Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr −/− mouse experimental model

Engel, Daiane F.; Oliveira, Jade de; Lopes, Jadna Bogado; Santos, Danúbia Bonfanti; Moreira, Eduardo Luiz Gasnhar; Farina, Marcelo; Rodrigues, Ana Lúcia S.; Brocardo, Patricia de Souza; de, Andreza Fabro

doi:10.1016/j.bbr.2016.05.029

Cited by 29 publications

(22 citation statements)

References 56 publications

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“…The aforementioned model studies associated hypercholesterolemia with depression in hypercholesterolemic mice via monoaminergic metabolism. Specifically, they reported increased monoamine oxidase (MAO) A and B activity in the hippocampus of mice [ 63 , 64 ]. Thus providing one possible reason why elevated levels of cholesterol are able to produce depression much like decreased levels are able to, but via independent mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

et al. 2018

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BackgroundCholesterol has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence about crucial requirement of neuron membrane cholesterol in the organization and function of the 5-HT1A serotonin receptor. For this, low cholesterol level has been reported to be associated with depression and suicidality. However there have been inconsistent reports about this finding and the exact relationship between these factors remains controversial. Therefore, we investigated the link between serum cholesterol and its fractions with depression disorder and suicide attempt in 467 adult subjects in Mexican mestizo population.MethodsPlasma levels of total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had undergone an episode of suicide attempt, and 206 healthy controls.ResultsA significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglyceride serum levels was observed in the groups of MDD patients and suicide attempt compared to those without suicidal behavior (p < 0.05). After adjusting for covariates, lower cholesterol levels were significantly associated with MDD (OR 4.229 CI 95% 2.555 – 7.000, p<.001) and suicide attempt (OR 5.540 CI 95% 2.825 – 10.866, p<.001)ConclusionsThese results support the hypothesis that lower levels of cholesterol are associated with mood disorders like MDD and suicidal behavior. More mechanistic studies are needed to further explain this association.

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Section: Discussionmentioning

confidence: 99%

“…In the future, it will be important to profoundly analyze the contradictory results reported with regard to cholesterol's role in depression. [ 63 , 64 ]. This would help to verify if cholesterol is, in fact, a viable biomarker for neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

et al. 2018

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“…A quite recent experimental study by Engel et al. 29 aimed to investigate this pathophysiological association and concluded that depressive-like behavior in hypercholesterolemic mice is accompanied by alterations in the monoaminergic metabolism, providing new evidence about the association between hypercholesterolemia and depression.…”

Section: Discussionmentioning

confidence: 99%

Gender-Based Differences in Anxiety and Depression Following Acute Myocardial Infarction

Šerpytis¹,

Navickas²,

Lukavičiūtė³

et al. 2018

Arquivos Brasileiros De Cardiologia

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BackgroundAmong patients with heart disease, depression and anxiety disorders are highly prevalent and persistent. Both depression and anxiety play a significant role in cardiovascular disease progression and are acknowledged to be independent risk factors. However, there is very little gender-related analysis concerning cardiovascular diseases and emotional disorders.ObjectiveWe aimed to evaluate depression and anxiety levels in patients suffering from myocardial infarction [MI] within the first month after the MI and to assess the association between cardiovascular disease risk factors, demographic indicators and emotional disorders, as well as to determine whether there are gender-based differences or similarities.MethodsThis survey included demographic questions, clinical characteristics, questions about cardiovascular disease risk factors and the use of the Hospital Anxiety and Depression Scale [HADS]. All statistical tests were two-sided, and p values < 0.05 were considered statistically significant.ResultsIt was determined that 71.4% of female and 60.4% of male patients had concomitant anxiety and/or depression symptomatology (p = 0.006). Using men as the reference point, women had an elevated risk of having some type of psychiatric disorder (odds ratio, 2.86, p = 0.007). The HADS-D score was notably higher in women (8.66 ± 3.717) than men (6.87 ± 4.531, p = 0.004). It was determined that male patients who developed depression were on average younger than those without depression (p = 0.005).ConclusionsWomen demonstrated an elevated risk of having anxiety and/or depression disorder compared to men. Furthermore, depression severity increased with age in men, while anxiety severity decreased. In contrast, depression and anxiety severity was similar for women of all ages after the MI. A higher depression score was associated with diabetes and physical inactivity, whereas a higher anxiety score was associated with smoking in men. Hypercholesterolemia was associated with both higher anxiety and depression scores, and a higher depression score was associated with physical inactivity in women.

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“…Nevertheless, changes in brain cholesterol have been implicated in numerous neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease, Parkinson's disease, and Niemann-Pick disease 44 . For example, hypercholesterolemia causes impairment of dopamine signaling and psychomotor dysfunction in mice [45][46][47][48] . Increases in cholesterol levels have been shown to elevate beta-amyloid precursor protein levels in cholesterol-enriched lipid rafts 49 and are associated with increased risk for AD 50 .…”

Section: Discussionmentioning

confidence: 99%

Structural basis of GIRK2 channel modulation by cholesterol and PIP₂

Mathiharan

Glaaser

Zhao

et al. 2020

Preprint

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Significance/Impact:• GIRK2 is one of the primary GIRK channels in brain. Characterization of cholesterol binding in GIRK2 provides new therapeutic sites for modulating these channels.• Many ion channels are modulated by cholesterol, but the molecular basis of this modulation has been elusive.• First cryoEM structures of pore-forming Kir alpha subunit. Word counts: Abstract (136) -Main text (3048)ABSTRACT G protein-gated inwardly rectifying potassium (GIRK) channels play important roles in controlling cellular excitability in the heart and brain. While structural data begin to unravel the molecular basis for G protein and alcohol dependent activation of GIRK channels, little is known about the modulation by cholesterol. Here, we present cryo-electron microscopy (cryoEM) structures of GIRK2 in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS), and PIP 2 . The structures and their comparison reveal that CHS binds near PIP 2 in lipid-facing hydrophobic pockets of the transmembrane domain (TMD). CHS potentiates the effects of PIP 2 , which stabilizes the inter-domain region and promotes the engagement of the cytoplasmic domain (CTD) onto the transmembrane region. The results suggest that CHS acts as a positive allosteric modulator and identify novel therapeutic sites for modulating GIRK channels in the brain.* is shown with a dashed square.

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Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr −/− mouse experimental model

Cited by 29 publications

References 56 publications

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

Gender-Based Differences in Anxiety and Depression Following Acute Myocardial Infarction

Structural basis of GIRK2 channel modulation by cholesterol and PIP₂

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Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr −/− mouse experimental model

Cited by 29 publications

References 56 publications

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

Hypocholesterolemia is an independent risk factor for depression disorder and suicide attempt in Northern Mexican population

Gender-Based Differences in Anxiety and Depression Following Acute Myocardial Infarction

Structural basis of GIRK2 channel modulation by cholesterol and PIP2

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Structural basis of GIRK2 channel modulation by cholesterol and PIP₂