Inherited Depression Linked To Brain Cortex Thinning

US scientists conducting the largest ever imaging study of depression found that a thinning of the brain’s cortex in the right hemisphere appeared
to be linked to inherited or the familial form of depression.

The research was led by Dr Myrna Weissman, professor of epidemiology in psychiatry, Columbia University College of Physicians and Surgeons, and
director of the Division of Epidemiology at the New York State Psychiatric Institute and is to be published online in the Proceedings of the
National Academy of Sciences (PNAS)

The first author of the study was Dr Bradley Peterson, director of Child & Adolescent Psychiatry and director of MRI Research in the Department of
Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute.

Weissman, Peterson and colleagues found that the right brain cortex of people at high risk of developing depression was 28 per cent thinner compared
with that of people with no known risk. The cortex is the outermost layer of the brain.

The researchers said they were amazed by this result: this amount of thinning is on a par with the amount of brain loss they see in people with
Alzheimer’s disease and schizophrenia.

Peterson told the press that:

“The difference was so great that at first we almost didn’t believe it.”

“But we checked and re-checked all of our data, and we looked for all possible alternative explanations, and still the difference was there,” he

Speculating on how a thinner cortex may be linked to depression, Peterson said perhaps it disrupts a person’s ability to pay attention to and make sense
of social and emotional cues from others.

The researchers also tested participants’ level of inattention to and memory of social cues and they found that the ones who performed the worst had
the least brain matter in the right cortex.

For the study, using MRI brain imaging, Weissman, Peterson and colleagues compared the thickness of the cortex in 131 people aged between 6 and 54 with and without a
family history of depression.

The participants were pulled from an earlier study which Weissman had started 27 years ago: the Children at High and Low Risk of Depression study.
Weissman had identified people with moderate to severe depression, and those with no such history, and followed their families for 25 years. She
found that depression was handed down in the high risk families. This latest imaging study is part of the 20 year follow up, when Weissman asked
Peterson to collaborate on the imaging. The cohort now includes three generations.

The brain imaging showed that the brains of biological offspring of depressed people had structural differences that didn’t show up in the offspring of
people with no history of mental illness.

The researchers found that thinning on the right side of the brain was linked to a raised risk of depression, it was not linked to higher incidence of
depression itself. It was only those people who also had less brain matter on the left side who went on to develop depression or anxiety.

Peterson said:

“Our findings suggest rather strongly that if you have thinning in the right hemisphere of the brain, you may be predisposed to depression and may also
have some cognitive and inattention issues.”

But he went on to explain that:

“The more thinning you have, the greater the cognitive problems. If you have additional thinning in the same region of the left hemisphere, that seems
to tip you over from having a vulnerability to developing symptoms of an overt illness.”

Peterson suggested that if the way the illness develops starts with thinning of the cortex, then maybe treatments can target this. For example, perhaps
current methods for improving attention and memory, with and without drugs used to treat ADHD, could turn out to be effective for people who have
familial depression and this pattern of cortical thinning.

Perhaps treating their inattention could improve the way they process social information. But he said although it might be a plausible hypothesis,
it was also highly speculative.

Peterson and Weissman plan to look at more brain images, this time using fMRI, to examine more closely how particular patterns of thinning affect
how the brain behaves during attentional tasks in people with and without a history of familial depression.

They also hope to find out which types of cells are most affected by the reduced brain matter, and the causal pathways that lead from cortical thinning
to depression, plus by studying DNA of participants, discover any genes that might raise the risk of developing depression and/or the risk of having
more thinning in the cortex.

The study was sponsored by the National Institute of Mental Health of the National Institutes of Health.

“Cortical thinning in persons at increased familial risk for major depression.”
Peterson BS, et al
PNAS 2009.

Sources: Columbia University Medical Center.

Written by: Catharine Paddock, PhD

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