INCREASED NUMBERS OF CORTICOTROPIN-RELEASING HORMONE EXPRESSING NEURONS IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS OF DEPRESSED-PATIENTS

The hypothalamo-pituitary-adrenal (HPA) axis is known to be activated in depressed patients. Although direct evidence is lacking, this activ ation is hypothesized to be due to hyperactivity of corticotropin-rele asing hormone (CRH) neurons of the hypothalamic paraventricular nucleu s (PVN). Recent immunocytochemical studies in experimental animals and in humans showed that the number of CRH-expressing neurons correlated with the activity of these neurons. In addition, colocalization of AV P in CRH neurons has been shown to be an index for the secretory activ ity. Therefore, we estimated the total number of CRH-immunoreactive ne urons and their fraction showing colocalization with AVP in the PVN of 10 control subjects and of 6 depressed patients who were diagnosed to be suffering from a major depression or a bipolar disorder. The mean total number of CRH-expressing neurons of the 6 depressed patients was four times higher, and the number of CRH neurons co-expressing AVP wa s almost three times higher than those in the control group. We also d etermined the two activity parameters of CRH neurons in the PVN of 2 s ubjects with a depressive organic mood syndrome or a depressive disord er not otherwise specified. In these two 'non-major depressed' subject s, the activity parameters of CRH neurons were comparable to those of control subjects. Our observations strongly support the hypothesis tha t CRH neurons in the PVN are hyperactivated in major depressed patient s. This hyperactivity might be causally related to at least part of th e symptomatology of depression.