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.

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.

Impaired implicit learning in adults with anorexia nervosa.

OBJECTIVE: Cognitive alterations play an important role in the pathophysiology and treatment of anorexia nervosa (AN). Previous studies suggest that some implicit learning processes may be inhibited in AN. However, this has not yet been fully explored. The purpose of this study is to analyze implicit learning in patients with AN in comparison to healthy controls. METHODS: In this pilot-study, a total of 21 patients diagnosed with AN and 21 matched controls were administered the weather prediction task (WPT), a probabilistic implicit category learning task that consists of two sub-variants. During the feedback (FB) version of the task, participants learn associations between tarot cards and weather outcomes via an operant learning model through which they receive immediate FB on their answers, whereas during the paired associate (PA) variant, participants are directly asked to memorize given associations. RESULTS: AN patients showed selective impairment on the FB task where they scored significantly lower both in comparison to controls (p = .001) who completed the same task and when compared to their own performance on the PA variant (p = .006). Clinical measures showed no significant correlations with test scores. DISCUSSION: Our results demonstrate implicit FB learning deficiencies in adult patients with AN. These impairments may have an impact on the effect of psychotherapeutic interventions and could partially explain the lack of treatment response in AN. Further studies are necessary to derive when and through which mechanisms these alterations originate, and to what extent they should be considered during treatment of the disorder. PUBLIC SIGNIFICANCE: Cognitive impairments pose a challenge in the management of anorexia nervosa. Improved comprehension of cognitive alterations could lead to a greater understanding of the disease and adaptation of psychotherapeutic treatments. In this study, we found that implicit feedback learning in anorexia nervosa is impaired compared to healthy controls. This could indicate the necessity of treatment adaptations in the form of therapy tools without feedback and a larger focus on psychoeducation.

Delirium-associated medication in people at risk: A systematic update review, meta-analyses, and GRADE-profiles.

BACKGROUND: Drug-associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium-associated medication is uncertain due to a lack of high-quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium. METHODS: A systematic update review and meta-analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug-delirium associations were pooled in meta-analyses using the random-effects model. Quality of evidence was assessed using the GRADE-approach. This study is preregistered with OSF (DOI https://doi.org.10.17605/OSF.IO/4PUHY). RESULTS: The 31 eligible studies, presenting results for 24 medication classes were identified. Meta-analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72-1.28; high-quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15-0.40), Ketamine (OR: 0.72, 95% CI 0.35-1.46) or corticosteroids (OR: 0.69, 95% CI 0.32-1.50; moderate quality evidence, respectively). Low-level evidence suggests a three-fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04-9.26). Opioids, benzodiazepines, H1 -antihistamines, and antidepressants did not reach reliable evidence levels in our analyses. CONCLUSION: We investigated the retrievable body of evidence for delirium-associated medication. The results of this systematic review were then interpreted in conjunction with other evidence-based works and guidelines providing conclusions for clinical decision-making.

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.

[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.

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.

[Symptom Monitoring and Detection of Early Warning Signs in Bipolar Episodes Via App - Views of Patients and Relatives on e-Health Need]. / Notwendigkeit für Symptom-Monitoring und Frühwarnzeichenerkennung bipolarer Episoden durch eine App? ­ Ansichten von PatientInnen und Angehörigen zu e-health Bedarf.

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.

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.

Body Mass Index Predicts Decline in Executive Function in Bipolar Disorder: Preliminary Data of a 12-Month Follow-up Study.

INTRODUCTION: Obesity and associated risk factors have been linked to cognitive decline before. OBJECTIVES: In the present study, we evaluated potential cumulative negative effects of overweight and obesity on cognitive performance in euthymic patients with bipolar disorder (BD) in a longitudinal design. METHODS: Neurocognitive measures (California Verbal Learning Test, Trail Making Test [TMT] A/B, Digit-Symbol-Test, Digit-Span, d2 Test), anthropometrics (e.g., body mass index [BMI]), and clinical ratings (Hamilton Depression Scale, Young Mania Rating Scale) were collected over a 12-month observation period. Follow-up data of 38 patients with BD (mean age 40 years; 15 males, 23 females) were available. RESULTS: High baseline BMI predicted a decrease in the patient's performance in the Digit-Span backwards task measuring working memory performance. In contrast, cognitive performance was not predicted by increases in BMI at follow-up. Normal weight bipolar patients (n = 19) improved their performance on the TMT B, measuring cognitive flexibility and executive functioning, within 1 year, while overweight bipolar patients (n = 19) showed no change in this task. CONCLUSIONS: The results suggest that overweight can predict cognitive performance changes over 12 months.

Probiotic Treatment in Individuals with Euthymic Bipolar Disorder: A Pilot-Study on Clinical Changes and Compliance.

The importance of the microbiome for psychological well-being has gained rising interest in the last decade. A strategy to examine the role of the microbiome in different diseases is the intake of supplements that modulate the gut microbiome. Despite promising results in animal studies, research in humans is sparse to date and especially in individuals with psychiatric disorders almost missing. The current report of the ProbioBIP-one pilot study aims at describing general effects of the intake of the probiotic OMNi-BiOTiC Stress repair® on psychological parameters as well as gastrointestinal symptoms and general compliance in a cohort of euthymic individuals with bipolar disorder (BD), receiving daily probiotic treatment over a time period of 3 months. Twenty-seven individuals with BD took part in the present study (mean age = 50.7 years, SD = 12.2; females 40.7%). In sum, there was a high compliance rate with 81.5% of the study participants completing all 3 study visits and 85% of planned probiotic ingestions taken. Gastrointestinal problems were prevalent in more than half of the patients at the time of inclusion (t1). Expectedly, in the whole cohort, a high proportion of study participants experienced changes concerning digestion during probiotic treatment, around one third reported positive changes (reduced flatulence and easier and more frequent bowel movements) after 1 month (t2) and further after 3 months (t3). In contrast, a smaller part of study participants reported gastrointestinal discomfort after 1 and after 3 months (mainly flatulence and obstipation). We found a significantly reduced cognitive reactivity to sad mood between t2 and t3 indicating that participants under probiotic supplementation perceived themselves to be less distracted by ruminative thoughts. Further changes in psychiatric symptoms were small due to the euthymic state and already low scoring at the time of inclusion. Nevertheless, we found a significant symptom reduction in the rating scales measuring manic symptoms. From a clinical point of view, probiotic supplementation might provide a well-tolerated tool to positively influence gastrointestinal quality of life as well as mental and somatic health, cognition and immune response and potentially have effects on psychiatric symptoms.

The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study.

INTRODUCTION: Cognitive dysfunction is prevalent in depressive as well as manic episodes in individuals with Bipolar Disorder (BD). Even more, after symptom remission, many individuals with BD experience persisting cognitive impairment also in euthymic periods, leading to high illness burden and low quality of life. According to a recent research in animals and healthy humans, microbiota may influence cognitive processes via the brain-gut axis. A strategy to examine the role of the microbiota in different diseases is the intake of supplements that modulate the gut microbiome. The aim of this pilot study was to analyze the impact of probiotic supplements on cognitive parameters in a cohort of euthymic individuals with BD, receiving daily probiotic treatment over a time period of 3 months. METHODS: A total of 20 euthymic individuals with BD received probiotic supplement over a time period of 3 months and completed a cognitive test battery at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3 months of probiotic intake). RESULTS: We found a significant improvement of performance concerning attention and psychomotor processing speed measured with the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment (F = 8.60; η2 = 0.49, p < 0.01). Furthermore, executive function measured with the TMT-B, increased significantly over 3 months (F = 3.68; η2 = 0.29, p < 0.05). CONCLUSION: The results confirm the hypotheses that probiotic supplement might help stable individuals with BD to improve the cognitive function, which in turn might lead to better psychosocial, occupational, work and financial functioning. Nevertheless, the idea of this potential new treatment is challenging because of the variety of the human's gut microbiota.

Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.

OBJECTIVES: Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported. METHODS: The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. RESULTS: MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. CONCLUSIONS: A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population.

Changes in tryptophan breakdown associated with response to multimodal treatment in depression.

Background: Research on depression showed that dysregulations in tryptophan (TRP), kynurenine (KYN), and its KYN pathway metabolites are key aspects in the development and maintenance of depressive symptoms. In our previous reports, we described sex-specific changes in TRP breakdown as well as changes in KYN and KYN/TRP in association with treatment response and inflammatory and metabolic parameters. However, results of treatment effects on KYN pathway metabolites as well as how pathway changes are related to treatment response remain sparse. Objective: We investigated potential changes of KYN and KYN pathway metabolites in association with therapeutic response of individuals with depression during a six-week multimodal psychiatric rehabilitation program. Methods: 87 participants were divided into treatment responders and non-responders (48 responders, 39 non-responders; 38 male, 49 female; M age = 51.09; SD age = 7.70) using scores of psychological questionnaires. KYN pathway metabolites serum concentrations as well as their ratios were collected using high performance liquid chromatography. Changes over time (time of admission (t1) vs. time of discharge (t2)) were calculated using repeated measure analyses of (co)variance. Results: Non-responders exhibited higher levels of 3-Hydroxyanthralinic acid (3-HAA), nicotinic acid (NA), and 3-HAA/KYN, independently of measurement time. NA levels decreased, while 3-HAA levels increased over time in both groups, independently of treatment response. 3-HK/KYN levels decreased, while KYN levels increased in non-responders, but not in responders over time. Discussion: The results indicate that some compounds of the KYN pathway metabolites can be altered through multimodal long-term interventions in association with treatment response. Especially the pathway degrading KYN further down to 3-HAA and 3-HK/KYN might be decisive for treatment response in depression.

Better understanding of c-reactive protein and leukocytes in psychiatric inpatients with affective disorders: A biopsychosocial approach.

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.

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.

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.

Effects of Metabolic Syndrome and Sex on Stress Coping Strategies in Individuals with Depressive Disorder.

Metabolic syndrome (MetS) is related to depression and contributes to reduced life expectancy in individuals with mental disorders. Stress coping strategies are important factors in the development and maintenance of depressive disorders and have been related to metabolic disturbances. The aim of this study was to determine whether there is a difference in the use of positive (re- and devaluation, distraction, and control) and negative stress coping strategies in relation to patients' MetS. A sample of 363 individuals (n female = 204, n male = 159) with a diagnosis of depression was measured with the Stress Coping Style Questionnaire and the Beck Depression Inventory. In addition, we collected data on MetS (waist circumference, triglycerides, high-density lipoprotein, fasting glucose/diabetes, blood pressure/hypertonia) according to the International Diabetes Federation. A 2 × 2 design including Mets (with vs. without) and sex (female vs. male) was performed to test for differences in stress coping strategies. Individuals with depression and MetS scored higher on distraction strategies than depressed individuals without MetS (p < 0.01, corrected with false discovery rate). In addition, we found sex differences in stress coping strategies indicating that women with depression scored higher on distraction strategies (p < 0.001, FDR corrected), as well as negative strategies (p < 0.001, FDR corrected), than men. No significant interaction between MetS and sex was found regarding the higher value of stress coping strategies. Findings suggest that individuals with depression and MetS used distraction strategies to a higher amount to cope with stress, which could be stress eating in some cases, than those without MetS. Women with depressive disorders had higher values than men on other coping strategies in our sample of individuals with depression. A better understanding of MetS and sex-specific differences in stress coping strategies might help to plan more effective preventive strategies and personalized treatment options for depression.

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies.

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.

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.