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Tijdschrift voor Psychiatrie 56 (2014) 11, 717 - 725

Review article

Brain activation as endophenotype for investigating genetics of depression

E. Opmeer, R. Kortekaas, A. Aleman

background Many factors are involved in the pathogenesis of depression. This article provides an overview of the results given in the thesis entitled 'Linking Depression’, in which some putative underlying neurobiological and genetic mechanisms of depression are examined.
aim To gain more insight in brain activity as endophenotype for depression.
method As part of the Netherlands Study of Depression and Anxiety (nesda), 301 people, including patients with depression and/or anxiety and healthy volunteers, underwent functional magnetic resonance imaging (fmri) and genotyping.
results During the processing of negative emotions, patients with depression showed a pattern of heightened limbic activation but less prefrontal activation. The same pattern, but in reverse, was seen during the processing of positive emotions. We showed that the disc1, comt and npy genes were associated with brain activation patterns comparable to those seen in patients with depression. In addition, in cases of depression, there was a different kind of relationship between these genes and brain activation.
conclusion Depression is characterised by the disturbed processing not only of negative emotions but also of positive emotions. In addition, the studies we describe contribute to our insight into the neurobiology of depression and relevant genetic influences because the results demonstrate that depression alters the relationship between genes and brain activation.

keywords brain activity, depression, endophenotype, genetics, neuroimaging, risk factors