Early-life adversity predicting the incidence of multisite chronic pain in the general population.

INTRODUCTION: Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort. METHODS: Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35-75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features. RESULTS: Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13-3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45-12.18). CONCLUSION: These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.

Using Existing Clinical Data to Measure Older Adult Inpatients' Frailty at Admission and Discharge: Hospital Patient Register Study.

BACKGROUND: Frailty is a widespread geriatric syndrome among older adults, including hospitalized older inpatients. Some countries use electronic frailty measurement tools to identify frailty at the primary care level, but this method has rarely been investigated during hospitalization in acute care hospitals. An electronic frailty measurement instrument based on population-based hospital electronic health records could effectively detect frailty, frailty-related problems, and complications as well be a clinical alert. Identifying frailty among older adults using existing patient health data would greatly aid the management and support of frailty identification and could provide a valuable public health instrument without additional costs. OBJECTIVE: We aim to explore a data-driven frailty measurement instrument for older adult inpatients using data routinely collected at hospital admission and discharge. METHODS: A retrospective electronic patient register study included inpatients aged ≥65 years admitted to and discharged from a public hospital between 2015 and 2017. A dataset of 53,690 hospitalizations was used to customize this data-driven frailty measurement instrument inspired by the Edmonton Frailty Scale developed by Rolfson et al. A 2-step hierarchical cluster procedure was applied to compute e-Frail-CH (Switzerland) scores at hospital admission and discharge. Prevalence, central tendency, comparative, and validation statistics were computed. RESULTS: Mean patient age at admission was 78.4 (SD 7.9) years, with more women admitted (28,018/53,690, 52.18%) than men (25,672/53,690, 47.81%). Our 2-step hierarchical clustering approach computed 46,743 inputs of hospital admissions and 47,361 for discharges. Clustering solutions scored from 0.5 to 0.8 on a scale from 0 to 1. Patients considered frail comprised 42.02% (n=19,643) of admissions and 48.23% (n=22,845) of discharges. Within e-Frail-CH's 0-12 range, a score ≥6 indicated frailty. We found a statistically significant mean e-Frail-CH score change between hospital admission (5.3, SD 2.6) and discharge (5.75, SD 2.7; P<.001). Sensitivity and specificity cut point values were 0.82 and 0.88, respectively. The area under the receiver operating characteristic curve was 0.85. Comparing the e-Frail-CH instrument to the existing Functional Independence Measure (FIM) instrument, FIM scores indicating severe dependence equated to e-Frail-CH scores of ≥9, with a sensitivity and specificity of 0.97 and 0.88, respectively. The area under the receiver operating characteristic curve was 0.92. There was a strong negative association between e-Frail-CH scores at hospital discharge and FIM scores (rs=-0.844; P<.001). CONCLUSIONS: An electronic frailty measurement instrument was constructed and validated using patient data routinely collected during hospitalization, especially at admission and discharge. The mean e-Frail-CH score was higher at discharge than at admission. The routine calculation of e-Frail-CH scores during hospitalization could provide very useful clinical alerts on the health trajectories of older adults and help select interventions for preventing or mitigating frailty.

Dietary patterns, inflammatory biomarkers and cognition in older adults: An analysis of three population-based cohorts.

BACKGROUND: Targeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts. METHODS: In this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up. RESULTS: We included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant. CONCLUSION: Diet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

Benzodiazepine-receptor agonist prescription in a population of hospitalised patients in four psychogeriatric units in Switzerland.

The aim of this study is to describe the patterns of prescription of benzodiazepine-receptor agonists in hospitalised patients in four psychogeriatric units in Switzerland. This is a retrospective cross-sectional study that included patients aged 65 years or more hospitalised in one of the four psychogeriatric units of a university hospital in Switzerland during 2019. The presence, type and dose of benzodiazepine-receptor agonists was assessed at admission and at discharge. Three-hundred and eighty-six patients (214 women, 78.2 ± 8.1 years) were included in the study; 33.4% of patients had at least one benzodiazepine-receptor agonist at admission and 22.5% at discharge. The relative reduction of benzodiazepine-receptor agonists prescription in standardised dose was 78%. Age was found to be a protective factor against benzodiazepine-receptor agonists prescription at admission (adjusted odds ratio 0.94, confidence interval 0.91-0.98), and diagnosis of substance abuse was found to be a risk factor (adjusted odds ratio 4.43, confidence interval 1.42-17.02). Longer hospital stays (> 14 days) were associated with higher reduction of benzodiazepine-receptor agonists. The prevalence of a prescription of benzodiazepine-receptor agonists at admission was high, but during the psychogeriatric hospitalisation benzodiazepine-receptor agonists prescription decreased both in absolute and relative terms.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. RESULTS: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (ß = 0.25, p = .034 and ß = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). CONCLUSION: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

Increased sexual function after intake of clomethiazole.

An octogenarian woman showed increased sexual function after replacing alprazolam with clomethiazole, a sedative-hypnotic drug commonly prescribed in French-speaking Switzerland for the treatment of anxiety and insomnia in elderly patients. The patient's sexual symptoms did not improve after resuming alprazolam, but disappeared after interrupting clomethiazole, and did not reappear when alprazolam was discontinued. Considering the chronology of the events, increased sexual function was likely a manifestation of the introduction of clomethiazole. However, because alprazolam was interrupted when clomethiazole was introduced, we cannot exclude an association between increased sexual function and alprazolam interruption.

Aripiprazole dose associations with metabolic adverse effect: Results from a longitudinal study.

OBJECTIVE: Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. METHODS: 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. RESULTS: Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: -0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). CONCLUSION: Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred.

Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease.

ABSTRACT: We describe a patient suffering from probable Kufs disease who developed a neuroleptic malignant syndrome (NMS) after use of an antipsychotic agent over some weeks during hospitalization due to neuropsychiatric symptoms. Transferred to the neurology department, the patient quickly developed catatonic features. She did not respond to usual medical treatment but did respond to electroconvulsive therapy (ECT). The patient worsened following a nosocomial SARS-CoV-2 infection but improved again during a second course of ECT. We discuss Kufs disease as a potential risk factor for NMS and address the link between NMS and catatonia as well as the indication for ECT in both disorders. We also discuss the impact of SARS-CoV-2 infection on the clinical outcome. We describe the long recovery process and the secondary worsening of the patient on a cognitive level.

Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients.

BACKGROUND: Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders. METHODS: The study used TDM data from the PsyMetab cohort, including 547 daily dose-normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates. RESULTS: In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (ß = -0.65, P < 0.001), valproate users (ß = -0.53, P = 0.002), and inpatients (ß = -0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (ß = -0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (ß = -2.80, P < 0.001), with significant interactions with age (ß = 0.025, P < 0.001) and body weight (ß = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight. CONCLUSIONS: The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.

Profiles of centenarians' functioning: linking functional and cognitive capacity with depressive symptoms.

BACKGROUND: Despite most centenarians facing age-related declines in functional and cognitive capacities, the severity of these declines varies among individuals, as does the maintenance of good mental health (e.g., depressive symptoms) despite these declines. This study aims to examine this heterogeneity in centenarians from the Second Heidelberg Centenarian Study, which collected data from 112 centenarians living in Germany. In our study, we focus on a subsample of 73 centenarians who provided self-reports for our measures of interest (M age = 100.4, SD age = 0.55). METHODS: We examined correlations between functional capacity (i.e., PADL, IADL), cognitive capacity (i.e., MMSE), and depressive symptoms (i.e., GDS), and the existence of different profiles using hierarchical clustering. RESULTS: Higher functional capacity was related to higher cognitive capacity and to fewer depressive symptoms. Yet, higher cognitive capacity was associated with more depressive symptoms. Hierarchical clustering analysis elucidated this contradiction by identifying three profiles: low-capacity individuals (i.e., 24 individuals had low functional and cognitive capacities, with low depressive symptoms), high-capacity individuals (i.e., 33 individuals with high functional and cognitive capacities, with low depressive symptoms), and low-functional-high-cognitive-capacity individuals (i.e., 16 individuals showed low functional but high cognitive capacity, with high depressive symptoms). Our post-hoc analyses highlighted arthritis and pain as risk factors for functional dependence and depression. CONCLUSIONS: Our findings emphasize the importance of identifying centenarian subgroups with specific resource- and risk profiles to better address their needs, and of treating pain to improve functional capacity and mental health in centenarians.

Using AI-Based Technologies to Help Nurses Detect Behavioral Disorders: Narrative Literature Review.

BACKGROUND: The behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia and have multiple negative consequences. Artificial intelligence-based technologies (AITs) have the potential to help nurses in the early prodromal detection of BPSD. Despite significant recent interest in the topic and the increasing number of available appropriate devices, little information is available on using AITs to help nurses striving to detect BPSD early. OBJECTIVE: The aim of this study is to identify the number and characteristics of existing publications on introducing AITs to support nursing interventions to detect and manage BPSD early. METHODS: A literature review of publications in the PubMed database referring to AITs and dementia was conducted in September 2023. A detailed analysis sought to identify the characteristics of these publications. The results were reported using a narrative approach. RESULTS: A total of 25 publications from 14 countries were identified, with most describing prospective observational studies. We identified three categories of publications on using AITs and they are (1) predicting behaviors and the stages and progression of dementia, (2) screening and assessing clinical symptoms, and (3) managing dementia and BPSD. Most of the publications referred to managing dementia and BPSD. CONCLUSIONS: Despite growing interest, most AITs currently in use are designed to support psychosocial approaches to treating and caring for existing clinical signs of BPSD. AITs thus remain undertested and underused for the early and real-time detection of BPSD. They could, nevertheless, provide nurses with accurate, reliable systems for assessing, monitoring, planning, and supporting safe therapeutic interventions.

Mental health among centenarians living in Switzerland.

BACKGROUND: Given the increasing number of people achieving exceptionally long lifespans, there is an urgent need for a better understanding of mental health in centenarians. This study aimed to understand the prevalence of mental health conditions-depressive symptoms, anxiety, sleep disturbances, disinhibition, and aberrant motor behaviour-among centenarians in Switzerland. METHODS: Data were collected from N = 169 participants via telephone interviews or paper questionnaires, either directly from centenarians or through proxy informants. Half the data were collected during a period when protective measures were imposed due to the COVID-19 pandemic, and half were collected after the measures were lifted. RESULTS: Mental health conditions were prevalent in our sample, particularly depressive symptoms (44.51%) and anxiety (42.17%). Significant positive associations were found between depressive symptoms and anxiety, and between disinhibition and aberrant motor behaviour. Furthermore, we identified statistical predictors for the occurrence of mental health conditions. Notably, institutionalised living increased the odds of depressive symptomatology, while those with higher education levels or an absence of cognitive impairment experienced more sleep disturbances. Finally, cognitive impairment was linked to increased disinhibition and aberrant motor behaviour. CONCLUSIONS: The high prevalence of mental health conditions underscores the need for proactive mental health care strategies in advanced old age. Moreover, it is vital to consider the interconnected nature of mental health conditions and to prioritise vulnerable groups, such as centenarians in institutional settings.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n=76) or mild cognitive impairment (n=75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Linear regression and ROC analyses were used to address the associations of interest. RESULTS: Higher GFAP levels were associated with NPS at baseline (ß=0.23, p=.008). Higher NfL and GFAP levels were associated with the presence of NPS at follow-up (ß=0.29, p=.007 and ß=0.28, p=.007, respectively) and with an increase in the NPI-Q severity score over time (ß=0.23, p=.035 and ß=0.27, p=.011, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.73 to 0.84, p=.007) and AD pathology (AUC 0.79 to 0.86, p=.006), but not of cognitive decline (AUC 0.79 to 0.84, p=.068). CONCLUSION: Plasma GFAP is associated with NPS while NfL and GFAP are both associated with future NPS and NPS severity. Considering the presence of NPS along with blood-based AD-biomarkers may improve diagnosis and prediction of clinical progression of NPS and inform clinical decision-making in non-demented older people.

Associations of Valproate Doses With Weight Gain in Adult Psychiatric Patients: A 1-Year Prospective Cohort Study.

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population.Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes.Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year (P < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P < .001 and +0.12%, P = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg (P = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month (P = .004), whereas a trend was observed for women (+0.40%, P = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period.Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.

BACKGROUND: Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. RESULTS: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10-8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10-8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association). CONCLUSION: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.

Cholesterol-metabolism, plant sterols, and long-term cognitive decline in older people - Effects of sex and APOEe4.

Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk.

[Psychiatry: what's new in 2023]. / Psychiatrie : ce qui a changé en 2023.

Resistance to treatment in psychiatry can arise from a variety of causes, and here we look at two strategies that can improve this problem. First, we discuss the role of patients' relatives; in addition to family therapy interventions, setting up groups of relatives makes it possible to increase their skills in helping their sick relative and to help each other in this process. And finally, we look at the option of interventional psychiatry. These methods, which have been greatly enriched in recent years, are now available in the interventional psychiatry unit recently opened in the new Cery psychiatric hospital in Lausanne.

La résistance au traitement en psychiatrie peut découler de multiples causes ; deux stratégies pouvant améliorer ce problème sont abordées dans cet article. En premier lieu, le rôle des proches des patients ; au-delà d'interventions de thérapie de famille, la mise en place de groupes de proches permet d'augmenter leurs compétences à aider leur proche malade et de s'entraider dans cette démarche. Et enfin, l'option que peuvent constituer les approches de psychiatrie interventionnelle. Ces méthodes se sont grandement enrichies au cours des dernières années et sont maintenant accessibles dans l'Unité de psychiatrie interventionnelle récemment ouverte dans le nouvel hôpital psychiatrique de Cery, récemment inauguré à Lausanne.

Metabolic disturbances are risk factors for readmission to psychiatric hospitals in non-smokers but not in smokers: results from a Swiss psychiatric cohort and in first-episode psychosis patients.

Background: Psychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission. Methods: Between 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances. Results: A total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission. Conclusion: The observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Obstructive sleep apnea and cognitive functioning in the older general population: The moderating effect of age, sex, ApoE4, and obesity.

Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.