Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Theory of mind abilities during the course of bipolar disorder: A longitudinal study using mixed models.

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.

PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression.

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.

The influence of chronic inflammation on the illnesscourse of bipolar disorder: A longitudinal study.

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.

Machine-based learning of multidimensional data in bipolar disorder - pilot results.

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.

Exploring the genetics of lithium response in bipolar disorders.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Vitamin D Status in Bipolar Disorder.

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)2D, 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)2D, 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)2D/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)2D. 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)2D (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.

The Influence of Vitamin D Status on Cognitive Ability in Patients with Bipolar Disorder and Healthy Controls.

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.

Impact of the COVID-19 Pandemic on Productivity of Workers in the Health Sector between Working in a Hospital and from Home.

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: χ2 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.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3ß. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.

Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.

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 >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.

The Big Five as Predictors of Cognitive Function in Individuals with Bipolar Disorder.

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.

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.

Feeling Informed and Safe Are Important Factors in the Psychosomatic Health of Frontline Workers in the Health Sector during the COVID-19 Pandemic in Austria.

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.

[COVID-19 and Bipolar Affective Disorder: Subjective Changes in Lifestyle Variables During the First Lockdown During the COVID-19 Pandemic in Austria]. / COVID-19 und bipolare affektive Störung: Subjektive Veränderung der Lebensstilvariablen während des ersten Lockdowns in der COVID-19-Pandemie in Österreich.

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.

Sleep quality among workers in the health sector exposed to the COVID-19 pandemic.

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.

The Outcome of Psychiatric Rehabilitation Treatment Depends on Affective State at the Time of Admission.

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.

Eating Habits and Eating Disorder Associated Behavior in Bipolar Disorder.

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.

The PROVIT Study-Effects of Multispecies Probiotic Add-on Treatment on Metabolomics in Major Depressive Disorder-A Randomized, Placebo-Controlled Trial.

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.