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Biol Psychiatry. 2007 Dec 1;62(11):1317-23. Epub 2007 May 3.

Grandchildren at high and low risk for depression differ in EEG measures of regional brain asymmetry.

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  • 1Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.



Electrophysiologic studies have found abnormalities of alpha asymmetry in depressed adults and offspring of depressed parents, which have been hypothesized to be vulnerability markers of depression. Resting electroencephalogram (EEG) was measured in grandchildren participating in a multigenerational high-risk study.


Electroencephalogram from 12 electrodes at six homologous sites over each hemisphere (digitally linked-ears reference) was compared in right-handed grandchildren in three groups: 1) both parent and grandparent having major depressive disorder (MDD; n = 19); 2) either parent or grandparent having MDD (n = 14); and 3) neither having MDD (n = 16).


Grandchildren with both depressed parent and grandparent showed greater alpha asymmetry, with relatively less right than left hemisphere activity, when compared with those with neither depressed parent nor grandparent. This difference was present over the parietal region in the eyes-closed condition. Grandchildren having either depressed parent or grandparent also tended to show heightened alpha asymmetry at parietal sites, but they did not differ significantly from those with neither depressed parent nor grandparent. Low-risk grandchildren with neither depressed parent nor grandparent showed no significant alpha asymmetry.


High-risk grandchildren displayed a parietal alpha asymmetry similar to that seen in adolescents or adults having a MDD and in second-generation offspring of parents concordant for MDD. Its presence in high-risk offspring and grandchildren without a lifetime history of MDD supports the hypothesis that an alpha asymmetry indicative of relatively less right than left parietal activity is an endophenotypic marker of vulnerability to a familial form of major depression.

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