•We conducted a study on 190 Individuals with bipolar affective disorder.•We examined the levels of inflammatory parameters, clinical stagind parameters and illness course.•In female patients, there ...was a positive correlation between levels of hsCRP and IL-6 and the number of illness episodes.•Levels of hsCRP and IL-6 were positively correlated with current manic symptoms as measured using YMRS.
Immunological/inflammatory processes have been proposed to play an important role in the pathophysiology of mood disorders, including bipolar disorder (BD). The present study aimed to examine the influence of immune activation, measured on the basis of inflammatory markers, on the course of illness, proxied by the number of affective episodes, in patients with BD.
We investigated the relationship between high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6), two inflammatory markers and characteristics of course of illness (e.g. number of affective episodes, depressive and manic symptoms) amongst a group of 190 individuals with BD.
Among females with BD, there was a positive correlation between levels of hsCRP and the number of manic and depressive episodes. Moreover, levels of hsCRP and IL-6 were positively correlated with current manic symptoms, as measured by Young-Mania-Rating-Scale. There were no significant correlations between levels of the foregoing inflammatory markers, and manic and depressive symptoms in male individuals with BD. Furthermore, compared to their untreated counterparts, female patients treated with lithium demonstrated higher levels of hsCRP and male patients treated with atypical antipsychotics lower levels of hsCRP, respectively.
Our results are suggesting that the association between inflammatory state and affective response in patients with BD may be gender-dependent. A future research would be to evaluate whether or not these gender differences can be observed in other inflammatory pathways associated with BD.
•Bipolar individuals showed deficits in ToM, measured by the reading the mind in the eyes Test, compared to healthy controls over a course of 4.5 years.•ToM deficits contribute to social and ...executive dysfunction in euthymic bipolar individuals.•First 4.5-year longitudinal study on theory of mind deficits and bipolar disorder, but with limited data.
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.
•Gene expression of Unfolded Protein Response (e.g. BIP, CHOP, XBP1) was analysed in Bipolar Disorder and controls.•BiP gene expression was significantly higher in Bipolar Disorder.•Reduced total and ...unspliced XPB1 levels were detected in Bipolar Disorder.•XBP1 splicing itself was not altered in Bipolar Disorder.
Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.
RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).
BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η2 = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η2 = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η2 = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η2 = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η2 = 0.005). Gene expression did not differ between euthymia, depression and mania.
BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.
Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present ...study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.
Synopsis
The involvement of microRNAs in the pathogenesis of schizophrenia is not well-understood. This study shows that miR-99b-5p regulates Z-DNA binding protein 1 (Zbp1) to control inflammatory responses in microglia and the development of schizophrenia-like symptoms in mice.
miR-99b-5p is downregulated in the blood and brains of schizophrenia patients.
miR-99b-5p inhibition induces schizophrenia-like phenotypes in mice and microglial inflammation.
Zbp1 is a novel miR-99b-5p target in microglia.
Zbp1 antisense oligos ameliorate the pathological outcomes of decreased miR-99b-5p levels.
Dysregulation of a novel miR-99b-5p-Zbp1 (Z-DNA binding protein 1) pathway in microglia induces inflammatory responses and schizophrenia-like phenotypes in mice.
The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in ...kynurenine metabolism are associated with current mood symptoms in bipolar disorder.
Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations.
Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid.
Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.
Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the ...neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.
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.
Bipolar disorders are ranked amongst the top ten causes of global disability and cause high health care costs. Previous studies have showed that mood stabilizing drug therapy combined with ...psychological treatments lead to significantly fewer relapses and a reduction in hospitalization rates. However, there is a wide spectrum of psychosocial intervention methods for individuals and groups which have been insufficiently examined on a scientific basis.
Studies published between 2003 and 2015 on different types of adjuvant psychosocial group interventions in the MESH database were reviewed and evaluated for their efficacy on patients with bipolar disorder related to the relapse ratio by a meta-analysis.
The meta-analysis included 24 intervention groups and showed that 75% of treated groups under medication and psychosocial therapy had a lower risk of a relapse than the control groups which only received medication therapy.
The meta-analysis includes a number of trials with participants in different phases of disease course and study designs, the number of studies in each analyzed intervention group was not balanced and many studies focused on recovery and recurrence of episodes, precluding identification of the impact on subsyndromal symptoms
Adjuvant psychosocial interventions seem to be indispensable for patients, their relations as well as for saving costs in the health care system. Nevertheless, an evaluation of effectiveness and impact factors of different psychosocial intervention methods needs further research.
•The meta-analysis shows that bipolar patients who received adjuvant psychotherapy have a lower risk ratio for relapse.•All analyzed studies had different study designs and durations as well as testing tools which complicated the comparison.•There is a need for further research on different intervention methods for bipolar patients.
No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.
To define a reproducible profile of lipid alterations in the blood plasma of ...patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD).
This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria DE-AT), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020.
Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry.
Blood lipid levels were assessed in 980 individuals (mean SD age, 36 13 years; 510 male individuals 52%) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean SD age, 34 13 years; 323 male individuals 56%). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: Pearson correlation r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids.
In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.
•People with BD had more depression and somatization than HC during the pandemic.•Distress due to social distancing was related to all clinical symptoms in BD.•COVID-19 fears were related to more ...anxiety and worse sleep quality in BD.•Individuals with BD had more negative lifestyle changes during the crisis than HC.•Individuals with BD should be specifically supported during social distancing.
The COVID-19 pandemic affects both mentally healthy and ill individuals. Individuals with bipolar disorder (BD) constitute an especially vulnerable group. A multicentric online study was conducted in Austria, Denmark, and Germany after the first lockdown phase in 2020. In total, 117 healthy controls (HC) were matched according to age and sex to 117 individuals with BD. The survey included the Brief Symptom Inventory-18, Beck Depression Inventory-2, Pittsburgh Sleep Quality Index, and a self-constructed questionnaire assessing COVID-19 fears, emotional distress due to social distancing, lifestyle, and compliance to governmental measures. In individuals with BD, increased symptoms of depression, somatization, anxiety, distress due to social distancing, and poorer sleep quality were related to emotional distress due to social distancing. The correlation between emotional distress due to social distancing and anxiety showed 26% of shared variance in BD and 11% in HC. Negative lifestyle changes and lower compliance with COVID-19 regulatory measures were more likely to be observed in individuals with BD than in HC. These findings underscore the need for ongoing mental health support during the pandemic. Individuals with BD should be continuously supported during periods of social distancing to maintain a stable lifestyle and employ strategies to cope with COVID-19 fears.
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