Australasian Microarray & Associated Technologies Association, AMATA

Harley, JA, Doudney, K, Joyce, PR and Kennedy, MA
Departments of Psychological Medicine and Pathology, University of Otago Christchurch, New Zealand.

Melancholia, the excess production of black bile, was described by Hippocrates and others to explain the condition now known as major depression. Therapies for depression are primarily pharmacological and are efficacious. However challenges remain: the lag to therapeutic response is long and many patients do not respond to the first antidepressant they are prescribed. An ability to inform patients of their prognosis following initiation of therapy would be empowering for patients, their families and physicians alike.

The actions of antidepressants are closely linked to the promotion of neurogenesis and the modulation of synaptic plasticity, events that require modification of gene expression in the brain. Changes induced in the brain by these drugs may be reflected by expression differences in a more readily sampled tissue, the blood.

With the development of advanced molecular biology techniques including whole genome expression arrays we have the capability of screening for new markers such as changes in transcription of RNA in Peripheral Blood Mononuclear Cells (PBMCs). PBMCs are mixed population of lymphocytes and monocytes which are exposed to antidepressants in plasma. They have previously been shown to express the serotonin transporter and expression changes have been observed in studies of posttraumatic stress disorder.

We aim to identify new biomarkers of antidepressant response by performing whole genome expression arrays on PBMCs collected from rats treated with citalopram or fluoxetine. Candidates from the arrays will be confirmed by quantitative PCR. The ultimate aim is to transfer assays of PBMC mRNA to cohorts of human patients at the initiation of antidepressant therapy to determine if these putative biomarkers have clinical utility.