Audrey Gruss knows the devastation of depression -- her mother suffered from the enigmatic mood disorder most of her adult life, misdiagnosed, over-medicated and even treated with electroconvulsive "shock" therapy during the 1960s and 70s.
"None of the doctors ever told us what was happening," said Gruss. "We were embarrassed, ashamed and frightened."
When her mother died in 2005, Gruss vowed to find out why doctors couldn't "do more to make her whole."
In 2006, Gruss founded the Hope for Depression Research Foundation (HDRF), named for her mother, and dedicated to using the psychology of emotion and neuroscience to better diagnose -- and perhaps one day cure -- the disorder.
And now, research funded by HDRF has for the first time been able to use brain imaging to link the lack of maternal attachment to depression, a disorder that strikes more than 1 in 20 Americans over the age of 12.
The study, by researchers at Beth Israel Medical Center, Columbia University and Albert Einstein Medical Center in New York City and published in the December issue of the journal Plos ONE, "meshed perfectly" with Gruss's goals.
Showing women a photo of their mother, and imaging their brains, consistently showed differences between those who were depressed and those who were not.
There is no clear diagnosis for depression, and many slip under the medical radar with subtle symptoms of chronic fatigue. If doctors can find a brain imaging tool to reliably identify the disorder, many like Gruss's mother might be helped.
"Freud comes in to this," said co-author and psychiatrist Dr. Igor Galynker of Beth Israel Medical Center. "He blamed everything on the mother and it turns out the mother is absolutely the strongest gauge of depression you have."
Researchers studied 28 young women -- 14 who suffered from mild to moderate depression and 14 who did not. The women's brains were scanned in an MRI machine as they were each shown four photos: a friend, a younger female stranger, an older woman they did not know and their mother.
The photos of two strangers and the friend were controls to ensure that the observed brain activity pertained only to the mother and was not just associated with familiarity or friendship.
"We asked them to think two things: how related they are to the picture and how close they feel and how much they like the person in the picture," Galynker.
"We compared the subjective activity from the mother and the friend and the two strangers. What we were left with was the pure mother affect."
In the women who were depressed, the photo of mother elicited a strong sadness response in the brain. The scans were able to predict depression in about 90 percent of the women.
The most pronounced brain changes were seen in the left anterior paracingulate gyrus, which coordinates sensory output with emotions.
"The area is involved in processing your affect and how you feel," said Galynker. "This is also the area that gets activated when you are in conflict or social interactions."
"Our hypothesis is that the brains in people who were sad are activated more to a sad picture," he said. "When you are depressed you interpret everything in a way that is sad. The glass is always half empty."
Galynker said this research is important, because it might one day lead to better diagnosis and would give therapists a new psychological tool to talk about the patient's relationship with her mother.
"There is no tool for imaging depression -- like diagnosing a broken ankle or low cardiac function or a metastic tumor, so this is the first paper that does something like that -- a real life sample," said Galynker. "It's an unusual achievement."
Scientists speculate that depression can be caused by a combination of factors, including childhood trauma, genetics and stress.
Freud believed that the earliest relationship with mother was critical for the development of a healthy psyche, even though some of his theories, like "penis envy," the "Oedipus complex," have since been discredited.
Modern psychiatrists agree that insecure attachment in the first few years of life can lead to anxiety, personality disorders and depression in adulthood. Secure attachment -- or maternal bonding, which begins in the earliest weeks of life until the age of about 1 or 2 -- leads to success in life.
The poignant irony of this study about mothers does not escape Gruss, who was strongly attached to her own mother.
"She was elegant and creative, funny and talented," she said.
Her mother, Hope Butvydas, had a catatonic breakdown in her late 30s and never fully recovered. Gruss said the stress and uncertainty of emigrating with her cavalry-officer husband and two young daughters from Lithuania after World War II may have been to blame.
"Mother was always kind of high strung and intense," said Gruss. "It was the shock of leaving her homeland during the war and giving birth to a child in Germany and coming to the United States and not speaking the language."
Today, the HDRF is supporting a variety of research projects, including epigenetics and other studies in "separation distress" using animal models. It has also established a depression task force that includes seven of the "most brilliant minds in the field," according to Gruss.
"There has not been one new medication since Prozac, which came out in 1985," she said. "There has been no change in the basic treatment of depression. It's staggering how little we know."
Galynker's research is not "only a beginning," but a "major breakthrough," she said.
For her, the photos of her mother elicit warm feelings. It was she who encouraged Gruss to study biology in college and ultimately gave her the tools to support scientific research.
"Even now, when I walk past her photos, something happens to me, I loved her so much," said Gruss. "She was my guiding light."