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Study links amyloid beta, serotonin to predicting late-life depression and response to antidepressants

A breakthrough study by Johns Hopkins University researchers may aid doctors in determining which elderly patients will respond best to antidepressants and which may be at additional risks for memory decline.

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According to the American Geriatrics Society’s Health in Aging Foundation, late-life depression is associated with greater risk for cognitive decline and between 1% and 2% of American adults over age 65 have major depression. (Stock photo)

Johns Hopkins Medicine researchers have released a study that identified a pattern they believe predicts late-life depression and response to antidepressants.

The study found that an accumulation of amyloid beta proteins, associated with cognitive decline later in life, coupled with a reduction of serotonin -- a naturally occurring substance that functions as a neurotransmitter to carry signals between nerve cells -- has been found to provide researchers with a diagnostic tool that could aid in predicting best responses to antidepressants. It will also likely identify who may be at risk for memory decline.

As part of a series of studies aimed at imaging the human brain to detect early signs of aging and cognitive decline, researchers say their findings — published in the journal of Translational Psychiatry — suggest that the more a person expresses accumulation of amyloid beta proteins and a decrease in serotonin, the more severe the depression might be.

“What’s unique about PET scans is that they enable us to look at chemicals localized in the living brain in relation to amyloid beta proteins associated with memory loss,” said Gwenn Smith, Ph.D. and Richman professor of Alzheimer’s and Related Dementias in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine .

Smith added, “This was fundamental for our work because we were able to test hypotheses from past research on mice with dementia for our imaging study in the human brain.”

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Late-life depression, a very common psychiatric disorder found in advanced aged people, refers to a major depressive episode in some cases for the first time. According to the American Geriatrics Society ’s Health in Aging Foundation, late-life depression is associated with greater risk for cognitive decline and between 1% and 2% of American adults over age 65 have major depression. They report that more women than men have reported symptoms, but despite the data they believe that the numbers may actually be higher as older adults are less likely than younger people to admit, or even realize, they are depressed.

As part of the Johns Hopkins Medicine study, researchers analyzed data collected from 40 participants over age 60 who were evenly split between men and women. Of the participants, 20 were unmedicated and were experiencing late-life depression without bipolar or psychotic symptoms. All participants had a series of screenings, including physical and neurological examinations, laboratory and toxicology testing, and psychiatric and neuropsychological evaluations. They also were given a standard Mini-Mental State Exam — a test used to identify cognitive impairment — as well as a psychiatric interview.

The data was then compared with those from a control group of 20 healthy, nondepressed older adults and the findings could be a breakthrough.

In a series of tests using radiotracers — short-acting radioactive molecules that “light up” in a PET scan — the researchers looked at both sets of participants for the amounts of amyloid beta proteins and serotonin transporter, a protein that regulates the amount of serotonin in nerve cells, and what they found was when analyzed using a mathematical formula it was identified that a pattern showed how amyloid beta protein accumulation related to serotonin transporters.

The pattern, Smith says, was significantly higher in the late-life depression group, indicating that a decrease in serotonin transporters could be directly linked to higher levels of amyloid beta proteins in different areas of the brain — and in turn, to depression.

The research also examined the relationship between the mathematically derived pattern and the severity of depression, finding that for all study participants a correlation between decreased serotonin and increased amyloid beta protein patterns were seen — with the greater deviance being found in those expressing depressive symptoms.
Lower serotonin levels, say the researchers, were previously linked to depression as selective serotonin reuptake inhibitors — antidepressants that increase the amount of the brain chemical to a more normal level — have been prescribed for treatment of major depressive disorders, anxiety disorders and other psychological conditions.

“Our work reinforces the role of serotonin in late-life depression and the proteins associated with memory loss,” Smith said. “Our aim is to use this as a diagnostic tool to predict who will respond best to antidepressants and who may be at risk for memory decline.”

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