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Zusammenfassung Hintergrund Der Beginn und Frühwarnzeichen von Krankheitsepisoden der bipolaren Störung werden von Betroffenen häufig erst spät erkannt. Je früher eine Krankheitsepisode behandelt wird, desto prognostisch günstiger ist der Verlauf. Die Symptomüberwachung per Smartphone-Applikation (App) könnte eine innovative Möglichkeit darstellen, um Frühwarnzeichen zu erkennen und schneller mit den richtigen Strategien darauf zu reagieren. Das Ziel dieser Studie war es zu evaluieren, ob PatientInnen mit bipolarer Erkrankung und deren Angehörige eine technische Unterstützung durch eine App als sinnvoll und praktikabel in der Früherkennung sowie in der Behandlung erachten. Methoden In der vorliegenden Studie wurden 51 PatientInnen mit bipolarer Störung und 28 Angehörige befragt. Es wurde ermittelt, ob die ProbandInnen Frühwarnzeichen in Form von Verhaltensänderungen derzeit subjektiv ausreichend und rechtzeitig wahrnehmen können. Zudem wurde erhoben, ob die StudienprobandInnen ein Smartphone als Behandlungsunterstützung nutzen würden. Ergebnisse Obwohl sich 94,1% der befragten PatientInnen und 78.6% der Angehörigen gut über die Erkrankung informiert fühlten, waren 13,7% beziehungsweise 35,7% mit den derzeitigen Behandlungsmöglichkeiten nicht zufrieden. Frühwarnzeichen jeder depressiven Entwicklung wurden von 25,5% der PatientInnen wahrgenommen (Angehörige 10,7%). Jede (hypo)manische Entwicklung wurde lediglich von 11,8% der PatientInnen wahrgenommen (Angehörige 7,1%). 88,2% der PatientInnen und 85,7% ihrer Angehörigen bemerkten zu Beginn einer Depression und 70,6% beziehungsweise 67,9% zu Beginn einer (hypo)manischen Episode wiederkehrend dieselben Symptome (insbesondere Veränderungen der körperlichen Aktivität, des Kommunikationsverhaltens und des Schlaf-Wach-Rhythmus). 84,3% der PatientInnen und 89,3% der Angehörigen gaben an, dass sie eine technische Unterstützung, welche auf Veränderungen in Stimmungs- und Aktivitätslage aufmerksam macht, als sinnvoll erachten und dass sie eine Smartphone-App für die Behandlung nutzen würden. Diskussion Die derzeitigen Möglichkeiten zur Wahrnehmung von Frühwarnzeichen einer depressiven oder (hypo)manischen Episode bei bipolarer Störung sind klinisch unzureichend. Bei Betroffenen und Angehörigen besteht der Wunsch nach innovativen, technischen Unterstützungen. Die rechtzeitige Früherkennung von Krankheitssymptomen, die sich oft in Veränderungen von Verhaltens- oder Aktivitätsmustern äußert, ist für den Verlauf essentiell. Apps könnten hierbei durch objektive, kontinuierliche und individuelle Datenerhebung in der Zukunft für die klinische Behandlung und die Forschung genutzt werden.

Background & Objectives: 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. Conclusion: 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.

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.

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.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.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.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.Der Beginn und Frühwarnzeichen von Krankheitsepisoden der bipolaren Störung werden von Betroffenen häufig erst spät erkannt. Je früher eine Krankheitsepisode behandelt wird, desto prognostisch günstiger ist der Verlauf. Die Symptomüberwachung per Smartphone-Applikation (App) könnte eine innovative Möglichkeit darstellen, um Frühwarnzeichen zu erkennen und schneller mit den richtigen Strategien darauf zu reagieren. Das Ziel dieser Studie war es zu evaluieren, ob PatientInnen mit bipolarer Erkrankung und deren Angehörige eine technische Unterstützung durch eine App als sinnvoll und praktikabel in der Früherkennung sowie in der Behandlung erachten.In der vorliegenden Studie wurden 51 PatientInnen mit bipolarer Störung und 28 Angehörige befragt. Es wurde ermittelt, ob die ProbandInnen Frühwarnzeichen in Form von Verhaltensänderungen derzeit subjektiv ausreichend und rechtzeitig wahrnehmen können. Zudem wurde erhoben, ob die StudienprobandInnen ein Smartphone als Behandlungsunterstützung nutzen würden.Obwohl sich 94,1% der befragten PatientInnen und 78.6% der Angehörigen gut über die Erkrankung informiert fühlten, waren 13,7% beziehungsweise 35,7% mit den derzeitigen Behandlungsmöglichkeiten nicht zufrieden. Frühwarnzeichen jeder depressiven Entwicklung wurden von 25,5% der PatientInnen wahrgenommen (Angehörige 10,7%). Jede (hypo)manische Entwicklung wurde lediglich von 11,8% der PatientInnen wahrgenommen (Angehörige 7,1%). 88,2% der PatientInnen und 85,7% ihrer Angehörigen bemerkten zu Beginn einer Depression und 70,6% beziehungsweise 67,9% zu Beginn einer (hypo)manischen Episode wiederkehrend dieselben Symptome (insbesondere Veränderungen der körperlichen Aktivität, des Kommunikationsverhaltens und des Schlaf-Wach-Rhythmus). 84,3% der PatientInnen und 89,3% der Angehörigen gaben an, dass sie eine technische Unterstützung, welche auf Veränderungen in Stimmungs- und Aktivitätslage aufmerksam macht, als sinnvoll erachten und dass sie eine Smartphone-App für die Behandlung nutzen würden.Die derzeitigen Möglichkeiten zur Wahrnehmung von Frühwarnzeichen einer depressiven oder (hypo)manischen Episode bei bipolarer Störung sind klinisch unzureichend. Bei Betroffenen und Angehörigen besteht der Wunsch nach innovativen, technischen Unterstützungen. Die rechtzeitige Früherkennung von Krankheitssymptomen, die sich oft in Veränderungen von Verhaltens- oder Aktivitätsmustern äußert, ist für den Verlauf essentiell. Apps könnten hierbei durch objektive, kontinuierliche und individuelle Datenerhebung in der Zukunft für die klinische Behandlung und die Forschung genutzt werden.

Background: 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 UP!.Methods:UP! was used by 22 individuals with bipolar disorder and 23 controls. Participants recorded their time of falling asleep and waking-up using UP! 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).Results: With UP!, our study did not find strong reservations concerning data protection or continual smartphone usage. Correlation analysis demonstrates UP! to be a valid tool for measuring falling asleep and waking-up times.Discussion: 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 UP! 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.

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.

Background The coronavirus disease (COVID-19) pandemic, a global health crisis, has resulted in widespread socioeconomic restrictions including lockdown, social distancing, and self-isolation. To date, little is known about the psychological impact of the COVID-19 pandemic and lockdown on patients with bipolar disorder as a particularly vulnerable group. Methods An online survey was conducted in Austria at two points of measurement (T1 April 2020 during the first lockdown vs. T2 May 2020 at post-lockdown). The sample comprises 20 patients with bipolar disorder (mean age = 49.4 ± 15.6 years) and 20 healthy controls (mean age = 32.7 ± 9.6 years). A 2 × 2 factorial design to compare two time points (T1 vs. T2) and two groups (patients vs. healthy controls) was used. Main outcome measures included the Brief Symptom Inventory-18 (BSI-18) and a (non-validated and non-standardized) assessment to determine COVID-19 fears and emotional distress due to social distancing. Multiple linear regression analyses were used to assess the longitudinal association of COVID-19 fears/emotional distress due to social distancing during lockdown (T1) and psychological symptoms after lockdown (T2). Results At T1, results demonstrated higher scores in BSI-18 subscales depression, anxiety and global severity index as well as emotional distress due to social distancing in bipolar patients compared to controls. There was a significant time x group interaction in the BSI-18 subscale somatization showing a decreasing trend in patients with BD compared to controls. No time effects in BSI-18 subscales or COVID-19 fears/emotional distress due to social distancing were observed. Regression analyses showed that COVID-19 fears during lockdown predicted somatization, only in patients. Conclusions There was a connection between the lockdown measures and somatization symptoms observed in patients. When the first steps of easing the social restrictions in May 2020 took place, somatization decreased only in the bipolar compared to the control group. Higher COVID-19 fears during lockdown predicted later symptoms at post-lockdown. Long-term impacts of the COVID-19 pandemic need further investigations to improve current therapeutic approaches and prevent fears and distress during lockdown in individuals with bipolar disorder in times of crisis.

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&ndash, 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.

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 (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p &lt, 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. 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.

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.

Objectives: 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.Methods: 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.Results: 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 individualsConclusions: 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.

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.

Background 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. Methods 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. Results 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. Limitations 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 Conclusions 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.

ZusammenfassungDas Eye Movement Desensitization and Reprocessing (EMDR) ist eine therapeutische Methode, deren Wirksamkeit in der Behandlung von traumatischen Erkrankungen gezeigt werden konnte. Seit der Annahme eines spezifischen Suchtgedächtnisses bildet EMDR auch für Substanzgebrauchsstörungen einen eigenen Anwendungsbereich. Die vorliegende Überblicksarbeit fasst den aktuellen Forschungsstand zu EMDR-Behandlungseffekten bei stoffgebundenen Abhängigkeitserkrankungen zusammen. Mithilfe der Datenbanken PubMed und PsychInfo wurde eine systematische Literaturrecherche durchgeführt, wobei vier relevante Studien identifiziert wurden. Bei der Behandlung mit EMDR zeigte sich eine Reduktion des Cravings, der Angst und der Depressionswerte, sowie eine Verbesserung der Emotionsregulierung und des Selbstwertgefühls. Erste Ergebnisse verweisen auf das hohe therapeutische Potential von EMDR für den Bereich der Substanzgebrauchsstörungen

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.

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.

Background: Bipolar disorder (BD) is characterized by mood fluctuations, which are often recognized late by those who are affected. Symptom monitoring via smartphone seems to be an inexpensive and feasible method to detect these fluctuations earlier. The aim of an application (app) for smartphones is to record individual activity patterns (e.g. physical activity, sleep-wake rhythm, digital communication) as characteristic for mood swings in individuals with BD. Methods: We developed the UP! app for Android smartphones, which collects subjective mood daily and continuous data about movement, exercise, sleep duration and intensity of digital communication via GPS and sensors. This pilot trial will include 24 individuals with BD and 24 healthy controls (HC) without a mental disorder. The main aim of this study is to assess the app’s validity to detect mood fluctuations and illness episodes in comparison to a clinical psychiatric interview, validated questionnaires and a fitness tracker. A second aim is to determine whether changes in activity patterns, measured with the app, can detect early warning symptoms of depressive and/or manic episodes. The third aim is the evaluation of users’ acceptance of the app. The recruitment of participants (planned n=48) is ongoing. Discussion: Behavior patterns recognition via smartphone could present an innovative, technological tool for the early detection of BD episodes and could be valuable for long-term research. Registration Details: The trial is approved by the ethics committee of the Medical University Graz, Austria (29-290 ex 16/17). The trial is registered at ClinicalTrials.gov as NCT03275714.

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.Zur Vermeidung affektiver Krankheitsphasen im Rahmen der bipolar affektiven Störung erfolgt die psychopharmakologische Behandlung mittels sogenannter Phasenprophylaktika. Traditionell werden unter diesem Begriff die Wirkstoffe Lithium, Valproat, Lamotrigin und Carbamazepin zusammengefasst. Moderne Therapiekonzepte zur Phasenprophylaxe berücksichtigen ebenfalls Antipsychotika der zweiten Generation. In dieser Literaturrecherche sollen die Zusammenhänge zwischen den biologischen Veränderungen des Gehirns und der Einnahme von Lithium dargestellt werden. Hierbei werden Daten aus makrostruktureller, mikrostruktureller und spektroskopischer Bildgebung angeführt.Daten zu Veränderungen der Makrostruktur unter Lithiumtherapie sind quantitativ am stärksten untersucht. So scheint Lithium im Zusammenhang mit einer Vergrößerung des Volumens von kortikaler und subkortikaler grauer Substanz zu stehen. Des Weiteren zeigt sich unter Lithiumtherapie eine geringradigere mikrosturkurelle Veränderung in Marklageralrealen was auf einen möglichen neuroprotektiven Effekt von Lithium zurückzuführen sein könnte. An Hand der 7-Lithium-MR-Spektroskopie konnte gezeigt werden, dass remittierte und nicht-remittierte Patientinnen und Patienten signifikante intrazerebrale Konzentrationsunterschiede aufzeigen.Präklinische Daten weisen auf lithiuminduzierte promitotische, als auch antiapoptotische Mechanismen hin und stützen somit die Hypothese eines volumenerhaltenden Effektes mittels Neurogenese. Jedoch könnten hinsichtlich des Lithiums auch osmotische und physikalische Effekte maßgebliche Ursachen für die Volumenzunahme in der makrostrukturellen Bildgebung bilden.Das mehrheitliche Vorhandensein von Querschnittsstudien zu dieser Thematik und kleine Kohortengrößen stellen typische Limitationen der untersuchten Studien dar.Hinsichtlich der Forschung zum Lithiummetabolismus könnte insbesondere die 7-Lithium-Spektroskopie zukünftig eine Methode darstellen, um diesbezügliche pharmakokinetische Unterschiede zwischen remittierten und nicht-remittierten Patienten aufzuklären.

In psychiatric disorders, neurocognitive impairments are prevalent and have been associated with poor outcome. Deficits in Theory of Mind (ToM, “mentalising”) have also been observed in bipolar disorder (BD); however, the literature shows inconsistent data. The aim of this study was to explore ToM performance in a well-characterized sample of euthymic individuals with BD and its relationship with neurocognitive function. One hundred sixteen euthymic patients with BD between 18 and 74 years (mean age = 42.4, SD = 13.8) and 79 healthy controls (mean age = 39.8, SD = 16.5) were investigated with an extensive neurocognitive test battery (Trail Making Test A/B, d2 Test of Attention, Stroop Color-Word Test, California Verbal Learning Test, Multiple Choice Vocabulary Test). Additionally, all participants were given the Reading the Mind in the Eyes Test (RMET) to measure affective ToM, the ability to make assumptions about other people´s feelings. Overall, “Eyes Reading” performance was not impaired in individuals with BD compared with controls. However, a significant relationship between RMET and verbal memory in BD was shown, particularly in males. Data showed worse RMET performance in patients with memory deficits compared to patients without memory deficits and controls. Due to cross-sectional data, no conclusions can be made with respect to cause and effect.

Objectives: 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 o...

Objectives The gut microbiome harbors substantially more genetic material than our body cells and has an impact on a huge variety of physiological mechanisms including the production of neurotransmitters and the interaction with brain functions through the gut-brain-axis. Products of microbiota can affect methylation according to preclinical studies. The current investigation aimed at analyzing the correlation between gut microbiome diversity and the methylation of the clock gene ARNTL in individuals with Bipolar Disorder (BD). Methods Genomic DNA was isolated from fasting blood of study participants with BD (n = 32). The methylation analysis of the ARNTL CG site cg05733463 was performed by bisulfite treatment of genomic DNA with the Epitect kit, PCR and pyrosequencing. Additionally, DNA was extracted from stool samples and subjected to 16S rRNA sequencing. QIIME was used to analyze microbiome data. Results Methylation status of the ARNTL CpG position cg05733463 correlated significantly with bacterial diversity (Simpson index: r= -0.389, p = 0.0238) and evenness (Simpson evenness index: r= -0.358, p = 0.044). Furthermore, bacterial diversity differed significantly between euthymia and depression (F(1,30) = 4.695, p = 0.039). Discussion The results of our pilot study show that bacterial diversity differs between euthymia and depression. Interestingly, gut microbiome diversity and evenness correlate negatively with methylation of ARNTL, which is known to regulate monoamine oxidase A transcription. We propose that alterations in overall diversity of the gut microbiome represent an internal environmental factor that has an epigenetic impact on the clock gene ARNTL which is thought to be involved in BD pathogenesis.

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 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. 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.

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.

Introduction Bipolar disorder (BD) is accompanied by a high number of comorbidities and associated with an overall increased mortality. Especially obesity, systemic inflammatory processes and cognitive deficits are highly prevalent and increase with the course of illness. Physical activity (PA) is associated with beneficial effects on somatic comorbidities such as obesity or cardiovascular disease in individuals without psychiatric disorder. Furthermore, PA might increase neurocognitive performance and reduce systemic inflammation. Objective The aim of the study was to investigate the association between PA and neurocognitive function in euthymic individuals suffering from BD. Methods and participants 120 individuals with BD, euthymic at test time, completed the self-reported International Physical Activity Questionnaire (IPAQ) assessing PA of the past seven days and were accordingly assigned to a specific activity category (low, moderate or vigorous). Furthermore, clinical parameters were gathered and cognitive tests analysing verbal-dependent intelligence, attention, executive functioning as well as memory were administered. Results Female individuals in the vigorous PA group performed significantly higher in most of the cognitive domains compared to females with moderate or low PA. In males, we only found a significant difference in one test for attention between moderate/vigorous and the low activity group. Conclusion Differences between PA groups in cognitive performance in female individuals with BD were obvious in almost all cognitive domains. As cognitive deficits are strongly associated with a worse course of disease and outcome, PA might offer a concomitant therapy targeting not only somatic comorbidities such as obesity and cardiovascular disease, but also neurocognition.

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