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Family history, brain thinning and depression: The road to sadness

March 23, 2009 |  5:19 pm

Even before the sadness settles in, the brains of people with a family history of depression look different and work differently than those of people with no depressive family history, a team of researchers from Columbia University has shown. The study, published today in the Proceedings of the National Academy of Sciences, is one of the first to provide some insight into how -- for those with a family history of depression -- the illness progresses from symptoms that are barely perceptible to a disabling mood disorder.

On average, those with a family history of depression appear to have brains that are 28% thinner in the right cortex -- the outermost layer of the brain -- than those with no known family history of the disease. That cortical thinning, said the researchers, was on a scale similar to that seen in patients with Alzheimer's disease or schizophrenia. 

"These are really impressive anatomical differences," says Dr. Bradley Peterson, the lead author of the study. But Peterson added that the greater the anatomical differences seen in patients, on average, the more severe were their symptoms of cognitive impairment. Subjects who showed cortical thinning in the left hemisphere of the brain went on to develop the hallmark symptoms of clinical depression or anxiety, the researchers found.

People who suffer from major depressive disorder are sad, yes. But researchers have long noted that most depressives have a wide range of other, cognitive problems: They often have trouble concentrating, they frequently fail to pick up on social cues -- such as facial expressions -- that don't conform with their negative thoughts, and their memories sometimes seem full of holes. That intellectual fog would seem to be a logical consequence of depression. But researchers have never really known what an illness most recognizable as sadness had to do with cognitive problems, and which came first.

The PNAS study offers the first tantalizing clues to that mysterious relationship. Columbia University researchers Dr. Bradley Peterson and Myrna Weissman used functional magnetic resonance imaging to peer into the brains of 131 subjects between 6 and 54 years old, with and without a family history of depression. Comparing the two populations -- and comparing the brains of those with overt symptoms of depression and those merely at hereditary risk, allowed the researchers to sketch a road map to the development of depression in those with a family history.

That road map suggests that, far from being the consequence of depression, the cognitive problems suffered by the depressed may be among the causes of their disease. Poor attention and memory skills, faulty reading of social cues, and patterns of thought and reaction that are a bit off may be the consequence of an underlying structural difference in the brain. If the thinning of the cortex spreads to the left side, the individual may no longer be able to compensate for her cognitive weaknesses, prompting a descent into full-blown depression.

Peterson says the research also suggests some ways in which mental health clinicians might intervene early to head off the development of depression in those at highest risk. For those with early signs of cortical thinning, psychotherapy, coaching, skills training and even medications used to treat symptoms of ADHD might prevent further deterioration of brain tissue and block the development of depression, Peterson said.

"We know that the brain changes itself in response to experience," Peterson said. Early intervention might help foster social and cognitive success and minimize the missed cues, forgotten lessons and self-defeating reasoning that come with cortical thinning. And that might spell the difference between being at risk for depression and being depressed. Caught early, cortical thinning "doesn't fate you to becoming depressed or anxious," Peterson said.

-- Melissa Healy

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Comments (5)

These are fascinating findings - my family has a history of depression (3 generations have undergone ECT, and the 2 generations alive have several taking antidepressants) and a number of family members seem to have below average abilities to pick up on social cues, despite having above average intelligence. Several of these family members also appear to have ADD. It never occured to me that all these characteristics might be related. I'd be happy to participate in a brain study like this if researchers continue to look at this hypothesis.

So that old saying "You can never be too thin" doesn't always hold up. I assume that this was a "double blind" study, where the researches were unaware of which subjects were labeled as '"depressives" and which were labeled as just sad.

Not really. What would researchers into emotional problems be doing without their MRI machines? i guess they would just have to try to understand why people with depressed parents often times grew up to be depressed themselves. It is depressing to me to imagine how much $$$ goes down the drain in these "scientific" studies. While the people on the "street" continue to suffer. Misunderstood.

I would like to recirve more scientifc documents in this field

There's no link to the NAS study in the article, and it is not easily found via search.

Please insert a link to the study this article is based on!

This is not spurious research. Most of our problems result from human behavior. Depression is pretty widespread, and there is still no way to easily diagnose it and quantify it. One's emotional life and professional productivity can be deeply affected by it--I'm speaking as one who has lived through this. Nobody challenges the validity of research into the changes in the brains of Alzheimers patients. Let's find out whether these other disorders have physical bases. That way we could eventually quantify them and perhaps rely on several treatments that would be effective early, and avoid the exclusive use of drugs.



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