Publications by authors named "Armin Birner"

39 Publications

Monitoring Sleep Changes via a Smartphone App in Bipolar Disorder: Practical Issues and Validation of a Potential Diagnostic Tool.

Front Psychiatry 2021 24;12:641241. Epub 2021 Mar 24.

Department of Psychiatry & Psychotherapeutic Medicine, Medical University Graz, Graz, Austria.

Sleep disturbances are common early warning signs of an episode of bipolar disorder, and early recognition can favorably impact the illness course. Symptom monitoring via a smartphone app is an inexpensive and feasible method to detect an early indication of changes such as sleep. The study aims were (1) to assess the acceptance of apps and (2) to validate sleeping times measured by the smartphone app . was used by 22 individuals with bipolar disorder and 23 controls. Participants recorded their time of falling asleep and waking-up using for 3 weeks. Results were compared to a validated accelerometer and the Pittsburgh Sleep Quality Index. Additionally, participants were interviewed regarding early warning signs and their feedback for apps as monitoring tools in bipolar disorder (NCT03275714). With , our study did not find strong reservations concerning data protection or continual smartphone usage. Correlation analysis demonstrates to be a valid tool for measuring falling asleep and waking-up times. Individuals with bipolar disorder assessed the measurement of sleep disturbances as an early warning sign with a smartphone as positive. The detection of early signs could change an individual's behavior and strengthen self-management. The study showed that can be used to measure changes in sleep durations accurately. Further investigation of smartphone apps' impact to measure other early signs could significantly contribute to clinical treatment and research in the future through objective, continuous, and individual data collection.
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http://dx.doi.org/10.3389/fpsyt.2021.641241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024465PMC
March 2021

The Relationship Between Food Craving, Appetite-Related Hormones and Clinical Parameters in Bipolar Disorder.

Nutrients 2020 Dec 29;13(1). Epub 2020 Dec 29.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, 8036 Graz, Austria.

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.
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http://dx.doi.org/10.3390/nu13010076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824587PMC
December 2020

PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial.

Nutrients 2020 Nov 8;12(11). Epub 2020 Nov 8.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, 8036 Graz, Austria.

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. and were more abundant and β-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.
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http://dx.doi.org/10.3390/nu12113422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695208PMC
November 2020

C-Reactive Protein as a Possible Predictor of Trail-Making Performance in Individuals with Psychiatric Disorders.

Nutrients 2020 Oct 2;12(10). Epub 2020 Oct 2.

Therapiezentrum Justuspark, 4540 Bad Hall, Austria.

Cognitive dysfunction is a prominent feature of psychiatric disorders. Studies have shown that systemic low-grade inflammation is crucial in the development of cognitive deficits across psychiatric disorders. The aim of this study was to further examine the role of inflammation and inflammatory mediators in cognitive function in psychiatric disorders. This study included 364 inpatients (53% females) with International Classification of Diseases (ICD)-10 F3 (affective disorders) and F4 (neurotic, stress-related, and somatoform disorders) diagnoses. The mean age was 52 years (22 to 69 years) and the median body mass index was 27.6. Cognitive function was assessed with the Color-Word Interference Test after Stroop and the Trail-Making Test A/B. Multiple linear regression models were calculated to assess the predictive value of C-reactive protein and the kynurenine/tryptophan ratio on cognitive function controlling for age, sex, education, premorbid verbal intelligence quotient illness duration, depressive symptoms, and obesity-related parameters (e.g., body mass index, high-density lipoprotein). Our data confirm that in patients with psychiatric disorders, C-reactive protein serum concentration is a relevant and important predictor of Trail-Making Test B performance, measuring cognitive flexibility. The effect size of this association did not change much after adding clinical and metabolic variables into the regression model. The kynurenine/tryptophan ratio was not related to cognitive test scores. The involvement of C-reactive protein as a peripheral inflammatory marker in cognitive flexibility and psychomotor processing speed in psychiatric illness can be concluded.
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http://dx.doi.org/10.3390/nu12103019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599970PMC
October 2020

Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.

Nutrients 2020 Aug 26;12(9). Epub 2020 Aug 26.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Auenbruggerplatz 31, 8036 Graz, Austria.

Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (), nuclear factor kappa B subunit 1 () and interleukin-6 (). In we found no significant main effects for group ( = 1.33, = ns) nor time ( = 0.00, = ns), but interaction was significant ( = 5.67, < 0.05). The intervention group showed decreasing gene expression levels while the placebo group showed increasing gene expression levels of . Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.
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http://dx.doi.org/10.3390/nu12092575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551871PMC
August 2020

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

Neuropsychobiology 2021 26;80(1):1-11. Epub 2020 May 26.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University Graz, Graz, Austria.

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.
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http://dx.doi.org/10.1159/000505784DOI Listing
May 2020

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.

Mol Psychiatry 2020 Mar 16. Epub 2020 Mar 16.

Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLiGen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
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http://dx.doi.org/10.1038/s41380-020-0689-5DOI Listing
March 2020

Reduced Brain Electric Activity and Functional Connectivity in Bipolar Euthymia: An sLORETA Source Localization Study.

Clin EEG Neurosci 2020 May 17;51(3):155-166. Epub 2019 Dec 17.

Department of Psychiatry, Psychotherapy and Psychosomatics, The KEY Institute for Brain-Mind Research, University Hospital of Psychiatry, Zurich, Switzerland.

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients.
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http://dx.doi.org/10.1177/1550059419893472DOI Listing
May 2020

Total gray matter volume is reduced in individuals with bipolar disorder currently treated with atypical antipsychotics.

J Affect Disord 2020 01 19;260:722-727. Epub 2019 Sep 19.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Auenbruggerplatz 31, A-8036, Graz, Austria.

Background/aims: Recent evidence indicates that the intake of atypical antipsychotics (AAP) is associated with gray matter abnormalities in patients with psychiatric disorders. We explored if patients with bipolar disorder (BD) who are medicated with AAP exhibit total gray matter volume (TGV) reduction compared to BD individuals not medicated with AAP and healthy controls (HC).

Methods: In a cross-sectional design, 124 individuals with BD and 86 HC underwent 3T-MRI of the brain and clinical assessment as part of our BIPFAT-study. The TGV was estimated using Freesurfer. We used univariate covariance analysis (ANCOVA) to test for normalized TGV differences and controlled for covariates.

Results: ANCOVA results indicated that 75 BD individuals taking AAP had significantly reduced normalized TGV as compared to 49 BD not taking AAP (F = 9.995, p = .002., Eta = 0.084) and 86 HC (F = 7.577, p = .007, Eta = 0.046).

Limitations: Our cross-sectional results are not suited to draw conclusions about causality. We have no clear information on treatment time and baseline volumes before drug treatment in the studied subjects. We cannot exclude that patients received different psychopharmacologic medications prior to the study point. We did not included dosages into the calculation. Many BD individuals received combinations of psychopharmacotherapy across drug classes. We did not have records displaying quantitative alcohol consumption and drug abuse in our sample.

Conclusions: Our data provide further evidence for the impact of AAP on brain structure in BD. Longitudinal studies are needed to investigate the causal directions of the proposed relationships.
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http://dx.doi.org/10.1016/j.jad.2019.09.068DOI Listing
January 2020

Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder.

Curr Top Med Chem 2020 ;20(15):1344-1352

Department of Psychiatric and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Background & Objective: 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.

Methods: 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.

Results: 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.

Discussion: 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.
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http://dx.doi.org/10.2174/1568026619666190802145128DOI Listing
March 2021

Physical health in individuals with psychiatric disorders in Austria.

J Affect Disord 2019 10 2;257:38-44. Epub 2019 Jul 2.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Austria.

Introduction: The association between severe psychiatric disorders and metabolic syndrome is well documented and goes along with a reduced life expectancy. The prevalence of medical comorbidities in individuals suffering from psychiatric disorders in Austria has not yet been examined; aim of this study was to analyze the prevalence of comorbid somatic disorder in individuals diagnosed with psychiatric disorders in Austria.

Methods: Patients (n = 600) with a life-time diagnosis of mood and anxiety disorders undergoing a six-week course of intensive treatment in a psychiatric rehabilitation center were recruited. Prevalent somatic and psychological conditions, anamnestic data, medical history, blood samples, clinical and psychological tests as well as medication were examined to determine somatic and psychiatric diagnoses.

Results: Metabolic disorders were highly prevalent especially in individuals diagnosed with affective disorders, respectively in bipolar disorder. Furthermore, obesity and thyroid dysfunction were found in about 40% of individuals diagnosed with bipolar disorder in the present study. Significant gender differences were found in CVD and hypertension with higher prevalence in men, while thyroid dysfunction occurred more often in women also compared to the general female population.

Conclusions: Characterizing somatic comorbidity in individuals with psychiatric disorders can stimulate research to better understand possible shared etiologic factors and has public health implications for improving models of care. This could have a positive effect on the course of mental disorders, and additionally improve social integration and life expectancy. Knowledge about sex differences should be used to further improve individualized treatment of individuals with psychiatric disorders.
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http://dx.doi.org/10.1016/j.jad.2019.06.045DOI Listing
October 2019

Weight Gain During Treatment of Bipolar Disorder (BD)-Facts and Therapeutic Options.

Front Nutr 2019 11;6:76. Epub 2019 Jun 11.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Bipolar disorder (BPD) is a mood disorder, which is characterized by alternating affective states, namely (hypo)mania, depression, and euthymia. Evidence is growing that BPD has indeed a biologic substrate characterized by chronic inflammation, oxidative stress, and disturbed energy metabolism. Apart from this, there is obviously a hereditary component of this disease with multi-genetic factors. Most probably a susceptibility threshold favors the outbreak of clinical disease after a cascade of stress events that remain to be elucidated in more detail. Evidence is also growing that weak points in brain energy metabolism contribute to outbreak and severity of BPD. Conventional psychopharmacologic therapy must be reassessed under the aspects of weight cycling and development of central obesity as a deterioration factor for a worse clinical course leading to early cardiovascular events in BPD subgroups.
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http://dx.doi.org/10.3389/fnut.2019.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579840PMC
June 2019

[The relationship between intake of lithium and neuroradiological alterations in bipolar disorder. Are there predictors of clinical remission?]

Fortschr Neurol Psychiatr 2019 Sep 19;87(9):483-491. Epub 2018 Nov 19.

Medizinische Univerisität Graz, Universitätsklinik für Psychiatrie und psychotherapeutische Medizin.

For avoiding affective episodes, patients with bipolar disorders are treated with mood stabilizers. Under that term, the substances lithium, valproic acid, lamotrigine and carbamazepine are included. In the light of upcoming new psychiatric concepts, the use of second generation antipsychotics is also taken into consideration in pharmacological treatment. In this review, the relation between brain structure and the use of lithium in bipolar disorders is examined. Therefore, results from MRI-, DTI-, SPECT-studies assessing this relation, were included.Most of the studies are cross-sectional and examined the effects of lithium. The latter is associated with increased cortical and sub-cortical gray matter volume and ameliorative white matter microstructure. 7-lithium spectroscopy showed a significant difference in brain-lithium concentrations between remitted and non-remitted patients.There are preclinical studies reporting induction of promitotic and antiapoptotic effects by lithium. This literature underpins the hypothesis of lithium-induced neurogenesis. However, osmotic and physical effects of lithium could also explain the demonstrated volume gain in bipolar human brain.Cross-sectional design and small patient groups are typical limitations of numerous studies included in this review.Notably, with the 7-lithium spectroscopy of the central nervous system, new perspectives in clinical research to clarify pharmacokinetic differences between remitted and non-remitted bipolar patients can be established in future.
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http://dx.doi.org/10.1055/a-0637-1820DOI Listing
September 2019

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

Neuropsychobiology 2020 19;79(1):71-79. Epub 2018 Oct 19.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

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.
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http://dx.doi.org/10.1159/000493867DOI Listing
November 2020

Psychopathic personality factor "Fearless dominance" is related to low self-reported stress-levels, fewer psychiatric symptoms, and more adaptive stress coping in psychiatric disorders.

Psychiatry Res 2018 12 13;270:68-77. Epub 2018 Sep 13.

TZ Justuspark, Bad Hall, Austria.

The aim of this cross-sectional study was to test the idea that the psychopathic trait "Fearless dominance" (FD) may be associated with reduced psychological stress symptoms and better stress coping strategies in psychiatric patients, whereas the factor "Self-centered impulsivity" (SCI) may be associated with more stress and maladaptive stress coping. The investigation included 626 individuals with psychiatric disorders treated in a psychiatric rehabilitation program. The participants were tested with the Psychopathic Personality Inventory Revised (PPI-R) and completed several clinical scales measuring stress experience and stress coping (Symptom-Checklist Revised, Trier Inventory for Chronic Stress, The Stress Coping Style Questionnaire 78). Consistent with the hypothesis, structural equation modeling results showed that self-reported stress levels and adaptive stress coping strategies might be explained by psychopathic FD traits in the psychiatric sample. Supplemental subscale analyses showed that especially the PPI-R scales Stress Immunity and Social Influence were positively related to adaptive stress coping. The second model of SCI did not fit our data well. In conclusion, individuals with psychopathic FD traits may experience less stress symptoms during residential care. Well-designed prospective trials may ultimately answer the question whether psychopathic traits could be viewed as serving a buffer function in the development of depression.
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http://dx.doi.org/10.1016/j.psychres.2018.09.018DOI Listing
December 2018

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

Neuropsychobiology 2018 Sep 18:1-8. Epub 2018 Sep 18.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

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.
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http://dx.doi.org/10.1159/000492537DOI Listing
September 2018

A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode.

Bipolar Disord 2019 02 26;21(1):40-49. Epub 2018 Jul 26.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Objectives: There is evidence that the gut microbiota plays a major role in the pathogenesis of diseases of the central nervous system through the gut-brain axis. The aim of the present study was to analyze gut microbiota composition in bipolar disorder (BD) and its relation to inflammation, serum lipids, oxidative stress, tryptophan (TRP)/kynurenine (KYN) levels, anthropometric measurements and parameters of metabolic syndrome. Further, microbial community differences of individuals with BD compared with healthy controls (HC) were explored.

Methods: In this cross-sectional study, we performed 16S rRNA gene sequencing of stool samples from 32 BD individuals and 10 HC. Laboratory parameters included inflammatory markers, serum lipids, KYN, oxidative stress and anthropometric measures. Microbial community analysis and correlation to clinical parameters was performed with QIIME, differential abundance analysis of taxa encompassed linear discriminant analysis effect size (LEfSe).

Results: We found a negative correlation between microbial alpha-diversity and illness duration in BD (R = -0.408, P = 0.021). Furthermore, we identified bacterial clades associated with inflammatory status, serum lipids, TRP, depressive symptoms, oxidative stress, anthropometrics and metabolic syndrome in individuals with BD. LEfSe identified the phylum Actinobacteria (LDA= 4.82, P = 0.007) and the class Coriobacteria (LDA= 4.75, P = 0.010) as significantly more abundant in BD when compared with HC, and Ruminococcaceae (LDA= 4.59, P = 0.018) and Faecalibacterium (LDA= 4.09, P = 0.039) as more abundant in HC when compared with BD.

Conclusions: The present findings suggest that causes and/or consequences of BD may also lie outside the brain. Exploratory research of the gut microbiota in affective disorders like BD may identify previously unknown underlying causes, and offer new research and therapeutic approaches to mood disorders.
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http://dx.doi.org/10.1111/bdi.12682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585963PMC
February 2019

Adiponectin is decreased in bipolar depression.

World J Biol Psychiatry 2019 12 20;20(10):813-820. Epub 2018 Sep 20.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Graz, Austria.

Bipolar disorder (BD) is often accompanied by medical comorbidities, which affect illness course and prognosis. Adipokines may not only be involved in the aetiopathogenetic mechanisms of these comorbidities; there might be an association between adipokines and the neuropsychiatric core features of BD such as mood disturbances and cognitive deficits. In this investigation, fasting blood samples from 120 individuals with BD (75 euthymic and 45 with mild depressive symptoms) and 68 control subjects were taken and adiponectin and leptin concentrations were analysed. We found that, in female participants, adiponectin levels differed significantly between patients and controls indicating lower levels in individuals with BD, even after controlling for BMI ((1,92) = 4.65,  = 0.034, partial η = 0.05). After stratification by mood status we found a significant difference in adiponectin between controls, euthymic and depressive patients ((2, 180) = 4.90,  = 0.008, partial η = 0.05). This investigation confirms previous findings of an association between low adiponectin levels and depressive state in individuals with BD. Beyond its immediate effect on central nervous system function, adiponectin might interfere with pathophysiological mechanisms of BD and its somatic comorbidities via involvement in metabolic and inflammatory processes.
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http://dx.doi.org/10.1080/15622975.2018.1500033DOI Listing
December 2019

Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.

Bipolar Disord 2019 02 28;21(1):68-75. Epub 2018 Jun 28.

Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.

Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.

Methods: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.

Results: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.

Conclusions: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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http://dx.doi.org/10.1111/bdi.12659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585855PMC
February 2019

Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder.

Front Psychiatry 2018 31;9:207. Epub 2018 May 31.

Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland.

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset ( = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with showing the strongest association with the continuous trait ( = 9.80E-04) and with the dichotomous phenotype ( = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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http://dx.doi.org/10.3389/fpsyt.2018.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991073PMC
May 2018

Branched-chain amino acids are associated with metabolic parameters in bipolar disorder.

World J Biol Psychiatry 2019 12 27;20(10):821-826. Epub 2018 Jul 27.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analysed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters. BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton Depression-Scale, and Beck Depression Inventory II, in male individuals Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases or insulin resistance), health state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.
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http://dx.doi.org/10.1080/15622975.2018.1487077DOI Listing
December 2019

Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.

Psychoneuroendocrinology 2018 09 21;95:113-119. Epub 2018 May 21.

Institute of Pathophysiology and Immunology, Medical University of Graz, Heinrichstrasse 31A, 8010 Graz, Austria.

Background: 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.

Methods: 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).

Results: BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η = 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 η = 0.005). Gene expression did not differ between euthymia, depression and mania.

Discussion: 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.
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http://dx.doi.org/10.1016/j.psyneuen.2018.05.029DOI Listing
September 2018

The relationship between inflammatory state and quantity of affective episodes in bipolar disorder.

Psychoneuroendocrinology 2018 04 3;90:61-67. Epub 2018 Feb 3.

Medical University of Graz, Department of Psychiatry and Psychotherapeutic Medicine, Graz, Austria.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.psyneuen.2018.01.024DOI Listing
April 2018

Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.

JAMA Psychiatry 2018 01;75(1):65-74

Douglas Mental Health University Institute, McGill University, Montreal, Canada.

Importance: Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).

Objectives: To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.

Design, Setting, And Participants: A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.

Main Outcomes And Measures: Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.

Results: Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.

Conclusions And Relevance: This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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http://dx.doi.org/10.1001/jamapsychiatry.2017.3433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833535PMC
January 2018

"ABC"-The Awareness-Body-Chart: A new tool assessing body awareness.

PLoS One 2017 16;12(10):e0186597. Epub 2017 Oct 16.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Background: Despite the importance of body awareness for health and well-being there is still a lack of valid assessment tools to scan proper body awareness. To respond to the limitations of questionnaires (reading/interpretation problems) the Awareness-Body-Chart (ABC) was designed to assess body awareness by colouring 51 regions according to their awareness. The objective of this study was to investigate the psychometric characteristics of the ABC.

Methods: In a questionnaire-study, 106 students in Graz (79 females, 27 males, age median 21 (IQR 20-23) years) filled in the ABC, furthermore a German body awareness questionnaire "KEKS", and the Beck Depression Inventory II. Factor structure, internal consistency, and retest reliability of the ABC were investigated. Correlations of the ABC with the KEKS and the Beck Depression Inventory II and comparisons of subgroups were conducted.

Results: Through factor analyses, 14 factors with clear assignments to body parts could be categorized: cranium, face, cervical/lumbar region, chest/abdomen, back, shoulder, upper arm, lower arm/elbow, hand, genital area, thigh/hip, knee, lower leg, and foot. The 14 body parts and the total score showed acceptable to high Cronbach's alphas (α = .64 - .97). The test-retest reliability showed values between ρ = .71 and ρ = .96. The correlation of the ABC and KEKS (r = .66, p < .001) confirmed validity. Further indications of validity could be seen in comparisons of subgroups and in correlations with the Beck Depression Inventory II.

Conclusion: The ABC proved good psychometric properties with acceptable to high internal consistency, acceptable to high retest reliability and high construct validity. It is an easy-to-use tool for clinical settings and research. The ABC opens new insights into body awareness-patterns of various subgroups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643115PMC
November 2017

Tryptophan breakdown and cognition in bipolar disorder.

Psychoneuroendocrinology 2017 Jul 27;81:144-150. Epub 2017 Apr 27.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Graz, Austria.

Introduction: It has been demonstrated that bipolar disorder (BD) is often accompanied by cognitive deficits across all subdomains including verbal memory, attention and executive functioning. Cognitive deficits are observed both during episodes of mania or depression, as well as during the euthymic phase. It has been proposed that chronic immune-mediated inflammation in the central nervous system results in alterations in neural structures that subserve cognitive function. Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity. Herein, we sought to determine whether serum levels of kynurenine and/or its metabolites were associated with cognitive function in BD.

Methods: In this investigation 68 euthymic individuals with BD according to DSM-IV completed a cognitive test battery to asses premorbid intelligence (Multiple Choice Word Test; MWT-B), verbal memory (California Verbal Learning Test; CVLT), attention (d2 Test of Attention; d2 test, Trail Making Test-A; TMT-A, Stroop word reading/Stroop color naming) and executive functioning (TMT-B, Stroop interference). In addition, fasting blood samples were taken and serum levels of kynurenine and its metabolites 3-hydroxykynurenine and kynurenic acid were analyzed. Subsequently ratios were formed from individual parameters. Patient data were compared with those of a mentally healthy control group (n=93).

Results: In male participants with BD only we found a significant negative correlation between the 3-hydroxykynurenine to kynurenic acid ratio and performance on the CVLT. Additionally, the kynurenine to 3-hydroxykynurenine ratio was associated with performance on a sub-score of the CVLT. Those associations were neither present in female individuals with BD nor in the control group.

Discussion: Our findings suggest that a shift towards the hydroxykynurenine arm of the kynurenine pathway may be associated with poorer memory performance due to its effects on neuronal functioning and neurogenesis in the hippocampus. Our results implicate a mechanistic role of central inflammatory processes in cognitive functions in adults with bipolar disorder.
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http://dx.doi.org/10.1016/j.psyneuen.2017.04.015DOI Listing
July 2017

Increased breakdown of kynurenine towards its neurotoxic branch in bipolar disorder.

PLoS One 2017 27;12(2):e0172699. Epub 2017 Feb 27.

Department for Psychiatry and Psychotherapy, Medical University of Graz, Graz, Austria.

Introduction: Bipolar disorder (BD) is a chronic psychiatric disease which can take most different and unpredictable courses. It is accompanied by unspecific brainstructural changes and cognitive decline. The neurobiological underpinnings of these processes are still unclear. Emerging evidence suggests that tryptophan catabolites (TRYCATs), which involve all metabolites of tryptophan towards the kynurenine (KYN) branch, are involved in the etiology as well as in the course of BD. They are proposed to be mediators of immune-inflammation and neurodegeneration. In this study we measured the levels of KYN and its main catabolites consisting of the neurotoxic hydroxykynurenine (3-HK), the more neuroprotective kynurenic acid (KYNA) and anthranilic acid (AA) and evaluated the ratios between end-products and substrates as proxies for the specific enzymatic activity (3-HK/KYN, KYNA/KYN, AA/KYN) as well as 3-HK/KYNA as a proxy for neurotoxic vs. neuroprotective end-product relation in individuals with BD compared to healthy controls (HC).

Methods: We took peripheral TRYCAT blood levels of 143 euthymic to mild depressive BD patients and 101 HC. For statistical analyses MANCOVA's controlled for age, sex, body mass index, cardiovascular disease and smoking were performed.

Results: The levels of KYNA (F = 5,579; p <.05) were reduced in BD compared to HC. The enzymatic activity of the kynurenine-3-monooxygenase (KMO) reflected by the 3-HK/KYN ratio was increased in BD individuals compared to HC (F = 5,394; p <.05). Additionally the ratio of 3-HK/KYNA was increased in individuals with BD compared to healthy controls (F = 11,357; p <.01).

Discussion: In conclusion our findings subserve the concept of KYN -pathway alterations in the pathophysiology of BD. We present evidence of increased breakdown towards the neurotoxic branch in KYN metabolism even in a euthymic to mild depressive state in BD. From literature we know that depression and mania are accompanied by inflammatory states which should be capable to produce an even greater imbalance due to activation of key enzymes in the neurotoxic direction of KYN -conversion. These processes could finally be involved in the development of unspecific brain structural changes and cognitive deficits which are prevalent in BD. Further research should focus on state dependent changes in TRYCATs and its relation to cognition, brain structure and staging parameters.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172699PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328271PMC
September 2017

Acceptance of the Use of Pedometers in Individuals with Bipolar Disorder.

Fortschr Neurol Psychiatr 2017 Feb 24;85(2):86-91. Epub 2017 Feb 24.

Psychiatrie und Psychotherapeutische Medizin, Medizinische Universitat Graz.

Before patients with bipolar disorder (BD) can begin to perform balanced physical activity, they have to overcome many difficulties. The aim of this study was to examine the acceptance of pedometers as a self-assessment tool in people with BD. Patients who participated in an intervention study with body-oriented groups and psychoeducation groups at the Medical University of Graz/ Department of Psychiatry were invited to use pedometers on a daily basis and keep pedometer diaries over a period of 24 weeks. Most of the patients were satisfied with the pedometers and found them helpful for their health. The difficulties in the study were to recruit patients for this exercise trial, their lack of adherence to the programme and a high dropout rate. Out of the 130 invited patients, 41 came to the baseline investigation, 27 of them took part in the group interventions and 14 used pedometers and handed in the pedometer diaries. For clinical practice, specific motivational interventions are recommended to stimulate individuals with BD to engage in regular physical exercise.
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http://dx.doi.org/10.1055/s-0042-124506DOI Listing
February 2017

Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL.

World J Biol Psychiatry 2018 14;19(sup2):S21-S29. Epub 2016 Oct 14.

h Institute of Neuropathology , University of Bonn , Germany.

Objectives: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls.

Methods: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing. Analysis of covariances considering the covariates age, body mass index, sex, smoking, lithium and anticonvulsant intake were performed to test methylation differences between BD and controls.

Results: Methylation at cg05733463 of ARNTL was significantly higher in BD than in controls (F(1,209) = 44.500, P < .001). In contrast, methylation was significantly lower in BD at PS2_POS1 compared to controls (F(1,128) = 5.787, P = .018) and by trend at PS2_POS2 (F(1,128) = 3.033, P = .084) and POS7 (F(1,34) = 3.425, P = .073).

Conclusions: Methylation of ARNTL differed significantly between BD and controls. Thus, our study suggests that altered epigenetic regulation of ARNTL might provide a mechanistic basis for better understanding circadian rhythms and mood swings in BD.
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http://dx.doi.org/10.1080/15622975.2016.1231421DOI Listing
June 2019

Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.

Hum Mol Genet 2016 08 21;25(15):3383-3394. Epub 2016 Jun 21.

Institute of Human Genetics, University of Bonn, Germany.

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10   ; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10   ; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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http://dx.doi.org/10.1093/hmg/ddw181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179929PMC
August 2016