Mechanistic insights into how a statin-based drug stifles anxiety and depression: Simvastatin, a lipid-lowering agent, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene, 26/September/2018, 11.22 pm

Introduction: What they say: 

A study from Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA; and Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA shows that “Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice.” This research paper was published, in the May 2017 issue of the journal “Nature communications” [One of the best research journals in Metabolism with an I.Fs of ], by Prof.Hochedlinger K, Ryan M. Walsh and others.

What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Mechanistic insights into how a statin-based drug stifles anxiety and depression:  Simvastatin, a lipid-lowering agent, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene

From the significance of the study to Public health relevance:

Given that: (1) one in three suffer from anxiety-related disorders worldwide; (2) nearly 12% of world population suffer from anxiety-related disorders in any given year; (3) 5-30% of people suffer from anxiety at some point in their lives; (4) 40 million adults in the US suffer from anxiety disorders; (5) nearly $42 billion a year spent in the US to treat anxiety disorders; (6) anxiety and depression are associated with higher rate of morbidity; (7) the percentage of people who suffer from anxiety is more from developed countries than from developing countries, while the opposite is true with depression; and (8) the global economic cost spent in the treatment of anxiety and depression occupies the significant portion of health care bill, there is an urgent need to find: (i) a way to cure  long term anxiety and depression that are leading to a number of serious health complications; (ii) a way to induce resilience to anxiety and depression; (iii) a cheaper alternative to the existing expensive drugs; and (iv) a side-effect-free Natural product-based drug that not only alleviates, but also cures anxiety and depression.

What is known?

Mutations in PHF8, a histone demethylase, has been shown to result in cognitive defects and cleft lip/palate. However, its role in other physiological processes remains to be determined.

Prof.Hochedlinger Konrad’s research team has recently shown that knocking out PHF8/JMJD1.2 in mice results in: (1) no cognitive impairment; (2) up-regulation of serotonin receptors Htr1a and Htr2; (3) normalization of Serotonin signalling; and (4) resistance to stress-induced anxiety- and depression-like behaviour, suggesting that inhibiting the expression of PHF8 may aid in the treatment of anxiety and depression.

From research findings to Therapeutic opportunity:

One of the best selling lipid-lowering agent Simvastatin has also been shown to attenuate anxiety and depression. However, the mechanism of action remains far from clear.

This study suggests that Simvastatin, by increasing the expression of its target gene, it may decrease the expression of PHF8. Thereby, it may: (1) increase the expression of genes involved in serotonin signaling such as Htr1a and Htr2a; (2) normalize serotonin signaling; (3) promote resistance to stress-induced anxiety, and (4) heighten resistance to stress-induced depression-like behavior. Thus, pharmacological formulations encompassing “Simvastatin or its analogs, either alone or in combination with other drugs, may be used to treat anxiety and depression; and promote resistance to depression- and anxiety-like behaviors (fig 1).[easy_payment currency=”USD”]

Given the mechanistic basis of how Simvastatin may function as an anti-depressive agent,  physicians and psychologists may consider: treating their needy patients with Simvastatin or beginning a clinical trial.  

Figure1. Mechanistic insights into how Simvastatin decreases PHF8 levels, increases serotonin receptors Htr1a and Htr2a levels and promotes resistance to depression-like and anxiety-like behaviors

Figure 2. The chemical structure of Simvastatin. Simvastatin functions as an anti-depressive agent through up-regulation of its target genes

Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

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Undisclosed mechanistic information: How Simvastatin decreases PHF8 levels, increases serotonin receptors Htr1a and Htr2a levels and promotes resistance to stress-induced anxiety and depression.

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References:

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Citation: Boominathan, L., Mechanistic insights into how a statin-based drug stifles anxiety and depression:  Simvastatin, a lipid-lowering agent, decreases PHF8 levels, increases the expression of serotonin receptors Htr1a and Htr2a, and promotes resistance to stress-induced -anxiety and -depression, via down-regulation of its target gene, 26/September/2018, 11.21 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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