Dataset Information

Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders.

ABSTRACT:

Objective

Low total cholesterol has been linked with adverse mental symptoms such as aggression and impulsivity in severe mental disorders (SMDs). This putative association may affect the clinician's decision making about cholesterol lowering in this patient group. Here, we investigated the associations between cholesterol levels, aggression, and impulsivity in a large representative sample of in- and outpatients with SMD.

Methods

Patients with schizophrenia- or bipolar spectrum disorders (N = 1 001) underwent thorough clinical characterization and blood sampling (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol). Aggression was characterized by the Positive and Negative Syndrome Scale Excited Component. Impulsivity was measured with the Barratt Impulsiveness Scale in a subsample of patients (N = 288). We used a multinomial logistic regression model to analyze the association between cholesterol and aggression and a multiple linear regression model to analyze the association between cholesterol and impulsivity, while controlling for confounders.

Results

We found no significant associations between cholesterol levels and aggression or impulsivity. There were no significant interactions between cholesterol and diagnostic group or inpatient versus outpatient status. Controlling for medication use, body mass index, alcohol or illicit substance use did not affect the results.

Conclusion

In this large sample of patients with schizophrenia- and bipolar spectrum disorders, we found no associations between cholesterol levels and aggression or impulsivity. This has clinical implications as patients with SMD are at increased CVD risk and currently undertreated with statins.

SUBMITTER: Hjell G

PROVIDER: S-EPMC7507477 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders.

Hjell Gabriela G Mørch-Johnsen Lynn L Holst René R Tesli Natalia N Bell Christina C Lunding Synve Hoffart SH Rødevand Linn L Werner Maren Caroline Frogner MCF Melle Ingrid I Andreassen Ole Andreas OA Lagerberg Trine Vik TV Steen Nils Eiel NE Haukvik Unn Kristin UK

Brain and behavior 20200717 9

<h4>Objective</h4>Low total cholesterol has been linked with adverse mental symptoms such as aggression and impulsivity in severe mental disorders (SMDs). This putative association may affect the clinician's decision making about cholesterol lowering in this patient group. Here, we investigated the associations between cholesterol levels, aggression, and impulsivity in a large representative sample of in- and outpatients with SMD.<h4>Methods</h4>Patients with schizophrenia- or bipolar spectrum d ...[more]

PMID: 32681586

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Project description:BackgroundImpulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders.MethodsImpulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions.ResultsImpulsivity was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms.ConclusionsWe report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.

Project description:BackgroundAlthough only a few patients with severe mental disorders (SMD) can commit violent behaviour in the community, violent behaviour aggravates the stigma towards patients with SMD. Understanding the subtypes of violent behaviour may be beneficial for preventing violent behaviour among patients with SMD, but it has rarely been studied.MethodsThis longitudinal study investigated 1914 patients with SMD in the community at baseline, and the follow-up period ranged from February 2021 to August 2021. The Barratt Impulsiveness Scale Version-11, the Buss-Perry Aggression Questionnaire, the Impulsive/Premeditated Aggression Scale, the Personality Diagnostic Questionnaire and the MacArthur Community Violence Instrument were used at baseline. The Modified Overt Aggression Scale was used to assess the occurrence of violent behaviour (outcome) during the follow-up period. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Latent class analysis was used to characterise the subtypes of patients with SMD who engaged in violent behaviour at follow-up.ResultsWe found that 7.2% of patients with SMD presented violent behaviour within six months in the community. Younger age (OR = 0.98, 95% CI = 0.96-1.00, p = 0.016) and no economic source (OR = 1.60, 95% CI = 1.10-2.33, p = 0.014) were risk factors for violent behaviour. Patients with SMD who engaged in violent behaviour could be classified into three subtypes: one class characterised by a history of violence and impulsivity, another class characterised by high levels of aggression and motor impulsivity, and the last class characterised by median cognitive impulsivity.ConclusionsSocio-demographic factors were risk factors for violent behaviour among patients with SMD, which could eliminate the discrimination toward this group. Impulsivity played a vital role in identifying the three subtypes of patients with SMD who engaged in violent behaviour. These findings may be helpful for the development of a personalised violence risk management plan for patients with SMD who commit violent behaviour in the community.

Project description:Suicide is major public health concern; one million individuals worldwide die by suicide each year of which there are many more attempts. Thus, it is imperative that robust and reliable indicators, or biomarkers, of suicide risk be identified so that individuals at risk can be identified and provided appropriate interventions as quickly as possible. Previous work has revealed a relationship between low levels of circulating cholesterol and suicide risk, implicating cholesterol level as one such potential biomarker, but the factors underlying this relationship remain unknown. In the present study, we applied a combination of bivariate polygenic and coefficient-of-relatedness analysis, followed by mediation analysis, in a large sample of Mexican-American individuals from extended pedigrees [N = 1897; 96 pedigrees (average size = 19.17 individuals, range = 2-189) 60% female; mean age = 42.58 years, range = 18-97 years, sd = 15.75 years] with no exclusion criteria for any given psychiatric disorder. We observed that total esterified cholesterol measured at the time of psychiatric assessment shared a significant genetic overlap with risk for suicide attempt (ρg = -0.64, p = 1.24 × 10-04). We also found that total unesterified cholesterol measured around 20 years prior to assessment varied as a function of genetic proximity to an affected individual (h2 = 0.21, se = 0.10, p = 8.73 × 10-04; βsuicide = -0.70, se = 0.25, p = 8.90 × 10-03). Finally, we found that the relationship between total unesterified cholesterol and suicide risk was significantly mediated by ABCA-1-specific cholesterol efflux capacity (βsuicide-efflux = -0.45, p = 0.039; βefflux-cholexterol = -0.34, p < 0.0001; βindirect = -0.15, p = 0.044). These findings suggest that the relatively well-delineated process of cholesterol metabolism and associated molecular pathways will be informative for understanding the neurobiological underpinnings of risk for suicide attempt.

Dataset Information

Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders.

Objective

Methods

Results

Conclusion

Publications

Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders.

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