NM breathing, 15% use MM breathing and 5% use NN breathing during resistance training. Conclusion: It seems, that various breathing regimens have none or only minor effect on muscular endurance performance and selected physiological parameters. NN seems to be as efficient as other two regimens, which are mostly used in practice (NM, MM). [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients. Methods: This study was an observational, cross-sectional, retrospective case-control study. Plasma hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Multivariate regression was used to analyze relationships between OS parameters and MMP-9, and clinical symptoms. Results: Our results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H2O2, and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P < 0.05). In schizophrenia patients, correlation analyses showed that H2O2 levels were significantly and positively correlated with PANSS positive scores, CAT and MDA levels were significant negatively correlated with PANSS negative scores and PANSS total scores, and MDA levels were significantly positively correlated with MMP-9 levels (all P < 0.05). However, we did not find that MMP-9 played an interaction role between OS parameters and PANSS total scores and subscales scores (all P > 0.05). Conclusions: Our results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Objectives: Olfactory function, serum tumor necrosis factor-α (TNF-α) and cognitive function were compared between bipolar disorder (BD) and schizophrenia (SP) patients in the remission stage combined with correlation analysis, with the aim of identifying new indicators for the auxiliary diagnosis of these psychiatric illnesses. Methods: A total of 46 euthymic BD patients, 42 clinically stable SP patients and 42 healthy controls (HC) were included in this study. Olfactory sensitivity (OS) and olfactory identification (OI) were assessed using Sniffin' Sticks test, and serum TNF-α levels were measured by ELISA. Clinical symptoms were evaluated with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, Hamilton anxiety scale, and the Positive and Negative Syndrome Scale (PANSS). Social function was evaluated with the Global Assessment Function (GAF) scale. Cognitive function was evaluated using the Trail Making Test-A (TMT-A) and Digit Cancellation Test (DCT). Results: OI and cognitive function scores and serum TNF-α levels were significantly lower in the BD and SP patients compared with the HC participants. There was no significant difference between the BD and SP groups, and there were no significant differences in OS among the three groups. OI score was positively correlated with years of education in both the BD and SP groups. OI score in the SP group was negatively correlated with age and PANSS score, and positively correlated with GAF score. In the BD group, OS was positively correlated with DCT II and DCT III. In the SP group, OS and OI scores were positively correlated with DCT III, and negatively correlated with TMT-A time. Furthermore, there was a positive correlation between TNF-α and DCT II in the BD group. There was no significant linear correlation between olfactory function and TNF-α in the BD or SP group. Conclusion: OI may be a trait marker for BD and SP. Some cognitive functions may be correlated not only with TNF-α in BD patients in remission, but also with olfactory function in BD and SP patients in remission. [ABSTRACT FROM AUTHOR]

Background: Addressing cognitive behavioral factors is associated with a favorable development of eating styles (i.e., increased levels of restrained eating, decreased levels of external and emotional eating) in individuals with overweight and obesity. Research suggests that the use of digital interventions that consider gender aspects regarding prevalence, comorbidities, and weight-related behaviors could enhance existing treatment options. This randomized controlled trial aimed to evaluate the effectiveness of the self-guided gender-sensitive mobile health intervention I-GENDO on restrained, emotional and external eating, body mass index, and physical activity at the end of the intervention, and at a 9- and 15-month follow-up. Methods: Two hundred thirteen individuals (67% female, body mass index: 33.35 ± 3.79 kg/m2) were randomly assigned to the intervention or control group. Multilevel models were calculated to investigate differences between groups. I-GENDO offered interactive modules addressing psychological content associated with obesity. Users were able to self-tailor intervention content based on their individual needs and life realities. Results: Restrained eating was higher in the intervention group after the intervention (95% CI: 0.20, 0.36) and at 9-months (95% CI: 0.07, 0.24). At 9-months, emotional eating among women was lower in the intervention group compared to the control group (95% CI: -0.44, -0,19). In the intervention group, external eating was lower after the intervention, which remained significant for women at 9 (95% CI: -0.40, -0.19) and 15-months (95% CI: -0.34, -0.13). Body mass index of men in the intervention group was 1.44 lower at 15-months than in the control group. No significant effects on physical activity were found. Conclusions: The I-GENDO intervention was effective in changing restrained eating of both women and men in the long-term, suggesting that a self-guided, gender-sensitive approach is promising. However, the differential effects on the outcome measures indicate that more research is warranted to examine distinct gender-sensitive mechanisms of digital psychological interventions (i.e., dose–response relationship, blended counselling). Trial registration: ClinicalTrials.gov identifier: NCT04080193, 06–09-2019. [ABSTRACT FROM AUTHOR]

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions. [ABSTRACT FROM AUTHOR]

Background: As a global pandemic, The Corona Virus Disease 2019 (COVID-19) has brought significant challenges to the primary health care (PHC) system. Health professionals are constantly affected by the pandemic’s harmful impact on their mental health and are at significant risk of job burnout. Therefore, it is essential to gain a comprehensive understanding of how their burnout was affected. The study aimed to examine the relationship between COVID-19 event strength and job burnout among PHC providers and to explore the single mediating effect of job stress and work engagement and the chain mediating effect of these two variables on this relationship. Methods: Multilevel stratified convenience sampling method was used to recruit 1148 primary medical staff from 48 PHC institutions in Jilin Province, China. All participants completed questionnaires regarding sociodemographic characteristics, COVID-19 event strength, job stress, work engagement, and job burnout. The chain mediation model was analyzed using SPSS PROCESS 3.5 Macro Model 6. Results: COVID-19 event strength not only positively predicted job burnout, but also indirectly influenced job burnout through the mediation of job stress and work engagement, thereby influencing job burnout through the “job stress → work engagement” chain. Conclusions: This study extends the application of event systems theory and enriches the literature about how the COVID-19 pandemic impacted PHC medical staff job burnout. The findings derived from our study have critical implications for current and future emergency response and public policy in the long-term COVID-19 disease management period. [ABSTRACT FROM AUTHOR]

Background: TAMs (tumor-associated macrophages) infiltration promotes the progression of esophageal cancer (EC). However, the underlying mechanisms remain unclear. Methods: Abnormal expression of LINC01592 from EC microarrays of the TCGA database was analyzed. LINC01592 expression level was validated in both EC cell lines and tissues. Stable LINC01592 knockdown and overexpression of EC cell lines were established. In vitro and in vivo trials were conducted to test the impact of LINC01592 knockdown and overexpression on EC cells. RNA binding protein immunoprecipitation (RIP), RNA pulldown assays, and Immunofluorescence (IF) were used to verify the combination of E2F6 and LINC01592. The combination of E2F6 and NBR1 was verified through the utilization of ChIP and dual luciferase reporter assays. Results: LINC01592 is carried and transferred by exosomes secreted by M2-TAMs to tumor cells. The molecular mechanism underlying the promotion of NBR1 transcription involves the direct binding of LINC01592 to E2F6, which facilitates the nuclear entry of E2F6. The collaborative action of LINC01592 and E2F6 results in improved NBR1 transcription. The elevation of NBR1 binding to the ubiquitinated protein MHC-I via the ubiquitin domain caused a higher degradation of MHC-I in autophagolysosomes and a reduction in MHC-I expression on the exterior of cancerous cell. Consequently, this caused cancerous cells to escape from CD8+ CTL immune attack. The tumor-promoting impacts of LINC01592, as well as the growth of M2-type macrophage-driven tumors, were significantly suppressed by the interruption of E2F6/NBR1/MHC-I signaling through the effect of siRNA or the corresponding antibody blockade. Significantly, the suppression of LINC01592 resulted in an upregulation of MHC-I expression on the tumor cell membrane, thereby enhancing the efficacy of CD8+ T cell reinfusion therapy. Conclusions: The investigation conducted has revealed a significant molecular interaction between TAMs and EC via the LINC01592/E2F6/NBR1/MHC-I axis, which facilitates the progression of malignant tumors. This suggests that a therapeutic intervention targeting this axis may hold promise for the treatment of the disease. [ABSTRACT FROM AUTHOR]

Background: Since diagnosis of mood disorder heavily depends on signs and symptoms, emerging researches have been studying biomarkers with the attempt to improve diagnostic accuracy, but none of the findings have been broadly accepted. The purpose of the present study was to construct a preliminary diagnostic model to distinguish major depressive disorder (MDD) and bipolar disorder (BD) using potential commonly tested blood biomarkers. Methods: Information of 721 inpatients with an ICD-10 diagnosis of MDD or BD were collected from the electronic medical record system. Variables in the nomogram were selected by best subset selection method after a prior univariable screening, and then constructed using logistic regression with inclusion of the psychotropic medication use. The discrimination, calibration and internal validation of the nomogram were evaluated by the receiver operating characteristic curve (ROC), the calibration curve, cross validation and subset validation method. Results: The nomogram consisted of five variables, including age, eosinophil count, plasma concentrations of prolactin, total cholesterol, and low-density lipoprotein cholesterol. The model could discriminate between MDD and BD with an area under the ROC curve (AUC) of 0.858, with a sensitivity of 0.716 and a specificity of 0.890. Conclusion: The comprehensive nomogram constructed by the present study can be convenient to distinguish MDD and BD since the incorporating variables were common indicators in clinical practice. It could help avoid misdiagnoses and improve prognosis of the patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have frequently reported a high prevalence of co-occurring anxiety and depression among people who experienced stressful events in childhood. However, few have noted the symptomatic relationship of this comorbidity among childhood sexual abuse (CSA) survivors. Therefore, this study's objectives were as follows: (1) to examine the relationship across symptoms between anxiety and depression among CSA survivors; (2) to compare differences between male and female network structures among CSA survivors. Methods: A total of 63 Universities and Colleges in Jilin Province, China, covered 96,218 participants in this study, a sub-set data of which met the criteria of CSA was analyzed with the network analysis. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), measured CSA. Anxiety was measured by the seven-item Generalized Anxiety Disorder Scale (GAD-7), and depression was measured by the Patient Health Questionnaire (PHQ-9). The sex difference between anxiety and depression among CSA survivors was compared. Results: 3,479 college students reported the experience of CSA (CTQ-SF total scores ≥ 8), with a prevalence of 3.62% (95% CI: 3.50–3.73%). Among CSA survivors, control worry, sad mood, and energy were central and bridge symptoms of the anxiety and depression network. Meanwhile, male CSA survivors appeared to have a stronger correlation between guilt and suicide, but female CSA survivors seemed to have a stronger correlation between control worry and suicide. Moreover, the edge of control worry-relax-afraid was stronger in the male network, while the edge of restless-relax was stronger in the female network. Conclusion: Control worry, sad mood, and energy are crucial to offer targeted treatment and to relieve anxiety and depression symptoms for CSA survivors. Guilt needs more attention for male CSA survivors, while control worry remains more important for female CSA survivors to reduce suicidal ideation and suicide attempts. [ABSTRACT FROM AUTHOR]

Background: People with severe mental illness (e.g. psychosis, bipolar disorder) experience poor oral health compared to the general population as shown by more decayed, missing and filled teeth and a higher prevalence of periodontal disease. Attending dental services allows treatment of oral health problems and support for prevention. However, people with severe mental illness face multiple barriers to attending routine dental appointments and often struggle to access care. Link work interventions use non-clinical support staff to afford vulnerable populations the capacity, opportunity, and motivation to navigate use of services. The authors have co-developed with service users a link work intervention for supporting people with severe mental illness to access routine dental appointments. The Mouth Matters in Mental Health Study aims to explore the feasibility and acceptability of this intervention within the context of a feasibility randomised controlled trial (RCT) measuring outcomes related to the recruitment of participants, completion of assessments, and adherence to the intervention. The trial will closely monitor the safety of the intervention and trial procedures. Methods: A feasibility RCT with 1:1 allocation to two arms: treatment as usual (control) or treatment as usual plus a link work intervention (treatment). The intervention consists of six sessions with a link worker over 9 months. Participants will be adults with severe mental illness receiving clinical input from secondary care mental health service and who have not attended a planned dental appointment in the past 3 years. Assessments will take place at baseline and after 9 months. The target recruitment total is 84 participants from across three NHS Trusts. A subset of participants and key stakeholders will complete qualitative interviews to explore the acceptability of the intervention and trial procedures. Discussion: The link work intervention aims to improve dental access and reduce oral health inequalities in people with severe mental illness. There is a dearth of research relating to interventions that attempt to improve oral health outcomes in people with mental illness and the collected feasibility data will offer insights into this important area. Trial registration: The trial was preregistered on ISRCTN (ISRCTN13650779) and ClinicalTrials.gov (NCT05545228). [ABSTRACT FROM AUTHOR]

Background: Emotion regulation theories and the negative urgency concept assume that negative mood increases binge eating. Negative emotions are considered as a trigger for binge eating, while binge eating itself is regarded as an impulsive behavior and should thus be increased within the negative urgency concept. Anger might be a specific negative emotion triggering binge eating in patients with binge eating disorder (BED). We investigated how inhibitory control as one main factor of impulsivity is influenced by anger stimuli in patients with BED and two control groups. Methods: We compared patients with BED (N = 20) with normal-weight healthy control participants (NW-CG, N = 20) and BMI-matched overweight and obese control participants (BMI-CG, N = 18). We used the emotional Stop Signal task (eSST) to investigate inhibitory control, where we presented angry facial expressions in comparison with neutral facial expressions as emotional stimuli. Results: All participants showed decreased inhibitory control in the angry versus neutral condition, i.e., a faster Stop Signal Reaction Time and a lower percentage of correct reactions. However, no significant group differences emerged in terms of performance. Performance in the eSST did not correlate with negative urgency, disorder- or emotion-related characteristics. Conclusions: The current pilot study does not deliver evidence for decreased inhibitory control towards angry stimuli in patients with BED, as we detected a general and not disorder-related effect in all participants that might represent the conjunction of inhibitory control and anger. A direct mood induction technique might have led to different results. Further research in healthy and clinical groups is needed. Plain English summary: Several theories suggest that binge eating episodes are often appearing in negative mood and anger is one specific emotion that might commonly trigger binge eating. The aim of this study was to investigate inhibitory control under anger in patients with binge eating disorder (BED). Inhibitory control is a specific component of impulsivity and further studies suggest that inhibitory control deficits are related to binge eating. We compared patients with BED with normal-weight participants and overweight or obese participants as control groups in a specific inhibitory control task, where faces with angry or neutral expressions were presented and participants should stop, i.e. inhibit their reactions. All participants had more inhibitory control deficits when they viewed angry faces in comparison with neutral expressions, and patients with BED did not differ from the participants of the two control groups. Thus, all participants react on anger with increased impulsivity indicating that patients with BED seem to have no specific deficit in this regard. As this was a pilot study, further studies should investigate the interplay of several emotions and impulsivity in healthy and clinical groups. [ABSTRACT FROM AUTHOR]

Background: Previous neuroimaging findings have demonstrated the association between anhedonia and the hippocampus. However, few studies have focused on the structural changes in the hippocampus in major depressive disorder (MDD) patients with anhedonia. Meanwhile, considering that multiple and functionally specialized subfields of the hippocampus have their own signatures, the present study aimed to investigate the volumetric alterations of the hippocampus as well as its subfields in MDD patients with and without anhedonia. Methods: A total of 113 subjects, including 30 MDD patients with anhedonia, 40 MDD patients without anhedonia, and 43 healthy controls (HCs), were recruited in the study. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and the automated hippocampal substructure module in FreeSurfer 6.0 was used to evaluate the volumes of hippocampal subfields. We compared the volumetric differences in hippocampal subfields among the three groups by analysis of variance (ANOVA, post hoc Bonferroni), and partial correlation was used to explore the association between hippocampal subregion volumes and clinical characteristics. Results: ANOVA showed significant volumetric differences in the hippocampal subfields among the three groups in the left hippocampus head, mainly in the cornu ammonis (CA) 1, granule cell layer of the dentate gyrus (GC-ML-DG), and molecular layer (ML). Compared with HCs, both groups of MDD patients showed significantly smaller volumes in the whole left hippocampus head. Interestingly, further exploration revealed that only MDD patients with anhedonia had significantly reduced volumes in the left CA1, GC-ML-DG and ML when compared with HCs. No significant difference was found in the volumes of the hippocampal subfields between MDD patients without anhedonia and HCs, either the two groups of MDD patients. However, no association between hippocampal subfield volumes and clinical characteristics was found in either the subset of patients with anhedonia or in the patient group as a whole. Conclusions: These preliminary findings suggest that MDD patients with anhedonia exhibit unique atrophy of the hippocampus and that subfield abnormalities in the left CA1 and DG might be associated with anhedonia in MDD. [ABSTRACT FROM AUTHOR]

Background: The development of machine learning models for aiding in the diagnosis of mental disorder is recognized as a significant breakthrough in the field of psychiatry. However, clinical practice of such models remains a challenge, with poor generalizability being a major limitation. Methods: Here, we conducted a pre-registered meta-research assessment on neuroimaging-based models in the psychiatric literature, quantitatively examining global and regional sampling issues over recent decades, from a view that has been relatively underexplored. A total of 476 studies (n = 118,137) were included in the current assessment. Based on these findings, we built a comprehensive 5-star rating system to quantitatively evaluate the quality of existing machine learning models for psychiatric diagnoses. Results: A global sampling inequality in these models was revealed quantitatively (sampling Gini coefficient (G) = 0.81, p <.01), varying across different countries (regions) (e.g., China, G = 0.47; the USA, G = 0.58; Germany, G = 0.78; the UK, G = 0.87). Furthermore, the severity of this sampling inequality was significantly predicted by national economic levels (β = − 2.75, p <.001, R2adj = 0.40; r = −.84, 95% CI: −.41 to −.97), and was plausibly predictable for model performance, with higher sampling inequality for reporting higher classification accuracy. Further analyses showed that lack of independent testing (84.24% of models, 95% CI: 81.0–87.5%), improper cross-validation (51.68% of models, 95% CI: 47.2–56.2%), and poor technical transparency (87.8% of models, 95% CI: 84.9–90.8%)/availability (80.88% of models, 95% CI: 77.3–84.4%) are prevailing in current diagnostic classifiers despite improvements over time. Relating to these observations, model performances were found decreased in studies with independent cross-country sampling validations (all p <.001, BF10 > 15). In light of this, we proposed a purpose-built quantitative assessment checklist, which demonstrated that the overall ratings of these models increased by publication year but were negatively associated with model performance. Conclusions: Together, improving sampling economic equality and hence the quality of machine learning models may be a crucial facet to plausibly translating neuroimaging-based diagnostic classifiers into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Bipolar affective disorder (BAD) is a common severe mental health condition with a relapsing course that may include periods of hospital re-admissions. With recurrent relapses and admissions, the course, prognosis, and patient's overall quality of life can be affected negatively. This study aims to explore the rates and clinical factors associated with re-admission among individuals with BAD. Method: This study used data from a retrospective chart review of all records of patients with BAD admitted in 2018 and followed up their hospital records for four years till 2021 at a large psychiatric unit in Uganda. Cox regression analysis was used to determine the clinical characteristics associated with readmission among patients diagnosed with BAD. Results: A total of 206 patients living with BAD were admitted in 2018 and followed up for four years. The average number of months to readmission was 9.4 (standard deviation = 8.6). The incidence of readmission was 23.8% (n = 49/206). Of those readmitted during the study period, 46.9% (n = 23/49) and 28.6% (n = 14/49) individuals were readmitted twice and three times or more, respectively. The readmission rate in the first 12 months following discharge was 69.4% (n = 34/49) at first readmission, 78.3% (n = 18/23) at second readmission, and 87.5% (n = 12/14) at third or more times. For the next 12 months, the readmission rate was 22.5% (n = 11/49) for the first, 21.7% (n = 5/23) for the second, and 7.1% (n = 1/14) for more than two readmissions. Between 25 and 36 months, the readmission rate was 4.1% (n = 2/49) for the first readmission and 7.1% (n = 1/14) for the third or more times. Between 37 and 48 months, the readmission rate was 4.1% (n = 2/49) for those readmitted the first time. Patients who presented with poor appetite and undressed in public before admission were at increased risk of being readmitted with time. However, the following symptoms/clinical presentations, were protective against having a readmission with time, increased number of days with symptoms before admission, mood lability, and high energy levels. Conclusion: The incidence of readmission among individuals living with BAD is high, and readmission was associated with patients' symptoms presentation on previous admission. Future studies looking at BAD using a prospective design, standardized scales, and robust explanatory model are warranted to understand causal factors for hospital re-admission and inform management strategies. [ABSTRACT FROM AUTHOR]

Background: The nucleus accumbens (Nac) is a crucial brain region in the pathophysiology of major depressive disorder (MDD) patients with anhedonia. However, the relationship between the functional imaging characteristics of Nac subregions and anhedonia remains unclear. Thus, this study aimed to investigate the role of resting-state functional connectivity (rsFC) of the Nac subregions between MDD and anhedonia. Methods: We performed resting-state functional magnetic resonance imaging (fMRI) to measure the rsFC of Nac subregions in 55 MDD patients and 30 healthy controls (HCs). A two-sample t test was performed to determine the brain regions with varying rsFC among Nac subregions between groups. Then, correlation analyses were carried out to investigate the relationships between the aberrant rsFC of Nac subregions and the severity of anhedonia. Furthermore, we constructed a mediation model to explain the role of the aberrant rsFC of Nac subregions between MDD and the severity of anhedonia. Results: Compared with the HC group, decreased rsFC of Nac subregions with regions of the prefrontal cortex, insula, lingual gyrus, and visual association cortex was observed in MDD patients. In the MDD group, the rsFC of the right Nac shell-like subregions with the middle frontal gyrus (MFG)/superior frontal gyrus (SFG) was correlated with consummatory anhedonia, and the rsFC of the Nac core-like subdivisions with the inferior frontal gyrus (IFG)/insula and lingual gyrus/visual association cortex was correlated with anticipatory anhedonia. More importantly, the functional alterations in the Nac subregions mediated the association between anhedonia and depression. Conclusions: The present findings suggest that the functional alteration of the Nac subregions mediates the association between MDD and anhedonia, which provides evidence for the hypothesis that MDD patients have neurobiological underpinnings of reward systems that differ from those of HCs. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to (i) compare the maladaptive domains and facets according to the Alternative Model of Personality Disorders (AMPD) Criterion B in patients with a type II bipolar disorder (BD-II) or major depressive disorder (MDD) with healthy controls (HCs), and (ii) investigating the relationship between affective temperaments and these domains and facets in the total sample. Methods: Outpatients diagnosed with current BD-II (n = 37; female 62.2%) or MDD (n = 17; female 82.4%) based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and community HCs (n = 177; female 62.1%) in Kermanshah from July to October 2020 included this case-control study. All participants completed the Personality Inventory for DSM-5 (PID-5), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and the second version of the Beck Depression Inventory (BDI-II). Data were analyzed using analysis of variance (ANOVA), Pearson correlation, and multiple regression. Results: The score of patients with BD-II in all five domains and those with MDD in three domains including negative affectivity, detachment, and disinhibition are significantly higher than the HCs (p < 0.05). Depressive temperament (related to negative affectivity, detachment, and disinhibition) and cyclothymic temperament (related to antagonism and psychoticism) were the most important correlates of the maladaptive domains. Conclusions: Two unique profiles are proposed, including three domains of negative affectivity, detachment, and disinhibition associated with the depressive temperament for MDD, and two domains of antagonism and psychoticism related to cyclothymic temperament for BD-II. [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson's disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients. Objective: To investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients. Methods: Structural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method. Results: Early-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures. Conclusion: SCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: We studied whether provisional posttraumatic stress disorder (PTSD) moderated discharge (DC) and 6-month follow-up (FU) outcomes of multi-modal, integrated eating disorder (ED) residential treatment (RT) based upon principles of cognitive processing therapy (CPT). Methods: ED patients [N = 609; 96% female; mean age (± SD) = 26.0 ± 8.8 years; 22% LGBTQ +] with and without PTSD completed validated assessments at admission (ADM), DC and 6-month FU to measure severity of ED, PTSD, major depressive disorder (MDD), state-trait anxiety (STA) symptoms, and eating disorder quality of life (EDQOL). We tested whether PTSD moderated the course of symptom change using mixed models analyses and if ED diagnosis, ADM BMI, age of ED onset and LGBTQ + orientation were significant covariates of change. Number of days between ADM and FU was used as a weighting measure. Results: Despite sustained improvements with RT in the total group, the PTSD group had significantly higher scores on all measures at all time points (p ≤.001). Patients with (n = 261) and without PTSD (n = 348) showed similar symptom improvements from ADM to DC and outcomes remained statistically improved at 6-month FU compared to ADM. The only significant worsening observed between DC and FU was with MDD symptoms, yet all measures remained significantly lower than ADM at FU (p ≤.001). There were no significant PTSD by time interactions for any of the measures. Age of ED onset was a significant covariate in the EDI-2, PHQ-9, STAI-T, and EDQOL models such that an earlier age of ED onset was associated with a worse outcome. ADM BMI was also a significant covariate in the EDE-Q, EDI-2, and EDQOL models, such that higher ADM BMI was associated with a worse ED and quality of life outcome. Conclusions: Integrated treatment approaches that address PTSD comorbidity can be successfully delivered in RT and are associated with sustained improvements at FU. Improving strategies to prevent post-DC recurrence of MDD symptoms is an important and challenging area of future work. Plain English Summary: Posttraumatic stress disorder (PTSD) is common in patients with eating disorders and is associated with higher severity of symptoms and worse outcomes. However, this has not been studied extensively in patients admitted to higher levels of care, such as residential treatment. Using an integrated clinical approach based upon principles of cognitive processing therapy (CPT) and other evidence-based treatments, we studied outcomes at discharge and 6 months following discharge in 609 patients [96% female; mean age (± SD) = 26.0 ± 8.8 years; 22% LGBTQ +] with and without PTSD. All patients improved significantly and remained improved at follow-up compared to admission. However, all measured symptoms, including those of eating disorder, major depression, and state and trait anxiety, and a measure of quality of life, were worse in patients with PTSD at every time point (admission, discharge, and follow-up). The only significant worsening observed was for symptoms of major depression between discharge and follow-up. In conclusion, integrated treatment approaches that address PTSD and related problems can be successfully delivered in residential treatment and are associated with sustained improvements at 6 months following discharge. Improving strategies to prevent post-discharge recurrence of depressive symptoms is an important and challenging area of future work. [ABSTRACT FROM AUTHOR]