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Metabolism to Blame for Resistance to Antidepressants: Study

For many patients of depression who do not respond to conventional methods of treatment, the reason
could lie in their metabolism, says a recent study. The researchers from the Rockefeller University in New
York and the Karolinska Institutet, Sweden observed that depression is often marked by abnormalities in
the body, such as elevated blood sugar level. Thus, depression and metabolism are intrinsically entwined,
the researchers said.
Many patients who suffer from depression do not respond to conventional antidepressant treatment, so
we set out to examine the molecular changes that might explain this resistance, said first author of the
study Benedetta Bigio, a bioinformatics specialist in Bruce McEwens Rockefeller lab. She said that their
findings established a link between the activity of energy metabolism genes within one part of the brain
to a predisposition to depression and resistance to treatment.
Rats and mice with LAC developed depression-like symptoms
There are no known
causes why depression
is accompanied by
metabolic deformities,
like abnormal levels of
sugar and triglycerides,
a type of fat in the
blood. However, the
researchers managed
to have established a
link between the two
by studying collated
data on acetyl carnitine
produced naturally by
the brain, liver and
kidneys. They observed
that when given to rats
and mice, they rapidly
developed depression-like symptoms by enhancing harmful imbalances in the glutamate signaling system
in the brain.
They used those rats whose certain behaviors were akin to symptoms of depression in humans, such as
abhorrence of sweet solutions which are otherwise preferred by normal rats. The rats produced extremely
low levels of LAC, but they showed improvement in their behavior when given the compound.
Meanwhile, the researchers have also started to look for abnormalities in natural LAC levels of depressed
people. These LAC studies have opened a glut of avenues on to the neurobiology of depression treatment.
Resistance to treatment

In order to investigate the reason behind resistance to treatment, the researchers exposed the rats to
stressful situations in which the rodents were made to swim for a good 15 minutes. Next day, the rats
were tested with a shorter swim test. Those with successful LAC treatment swam more, while others
exhibited depression-like symptoms, such as immobility predicting an ineffective treatment.
Probing further into why such a discrepancy existed among the rats led the researchers to a region in the
brain within each rats hippocampus, called the ventral dentate gyrus (vDG), which is crucial for stress
When the genes were sequenced within this region, the researchers found differences in many genes
responsible for regulating metabolism among rats that responded well to the treatment, the ones that
didnt, and the untreated ones.
Clues from blood
The researchers found 27 genes that seemed to be involved in resistance to the low-dose LAC treatment
and hence, to antidepressants. The genes included those responsible for the bodys ability to use fatty
acids, as well as to respond to insulin.
If these findings hold true in humans, it is possible that altered levels of blood sugar or insulin may serve
as markers that could help doctors determine which patients are likely to do well on an antidepressant
before prescribing it, said Carla Nasca, a senior author and postdoc in the lab.
The research suggested that the role of vDG in energy metabolism should be taken into consideration in
developing new treatments for depression.
Recovery roadmap
Depression is a treatable mental health condition, which when left untreated can complicate matters.
Many are leading a healthy life post treatment intervention for depression. If a loved one is struggling
with depression and you are looking for depression treatment centers in Arizona, you can get in touch
with the Depression Helpline Arizona. You may call at our 24/7 helpline number 866-233-3895 for
immediate assistance. Our depression helpline chat can guide you to the best depression treatment
center in your vicinity.

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