Chromatin ultrastructural abnormalities in leukocytes, as peripheral markers of bipolar patients

This study investigated the ultrastructural conformation changes of the chromatin in blood leukocytes of bipolar patients, versus normal controls, by using the phosphotungstic acid-hematoxylin (PTAH) block-staining method, modified for electron microscopy, and the immunohistochemical localization of the histone H1, by the immunogold method. These two methods are basically complementary. If histone H1 immunolabeling is used, it shows that the immunogold labeling on chromatin is different in the three phases of the illness, i.e., high in normothymia and low in depression as well as in mania. However, in this particular tissue fixation (4% paraformaldehyde-1% glutaraldehyde in 0,1 M phosphate buffer), the heterochromatin in the nuclei remains identical in the three phases of the illness. On the other hand, the PTAH method shows exactly the area of electron-lucent condensed chromatin, separate from the area of electron-dense, decondensed, chromatin. The present data confirmed that both the clinical state of depression as well as that of mania display activated lymphocytes and neutrophils with their characteristic relaxed de-condensed chromatin. On the contrary, the state of normothymia shows a reversion to the condensed state of the chromatin, as it is observed in the leukocytes of the normal controls. The ultrastructural conformations of the chromatin, revealed by the PTAH method, in combination with the histone H1 immunogold labeling, applied in blood leukocytes, supports the use of these two methods, as screening methods of choice in investigating blood biological markers in mental illness.