Brain Drain

by Women's Brain Health Initiative:

According to the Canadian Mental Health Association, depression (also known as clinical or major depression) is a mood disorder that will affect one in eight Canadians at some point in their lives. On a global scale, depression is recognized as the leading cause of disability worldwide, impacting over 300 million people.

Although the symptoms of depression may be prevalent among older adults, it is important to understand that depression is not a typical part of aging. 

Studies are now showing, however, that individuals suffering from depression (at any age) may be accelerating the age of their brains, and making themselves more susceptible to other symptoms of ailing brain health.

To learn more about how depression impacts the brain, researchers at the Yale School of Medicine used a new brain-scanning technique to examine the brains of 20 participants – half of which were diagnosed with clinical depression and the other half of which were deemed healthy after undergoing a comprehensive psychiatric assessment.

Research in the past has been dependent upon brain-scanning tools such as MRI (magnetic resonance imaging) scans, which can map out regions of the brain, but do not allow researchers to conduct an active review of synaptic activity (i.e. the connecting force sending information between neurons, cells, and muscles) in living humans.

With this new brain-scanning technique, an individual’s synapses can be mapped out using a radioactive molecule (developed by the research team) that binds to proteins found only in synapses. Researchers can then track that molecule and observe where it gathers in order to determine where synaptic density (i.e. the number of connections in the brain) is higher or lower.In this study, the researchers found that synaptic density begins to thin out ten years earlier in individuals with depression – namely, at the age of 40, as opposed to 50.

According to the lead author of the study, Dr. Irina Esterlis, this could result in “earlier memory loss, brain fog, slowing speech, and even earlier onset of age-related diseases like Alzheimer’s.” Although small scale, this study delivered the results that the researchers had expected: synapse density was 2% to 3% lower in individuals with chronic depression.

Dr. Esterlis believes that this research could bring us closer to understanding why women, who are twice as likely than men to suffer from depression, have triple the risk of developing Alzheimer’s disease compared to their male counterparts.

She added that “it could also help us develop and approve drugs to target the hippocampus, the brain region affected in both disorders.”

In another recent study, published in May 2018 in the American Academy of Neurology, researchers found a link between depression in older adults and memory problems. The study also suggested that those with greater symptoms of depression may have structural differences in the brain (compared to those without symptoms), including smaller brain volume and a 55% greater chance of small vascular lesions in the brain.

“Since symptoms of depression can be treated, it may be possible that treatment may also reduce thinking and memory problems,” said study author Dr. Adina Zeki Al Hazzouri of the University of Miami Miller School of Medicine in Florida.“

With as many as 25% of older adults experiencing symptoms of depression, it’s important to better understand the relationship between depression and memory problems.”

Psychologists at the University of Sussex have likewise found a link between depression and an acceleration of the rate at which the brain ages. Lead authors of the study, Dr. Darya Gaysina and Amber John from the EDGE (Environment, Development, Genetics and Epigenetics in Psychology and Psychiatry) Lab at the University of Sussex, are calling for greater awareness of the importance of supporting mental health to protect brain health in later life.

Although researchers have previously reported that individuals with depression or anxiety have an increased risk of dementia as they age, this was the first study to provide comprehensive evidence for the effect of depression on decline in overall cognitive function, in a general population

.As Dr. Gaysina observed, our populations are aging at a rapid rate, and the number of individuals living with decreasing cognitive abilities and dementia is expected to grow substantially over the next thirty years.

“Our findings should give the government even more reason to take mental health issues seriously and to ensure that health provisions are properly resourced,” said Dr. Gaysina.

“We need to protect the mental wellbeing of our older adults and to provide robust support services to those experiencing depression and anxiety in order to safeguard brain function in later life.”

This study was published in the May 2018 issue of Psychological Medicine.

SYMPTOMS VARY

Depression changes the way that individuals feel, leaving them with mental and physical symptoms for long periods of time. The symptoms can look quite different from person to person, and certain groups of people are at a greater risk of suffering from depression, including:

  • Youth: more than 250,000 Canadian youth (6.5% of individuals between the ages of 15 and 24) experience major depression each year;

  • Older adults: approximately 7% of seniors exhibit some symptoms of depression. This can be triggered by the loss of a spouse, a shrinking circle of friends, or the onset of an illness. It is also much more common among seniors living in care homes or who are suffering from dementia; and

  • Women: depression is diagnosed twice as much in women as it is in men. Some reasons for this difference may include life-cycle changes, hormonal changes, higher rates of childhood abuse or relationship violence, and social pressures. Since women are usually more comfortable seeking help for their health-related issues than men, it is possible that depression amongst men is underreported.

Depression is very treatable. In fact, with the right treatment, 80% of individuals with depression feel better or no longer experience symptoms at all.

SEX DIFFERENCES IN DEPRESSION

From early adolescence through adulthood, women are twice as likely as men to experience depression. A recent study, conducted by Dr. Naomi Eisenberger and colleagues, posits one reason why this may be the case, particularly for the kinds of depression that may be inflammatory in nature.

The researchers discovered that inflammation induces anhedonia in women, but not in men. Anhedonia is a common feature of depressive disorders, and is defined behaviourally by persistently low motivation and inability to experience pleasure or joy in things or activities.

In this study, over 100 healthy men and women were randomly assigned a placebo or a low-dose endotoxin, a substance that increases inflammation in a safe, time-limited manner. The researchers then measured activity in the reward region of the brain (i.e. the ventral striatum), while the participants completed a task in which they anticipated monetary reward.

The researchers found that women with greater inflammatory responses showed less brain response in anticipation of potential rewards, but the relationship was not present in men.

These findings – which were published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging in July 2019 – suggest that “women with chronic inflammatory disorders may be particularly vulnerable to developing depression through decreases in sensitivity to reward,” said first author Dr. Mona Moieni, a postdoctoral researcher in Dr. Eisenberger's laboratory. “Clinicians who treat female patients with inflammatory disorders may want to pay close attention to these patients for possible onset of depressive symptoms.”

HOPE

There is hope that researchers will soon have a better understanding of the relationship between depression and the aging brain, and some of the most innovative advances in research can be found at the Centre for Addiction and Mental Health (CAMH) – Canada’s largest mental health teaching hospital and one of the world’s leading research centres.

Researchers at CAMH are pioneering effective, new pharmacological treatments and developing new therapeutic molecules that show promise in reversing the memory loss linked to depression and aging.

In February 2019, Dr. Etienne Sibille, Deputy Director of the Campbell Family Mental Health Research Institute of CAMH, presented his research team’s latest findings in Washington, D.C., at the American Association for the Advancement of Science (AAAS) Annual Meeting.

He noted that these molecules not only rapidly improve symptoms of depression, but also appear to renew the underlying brain impairments causing memory loss.

Dr. Sibille expects to start testing the molecules in clinical research in two years. “We’ve shown that our molecules that enter the brain are safe, activate the target cells, and reverse the cognitive deficit of memory loss. If successful, the potential applications are great. Not only is there a lack of treatment for cognitive deficits in mental illness, but the brain improvements suggest the molecules could help to prevent the memory loss at the beginning of Alzheimer’s disease, potentially delaying its onset.”

“The current drugs used to treat depression were discovered by chance. Therefore, these other drugs are not based on the knowledge of what is deregulating the brain,” he continued. “We, however, are doing the opposite. Our work and research are directly informed by the pathology of the brain. Simply put, other drugs address the symptoms, not the illness.

Our target reverses some aspect of the pathology – not just symptoms, but underlying mechanisms, and this is what is creating the excitement.”

Dr. Sibille noted that the unmet therapeutic need and huge burden on quality of life of cognitive dysfunctions (for affected individuals and their respective families, as well as on the health care system more generally) highlight the urgency for a solution.Dr. Sibille also indicated that the original research findings were more “robust” in females than males. This is particularly encouraging in light of the fact that women experience higher rates of depression and Alzheimer’s disease than their male counterparts.

MANAGE YOUR BRAIN HEALTH, TODAY

The evidence to date about the relationship between depression and brain aging reinforces the importance of managing your brain health at all stages of your life, and, in particular, learning what preventative measures you can take to help minimize or avoid depression. This includes, amongst other things, managing your stress levels – perhaps by engaging in regular exercise, eating a healthy diet, and/or practicing mindfulness meditation.

As we get older, there are various milestones that may impact our state of mind such as retirement, moving to a care facility, changing financial security, serious illness, or the death of a loved one.

While the time to heal or adapt can vary from individual to individual, it is important to be cognizant of the symptoms of depression, and to ask for help and support when you need it.

If you are experiencing symptoms of depression, it is critical to talk to someone – whether that person is a family member, a friend, or a doctor. Help is also available through your local distress centre or crisis service, or you can even visit your local emergency department. There are also various educational resources available online, including on CAMH’s website (www.camh.ca).

Source: MIND OVER MATTER V9

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