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).
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.
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).
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.
Psychopathic personality traits (PPT) and depression have both been shown to worsen emotional and cognitive functions. Moreover, PPT and depression share similar underlying neuronal circuits tapping ...into the emotional and cognitive domains. However, little is known about the influence of PPT on emotion and cognition in individuals with depression.
This study aimed to examine the correlative relationships and moderating role of PPT in the association between emotional competence and cognitive functions in individuals with depression.
Data from 373 individuals diagnosed with depression (158 males, 215 females) were examined within a cohort study. Subjects filled out validated questionnaires surveying PPT and emotional competences. Furthermore, a comprehensive neuropsychological test battery was administered.
Correlation analyses revealed a significant positive association between emotional competence and cognitive functions. Further, negative associations between emotional competence and the PPT "Blame Externalisation" and "Careless Nonplanfulness," as well as positive associations with psychopathic "Social Potency" and "Stress Immunity" were found. Moderation analyses indicated a significant positive influence of psychopathic "Stress Immunity" and "Social Influence" on the relationship between emotional competence and cognitive functions.
The findings highlight the importance of integrating PPT in depression research. Considering PPT in depression treatment could also facilitate the therapeutic process by identifying individual traits as resilience-strengthening or potentially harmful factors for depressive symptomatology. This study represents a stepping stone for further research regarding the role of personality traits in psychiatric disorders and their treatment.
A relevant comorbidity of bipolar disorder (BD) is eating disorders (EDs). Crossed vulnerability factors as eating disorder-specific symptoms (EDSSs) may trigger the onset of both disorders in either ...direction. The Structured Inventory for Anorexic and Bulimic Eating Disorders for Self-Report was used to examine the occurrence of EDs in euthymic/subsyndromal individuals with BD ( n = 86) and healthy controls ( n = 86) matched for age and sex. Furthermore, we explored EDSSs with the subscales "general psychopathology and social integration," "bulimic symptoms," "body image and slimness ideal," "sexuality and body weight," "counteract," and "atypical binge." Higher rates of all EDSSs were reported in BD. Younger individuals with BD showed higher expression in "bulimic symptoms," "body image and slimness ideal," and "atypical binge" subscales. No participants fulfilled ED diagnosis. The findings show a link between EDSS and BD. Clinicians should pay attention to a multimodal intervention, considering risk factors, investigating eating habits and ED associated behaviors.
Background Research on depression showed that dysregulations in tryptophan (TRP), kynurenine (KYN), and its KYN pathway metabolites are key aspects in the development and maintenance of depressive ...symptoms. In our previous reports, we described sex-specific changes in TRP breakdown as well as changes in KYN and KYN/TRP in association with treatment response and inflammatory and metabolic parameters. However, results of treatment effects on KYN pathway metabolites as well as how pathway changes are related to treatment response remain sparse. Objective We investigated potential changes of KYN and KYN pathway metabolites in association with therapeutic response of individuals with depression during a six-week multimodal psychiatric rehabilitation program. Methods 87 participants were divided into treatment responders and non-responders (48 responders, 39 non-responders; 38 male, 49 female; M age = 51.09; SD age = 7.70) using scores of psychological questionnaires. KYN pathway metabolites serum concentrations as well as their ratios were collected using high performance liquid chromatography. Changes over time (time of admission (t1) vs. time of discharge (t2)) were calculated using repeated measure analyses of (co)variance. Results Non-responders exhibited higher levels of 3-Hydroxyanthralinic acid (3-HAA), nicotinic acid (NA), and 3-HAA/KYN, independently of measurement time. NA levels decreased, while 3-HAA levels increased over time in both groups, independently of treatment response. 3-HK/KYN levels decreased, while KYN levels increased in non-responders, but not in responders over time. Discussion The results indicate that some compounds of the KYN pathway metabolites can be altered through multimodal long-term interventions in association with treatment response. Especially the pathway degrading KYN further down to 3-HAA and 3-HK/KYN might be decisive for treatment response in depression.
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.
People with severe mental illnesses (SMI: schizophrenia, depressive disorder, bipolar disorder) have a high risk of being infected by viruses and suffer a more severe infection illness course than ...the general population. The aim of this literature review was to elucidate rates as well as immunogenicity and side effects of vaccinations in SMI.
All studies in the English or German language, which investigated either prevalence rates or effects of vaccinations in the target groups, were systematically searched in the databank PubMed by three independent authors using the PRISMA guidelines and discussed in more detail.
The search found 24 studies reporting epidemiological data and 16 investigating immunogenicity of vaccinations. The results on prevalence rates, antibody production, inflammation response and side effects were inconsistent. About interactions with psychotropic medication, only two studies on clozapine were found.
Only a few trials with heterogeneous samples have investigated prevalence and effects of vaccinations in SMI. Sex, age and other factors such as somatic comorbidities and special vaccination programmes have not been considered continuously and may influence rates as well. As individuals with SMI might be at special risk, further research on the willingness to be vaccinated as well as efficacy of vaccinations is needed.
The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize ...the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.
The ongoing pandemic of coronavirus disease (COVID-19) is a global health crisis that has posed enormous pressure on workers in the health sector (WHS), having a massive impact on their mental ...health. In this study, we aimed to evaluate the sleep quality of WHS during the pandemic and compare frontline WHS to those who are not directly engaged in the care of COVID-19 patients. This cross-sectional, self-reported online survey assessed the sleep quality of WHS in Austria using the Pittsburgh Sleep Quality Index (PSQI). The same questionnaire was sent out two times. Due to the unequal sample and anonymity of the study participants, we analyzed the data of each time point separate from each other. The first study was conducted in April/May 2020, during the first lockdown in Austria (Study1), and the second study was conducted in July/August 2020, when the social restrictions were loosened (Study2). T-test was used to compare the mean values of PSQI scores between frontline vs. non-frontline WHS, while two two-way ANCOVAs were used to analyze differences in the PSQI mean scores (controlled for age) for male vs. female between frontline vs. non-frontline WHS. During the first lockdown in Austria (Study1) we identified a shorter sleep duration of frontline WHS compared to the non-frontline group, however the difference in global PSQI score between these groups was statistically not significant. In the period after loosened restrictions (Study2) the sleep quality, sleep latency, sleep duration, sleep efficiency and global PSQI score was worse in frontline WHS compared to the non-frontline WHS. Furthermore, female WHS scored higher in the PSQI indicating a worse sleep than male WHS. In addition, nurses and nursing assistants had a higher prevalence of poor sleep quality than other occupational groups. Our results indicate that the COVID-19 pandemic negatively impacts the sleep of WHS, affecting particularly frontline WHS. Preventive interventions aiming to promote good sleep quality in WHS during a healthcare crisis like this pandemic are essential to enhance resilience and mitigate the vulnerability of this specific population.
Background:
Metabolic syndrome (MetS) is more prevalent in individuals with bipolar disorder and has a negative impact on cognition, in particular on executive function, which is already impaired in ...individuals with bipolar disorder compared to healthy controls.
Methods:
In a cross-sectional study, we compared 148 euthymic patients with bipolar disorder and 117 healthy controls in cognitive function depending on the diagnosis of MetS. A neuropsychological test battery was used including the Trail Making Test A/B, Stroop Color and Word Interference Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. In addition, MetS variables as well as the defining variables waist circumference, serum triglyceride levels, high-density lipoprotein cholesterol levels, blood pressure, fasting glucose levels, and body mass index were compared between patients and controls. In addition, illness-related variables were associated with MetS in individuals with bipolar disorder.
Results:
The prevalence of MetS in patients with bipolar disorder was higher than in controls (30.4 vs. 15.4%). Patients with bipolar disorder with MetS had impaired executive function compared to patients without MetS or healthy controls with and without MetS (
p
= 0.020). No MetS effects or interaction MetS × Group was found in attention/processing speed (
p
= 0.883) and verbal learning/memory (
p
= 0.373). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in bipolar disorder (
p
> 0.05).
Conclusion:
Bipolar disorder comorbid with MetS bears additional risk for impaired executive function. Executive function includes action planning, inhibition, and impulse control and could play a critical role in keeping long-term goals in mind associated with gaining and maintaining a healthy weight.
PDF
