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Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment.

ABSTRACT: Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors. Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses. Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors. Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

SUBMITTER: Reponen EJ

PROVIDER: S-EPMC8192708 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:An advance directive is a document specifying a person's preferences for treatment, should he or she lose capacity to make such decisions in the future. They have been used in end-of-life settings to direct care but should be well suited to the mental health setting. OBJECTIVES:To examine the effects of advance treatment directives for people with severe mental illness. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group's Register (February 2008), the Cochrane Library (Issue 1 2008), BIOSIS (1985 to February 2008), CINAHL (1982 to February 2008), EMBASE (1980 to February 2008), MEDLINE (1966 to February 2008), PsycINFO (1872 to February 2008), as well as SCISEARCH and Google - Internet search engine (February 2008). We inspected relevant references and contacted first authors of included studies. SELECTION CRITERIA:We included all randomised controlled trials (RCTs), involving adults with severe mental illness, comparing any form of advance directive with standard care for health service and clinical outcomes. DATA COLLECTION AND ANALYSIS:We extracted data independently. For homogenous dichotomous data we calculated fixed-effect relative risk (RR) and 95% confidence intervals (CI) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD) and their 95% confidence interval again using a fixed-effect model. MAIN RESULTS:We were able to include two trials involving 321 people with severe mental illnesses. There was no significant difference in hospital admission (n=160, 1 RCT, RR 0.69 0.5 to 1.0), or number of psychiatric outpatient attendances between participants given advanced treatment directives or usual care. Similarly, no significant differences were found for compliance with treatment, self harm or number of arrests. Participants given advanced treatment directives needed less use of social workers time (n=160, 1 RCT, WMD -106.00 CI -156.2 to -55.8) than the usual care group, and violent acts were also lower in the advanced directives group (n=160, 1 RCT, RR 0.27 CI 0.1 to 0.9, NNT 8 CI 6 to 92). The number of people leaving the study early were not different between groups (n=321, 2 RCTs, RR 0.92 CI 0.6 to 1.6). AUTHORS' CONCLUSIONS:There are too few data available to make definitive recommendations. More intensive forms of advance directive appear to show promise, but currently practice must be guided by evidence other than that derived from randomised trials. More trials are indicated to determine whether higher intensity interventions, such as joint crisis planning, have an effect on outcomes of clinical relevance.

Project description:People with severe mental illness (SMI), including schizophrenia and bipolar disorder, have excess rates of cardiovascular disease (CVD). Risk prediction models validated for the general population may not accurately estimate cardiovascular risk in this group.To develop and validate a risk model exclusive to predicting CVD events in people with SMI incorporating established cardiovascular risk factors and additional variables.We used anonymous/deidentified data collected between January 1, 1995, and December 31, 2010, from the Health Improvement Network (THIN) to conduct a primary care, prospective cohort and risk score development study in the United Kingdom. Participants included 38,824 people with a diagnosis of SMI (schizophrenia, bipolar disorder, or other nonorganic psychosis) aged 30 to 90 years. During a median follow-up of 5.6 years, 2324 CVD events (6.0%) occurred.Ten-year risk of the first cardiovascular event (myocardial infarction, angina pectoris, cerebrovascular accidents, or major coronary surgery). Predictors included age, sex, height, weight, systolic blood pressure, diabetes mellitus, smoking, body mass index (BMI), lipid profile, social deprivation, SMI diagnosis, prescriptions for antidepressants and antipsychotics, and reports of heavy alcohol use.We developed 2 CVD risk prediction models for people with SMI: the PRIMROSE BMI model and the PRIMROSE lipid model. These models mutually excluded lipids and BMI. In terms of discrimination, from cross-validations for men, the PRIMROSE lipid model D statistic was 1.92 (95% CI, 1.80-2.03) and C statistic was 0.80 (95% CI, 0.76-0.83) compared with 1.74 (95% CI, 1.63-1.86) and 0.78 (95% CI, 0.75-0.82) for published Cox Framingham risk scores. The corresponding results in women were 1.87 (95% CI, 1.76-1.98) and 0.79 (95% CI, 0.76-0.82) for the PRIMROSE lipid model and 1.58 (95% CI, 1.48-1.68) and 0.77 (95% CI, 0.73-0.81) for the Cox Framingham model. Discrimination statistics for the PRIMROSE BMI model were comparable to those for the PRIMROSE lipid model. Calibration plots suggested that both PRIMROSE models were superior to the Cox Framingham models.The PRIMROSE BMI and lipid CVD risk prediction models performed better in SMI compared with models that include only established CVD risk factors. Further work on the clinical effectiveness and cost-effectiveness of the PRIMROSE models is needed to ascertain the best thresholds for offering CVD interventions.

Project description:ObjectivesTo determine the association of long-term use of antipsychotics with the risk of dyslipidaemia.DesignA hospital-based cohort study.SettingElectronic health record data of adult mental health inpatients in all 19 specialised psychiatric hospitals in Beijing from 1 January 2005 to 31 December 2018 was obtained.ParticipantsParticipants were inpatients aged 18 years or older with at least two admissions, excluding those with diagnosed dyslipidaemia and fatty liver at the first admission. We included 22 329 adult inpatients with no dyslipidaemia and fatty liver at baseline. The exposure was antipsychotics use, defined as antipsychotics prescription in the treatment procedures of medical record preceding dyslipidaemia diagnosis during the follow-up period. 15 930 (71.34%) had antipsychotics use, and 6399 (28.66%) never had antipsychotics use. We used the length of follow-up as proxy for the duration of antipsychotics exposure.Primary outcome measuresThe primary outcome was newly recorded dyslipidaemia defined by International Classification of Diseases, 10th Revision codes.Results4069 inpatients had newly recorded dyslipidaemia during 73 418.07 person-years, the incidence rate was 5.54 per 100 person-years. The incidence rate was 7.22 per 100 person-years in the exposed group and 3.43 per 100 person-years in the unexposed group. Results of multivariate analysis showed that antipsychotics use was associated with higher risk of dyslipidaemia (adjusted HR, aHR 2.41, 95% CI 2.24 to 2.59, p<0.001), regardless of the duration of antipsychotics use. Inpatients aged 18-29 years had higher risk of dyslipidaemia (aHR 3.38, 95% CI 2.77 to 4.12, p=0.004) than those in other age groups. Inpatients without hypertension had substantially higher risk of dyslipidaemia after antipsychotic exposure.ConclusionsBoth short-term and long-term antipsychotics use was associated with higher risk of dyslipidaemia among Chinese inpatients with mental illness. Dyslipidaemia was especially prominent in young patients and those without hypertension.

Project description:Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings. Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics. Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.

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Adiponectin Is Related to Cardiovascular Risk in Severe Mental Illness Independent of Antipsychotic Treatment.

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