Chromatin Ultrastructural Abnormalities in Blood Leukocytes, as Peripheral Markers of Epigenetic Modifications in Bipolar, Schizophrenic and Alcoholic Patients

M. Chrysanthou Piterou1,2 , S. Havaki2,3 , I. Kloukina 2, B. Alevizos1, V. Kontaxakis1, J. Liappas1, M. R. Issidorides1,2


1University of Athens, Medical School, 1st Department of Psychiatry, Eginition Hospital, Athens, Greece.

2Neurobiology Research Institute, Theodor Theohari Cozzika Foundation, Athens, Greece

3University of Athens, Medical School, Laboratory of Histology and Embryology, Goudi, Greece


Recent studies suggest that an interplay among genetics, epigenetics, and environment plays a significant role in the etiology of psychiatric disorders. Epigenetic factors regulate gene expression mainly through changes in chromatin structure.


In the present study, we investigated the chromatin structure of the peripheral blood leukocytes in 15 bipolar patients, 12 first-episode drug-naive schizophrenic patients, and 10 alcohol-dependent individuals during the detoxification therapy, as well as in 10 normal control subjects. The ultrastructural conformation state of the chromatin was studied with the application of the phospho-tungstic acid hematoxylin (PTAH) histochemical method - modified for electron microscopy—on leukocyte pellets, and with the application of the Ammoniacal Silver Reaction (ASR) method. Furthermore, the immunohistochemical distribution of the linker Histone H1, which is a molecular marker of chromatin condensation, was studied on peripheral blood smears, for the light microscope, and on epoxy-thin sections of leukocyte pellets with the immunogold method, for the electron microscope.


Τhe PTAH and ASR methods, in combination with the histone H1 immunlabeling, confirmed that the clinical states of depression and mania, as well as schizophrenia and alcoholism, display activated lymphocytes and neutrophils with their characteristic relaxed de-condensed chromatin, indicating a more reactive genome in these patients. This activation was not observed in bipolar patients in the normothymic phase, while in the alcoholic individuals, it was inversely proportional to the period of abstinence from alcohol.


These results highlight the chromatin of leukocytes as a sensitive, peripheral, biological marker, capable of incorporating epigenetic influences, which controls the activity of the genome. The present study also confirms that blood leukocytes may serve as an easily accessible model to investigate alterations in immune–neuroendocrine interactions observed in psychiatric disorders, and may be used as a neuronal and genetic probe in experimental and clinical research in psychiatry.