How the brain changes when we grieve

• "We don’t want to get rid of grieving experiences but maybe people don’t need to have profound detrimental effects on their health," says Zoe Donaldson, a professor of neuroscience at the University of Colorado Boulder.
• Grief often extends beyond our emotions to our thoughts, behaviors and body. It may increase the risk of a heart attack just after a loved one dies and has been linked to an increased risk for cardiovascular disease, cancer and other chronic diseases. Parents who lose a child before reaching mid-life may have an increased risk of developing dementia later in life.
• Most people adapt to their loss but for some — an estimated 5-10% of people who have lost someone — grief can be prolonged.

How it works: The bonds we form with one another take biological forms in the brain — changes in hormones, the expression of genes and more.

• These neural maps inked from our experiences with someone frame the brain's predictions of our world that guide us through life: A partner who usually gets home first, a parent who calls on a birthday or a friend who joins you for coffee every week.
• Studies have found the brain's reward systems are activated by these relationships, motivating us to maintain these bonds and reunite with loved ones regularly.

"The trouble is that with the death of the loved one, that solution doesn't work anymore," says Mary-Frances O'Connor, a professor of clinical psychology and psychiatry at the University of Arizona, and the author of "The Grieving Brain: The Surprising Science of How We Learn from Love and Loss".

• Instead, there are conflicting streams of information: There is a memory of a funeral or a phone call with news that someone died, and a neurobiological attachment that says they are still here, she says.
• As a result, people can experience what Donaldson calls "unrequited yearning" — a frustrating state in which we seek someone but the brain isn't rewarded with their presence.
• "Grieving takes a long time to resolve these two streams of information and for the brain to be able to predict their absence instead of predicting their presence," says O'Connor, who conducted early studies on the neuroimaging of grieving 20 years ago. She describes it as a process akin to learning.

Details: Some researchers study the bonding behaviors of monogamous prairie voles (Microtus ochrogaster) as proxies for human attachment. The small rodents are a little larger than a mouse and form lifelong bonds with mates in the lab or in the wild.

• Studies have found that as prairie voles first bond, a set of genes associated with learning and memory turns on. As they settle into their partnership, a different pattern of genes in the brain's reward systems is expressed.
• When a prairie vole loses a partner, it appears stressed for some time but eventually is able to form new bonds. In the time in between, "many of the changes of the brain in forming a bond erode though it is not an entire reset," Donaldson says.

A pair of recent studies by Donaldson and her colleagues provides details about how memories might be uncoupled from yearning during grieving.

• In one new study, pairs of voles were housed together for two weeks. They were then separated from one another after 48 hours or four weeks, and the team looked at which genes were turned on and off in the nucleus accumbens, a site in the brain that plays a role in its reward system and social bonding.
• The researchers found a set of genes was expressed in male voles while they were with their partners and for at least two days after the voles were separated.
• Over four weeks of separation, that pattern of gene expression eroded. But, surprisingly, the males remembered — and preferred — their partner.
• Those genes could be involved in recovering from the loss of a partner, Alison Bell, who studies animal behavior and wasn't involved in the study, wrote in an accompanying article. But the researchers acknowledge the pattern of expression for these genes could be different from those in other brain regions involved in bonding that could help to maintain attachments.

In a second study, not yet peer-reviewed, Donaldson and her colleagues looked at the brain basis for yearning in prairie voles.

• Voles were trained to press levers that opened doors — one to their partner and another to a vole they didn't know.
• The voles pressed both levers but, using a tool to measure the release of dopamine in the brain at the sub-second level, the scientists found more dopamine was being released in the nucleus accumbens when they interacted with their partner. It happened when they were hitting the lever and anticipating reuniting with them and when the door opened and they were actually together.
• When they separated the voles for four weeks, less dopamine was released when they were reunited. They could remember their partner and would still go to them but the "reward is blunted to a point where there is no difference" and they could form a new bond.
• The team suggests the erosion of dopamine release during separation is "a potential mechanism for overcoming loss."

Keep in mind: Bonding in prairie voles and humans has some similarities but human love is "enriched by our complex understanding of ourselves and our most significant others," Donaldson and her colleagues recently wrote.

What to watch: There is an ongoing debate about when "normal" grief becomes pathological. Understanding the neurobiology of changes in the brain after a loss would help to inform that question as well as those about grief and its relationship to depression and loneliness.

• Grief and depression overlap and intersect but evidence suggests they are distinct.
• Grieving involves processing someone's death — we go over what happened in our minds. But rumination is a feature of depression and can have negative consequences. The question is, "How much of it is good, and when does it become problematic?" O'Connor says.

The bottom line: "As difficult as an experience grief is, from the perspective of the brain’s mechanisms, grief is a normal protective process," says Lisa Shulman, a neurologist at the University of Maryland and author of "Before and After Loss: A Neurologist's Perspective on Loss, Grief and Our Brain."

• "The more we can understand that, the more we can have some comfort with some of the strange periods we can have during periods of loss."