[Functional biomarkers of mood disorders: differential diagnosis and clinical classification with gene expression in peripheral leukocytes].

In order to identify the possible biomarkers of mood disorders, we measured the mRNA levels for a variety of genes in peripheral leukocytes of mood disorder patients in a depressive, as well as in a remissive state, comparing with healthy controls. We selected and measured the levels of genes of interest, which are listed as follows: glucocorticoid receptor, neurotrophic factors, cell adhesion molecules, SR protein splicing factors, transcription factors, epigenetic factors (histone deacetylase, sirtuin, DNA methyltransferase), since these molecules are suggested to be associated with the neural function, synaptic plasticity, and behaviors in animal models, as well as with the pathophysiology and pathogenesis of mood disorders. We found the three different types of biological markers: 1) state markers those revealed alterations of gene expression only in a depressive state of major depressive patients and/or bipolar depressive patients, 2) trait markers those showed altered gene expression both in a depressive and a remissive state of major depressive patients and/or bipolar depressive patients, and 3) markers of the treatment resistance those revealed different alterations of gene expression between treatment resistant and treatment responsive patients in a depressive state. The use of state and trait markers in combination would allow us to put a differential diagnosis between major depressive and bipolar depressive states, as well as between mood disorders and neurotic depressive states. Furthermore, candidate biomarkers of treatment resistance could be used to consider forward of applying the electric convulsive therapy even in an early stage of a depressive state.