Faulty Gene Linked to Depression and Cardiovascular Disease

Summary: A faulty gene linked to cardiovascular disease and metabolic conditions could be a new target in the fight against depression.

Source: University of Adelaide.

Researchers at the University of Adelaide say they may have discovered a new target in the fight against depression: a faulty gene that is linked to cardiovascular and metabolic conditions.

A team led by the University of Adelaide’s Discipline of Psychiatry has reviewed and attempted to replicate the findings of the growing body of research showing the types of genes expressed in the brain and surrounding tissues during depression.

The findings – published online ahead of print in the journal Neuroscience & Biobehavioral Reviews – have supported multiple theories of the underlying genetic causes of depression, and have highlighted one gene that until now has gone under the radar in relation to mood disorders.

“Depression is much more complex than most people think, and it includes dysfunction at multiple biological levels, from genes to brain regions, and blood circulating through the body,” says Professor Bernhard Baune, Head of Psychiatry at the University of Adelaide and lead author of the paper.

“The state of depression can also change over time, it goes through various phases and it may present with a large range of symptoms.

“In those circumstances, it shouldn’t be surprising that while there’s a growing body of research investigating the underlying genetics of depression, so far there have been inconsistent findings in various studies throughout the world.”

The team examined and re-analyzed in a novel way research covering 16 brain regions and five cell types from the peripheral nervous system. Across the body of work, they identified 57 differently expressed genes in the brain and 21 in the peripheral tissues.

“What we saw was overlap in genetic expression between the brain and peripheral tissues that strongly implicated a link between depression and cardiovascular disease,” Professor Baune says.

“Out of this, we identified the gene PXMP2 as a potential candidate for further investigation.”

PXMP2 plays a role in the permeability of microbodies called peroxisomes, which break down fatty acids in the body and convert them to energy.

PXMP2 plays a role in the permeability of microbodies called peroxisomes, which break down fatty acids in the body and convert them to energy. NeuroscienceNews.com image is for illustrative purposes only.
PXMP2 plays a role in the permeability of microbodies called peroxisomes, which break down fatty acids in the body and convert them to energy. NeuroscienceNews.com image is for illustrative purposes only.

“PXMP2 is robustly expressed during depression. However, to the best of our knowledge, neither this faulty gene in particular nor its related functions in metabolism have ever been investigated in relation to mood disorders of any kind,” Professor Baune says.

“With the shared pathways between cardiovascular disorders and depression, we suggest that faulty regulation of the PXMP2 gene may play a role in depressive disorders via specific metabolic pathways.”

Professor Baune says he doubts that one single gene has the biggest role to play.

“Our research on genetic networks also showed support for the wide range of theories that different genes may play a role in depression, including those involved in regulation of serotonin, melatonin and the immune system, among many others. Even so, PXMP2 represents a very strong, new target for future research programs,” he says.

About this genetics research article

Funding: This research has been funded by the National Health and Medical Research Council (NHMRC).

Source: Bernhard Baune – University of Adelaide
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Differential gene expression in brain and peripheral tissues in depression across the life span: A review of replicated findings” by Liliana G. Ciobanu, Perminder S. Sachdev, Julian N. Trollor, Simone Reppermund, Anbupalam Thalamuthu, Karen A. Mather, Sarah Cohen-Woods, and Bernhard T. Baune in Neuroscience and Biobehavioral Reviews. Published online August 24 2016 doi:10.1016/j.neubiorev.2016.08.018

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]University of Adelaide “Faulty Gene Linked to Depression and Cardiovascular Disease.” NeuroscienceNews. NeuroscienceNews, 13 September 2016.
<https://neurosciencenews.com/depression-genetics-cardiovascular-disease-5030/>.[/cbtab][cbtab title=”APA”]University of Adelaide (2016, September 13). Faulty Gene Linked to Depression and Cardiovascular Disease. NeuroscienceNew. Retrieved September 13, 2016 from https://neurosciencenews.com/depression-genetics-cardiovascular-disease-5030/[/cbtab][cbtab title=”Chicago”]University of Adelaide “Faulty Gene Linked to Depression and Cardiovascular Disease.” https://neurosciencenews.com/depression-genetics-cardiovascular-disease-5030/ (accessed September 13, 2016).[/cbtab][/cbtabs]


Abstract

Differential gene expression in brain and peripheral tissues in depression across the life span: A review of replicated findings

There is a growing body of research investigating the gene expression signature of depression at the genome-wide level, with potential for the discovery of novel pathophysiological mechanisms of depression. However, heterogeneity of depression, dynamic nature of gene expression patterns and various sources of noise have resulted in inconsistent findings. We systematically review the current state of transcriptome profiling of depression in the brain and peripheral tissues with a particular focus on replicated findings at the single gene level. By examining 16 brain regions and 5 cell types from the periphery, we identified 57 replicated differentially expressed genes in the brain and 21 in peripheral tissues. Functional overlap between brain and periphery strongly implicates shared pathways in a comorbid phenotype of depression and cardiovascular disease. The findings highlight dermal fibroblasts as a promising experimental model for depression biomarker research, provide partial support for all major theories of depression and suggest a novel candidate gene, PXMP2, which plays a critical role in lipid and reactive oxygen species metabolism.

“Differential gene expression in brain and peripheral tissues in depression across the life span: A review of replicated findings” by Liliana G. Ciobanu, Perminder S. Sachdev, Julian N. Trollor, Simone Reppermund, Anbupalam Thalamuthu, Karen A. Mather, Sarah Cohen-Woods, and Bernhard T. Baune in Neuroscience and Biobehavioral Reviews. Published online August 24 2016 doi:10.1016/j.neubiorev.2016.08.018

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  1. I should think that by now, the “biological least common denominator”, i.e., the most parsimonious connection between 1) cardiovascular disease (in the form of making “pits, pockmarks, and nooks and crannies” on the inside of blood vessels for LDL to “gunk up” in; and 2) the CNS anomalies in normal allostatic dynamics underlying major depressive disorder is that of a pro-inflammatory cytokine storm”…whether it has a genetic component or not. The first domino to fall and initiate such a phenomenon is typically abnormal TNF-alpha dynamics http://mobile.nytimes.com/blogs/well/2016/08/04/arthritis-drug-may-have-benefits-against-alzheimers
    ——–
    Perispinal Delivery is a direct route of drug administration for delivery of a compound to the brain; the area in which the injection is performed (known as vertebral venous plexus), is a bi-directional system; it can be conceptualized as an interface between the lymphatic system and the ventricular system of the Central Nervous System (CNS).

    A single injection into the vertebral venous plexus followed by Trendelenburg positioning directs the compound through the choroid plexus and into the ventricles. Therefore, this injection, which is subcutaneous and performed peripherally, is non-invasive.

    The ventricles intimately communicate with the brain parenchyma. The fact that compounds delivered via this route have been shown to reach neurons in the CNS and exert an effect on neuronal functioning demonstrates/indicates how PERIPHERAL administration of a ligand known to be incapable of Blood-Brain-Barrier penetration, generates a signal, which is neuronally communicated throughout the brain parenchyma.

    Amazingly, although the first suggestions of this were discovered via serendipity, in the late 1800’s when perispinal injection of the local anesthetic cocaine HCl was found to, indeed exert relevant pharmacodynamic activity in CNS…it is not until very recently, that Pharmacology texts have begun, in the chapter describing administration routes, to describe it.

    My guess is that some less prestigious texts fail to list it even as we discuss it.

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