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Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta2= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown. [ABSTRACT FROM AUTHOR]

Theory of mind (ToM) deficits, difficulties in recognizing the intentions, propensities, and beliefs of others have been shown in individuals with bipolar disorder in several studies; however, it is not yet elucidated how ToM abilities changes over the course of bipolar disorder and is related to illness symptoms. This is one of the first longitudinal studies to compare the ToM abilities of euthymic bipolar individuals and healthy controls over a four and a half years period. ToM abilities were measured using the Reading the Mind in the Eyes Test (RMET). A total of 91 euthymic bipolar individuals and 91 healthy controls were included in the analyses. Linear mixed models were used to compare ToM abilities of bipolar individuals and healthy controls. It was found that bipolar individuals scored lower on average on the RMET than healthy controls and that these RMET scores were stable over four and a half years. The results of this study suggest that ToM deficits are a stable (possibly endophenotypic) trait of bipolar disorder. This understanding can contribute to better identification, assessment, and treatment strategies for individuals with bipolar disorder, ultimately improving their overall care and outcome., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder., Methods: A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ., Results: In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=-0.539, p = 0.005), long delay free recall (r=-0.423, p = 0.035), and immediate recall sum trial 1-5 (r=-0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed., Conclusions: This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships., (© 2024. The Author(s).)

Background: Affective disorders (AD) have been linked to inflammatory processes, although the underlying mechanisms of this relationship are still not fully elucidated. It is hypothesized that demographic, somatic, lifestyle, and personality variables predict inflammatory parameters in AD., Aim: To identify biopsychosocial factors contributing to inflammation in AD measured with two parameters, C-reactive protein (CRP) and leukocytes., Methods: This observational study investigated 186 hospital inpatients diagnosed with AD using demographic parameters, serum inflammatory markers, somatic variables, psychological questionnaires, and lifestyle parameters. Hierarchical regression analyses were used to predict inflammatory markers from demographic, somatic, lifestyle, and personality variables., Results: Analyses showed that 33.8% of the variance of CRP was explained by body mass index and other somatic medication ( e.g. anti-diabetics), age and education, and age of affective disorder diagnosis. For leukocytes, 20.1% of the variance was explained by smoking, diet, metabolic syndrome (MetS), and anti-inflammatory medication ( e.g. non-steroidal anti-inflammatory drugs). Other psychiatric or behavioural variables did not reach significance., Conclusion: Metabolic components seem important, with mounting evidence for a metabolic affective disorder subtype. Lifestyle modifications and psychoeducation should be employed to prevent or treat MetS in AD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: C-reactive protein (CRP) is a systemic inflammatory marker, which indicates systemic inflammatory processes It is involved in different inflammatory processes of the body and is a reliable marker for the general inflammatory state of the body. High sensitive CRP seems to play a key role as a state and trait marker of bipolar disorder (BD). In the current study, we tried to determine the long-term effect of CRP levels on clinical symptoms and illness course of bipolar disorder., Methods: For the current study, we examined 106 patients with BD for a period of four years. Participants underwent a clinical screening for depressive and manic episodes with the Hamilton Depression Scale (HAMD) and the Young Mania Rating Score (YMRS) and a serological diagnostic for inflammatory parameters every six months, thus leading to 8 measurement times in total. Patients with the presence of severe medical or neurological comorbidities such as active cancer, chronic obstructive lung disease, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis and acute infections were not included in the study., Results: In our sample, 26% showed a mean hsCRP above 5 mg/dl. Those patients showed a significantly higher mean YMRS score than those with a mean hsCRP under 5 mg/dl during our observation period. Regarding HAMD there was no significant difference in hsCRP values. The existence of lithium treatment showed no significant influence on mean hsCRP levels between the start and endpoint., Conclusion: Individuals who were exposed to a higher level of inflammation over time suffered from more manic symptoms in this period. These findings underline the hypothesis that inflammatory processes have an accumulative influence on the illness course of BD, especially concerning manic symptoms and episodes., Competing Interests: Declaration of competing interest All authors disclose that there is no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence, the work of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Owing to the heterogenic picture of bipolar disorder, it takes approximately 8.8 years to reach a correct diagnosis. Early recognition and early intervention might not only increase quality of life, but also increase life expectancy as a whole in individuals with bipolar disorder. Therefore, we hypothesize that implementing machine learning techniques can be used to support the diagnostic process of bipolar disorder and minimize misdiagnosis rates., Materials and Methods: To test this hypothesis, a de-identified data set of only demographic information and the results of cognitive tests of 196 patients with bipolar disorder and 145 healthy controls was used to train and compare five different machine learning algorithms., Results: The best performing algorithm was logistic regression, with a macro-average F1-score of 0.69 [95% CI 0.66-0.73]. After further optimization, a model with an improved macro-average F1-score of 0.75, a micro-average F1-score of 0.77, and an AUROC of 0.84 was built. Furthermore, the individual amount of contribution per variable on the classification was assessed, which revealed that body mass index, results of the Stroop test, and the d2-R test alone allow for a classification of bipolar disorder with equal performance., Conclusion: Using these data for clinical application results in an acceptable performance, but has not yet reached a state where it can sufficiently augment a diagnosis made by an experienced clinician. Therefore, further research should focus on identifying variables with the highest amount of contribution to a model's classification., (© 2024 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Introduction: An increasing body of evidence suggests a strong relationship between gut health and mental state. Lately, a connection between butyrate-producing bacteria and sleep quality has been discussed. The PROVIT study, as a randomized, double-blind, 4-week, multispecies probiotic intervention study, aims at elucidating the potential interconnection between the gut's metabolome and the molecular clock in individuals with major depressive disorder (MDD)., Methods: The aim of the PROVIT-CLOCK study was to analyze changes in core clock gene expression during treatment with probiotic intervention versus placebo in fasting blood and the connection with the serum- and stool-metabolome in patients with MDD (n = 53). In addition to clinical assessments in the PROVIT study, metabolomics analyses with 1H nuclear magnetic resonance spectroscopy (stool and serum) and gene expression (RT-qPCR) analysis of the core clock genes ARNTL, PER3, CLOCK, TIMELESS, NR1D1 in peripheral blood mononuclear cells of fasting blood were performed., Results: The gene expression levels of the clock gene CLOCK were significantly altered only in individuals receiving probiotic add-on treatment. TIMELESS and ARNTL gene expression changed significantly over the 4-week intervention period in both groups. Various positive and negative correlations between metabolites in serum/stool and core clock gene expression levels were observed., Conclusion: Changing the gut microbiome by probiotic treatment potentially influences CLOCK gene expression. The preliminary results of the PROVIT-CLOCK study indicate a possible interconnection between the gut microbiome and circadian rhythm potentially orchestrated by metabolites., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH) 2 D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH) 2 D, were measured simultaneously with a validated liquid chromatography-tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH) 2 D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH) 2 D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH) 2 D ( r = -0.154, p = 0.040), as well as the Young Mania Rating Scale and the VMR ( r = -0.238, p = 0.015). Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.

Recent evidence on the association between vitamin D and cognition in mentally healthy individuals is inconsistent. Furthermore, the link between vitamin D and cognitive ability in individuals with bipolar disorder has not been studied yet. Thus, we aimed to investigate the association between 25-hydroxyvitamin D (25(OH)D), 24,25 dihydroxyvitamin D (24,25(OH)2D, the vitamin D metabolite ratio (VMR) and cognition in a cohort of euthymic patients with bipolar disorder. Vitamin D metabolites were measured simultaneously by liquid-chromatography tandem mass-spectrometry in serum samples from 86 outpatients with bipolar disorder and 93 healthy controls. Neither the inactive precursor 25(OH)D, nor the primary vitamin D catabolite 24,25(OH)2D, or the vitamin D metabolite ratio were significantly associated with the domains "attention", "memory", or "executive function" in individuals with bipolar disorder and healthy controls. Further, no vitamin D deficiency effect or interaction group × vitamin D deficiency was found in the cognitive domain scores. In summary, the present study does not support vitamin D metabolism as a modulating factor of cognitive function in euthymic BD patients. Considering the current study's cross-sectional design, future research should expand these results in a longitudinal setting and include additional aspects of mental health, such as manic or depressive symptoms, long-term illness course and psychopharmacological treatment.

Background: Due to the COVID-19 pandemic, workplaces in the medical field experienced changes. Non-frontline workers in the health sector (WHS) were in many cases allowed to work from home (WFH). Changes in work locations have affected the perception of productivity during the COVID-19 pandemic compared to the pre-pandemic perception. Studies regarding this research field are rare for WHS. The aim of the present study was to investigate the perception of productivity and its impact on symptoms of depression during the COVID-19 pandemic. The second objective was to assess the implications for post-pandemic work settings such as WFH or work scenarios in hospitals during pandemics., Methods: At three points in time during the COVID-19 pandemic (t1; n = 161: April 2020, t2; n = 1598 winter 2020/2021, t3; n = 1879 winter 2021/2022), an online survey of WHS (e.g., medical doctors, nurses, scientific staff) in Austria concerning their productivity in their current workplace (pre- and post-pandemic) was conducted. The online survey included questions about the perceptions of productivity changes (i.e., perceptions of lower, equal, and higher productivity, before and during the COVID-19 pandemic) in different work settings (e.g., working in a hospital or working from home), as well as standardized questionnaires like the Patient Health Questionnaire (PHQ-9), assessing symptoms of depression in WHS., Results: χ 2 tests showed that WHS working in hospitals experienced significantly fewer fluctuations in their perceptions of productivity than WHS working from home. An analysis of variance (ANOVA) indicated that WHS with a lower perception of productivity tended to have higher self-assessed depressive symptoms., Conclusion: The possibility of remaining working in the hospital in stressful scenarios like the COVID-19 pandemic might stabilize the feeling of productivity. Moreover, productivity is associated with self-assessed depressive symptoms. Hence, looking into the reasons behind this discrepancy between WHS in hospitals and those working from home might help to improve the home office modality and to create better structures, which are related to symptoms of depression.

The connection between cognitive function and the "Big Five" personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism) in the general population is well known; however, studies researching bipolar disorder (BD) are scarce. Therefore, this study aimed to investigate the Big Five as predictors of executive function, verbal memory, attention, and processing speed in euthymic individuals with BD (cross-sectional: n = 129, including time point t1; longitudinal: n = 35, including t1 and t2). Participants completed the NEO Five-Factor Inventory, the Color and Word Interference Test, the Trail Making Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. The results showed a significant negative correlation between executive function and neuroticism at t1. Changes in cognitive function between t1 and t2 did not correlate with and could not be predicted by the Big Five at t1. Additionally, worse executive function at t2 was predicted by higher neuroticism and lower conscientiousness at t1, and high neuroticism was a predictor of worse verbal memory at t2. The Big Five might not strongly impact cognitive function over short periods; however, they are significant predictors of cognitive function. Future studies should include a higher number of participants and more time in between points of measurement.

The global spread of the coronavirus disease (COVID-19) has created new challenges for the entire healthcare system, and those who work directly with the patients or even on the front lines with COVID-19 patients have been particularly stressed. Only a few studies are currently available investigating psychosomatic symptoms among healthcare workers, particularly frontline workers, over the entire pandemic period (2020-2022). There is also a lack of knowledge about strategies to prevent stress during and after a health crisis., Methods: An online survey was conducted at three times (April 2020, winter 2020/2021, and winter 2021/2022) during the COVID-19 pandemic in Austria. The sample included 160 healthcare workers at screening time 1, 1.361 healthcare workers at screening time 2, and 1.134 healthcare workers at screening time 3. The survey included COVID-19 work-related fears, satisfaction with the frontline work, and standardized inventories to assess psychosomatic symptoms, such as the Patient Health Questionnaire (PHQ-D)., Results: Psychosomatic symptoms were more common among women compared to men, and among frontline workers compared to non-frontline workers, especially during the course of the pandemic at t2 and t3. Self-reported scores of COVID-19 work-related fears were significantly associated with psychosomatic symptoms. Furthermore, in frontline workers, there was a significant association between the feeling of being safe and well-informed and psychosomatic symptoms., Conclusion: COVID-19 work-related fears and psychosomatic symptoms have been prevalent among healthcare workers throughout the pandemic. Feeling safe and informed appears to be essential to prevent psychosomatic symptoms, leading to a recommendation for employers in the healthcare sector to focus on communication and information. As frontline workers are especially prone to psychosomatic symptoms, more stress prevention programs for them will be essential to maintain productivity and reduce sick days and fluctuations in the healthcare system.

Introduction: The COVID-19 pandemic with its protective measures (e. g. lockdown) had far-reaching effects on everyone's well-being. The aim of this study was to examine lifestyle variables during the first Austrian lockdown in patients with bipolar disorder in comparison to a healthy control group and to assess subjective changes caused by the pandemic., Method: At the beginning of April 2020, an online survey of n=75 participants (35 people with bipolar disorder and 40 healthy controls) with standardized questionnaires (Beck Depression Inventory-2, Food Craving Inventory, Altman Self Rating Mania Scale) as well as non-standardized COVID-19-specific questions on the subject of "Psychological stress and effects of the COVID-19 pandemic in bipolar disorder" was created and distributed via LimeSurvey., Results: Both groups reported a negative impact on their mental health. The participants with bipolar disorder showed significantly higher values in the Beck Depression Inventory-2 score (p<0,001), in emotional distress due to social distancing (p=0,003) and significantly lower values in muscle-strengthening exercise (p=0,039) and in sport units (p=0,003) compared to the control group. In addition, patients with bipolar disorder smoked more often than individuals of the control group. People with bipolar disorder were 42,9% more likely to report they were less efficient during the pandemic, and 22,9% experienced weight gain compared to before the pandemic. The control group, on the other hand, was less efficient at 17,5% and 5,0% reported weight gain. However, a comparison with pre-pandemic data showed a decrease in food craving in both groups., Conclusion: This study provided first evidence of self-reported adverse effects on mental stress and lifestyle in people with bipolar disorder at the beginning of the COVID-19 pandemic. Psychiatric care and early interventions for patients with bipolar disorder would be particularly important in times of crisis in order to help maintain a healthy lifestyle and thus counteract unfavourable developments., Competing Interests: Alle Autorinnen/Autoren dieser Studie erklären keinen Interessenkonflikt., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality., Methods: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera., Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI &gt;8), compared to poor-sleep quality patients (PSQI ≤8)., Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The ongoing pandemic of coronavirus disease (COVID-19) is a global health crisis that has posed enormous pressure on workers in the health sector (WHS), having a massive impact on their mental health. In this study, we aimed to evaluate the sleep quality of WHS during the pandemic and compare frontline WHS to those who are not directly engaged in the care of COVID-19 patients. This cross-sectional, self-reported online survey assessed the sleep quality of WHS in Austria using the Pittsburgh Sleep Quality Index (PSQI). The same questionnaire was sent out two times. Due to the unequal sample and anonymity of the study participants, we analyzed the data of each time point separate from each other. The first study was conducted in April/May 2020, during the first lockdown in Austria (Study1), and the second study was conducted in July/August 2020, when the social restrictions were loosened (Study2). T-test was used to compare the mean values of PSQI scores between frontline vs. non-frontline WHS, while two two-way ANCOVAs were used to analyze differences in the PSQI mean scores (controlled for age) for male vs. female between frontline vs. non-frontline WHS. During the first lockdown in Austria (Study1) we identified a shorter sleep duration of frontline WHS compared to the non-frontline group, however the difference in global PSQI score between these groups was statistically not significant. In the period after loosened restrictions (Study2) the sleep quality, sleep latency, sleep duration, sleep efficiency and global PSQI score was worse in frontline WHS compared to the non-frontline WHS. Furthermore, female WHS scored higher in the PSQI indicating a worse sleep than male WHS. In addition, nurses and nursing assistants had a higher prevalence of poor sleep quality than other occupational groups. Our results indicate that the COVID-19 pandemic negatively impacts the sleep of WHS, affecting particularly frontline WHS. Preventive interventions aiming to promote good sleep quality in WHS during a healthcare crisis like this pandemic are essential to enhance resilience and mitigate the vulnerability of this specific population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tmava-Berisha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: A relevant comorbidity of bipolar disorder (BD) is eating disorders (EDs). Crossed vulnerability factors as eating disorder-specific symptoms (EDSSs) may trigger the onset of both disorders in either direction. The Structured Inventory for Anorexic and Bulimic Eating Disorders for Self-Report was used to examine the occurrence of EDs in euthymic/subsyndromal individuals with BD ( n = 86) and healthy controls ( n = 86) matched for age and sex. Furthermore, we explored EDSSs with the subscales "general psychopathology and social integration," "bulimic symptoms," "body image and slimness ideal," "sexuality and body weight," "counteract," and "atypical binge." Higher rates of all EDSSs were reported in BD. Younger individuals with BD showed higher expression in "bulimic symptoms," "body image and slimness ideal," and "atypical binge" subscales. No participants fulfilled ED diagnosis. The findings show a link between EDSS and BD. Clinicians should pay attention to a multimodal intervention, considering risk factors, investigating eating habits and ED associated behaviors., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In Austria, new approaches of rehabilitation programs focus on the prevention of mental illness and offer treatment not only for acute psychiatric patients, but also for those who are at risk of developing a mental disorder or have recovered from one.The aim of this study was to determine the effects of a psychiatric rehabilitation program on individuals with different mood states., Subjects and Methods: 600 patients with a history of affective disorder were tested at the time of admission to an Austrian inpatient psychiatric rehabilitation center. Data of extreme groups - patients who were depressed (n=59; BDI-II<9 and HAMD<8) or euthymic (n=59; BDI<18 and HAMD>19) at the time of therapy start - were analyzed. The participants completed the Maslach Burnout Inventory - General Survey, the Symptom Checklist - Revised and the Stress Coping Questionnaire at the beginning and the end of the 6-weeks rehabilitation program., Results: After 6 weeks, both groups showed significantly less psychiatric symptoms (BDI-II, HAMD, SCL-90, and negative coping strategies (SVF). Importantly, work-related stress symptoms ("burnout" symptoms) improved significantly in the euthymic group., Conclusions: Euthymic patients seem to be able to focus on work-related stress symptoms including reduced emotional exhaustion through treatment, while currently depressed patients primarily benefit by an improvement in general psychiatric symptomatology. The results indicate the crucial role of mood state validated with standardized psychological questionnaires BDI-II and HAMD at time of admission to such programs. These findings could have implications on treatment decisions for psychiatric patients and assist in making a forecast concerning ability to recover and treatment prognosis.

The gut-brain axis plays a role in major depressive disorder (MDD). Gut-bacterial metabolites are suspected to reduce low-grade inflammation and influence brain function. Nevertheless, randomized, placebo-controlled probiotic intervention studies investigating metabolomic changes in patients with MDD are scarce. The PROVIT study (registered at clinicaltrials.com NCT03300440) aims to close this scientific gap. PROVIT was conducted as a randomized, single-center, double-blind, placebo-controlled multispecies probiotic intervention study in individuals with MDD ( n = 57). In addition to clinical assessments, metabolomics analyses (1H Nuclear Magnetic Resonance Spectroscopy) of stool and serum, and microbiome analyses (16S rRNA sequencing) were performed. After 4 weeks of probiotic add-on therapy, no significant changes in serum samples were observed, whereas the probiotic groups' ( n = 28) stool metabolome shifted towards significantly higher concentrations of butyrate, alanine, valine, isoleucine, sarcosine, methylamine, and lysine. Gallic acid was significantly decreased in the probiotic group. In contrast, and as expected, no significant changes resulted in the stool metabolome of the placebo group. Strong correlations between bacterial species and significantly altered stool metabolites were obtained. In summary, the treatment with multispecies probiotics affects the stool metabolomic profile in patients with MDD, which sets the foundation for further elucidation of the mechanistic impact of probiotics on depression.

Background: The prevalence of metabolic syndrome and overweight/obesity is increased in bipolar disorder (BD) compared to the general population and is related to suicidality. The aim of this study was to examine the association between both the rate of suicidal ideation and suicide attempts and metabolic variables in individuals with BD., Methods: Anthropometric measures, socio-demographic data, suicide history and serum lipid levels were measured in 215 individuals with BD. Individuals were divided into normal weight, overweight and obese according to their body mass index (BMI), and metabolic syndrome was assessed using "The International Diabetes Federation"-criteria., Results: Of the 215 individuals studied, 80.9% reported suicidal ideation, 35.3% reported at least one suicide attempt and 30.7% were diagnosed with metabolic syndrome. Both metabolic syndrome and BMI were not related to suicide attempts. However, individuals with normal weight had more suicidal ideation than overweight individuals, while obese individuals did not differ from either group. Furthermore, there was no association between suicide attempts or suicidal ideation and serum lipid levels., Limitations: The cross-sectional design of the study, a non-standardized questionnaire for suicidality, and not controlling the medication intake are limiting factors., Conclusion: Contrary to expectations, a difference was found in the BMI categories and suicidal ideation, but not suicide attempts. Serum lipid levels were found to be unsuitable as possible biomarkers for suicidality in individuals with BD. Special attention should be paid to suicidal ideation and BMI rather than metabolic syndrome or lipid values when treating suicidal individuals with BD., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Throughout the COVID-19 pandemic, mental health of individuals with bipolar disorders (BD) is potentially more vulnerable, especially regarding COVID-19-related regulations and associated symptomatic changes. A multicentric online study was conducted in Austria, Germany, and Denmark during the COVID-19 pandemic. Overall, data from 494 participants were collected (203 individuals with BD, 291 healthy controls (HC)). Participants filled out questionnaires surveying emotional distress due to social distancing, fear of COVID-19, and the Brief Symptom Inventory-18 to assess symptom severity at four points of measurement between 2020 and 2021. General linear mixed models were calculated to determine the difference between the groups in these pandemic specific factors. Individuals with BD reported higher distress due to social distancing than HC, independently of measurement times. Fear of COVID-19 did not differ between groups; however, it was elevated in times of higher infection and mortality due to COVID-19. Individuals with BD reported higher psychiatric symptom severity than HC; however, symptom severity decreased throughout the measured time in the pandemic. Overall, individuals with BD experienced more distress due to the COVID-19 situation than HC. A supportive mental health system is thus recommended to ensure enhanced care, especially in times of strict COVID-19-related regulations.

Background: The onset and early warning signs of episodes of bipolar disorder are often realized late by those affected. The earlier an incipient episode is treated, the more prognostically favorable the course will be. Symptom monitoring via smartphone application (app) could be an innovative way to recognize and react to early warning signs more swiftly. The aim of this study was to find out whether patients and their relatives consider technical support through an app to be useful and practical in the early warning sign detection and treatment., Methods: In the present study, 51 patients with bipolar disorder and 28 relatives were interviewed. We gathered information on whether participants were able to perceive early warning signs in form of behavioral changes sufficiently and in a timely fashion and also whether they would use an app as treatment support tool., Results: Although 94.1% of the surveyed patients and 78.6% of their relatives felt that they were well informed about the disease, 13.7% and 35.7%, respectively were not fully satisfied with the current treatment options. Early warning signs of every depressive development were noticed by 25.5% of the patients (relatives 10.7%). Every (hypo)manic development was only noticed by 11.8% of the patients (relatives 7.1%); 88.2% of the patients and 85.7% of the relatives noticed the same symptoms recurrently at the beginning of a depression and 70.6% and 67.9%, respectively, at the beginning of a (hypo)manic episode (in particular changes in physical activity, communication behavior and the sleep-wake rhythm). 84.3% of the patients and 89.3% of the relatives stated that they considered technical support that draws attention to mood and activity changes as useful and that they would use such an app for the treatment., Discussion: The current options for perceiving early warning signs of a depressive or (hypo)manic episode in bipolar disorder are clinically inadequate. Those affected and their relatives desire innovative, technical support. Early detection of symptoms, which often manifest themselves in changes in behavior or activity patterns, is essentiell for managing the course of bipolar disorder. In the future, smartphone apps could be used for clinical treatment and research through objective, continuous and., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The COVID-19 pandemic affects both mentally healthy and ill individuals. Individuals with bipolar disorder (BD) constitute an especially vulnerable group. A multicentric online study was conducted in Austria, Denmark, and Germany after the first lockdown phase in 2020. In total, 117 healthy controls (HC) were matched according to age and sex to 117 individuals with BD. The survey included the Brief Symptom Inventory-18, Beck Depression Inventory-2, Pittsburgh Sleep Quality Index, and a self-constructed questionnaire assessing COVID-19 fears, emotional distress due to social distancing, lifestyle, and compliance to governmental measures. In individuals with BD, increased symptoms of depression, somatization, anxiety, distress due to social distancing, and poorer sleep quality were related to emotional distress due to social distancing. The correlation between emotional distress due to social distancing and anxiety showed 26% of shared variance in BD and 11% in HC. Negative lifestyle changes and lower compliance with COVID-19 regulatory measures were more likely to be observed in individuals with BD than in HC. These findings underscore the need for ongoing mental health support during the pandemic. Individuals with BD should be continuously supported during periods of social distancing to maintain a stable lifestyle and employ strategies to cope with COVID-19 fears., (Copyright © 2022. Published by Elsevier B.V.)

Bipolar disorder (BD) is associated with impairments in cognitive functions, in which metabolic factors, e.g., overweight, seem to play a significant role. The aim of this study was to investigate the association between nutritional factors and cognitive performance in euthymic individuals with BD. A study cohort of 56 euthymic individuals with BD was compared to a sample of 53 mentally healthy controls. To assess cognitive function, the following tests were applied: California Verbal Learning Test, Trail Making Test A/B, d2 Test of Attention-Revised, and Stroop's Color-Word Interference Test. Furthermore, a 4-day food record was processed to evaluate dietary intake of macronutrients, specific micronutrients, and food diversity. Body mass index and waist to height ratio were calculated to assess overweight and central obesity. Results showed no nutritional differences between individuals with BD and controls. Individuals with BD performed worse in the d2 test than controls. Hierarchical regression analyses yielded no association between cognitive and nutritional parameters. However, waist to height ratio was negatively correlated with almost all cognitive tests. Central obesity seems to affect cognitive functioning in BD, while the lack of finding differences in nutritional data might be due to problems when collecting data and the small sample size. Consequently, further studies focusing on objectively measuring food intake with adequate sample size are needed.

Immune-mediated inflammatory processes and oxidative stress are involved in the aetiopathogenesis of bipolar disorder (BD) and weight-associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found to be more active in BD, and associated with overweight/obesity. This study aimed to investigate tryptophan metabolism in BD compared to controls (C), stratified by weight classes, in a longitudinal setting, dependent on the incidence of BD episodes. Peripheral tryptophan, kynurenine, and neopterin were assessed in the serum of 226 BD individuals and 142 C. Three samples in a longitudinal assessment were used for 75 BD individuals. Results showed a higher kynurenine/tryptophan in both BD compared to C and overweight compared to normal weight persons. Levels remained stable over time. In the longitudinal course, no differences were found between individuals who were constantly euthymic or not, or who had an illness episode or had none. Findings indicate that tryptophan, kynurenine, and IDO-1 activity may play a role in pathophysiology in BD but are not necessarily associated with clinical manifestations. Accelerated tryptophan breakdown along the kynurenine axis may be facilitated by being overweight. This may increase the risk of accumulation of neurotoxic metabolites, impacting BD symptomatology, cognition, and somatic comorbidities.

Introduction: The coronavirus disease (COVID-19) pandemic and consequent restrictions including social distancing had a great impact on everyday life. To date, little is known about how the restrictions affected sleep, which is commonly disturbed in bipolar disorder (BD). The aim of this study was to elucidate sleep patterns during the pandemic in Austrian BD individuals., Methods: An online survey assessed sleep with the Pittsburgh Sleep Quality Index (PSQI) and COVID-19-associated attitudes, fears, and emotional distress of 20 BD individuals and 19 controls (HC) during the pandemic. The survey was conducted in April 2020, when very strict regulations were declared, and repeated in May, when they were loosened., Results: Individuals with BD reported overall poor sleep according to PSQI sum at both time points. Subjective sleep quality, sleep latency, daytime sleepiness, and PSQI sum were worse in individuals with BD than in HC. Individuals with BD informed themselves more frequently about pandemic-related topics. Higher information frequency and more COVID-19 fears (about the virus, own infection, contracting others) correlated with worse PSQI values. Regression models found in BD group that higher information frequency as well as higher COVID-19 fears in April predicted worse sleep characteristics in May, in particular subjective sleep quality, sleep duration, sleep efficiency, and daytime sleepiness., Conclusion: As sufficient sleep duration and quality are essential for well-being and particularly important for vulnerable BD individuals, it is important that information about the pandemic is gathered to a reasonable extent and mental health professionals include COVID-19-related fears when currently treating BD., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Metabolic syndrome (MetS) is more prevalent in individuals with bipolar disorder and has a negative impact on cognition, in particular on executive function, which is already impaired in individuals with bipolar disorder compared to healthy controls. Methods: In a cross-sectional study, we compared 148 euthymic patients with bipolar disorder and 117 healthy controls in cognitive function depending on the diagnosis of MetS. A neuropsychological test battery was used including the Trail Making Test A/B, Stroop Color and Word Interference Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. In addition, MetS variables as well as the defining variables waist circumference, serum triglyceride levels, high-density lipoprotein cholesterol levels, blood pressure, fasting glucose levels, and body mass index were compared between patients and controls. In addition, illness-related variables were associated with MetS in individuals with bipolar disorder. Results: The prevalence of MetS in patients with bipolar disorder was higher than in controls (30.4 vs. 15.4%). Patients with bipolar disorder with MetS had impaired executive function compared to patients without MetS or healthy controls with and without MetS ( p = 0.020). No MetS effects or interaction MetS × Group was found in attention/processing speed ( p = 0.883) and verbal learning/memory ( p = 0.373). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in bipolar disorder ( p > 0.05). Conclusion: Bipolar disorder comorbid with MetS bears additional risk for impaired executive function. Executive function includes action planning, inhibition, and impulse control and could play a critical role in keeping long-term goals in mind associated with gaining and maintaining a healthy weight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dalkner, Bengesser, Birner, Fellendorf, Fleischmann, Großschädl, Lenger, Maget, Platzer, Queissner, Schönthaler, Tmava-Berisha and Reininghaus.)