Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice

Tang, Congrong; Yu, Xu-Ben; Zhang, Haina; Cao, Yancheng; Yang, Fan; Xu, Lei-Mei; Sun, Ryan; Ye, Zi; Wang, Ye-Xuan; Jin, Liang

doi:10.1159/000503865

Cited by 10 publications

(5 citation statements)

References 54 publications

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“…Emerging evidence from animal studies suggests that lovastatin and atorvastatin may enhance the proteolytic cleavage of pro-BDNF [ 119 – 121 ], BDNF hippocampal concentrations [ 112 , 122 ] and α7nAChR-mediated activation of the PI3K/Akt-BDNF pathway [ 123 ], with a consequent positive influence on depressive-like behaviour. Agmatine and imidazoline receptors, whose function broadly relates to BDNF neurogenesis, NMDA neuroprotection and monoamine regulation, have also been involved in the antidepressant-like effect of simvastatin and atorvastatin [ 124 ].…”

Section: Resultsmentioning

confidence: 99%

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

et al. 2023

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Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins’ putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins’ effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins’ antidepressant effects while also improving our understanding of the physiopathological basis of depression.

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Section: Resultsmentioning

confidence: 99%

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

et al. 2023

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“…Aside from these broadly neuroprotective effects, statins may also promote hippocampal neuroplasticity, especially implicated in the pathophysiology of depression and response to antidepressant treatment ( 55 ), through the increase of brain-derived neurotrophic factor (BDNF) via direct ( 53 , 56 ) and tissue plasminogen activator (tPA) ( 57 – 59 ) and agmatine/imidazoline ( 60 ) pathways. However, higher hippocampal BDNF has also been associated to increased anxious behaviour in rats treated with statins ( 61 ).…”

Section: Introductionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

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Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

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“…2019; Yu et al . 2019) or lovastatin (Tang et al . 2020) were shown to attenuate the depressive behavior in rodents.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical effect of statin medication on depressive disorder in first-ever ischemic stroke patients: possible antidepressant-like effect prestroke and the opposite in continuous medication poststroke

Guo

Zhou

et al. 2021

International Clinical Psychopharmacology

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Poststroke depression (PSD) is the most frequent complication after stroke. Statin is a widely used prophylactic for stroke. However, some researchers reported that poststroke statin may lead to a depressive change in stroke patients. We aimed to study the effect of different statin medication timing especially prestroke timing on PSD to adopt appropriate intervention around stroke. Patients with first-ever ischemic stroke were consecutively observed from January 2012 to June 2017. They were grouped by different initiation time of statin treatment. The follow-up endpoints were set to: (1) diagnosis of PSD within 1-year and (2) censor data. Cox regression model adjusted for confounding factors was performed. A total of 1571 patients were included in the analyses, among which 210 (13.4%) were comorbided with PSD, and the median time of the course was 30 (14-98) days. The patients who received both pre-and poststroke statin treatment had 1.99 times (P = 0.037) the hazard faced by patients who did not receive that medication. In contrast, sole statin pretreatment may have the tendency to reduce the risk of PSD. Our findings provide the primary results for the prestroke statin medication. The initiation timing of continuous regular statin treatment ahead of ischemic stroke could have a correlation with a higher risk of PSD.

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Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice

Cited by 10 publications

References 54 publications

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

Paradoxical effect of statin medication on depressive disorder in first-ever ischemic stroke patients: possible antidepressant-like effect prestroke and the opposite in continuous medication poststroke

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