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There are other neurotransmitters that regulate how the brain changes and adapts over time, namely glutamate and GABA. Both work in parts of the brain that regulate mood and emotion, says

John Krystal, M.D., chair of the department of psychiatry at Yale School of Medicine. Plus there’s how the body responds to stress, along with hormone changes in women. When people

experience chronic stress, as they do in depression, there’s a drop in the number and strength of the synapses, the spaces where messages flow between neurons. The loss of the synaptic

connections contributes to the biology of depression. There are also structural and functional changes in the brain. Two major areas, the hippocampus and the cortex, shrink. And two other

areas of the brain become overactive: the hypothalamus, which coordinates the stress response, and the amygdala, which signals threat and generates negative emotions. “There are clear

differences between a healthy brain and a depressed brain,” said psychiatrist Rachel Katz, M.D., assistant professor at Yale University in a 2021 interview for _Yale Medicine_. “The

exciting thing is that when you treat that depression effectively, the brain goes back to looking like a healthy brain.” WHAT ARE THE RISK FACTORS FOR DEPRESSION? All those biological

changes of depression can be set in motion for several reasons. Social isolation and loneliness are risk factors for depression, and in 2018, 31 percent of women and 19 percent of men 65 and

older lived alone, according to a 2020 report from the Federal Interagency Forum on Aging. “Loneliness is certainly a predictor of depression,” Emery-Tiburcio says. Grief is not depression,

but grief can trigger depression, says psychiatrist J. John Mann, M.D., at Columbia University. Loss is a major life stress, and stressful life events can trigger depressive episodes,

particularly in people who may have experienced depression in the past. Nes / Getty Images TRIGGERS FOR DEPRESSION IN OLDER ADULTS Depression can develop for several reasons. Here are some

common ones. * Social isolation and loneliness * Major life stress, such as death of a loved one or heavy caregiving load * Previous depressive episodes * Family history of depression *

Illnesses such as Parkinson’s disease, dementia, heart disease and stroke * Economic problems * Sleep problems * Addiction or alcoholism * Lack of physical activity or physical limitations

“For the vast majority of people, [depressive] episodes start fairly early in life, mostly when they’re teenagers or in their 20s,” Mann says. “Depression for 80 percent of people is a

recurrent episodic disorder.” Episodes last three months, on average, though some can last years, he says. In between, there is a period of time when the person feels normal. For those who

developed depression earlier in life, Mann says, “the episodes tend to last longer as you get older, and the well interval tends to get shorter.” Depression can run in families, Mann says.

“A lot of the rest is accounted for by … childhood experiences, the kind of stresses that they’ve gone through in their lives.” Traumatic experiences, for example, can cause changes in the

brain that predispose people to depression. The same goes for living in poverty or having trouble accessing medical care or facing language barriers. A precarious socioeconomic situation may

also prevent people with depression from seeing a doctor for screening or treatment. Then, of course, there are diseases that are more common in older adults in which depression is a side

effect, such as Parkinson’s disease and dementia. And as people age, the blood vessels in their brains can stiffen, as in arteriosclerosis, causing damage in some brain areas, Mann says.

Along with increasing risk for stroke, he notes, those stiff vessels can boost risk for a type of depression called vascular depression. This is most common in older adults and can be

accompanied by cognitive decline as well as changes in mood, according to a 2022 report in _Dialogues in Clinical Neuroscience._ DIAGNOSIS AND TREATMENTS FOR DEPRESSION Primary care

providers can diagnose a person with depression after asking questions, such as when the symptoms began, how long they last, how often they occur, and whether they stop you from your usual

activities. The provider will want to rule out other causes, such as viral infections or thyroid problems, and consider any medications you’re taking, since some can cause depressive

symptoms. The stigma around mental health can get in the way of people’s receiving a diagnosis and treatment, especially older adults, Emery-Tiburcio says. “They grew up in the generation

where we don’t share our dirty laundry.” They often have the misguided idea, she explains, “that mental illness is a weakness as opposed to an illness.” But there are many options to treat

depression. And antidepressant pills shouldn’t always come first, Emery-Tiburcio says. For those who see a lot of stigma around depression and its treatment, she says, psychotherapy might be

a preferable first step rather than medication. Psychotherapy can be helpful even if the person with depression is also experiencing mild or moderate cognitive impairment, she says. It’s a

good fit for those feeling lonely as well, she adds. “Having someone to talk to is more preferable for a lot of older adults.”