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.
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.
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.
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 prevalence of metabolic syndrome and overweight/obesity is increased in bipolar disorder (BD) compared to the general population and is related to suicidality. The aim of this study was to ...examine the association between both the rate of suicidal ideation and suicide attempts and metabolic variables in individuals with BD.
Anthropometric measures, socio-demographic data, suicide history and serum lipid levels were measured in 215 individuals with BD. Individuals were divided into normal weight, overweight and obese according to their body mass index (BMI), and metabolic syndrome was assessed using “The International Diabetes Federation”-criteria.
Of the 215 individuals studied, 80.9% reported suicidal ideation, 35.3% reported at least one suicide attempt and 30.7% were diagnosed with metabolic syndrome. Both metabolic syndrome and BMI were not related to suicide attempts. However, individuals with normal weight had more suicidal ideation than overweight individuals, while obese individuals did not differ from either group. Furthermore, there was no association between suicide attempts or suicidal ideation and serum lipid levels.
The cross-sectional design of the study, a non-standardized questionnaire for suicidality, and not controlling the medication intake are limiting factors.
Contrary to expectations, a difference was found in the BMI categories and suicidal ideation, but not suicide attempts. Serum lipid levels were found to be unsuitable as possible biomarkers for suicidality in individuals with BD. Special attention should be paid to suicidal ideation and BMI rather than metabolic syndrome or lipid values when treating suicidal individuals with BD.
•Normal-weight individuals had more suicidal ideation than overweight individuals.•Both metabolic syndrome and BMI were not associated with suicide attempts.•Suicide attempts and suicidal ideation were not related to serum lipid levels.•Serum lipid levels might be unsuitable as biomarkers for suicidality in BD.•More attention should be paid to BMI when treating suicidal patients with BD.
There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its ...receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder.
In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy.
Participants had significant increases from baseline to week 4 in the TMTB standard score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p<0.001). Neither changes in mood rating scales nor metabolic parameters were associated with changes in cognitive performance (all p>0.05); however baseline insulin resistance (IR) and body mass index (BMI) moderated the changes in the composite Z-score (p=0.021 and p=0.046, respectively), indicating larger responses in individuals with higher IR and BMI at baseline. There was a significant increase in lipase (p<0.001), but individual values were above the upper limit of normality.
Small sample size, open-label design, lack of a placebo group.
Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial effects on objective measures of cognitive function. Larger studies with controlled trial designs are necessary to confirm and expand the results described herein.
•Cognitive deficits in mood disorders are highly prevalent and impactful.•Few interventions have evidence of pro-cognitive effects in mood disorders.•In this pilot study we explored the cognitive effect of a GLP-1R agonist.•4-week treatment with liraglutide was associated with cognitive improvements.•Liraglutide was also safe and well tolerated by individuals with mood disorders.
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