Could depression actually be a form of

infectious disease?
Date:
November 14, 2014
Source:
Stony Brook University
Summary:
Major depressive disorder (MDD) should be re-conceptualized as an infectious disease, according to a professor. A
new article suggests that major depression may result from parasitic, bacterial, or viral infection. The article presents
examples that illustrate possible pathways by which these microorganisms could contribute to the etiology of MDD.

Major depressive disorder (MDD) should be re-conceptualized as an infectious disease, according to

Turhan Canli, PhD, Associate Professor of Psychology and Radiology at Stony Brook University. In a paper
published in Biology of Mood & Anxiety Disorders, Dr.Canli suggests that major depression may result
from parasitic, bacterial, or viral infection. He presents examples that illustrate possible pathways by
which these microorganisms could contribute to the etiology of MDD.

MDD remains highly prevalent disease with some 15 to 20 percent of the population experiencing MDD at some
point. Recurrence is common, and pharmacological treatments have not changed. Because the causal aspects of the
disease are not clearly defined, research to find causes remains paramount to help improve treatments.

"Given this track record of MDD, I propose reconceptualizing the condition as some form of infectious disease,"
said Dr. Canli, who is also Director of Stony Brook's SCAN Center, a member of the Program in Neuroscience, and
a Senior Fellow in the Center for Medical Humanities, Compassionate Care, and Bioethics. "Future research should
conduct a concerted effort search of parasites, bacteria, or viruses that may play a causal role in the etiology of
MDD."

In the paper, Dr. Canli presents three arguments why reconceptualizing MDD as an infectious disease may be a
fruitful endeavor.

First, he points out that patients with MDD exhibit illness behavior such as loss of energy, and that inflammatory
biomarkers in MDD also suggest an illness-related origin. Second, he describes evidence that parasites, bacteria and
viruses that infect humans in a way that alters their emotional behavior. Thirdly, Dr. Canli brings the notion of the
human body as an ecosystem for microorganisms and the role of genetics.

Based on these points, Dr. Canli suggests a major research step would be to conduct large-scale studies with
depressed patients, controls, and infectious-disease related protocols to determine the association or causal nature of
infectious disease and depression.

http://www.sciencedaily.com/releases/2014/11/141114124307.htm
Changes in single gene's action can control
addiction- and depression-related behaviors
Date:
November 10, 2014
Source:
Mount Sinai Medical Center
Summary:
A new DNA regulatory technique modifies the environment around a single gene to control gene expression and
behavioral consequences, researchers report.

Regulation of a single, specific gene in a brain region related to drug addiction and depression is
sufficient to reduce drug and stress responses, according to a study conducted at the Icahn School of
Medicine at Mount Sinai and published October 27 online in the journal Nature Neuroscience.

Related Articles

 Gene
 DNA microarray
 BRCA1
 Allele
 BRCA2
 Gene therapy

The Mount Sinai study focuses on epigenetics, the study of changes in the action of human genes caused, not by
changes in DNA code we inherit from our parents, but instead by molecules that regulate when, where and to what
degree our genetic material is activated.

Previous research has found links between epigenetic regulation and the diseases of drug addiction and depression,
in both human patients and animal models. Such regulation derives, in part, from the function of transcription
factors, specialized proteins that bind to specific DNA sequences and either encourage or shut down the expression
of a given gene.

Using mouse models of human depression, stress and addiction, the current research team introduced synthetic-
transcription factors into a brain region called the nucleus accumbens at a single gene called FosB, which has been
linked by past studies to both addiction and depression. They found that changes to this single gene brought on by
the transcription factors made the study mice more resilient to stress and less likely to become addicted to cocaine.

Found in every cell of the body, DNA contains genes and the instructions needed for an organism to develop and
survive. To carry out these functions, DNA sequences are converted into messages that "tell" cells which proteins to
make, dictating the specific function of a given cell. While all cells contain the DNA that codes for every gene, most
genes are not activated at all times. The expression of a given gene depends on the action of transcription factors,
proteins that regulate the structure of DNA within the cell, allowing some genes to be active and others to be
repressed. Transcription factors act by epigenetic mechanisms: chemically modifying either the DNA itself, or the
histone proteins packaged around DNA that change shape given the right signal to make stretches of DNA available
to the protein building machinery.
"Earlier work in our laboratory found that several transcription factors and downstream epigenetic modifications are
altered by exposure to drugs or to stress and that these changes, in turn, control gene expression," says Eric J.
Nestler, MD, PhD, Nash Family Professor, Chair of the Department of Neuroscience and Director of the Friedman
Brain Institute at the Icahn School of Medicine at Mount Sinai, who led the study. "But because such epigenetic
regulation occurs at hundreds or thousands of genes, until now it had been impossible to determine the difference
between the mere presence of an epigenetic modification and its functional relevance to neuropsychiatric disease."

To directly address this issue, Elizabeth A Heller, PhD, lead author oan the paper, developed an innovative method
to control epigenetic regulation of FosB. Dr. Heller introduced synthetic transcription factors called Zinc Finger
Proteins (ZFPs), designed to target only a single gene out of 20,000, by incorporating them into a virus and injecting
that virus into the reward-related brain region. Study results indicate that upon binding to that one gene, the FosB-
ZFPs modified histones in the vicinity of the FosB gene, in order to either activate (turn on) or repress (turn off)
expression.

Expression of the FosB gene in nerve cells is both necessary and sufficient for drug and stress responsiveness in
mice. In particular, activation of FosB expression is linked to increased sensitivity to drugs and to resilience to stress
and is altered by exposure to such stimuli in the brains of mouse models and in drug-addicted and depressed human
patients.

"While drug addiction and depression are hereditary diseases that regulate gene expression in the brain, the field has
yet to uncover relevant mutations in gene sequence that underlie these disorders," says Dr. Heller. "Therefore, we
focused on changes in gene structure to probe the mechanism of action of such changes in drug and stress sensitivity
Our data is a critical first step towards developing novel therapeutics to combat these neuropsychiatric diseases. In
addition, the use of engineered transcription factors has broad implications outside of neuroscience because
epigenetic gene regulation underlies many diseases, including most forms of cancer."