The influence of chronic inflammation on the illnesscourse of bipolar disorder: A longitudinal study.

INTRODUCTION: C-reactive protein (CRP) is a systemic inflammatory marker, which indicates systemic inflammatory processes It is involved in different inflammatory processes of the body and is a reliable marker for the general inflammatory state of the body. High sensitive CRP seems to play a key role as a state and trait marker of bipolar disorder (BD). In the current study, we tried to determine the long-term effect of CRP levels on clinical symptoms and illness course of bipolar disorder. METHODS: For the current study, we examined 106 patients with BD for a period of four years. Participants underwent a clinical screening for depressive and manic episodes with the Hamilton Depression Scale (HAMD) and the Young Mania Rating Score (YMRS) and a serological diagnostic for inflammatory parameters every six months, thus leading to 8 measurement times in total. Patients with the presence of severe medical or neurological comorbidities such as active cancer, chronic obstructive lung disease, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis and acute infections were not included in the study. RESULTS: In our sample, 26% showed a mean hsCRP above 5 mg/dl. Those patients showed a significantly higher mean YMRS score than those with a mean hsCRP under 5 mg/dl during our observation period. Regarding HAMD there was no significant difference in hsCRP values. The existence of lithium treatment showed no significant influence on mean hsCRP levels between the start and endpoint. CONCLUSION: Individuals who were exposed to a higher level of inflammation over time suffered from more manic symptoms in this period. These findings underline the hypothesis that inflammatory processes have an accumulative influence on the illness course of BD, especially concerning manic symptoms and episodes.

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.

Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

Machine-based learning of multidimensional data in bipolar disorder - pilot results.

INTRODUCTION: Owing to the heterogenic picture of bipolar disorder, it takes approximately 8.8 years to reach a correct diagnosis. Early recognition and early intervention might not only increase quality of life, but also increase life expectancy as a whole in individuals with bipolar disorder. Therefore, we hypothesize that implementing machine learning techniques can be used to support the diagnostic process of bipolar disorder and minimize misdiagnosis rates. MATERIALS AND METHODS: To test this hypothesis, a de-identified data set of only demographic information and the results of cognitive tests of 196 patients with bipolar disorder and 145 healthy controls was used to train and compare five different machine learning algorithms. RESULTS: The best performing algorithm was logistic regression, with a macro-average F1-score of 0.69 [95% CI 0.66-0.73]. After further optimization, a model with an improved macro-average F1-score of 0.75, a micro-average F1-score of 0.77, and an AUROC of 0.84 was built. Furthermore, the individual amount of contribution per variable on the classification was assessed, which revealed that body mass index, results of the Stroop test, and the d2-R test alone allow for a classification of bipolar disorder with equal performance. CONCLUSION: Using these data for clinical application results in an acceptable performance, but has not yet reached a state where it can sufficiently augment a diagnosis made by an experienced clinician. Therefore, further research should focus on identifying variables with the highest amount of contribution to a model's classification.

Endoscopic trans-sphenoidal pituitary surgery does not impact postoperative nasal quality of life.

PURPOSE: The aim of this prospective longitudinal study was to assess both subjective quality of life using questionnaires and objective examination of nasal function with regard to olfaction, nasal air flow and mucociliary clearance in patients after minimally invasive, turbinate-preserving endoscopic transnasal trans-sphenoidal pituitary surgery. METHODS: Patients undergoing endoscopic transnasal pituitary surgery were recruited prospectively and examined during three study visits, preoperatively and 3 and 6 months postoperatively. We examined nasal function using sniffin' sticks test, rhinomanometry, saccharin transit time test, and endoscopic and radiological scores. In addition, the influence on subjective quality of life and mental health was recorded using the Sinonasal-Outcome-Test-20 (SNOT-20) and the Hospital-Anxiety-and-Depression-Scale (HADS). RESULTS: 20 patients undergoing endoscopic pituitary tumor resections were included. No significant changes in olfaction or mucociliary clearance were noted. Nasal air flow showed a tendency to increase in the postoperative course lacking significance. Both the endoscopy and the radiological scores showed a significant deterioration, especially after 3 months, with a trend towards improvement over time. However, neither the SNOT-20 nor the HADS showed significant changes compared to baseline. CONCLUSIONS: Our concept of minimally invasive endoscopic tumor resections on the pituitary gland with preservation of nasal turbinates shows low morbidity for the patient. Despite objectifiable surgery-associated changes in the nose, nasal physiology in terms of smell, airflow and mucociliary clearance can be preserved and the subjective quality of life of our patients remains stable.

Vitamin D Status in Bipolar Disorder.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH)2D, were measured simultaneously with a validated liquid chromatography-tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH)2D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -0.154, p = 0.040), as well as the Young Mania Rating Scale and the VMR (r = -0.238, p = 0.015). Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.

Machiavellianism and psychopathy affect sleep quality in people with affective disorders and mentally healthy individuals.

Introduction: Deteriorated sleep quality is a predisposing factor and symptom of affective disorders (AD). It is important to investigate factors driving the relationship between sleep and AD, such as personality traits. Previous research has shown that personality traits such as the Dark Triad personality traits (DT) narcissism, Machiavellianism, and psychopathy are associated with sleep problems and AD. The current study examined the moderating influence of the DT in the relationship between AD [versus healthy controls (HC)] and sleep quality. Methods: Data of 657 individuals (267 HC, 390 AD; 483 female, 166 male, eight diverse; Mage = 34.87, SDage = 13.86) were collected in an online survey, which administered the Pittsburgh Sleep Quality Index and the Short Dark Triad questionnaire. Results: Moderation analyses controlling for age and gender revealed that Machiavellianism (b = -0.76, p < 0.05, R2 = 0.35) and psychopathy (b = -1.15, p < 0.05, R2 = 0.35), but not narcissism (b = -0.20, p = 0.620, R2 = 0.35), had a negative effect on sleep quality. Specifically, this effect is more pronounced in the HC group, but sleep quality is generally worse in AD. Conclusion: Our findings indicate that Machiavellianism and psychopathy should be considered in the prevention and treatment of AD-associated sleep problems. Particularly, monitoring these traits could help to implement timely measures for the prevention of sleep problems, such as psychoeducation and sleep hygiene. The results highlight the role of personality in the aetiopathogenesis of AD and require further differentiation to examine the underlying pathways between the DT, sleep, and AD.

The Influence of Vitamin D Status on Cognitive Ability in Patients with Bipolar Disorder and Healthy Controls.

Recent evidence on the association between vitamin D and cognition in mentally healthy individuals is inconsistent. Furthermore, the link between vitamin D and cognitive ability in individuals with bipolar disorder has not been studied yet. Thus, we aimed to investigate the association between 25-hydroxyvitamin D (25(OH)D), 24,25 dihydroxyvitamin D (24,25(OH)2D, the vitamin D metabolite ratio (VMR) and cognition in a cohort of euthymic patients with bipolar disorder. Vitamin D metabolites were measured simultaneously by liquid-chromatography tandem mass-spectrometry in serum samples from 86 outpatients with bipolar disorder and 93 healthy controls. Neither the inactive precursor 25(OH)D, nor the primary vitamin D catabolite 24,25(OH)2D, or the vitamin D metabolite ratio were significantly associated with the domains "attention", "memory", or "executive function" in individuals with bipolar disorder and healthy controls. Further, no vitamin D deficiency effect or interaction group × vitamin D deficiency was found in the cognitive domain scores. In summary, the present study does not support vitamin D metabolism as a modulating factor of cognitive function in euthymic BD patients. Considering the current study's cross-sectional design, future research should expand these results in a longitudinal setting and include additional aspects of mental health, such as manic or depressive symptoms, long-term illness course and psychopharmacological treatment.

Metabolic Syndrome in Affective Disorders: Associations with Dark Triad Personality Traits.

Previous research has focused on the relationship between affective disorders (AD) and metabolic syndrome (MetS). Aside from biological and lifestyle factors, personality traits were identified as influencing aspects. In particular, the Dark Triad personality traits (DT; Machiavellianism, narcissism, psychopathy) were connected to both AD and worse somatic health, thus possibly resulting in MetS. This observational study aimed to investigate the associations between DT and anthropometric parameters and differences in the DT traits concerning the presence of MetS in individuals with AD. A total of 112 individuals (females = 59, males = 51, diverse = 2, Mage = 47.5, SDage = 11.5) with AD filled out the Short Dark Triad questionnaire. Body Mass Index (BMI) and MetS criteria, including blood pressure, waist circumference, lipid, and glucose levels, were assessed. For Machiavellianism, a positive association with BMI (r = 0.29, p < 0.05) and a negative association with systolic blood pressure (r = -0.23, p < 0.05) were found. No relationship between the overall MetS and DT score (r = 0.08, p = 0.409) was observed. The results were limited by the lack of a control group and the cross-sectional study design, which does not allow for the determination of causality. Machiavellianism was associated with a higher BMI and lower systolic blood pressure, indicating a deteriorating health effect of this trait. Possibly, the higher prevalence of MetS in AD stems from aspects such as lifestyle or medication intake, which might also be influenced by DT. Further research is needed to disentangle underlying mechanisms.

Impact of the COVID-19 Pandemic on Productivity of Workers in the Health Sector between Working in a Hospital and from Home.

BACKGROUND: Due to the COVID-19 pandemic, workplaces in the medical field experienced changes. Non-frontline workers in the health sector (WHS) were in many cases allowed to work from home (WFH). Changes in work locations have affected the perception of productivity during the COVID-19 pandemic compared to the pre-pandemic perception. Studies regarding this research field are rare for WHS. The aim of the present study was to investigate the perception of productivity and its impact on symptoms of depression during the COVID-19 pandemic. The second objective was to assess the implications for post-pandemic work settings such as WFH or work scenarios in hospitals during pandemics. METHODS: At three points in time during the COVID-19 pandemic (t1; n = 161: April 2020, t2; n = 1598 winter 2020/2021, t3; n = 1879 winter 2021/2022), an online survey of WHS (e.g., medical doctors, nurses, scientific staff) in Austria concerning their productivity in their current workplace (pre- and post-pandemic) was conducted. The online survey included questions about the perceptions of productivity changes (i.e., perceptions of lower, equal, and higher productivity, before and during the COVID-19 pandemic) in different work settings (e.g., working in a hospital or working from home), as well as standardized questionnaires like the Patient Health Questionnaire (PHQ-9), assessing symptoms of depression in WHS. RESULTS: χ2 tests showed that WHS working in hospitals experienced significantly fewer fluctuations in their perceptions of productivity than WHS working from home. An analysis of variance (ANOVA) indicated that WHS with a lower perception of productivity tended to have higher self-assessed depressive symptoms. CONCLUSION: The possibility of remaining working in the hospital in stressful scenarios like the COVID-19 pandemic might stabilize the feeling of productivity. Moreover, productivity is associated with self-assessed depressive symptoms. Hence, looking into the reasons behind this discrepancy between WHS in hospitals and those working from home might help to improve the home office modality and to create better structures, which are related to symptoms of depression.

The Association of Tube Weaning and Oral Skill Development in Infants With Tube Dependency: A Prospective Study.

OBJECTIVE: This study was the first of its kind by assessing oral skills development during and after applying the "Graz Model" of tube weaning. METHODS: This prospective case series study included data of 67 (35 females, 32 males, treated from March 2018 to April 2019) tube dependent children, who participated in the effective "Graz Model" of tube weaning. Parents filled out the standardized Pediatric Assessment Scale for Severe Feeding Problems (PASSFP) prior to and immediately after completion of the program. Paired sample t tests were conducted to examine pre-to-post changes in the children's oral skills. RESULTS: The study showed that oral skills increased significantly during tube weaning PASSFP score of 24.76 (standard deviation, SD = 12.38) prior to versus 47.97 (SD = 6.98) after completion of the program. Furthermore, significant changes in their sensory and tactile perception and in their general eating behavior were observed. Children also showed reduced oral aversion symptoms and food pocketing, could enjoy their meals, and increased their food repertoire. Mealtime duration could be decreased, and parents were less anxious about their infants' intake and less frustrated because of their children's eating behavior. CONCLUSION: The results of this study demonstrated for the first time that tube dependent children can improve their oral skills significantly during and after their participation in the child-led approach of the "Graz model" of tube weaning.

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies.

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.

Effects of Metabolic Syndrome and Sex on Stress Coping Strategies in Individuals with Depressive Disorder.

Metabolic syndrome (MetS) is related to depression and contributes to reduced life expectancy in individuals with mental disorders. Stress coping strategies are important factors in the development and maintenance of depressive disorders and have been related to metabolic disturbances. The aim of this study was to determine whether there is a difference in the use of positive (re- and devaluation, distraction, and control) and negative stress coping strategies in relation to patients' MetS. A sample of 363 individuals (n female = 204, n male = 159) with a diagnosis of depression was measured with the Stress Coping Style Questionnaire and the Beck Depression Inventory. In addition, we collected data on MetS (waist circumference, triglycerides, high-density lipoprotein, fasting glucose/diabetes, blood pressure/hypertonia) according to the International Diabetes Federation. A 2 × 2 design including Mets (with vs. without) and sex (female vs. male) was performed to test for differences in stress coping strategies. Individuals with depression and MetS scored higher on distraction strategies than depressed individuals without MetS (p < 0.01, corrected with false discovery rate). In addition, we found sex differences in stress coping strategies indicating that women with depression scored higher on distraction strategies (p < 0.001, FDR corrected), as well as negative strategies (p < 0.001, FDR corrected), than men. No significant interaction between MetS and sex was found regarding the higher value of stress coping strategies. Findings suggest that individuals with depression and MetS used distraction strategies to a higher amount to cope with stress, which could be stress eating in some cases, than those without MetS. Women with depressive disorders had higher values than men on other coping strategies in our sample of individuals with depression. A better understanding of MetS and sex-specific differences in stress coping strategies might help to plan more effective preventive strategies and personalized treatment options for depression.

The Big Five as Predictors of Cognitive Function in Individuals with Bipolar Disorder.

The connection between cognitive function and the "Big Five" personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism) in the general population is well known; however, studies researching bipolar disorder (BD) are scarce. Therefore, this study aimed to investigate the Big Five as predictors of executive function, verbal memory, attention, and processing speed in euthymic individuals with BD (cross-sectional: n = 129, including time point t1; longitudinal: n = 35, including t1 and t2). Participants completed the NEO Five-Factor Inventory, the Color and Word Interference Test, the Trail Making Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. The results showed a significant negative correlation between executive function and neuroticism at t1. Changes in cognitive function between t1 and t2 did not correlate with and could not be predicted by the Big Five at t1. Additionally, worse executive function at t2 was predicted by higher neuroticism and lower conscientiousness at t1, and high neuroticism was a predictor of worse verbal memory at t2. The Big Five might not strongly impact cognitive function over short periods; however, they are significant predictors of cognitive function. Future studies should include a higher number of participants and more time in between points of measurement.

Psychopathic personality traits stress immunity and social potency moderate the relationship between emotional competence and cognitive functions in depression.

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study.

Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.

Association between mitochondria-related genes and cognitive performance in the PsyCourse Study.

BACKGROUND: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. METHODS: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program. RESULTS: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests. LIMITATIONS: Moderate statistical power due to relatively small sample size. CONCLUSIONS: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

Feeling Informed and Safe Are Important Factors in the Psychosomatic Health of Frontline Workers in the Health Sector during the COVID-19 Pandemic in Austria.

The global spread of the coronavirus disease (COVID-19) has created new challenges for the entire healthcare system, and those who work directly with the patients or even on the front lines with COVID-19 patients have been particularly stressed. Only a few studies are currently available investigating psychosomatic symptoms among healthcare workers, particularly frontline workers, over the entire pandemic period (2020-2022). There is also a lack of knowledge about strategies to prevent stress during and after a health crisis. METHODS: An online survey was conducted at three times (April 2020, winter 2020/2021, and winter 2021/2022) during the COVID-19 pandemic in Austria. The sample included 160 healthcare workers at screening time 1, 1.361 healthcare workers at screening time 2, and 1.134 healthcare workers at screening time 3. The survey included COVID-19 work-related fears, satisfaction with the frontline work, and standardized inventories to assess psychosomatic symptoms, such as the Patient Health Questionnaire (PHQ-D). RESULTS: Psychosomatic symptoms were more common among women compared to men, and among frontline workers compared to non-frontline workers, especially during the course of the pandemic at t2 and t3. Self-reported scores of COVID-19 work-related fears were significantly associated with psychosomatic symptoms. Furthermore, in frontline workers, there was a significant association between the feeling of being safe and well-informed and psychosomatic symptoms. CONCLUSION: COVID-19 work-related fears and psychosomatic symptoms have been prevalent among healthcare workers throughout the pandemic. Feeling safe and informed appears to be essential to prevent psychosomatic symptoms, leading to a recommendation for employers in the healthcare sector to focus on communication and information. As frontline workers are especially prone to psychosomatic symptoms, more stress prevention programs for them will be essential to maintain productivity and reduce sick days and fluctuations in the healthcare system.

Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder.

Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers. Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD). Design, Setting, and Participants: This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020. Main Outcomes and Measures: Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry. Results: Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids. Conclusions and Relevance: In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

Delirium-associated medication in people at risk: A systematic update review, meta-analyses, and GRADE-profiles.

BACKGROUND: Drug-associated delirium is a common but potentially preventable neuropsychiatric syndrome associated with detrimental outcomes. Empirical evidence for delirium-associated medication is uncertain due to a lack of high-quality studies. We aimed to further investigate the body of evidence for drugs suspected to trigger delirium. METHODS: A systematic update review and meta-analyses of prospective studies presenting drug associations with incident delirium in adult study populations was conducted. Two authors independently searched MEDLINE, PsycINFO, Embase, and Google Scholar dated from October 1, 2009 to June 23, 2020, after screening a previous review published in 2011. The most reliable results on drug-delirium associations were pooled in meta-analyses using the random-effects model. Quality of evidence was assessed using the GRADE-approach. This study is preregistered with OSF (DOI https://doi.org.10.17605/OSF.IO/4PUHY). RESULTS: The 31 eligible studies, presenting results for 24 medication classes were identified. Meta-analyses and GRADE level of evidence ratings show no increased delirium risk for Haloperidol (OR: 0.96, 95% CI 0.72-1.28; high-quality evidence), Olanzapine (OR: 0.25, 95% CI 0.15-0.40), Ketamine (OR: 0.72, 95% CI 0.35-1.46) or corticosteroids (OR: 0.69, 95% CI 0.32-1.50; moderate quality evidence, respectively). Low-level evidence suggests a three-fold increased risk for anticholinergics (OR: 3.11, 95% CI 1.04-9.26). Opioids, benzodiazepines, H1 -antihistamines, and antidepressants did not reach reliable evidence levels in our analyses. CONCLUSION: We investigated the retrievable body of evidence for delirium-associated medication. The results of this systematic review were then interpreted in conjunction with other evidence-based works and guidelines providing conclusions for clinical decision-making.

Parenthood for childhood cancer survivors: unfounded fear of cancer development in offspring and related health behaviors.

Current literature reveals no increased risk for adverse non-hereditary health outcomes in the offspring of childhood cancer survivors (CCS), yet survivors reported concerns regarding their offspring's health. To investigate how the fear of cancer development in offspring influences parental behavior related to health and prevention, survey reports from 256 European adult CCS and 256 age- and sex-matched siblings who participated in a multicenter study on offspring health were analyzed in the present study. Analyses of covariance and chi-square tests were conducted to test for differences between CCS and siblings in outcome variables (all related to healthy parenting behavior). CCS reported higher fear levels (p = 0.044, Partial η2 = 0.01) and less alcohol consumption (p = 0.011, Phi = 0.12) and smoking (p = 0.022, Phi = 0.11) during pregnancy than siblings. In survivor families, children were breastfed less often (p < 0.001, Phi = 0.18). Partial correlation analyses showed that CCS' fear levels decreased with increasing age (r = -0.16, p = 0.014), time since oncological therapy (r = -0.19, p = 0.003), and number of children (r = -0.21, p = 0.001). Overall, due to their own experiences with cancer, many CCS harbor misperceptions regarding the health outcomes of their offspring. Although the fear decreases with increasing distance from the active disease, any fear should be taken seriously, even if unfounded, and combated through targeted educational measures.