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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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