Relationship among low cholesterol levels, depressive symptoms, aggression, hostility, and cynicism

ArticleinJournal of Clinical Lipidology 7(3):208-216 · May 2013with16 Reads
Impact Factor: 3.90 · DOI: 10.1016/j.jacl.2013.01.004 · Source: PubMed

BACKGROUND: Treatment guidelines for lipids have become increasingly more aggressive. However, naturally low or therapeutically reduced cholesterol levels may be associated with adverse psychological health symptoms, including depression, aggression, and hostility. OBJECTIVE: To examine relationships between low total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels and measures of psychosocial status among middle-aged adults. METHODS: A total of 1995 subjects enrolled in the Heart Strategies Concentrating on Risk Evaluation study with data on TC, LDL cholesterol, and self-reported ratings of psychological health were evaluated. To quantify ratings of depression, aggression, cynicism, and hostility, psychological measures included the Center for Epidemiologic Studies Depression Scale (CES-D) and Cook-Medley Hostility Inventory. RESULTS: Of 1995 participants, 25.1% were taking a lipid-lowering agent at baseline. Mean CES-D scores were similar between participants with low (<150 mg/dL) versus greater (≥150 mg/dL) TC and low (<100 mg/dL) versus higher (≥100 mg/dL) LDL cholesterol. However, among 22 participants with LDL cholesterol <70 mg/dL, the prevalence of clinically significant depressive symptomatology (CES-D score ≥16) was 31.8% compared with 12.1% in the remaining cohort (P = .005). In multivariable analysis, low LDL cholesterol (<100 mg/dL) was associated with cynicism (partial r = -0.14, P = .02) and hostility (partial r = -0.18, P = .004), but only in the subgroup of white subjects currently taking lipid-lowering medications. Low LDL cholesterol (versus non-low) was associated with greater aggression scores but only among participants currently taking psychiatric medications (3.4 ± 1.7 vs 2.8 ± 1.5, P = .02). CONCLUSIONS: Our data indicate mixed evidence for independent relationships between low total and LDL cholesterol levels and impaired psychological health.

    • "been associated with verbal aggression [Table III; Troisi and D'Argenio, 2006]. Similarly, for other lipoproteins, such as HDL-C and LDL-C, low levels have also been associated with both total aggression [Table I; Troisi and D'Argenio, 2006; Sahebzamani et al., 2013] and verbal aggression [Table III; Troisi and D'Argenio, 2006]. All these findings support the hypothesis that the association of low CNS cholesterol/lipoprotein levels with increased aggression is mediated through impaired synaptic 5HT transport. "
    [Show abstract] [Hide abstract] ABSTRACT: Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using examples from the aggression literature and psychiatric metabolomics studies, we argue that a better understanding of aggression would benefit from a more holistic approach such as provided by metabolomics.
    No preview · Article · Feb 2016 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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    • "However, in 2012, the U.S. Food and Drug Administration (FDA) approved a safety warning on the cognitive side effects associated with statins [1] . Psychological adverse events may include behavioral alterations such as irritability , impulsiveness and hostility [2][3][4][5][6][7], depression [8], as well as cognitive and memory impairments [9][10][11][12]. Nevertheless, the mechanisms of neuropsychiatric adverse effects have not been fully understood yet. "
    [Show abstract] [Hide abstract] ABSTRACT: Simvastatin and other statins (HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors) are extensively used in clinical practices and are very effective in decreasing serum low-density lipoprotein cholesterol. However, their effect on cholesterol synthesis in central nervous system and its behavioral consequences have not been fully understood yet. We have studied selected biologic traits potentially affected by statin treatment - serotonin (5-HT) uptake in platelets, membrane microviscosity in erythrocytes, cholesterol level in the brain (amygdala; hippocampus and prefrontal cortex), as well as behavioral changes in an elevated plus maze and open field test in male Long-Evans rats, which were treated by simvastatin (30mg/kg per day) for 2 or 4weeks. We demonstrated: 1) a decrease in both serotonin transporter (SERT) activity and membrane microviscosity after treatment with simvastatin, 2) lower cholesterol content in all tested brain regions in animals from the simvastatin treated group, and 3) longer time spent in the open arms and a higher number of entrances to the closed arms in the elevated plus maze by animals from the simvastatin group compared to animals from the control group, but no differences in behavior in the open field test. Taken together, our results confirmed complex alterations, including behavioral changes, after the cholesterol lowering treatment. Furthermore, we discuss the possibility that the behavioral changes, traditionally interpreted as an anxiolytic effect, may be interpreted as increased impulsivity. We also confirmed that such behavioral changes may be attributed to changes in serotonergic neurotransmission.
    Full-text · Article · Feb 2016 · Physiology & Behavior
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    • "For example, lower cholesterol levels have been found to significantly predict impulsivity (New et al., 1999; Ormiston et al., 2003; Pozzi et al., 2003), greater risk for internalizing problems including conduct disorder and antisocial personality disorder (Boston et al., 1996; Kaplan et al., 1997; Sutin et al., 2010), and depression (Ormiston et al., 2003; Steegmans et al., 2000; Tedders et al., 2011). However, the observed association between lower cholesterol levels and greater prevalence of depressive symptoms remains far from conclusive, with additional studies finding no significant association (Apter et al., 1999; Freedman et al., 1995; Pozzi et al., 2003; Repo-Tiihonen et al., 2002; Sahebzamani et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Background Low cholesterol levels have been found to be associated with a wide range of behavioral problems, including violent and criminal behavior, and a wide range of psychological problems including impulsivity, depression, and other internalizing problems. The casual mechanisms underlying these associations remain largely unknown, but genetic factors may play a role in the etiology of such associations as previous research has found significant genetic influence on cholesterol levels and various deleterious behavioral and psychological outcomes. The current study addressed this existing gap in the literature by performing a genetically sensitive test of the association between cholesterol levels and various outcomes including levels of self-control, depressive symptoms, anger expression, and neuroticism. Methods DeFries–Fulker (DF) analysis was used to analyze data from 388 twin pairs nested within the Survey of Midlife Development in the United States (MIDUS). Results The results of the genetically informed models revealed that high-density lipoprotein (HDL) cholesterol levels were negatively and significantly associated with depressive symptoms, had a marginally significant effect on neuroticism, and a nonsignificant effect on both anger expression and self-control. Limitations The findings may not extrapolate to the larger population of American adults since the subsample of twins with cholesterol information may not be nationally representative. Conclusions Genetic influences play a significant role in the association between cholesterol levels and various deleterious outcomes and failing to control for these influences may result in model misspecification and may increase the probability of detecting a significant association when one does not actually exist.
    Full-text · Article · Jan 2014
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