Background The interaction between health behaviors and medical adherence (MA) is well-researched in somatic disorders, however, little is known about this association in psychiatric disorders. We hypothesized that there is a relationship between health behaviors (smoking habits, alcohol consumption, exercise, diet, and preventive medical check-ups) and MA in affective disorders. Methods Data were collected in Austrian primary care waiting rooms with a self-report questionnaire. The study recorded data from (a) patients with affective disorders, (b) patients with other psychiatric diagnoses, and (c) individuals without psychiatric diagnoses. The groups were matched from the total sample (N = 176) according to sociodemographic variables (total n after adjustment = 84; n = 28 per group). Results There were no significant differences between groups in MA and health behavior, but a positive correlational association between dietary behavior and MA was observed only in affective disorders. Conclusion These findings suggest the implementation of targeted communication measures for patients with affective disorders, such as general practitioner counselling and patient education on both dietary behavior and MA. Health literacy on behalf of healthcare providers and adequate doctor-patient communication are important.

Lithium is a first-line treatment for bipolar disorder (BD), but weight gain is a common side effect, leading to physical comorbidities and reduced average life expectancy. Some individuals are predisposed to weight gain due to lithium therapy, indicating the need to explore metabolic differences to prevent health complications. This descriptive feasibility study aimed to explore metabolic parameters in lithium-naïve BD individuals who later gained weight during lithium therapy versus those who did not. Data from BD individuals (N = 10) were included, five of whom gained weight (≥ 5 kg) during lithium treatment and five who did not. Nuclear Magnetic Resonance spectroscopy was used to measure blood serum lipoprotein and inflammation parameters, as well as molecular metabolites before lithium treatment. Univariate t-tests and multivariate orthogonal partial least-squares discriminant analysis (oPLS-DA) were performed to observe metabolomic between-group differences. The multivariate oPLS-DA did not show significant differences between the groups, but data visualization suggested distinct metabolic profiles. Univariate analyses revealed significantly elevated lipoprotein parameters in the weight gain group, which did not remain significant after correction for multiple testing. Phenylalanine levels showed an observable but non-significant downward trend in the weight gain group (fold change = 0.40, p = .057). The findings suggest a link between weight gain during lithium therapy and altered lipoprotein metabolism, aligning with previous research. However, larger studies are needed to further explore the underlying mechanisms. These preliminary findings represent a stepping stone for personalized lithium treatment strategies, which could help mitigate adverse metabolic side effects and improve treatment adherence.

This scoping review synthesized evidence on vitamin D, parathyroid hormone (PTH), and serum calcium in bipolar disorder (BD) to evaluate their potential clinical utility. A systematic PubMed search identified original studies examining calcium metabolism biomarkers (vitamin D, PTH, serum calcium) exclusively in BD populations. Findings were synthesized narratively due to substantial methodological heterogeneity. Fourteen studies met inclusion criteria, with small sample sizes (median n = 55) and predominantly cross-sectional designs. Vitamin D comparisons between BD patients and controls yielded contradictory results: three studies reported significantly lower levels in BD patients, two found significantly higher levels, and three found no differences. Vitamin D deficiency definitions varied widely (< 25 to < 50 nmol/L), precluding meaningful comparisons. Four cognition studies showed inconsistent associations with vitamin D, with negative correlations, age-dependent effects, or no associations reported. Two small vitamin D supplementation studies in bipolar spectrum disorders yielded contradictory results in distinct populations, with one in youth and the other in adults. Data on PTH and calcium were sparse and inconsistent. Study limitations included a single database search, substantial study heterogeneity, and inadequate control for confounders, including seasonal variation. Evidence on calcium metabolism biomarkers in BD is contradictory and methodologically limited. Fundamental inconsistencies in vitamin D status between BD patients and controls, combined with conflicting supplementation data, preclude clinical recommendations. Routine vitamin D screening specifically for BD management cannot be supported. Large-scale, standardized studies are needed before clinical application.

INTRODUCTION:There has been an increasing focus on sex differences in bipolar disorder in recent years, yet much remains to be understood about their impact on clinical characteristics and treatment approaches. The aim of this study was to identify sex differences that could alter diagnosis and treatment strategies, potentially improving patient compliance and outcomes. METHODS:This retrospective study analysed data from interviews with 340 participants (171 men, 169 women; ages ranging from 18 to 82 years) from the BIPFAT/BIPLONG study at the specialised outpatient centre for bipolar disorder at the Medical University of Graz, Austria. We examined sex differences in clinical characteristics and drug therapy primarily using logistic and linear regression models, with chi-square tests and Mann-Whitney U tests applied as supplementary analyses for subgroup comparisons. RESULTS:Our findings revealed that the age of onset for bipolar disorder was earlier in women (B = -3.05, 95% confidence interval [CI] = [-5.08, -1.02], p = 0.003), with women reporting their first affective symptoms at an average age of 22.7 (standard deviation [SD] = 9.9) compared to 26.4 (SD = 12.1) in men. Comorbid obsessive-compulsive disorder was significantly more prevalent in women (OR = 2.24, 95% CI = [2.12, 41.33], p = 0.003). In comparison, men were shown to experience manic episodes per year more frequently (B = -0.32, 95% CI = [-0.59, -0.05], p = 0.019). Differences in treatment emerged only within specific age subgroups rather than the overall study sample. CONCLUSIONS:Taken together, we found fewer differences than expected, which suggests that factors other than sex play a greater role in the course of bipolar disorder. Our analysis indicates that more women are suffering from obsessive-compulsive disorder (OCD) as comorbidity than men, a topic that has not yet been extensively researched. While previous studies mostly show that men have an earlier onset of symptoms, we found the opposite in our sample. Another notable difference in illness course was that men experienced more manic episodes per year. Further research in this area is needed to verify our findings, ideally focusing specifically on OCD in bipolar men and women, as sex differences in this comorbidity remain underexplored.

BackgroundBipolar disorder is associated with impairments in cognition and psychosocial functioning. Although these impairments occur frequently, often persist during euthymic times, and worsen quality of life, the impact of cognitive abilities on functioning has not yet been fully elucidated.MethodsThe current study investigated the effects of cognitive domains (attention/psychomotor speed, verbal learning/memory, executive function) on psychosocial functioning cross-sectionally. Data from 210 euthymic individuals with bipolar disorder [101 female, 109 male; M(age) = 44.47; SD(age) = 14.25] were included into the analysis. A neurocognitive test battery was administered and the Global Assessment of Functioning was used to depict psychosocial functioning. Correlation analyses were conducted to observe the associations between functioning and the cognitive domains. Moreover, three hierarchical regression analyses were applied to predict functioning by each of the cognitive domains, while considering age, sex, and education as control variables.ResultsCorrelation analyses revealed that functioning was positively associated with attention/psychomotor speed and verbal learning/memory. However, the consecutive hierarchical regression analyses found that none of the cognitive domains were able predict functioning beyond the control variables age, sex, and education.ConclusionOur findings indicate that greater abilities in the domains of attention/psychomotor speed and verbal learning/memory are associated with better functioning. However, this association can be explained by other relevant variables such as age or education, indicating that cognitive abilities are not the sole contributor of psychosocial functioning. Investigating other measurements of functioning or cognitive abilities could lead to different results. Nevertheless, promoting cognitive abilities and autonomy in daily life remains an important aspect of therapy in bipolar disorder.

IntroductionC-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.MethodsFor 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.ResultsIn 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.ConclusionIndividuals 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.

Abstract 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.

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.

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.

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.

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.

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.

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.

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.

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.