We have long known that GH release is stimulated by catecholaminergic mechanisms, among others. For almost 30 years now, different GH stimulation tests have been used to prove whether GH response in depressed patients differs from controls and subjects with other psychiatric diseases. Most revealed significant differences between patients with major depression and healthy subjects or patients with minor depression, using various specific substances to challenge GH response. Patients with recurrent major depression exhibited a blunted GH Inhibitors,research,lifescience,medical response, which could be interpreted as cither decreased DA receptor sensitivity (challenge with apomorphine) or decreased α2PD98059 supplier -adrenoceptor sensitivity

(challenge with clonidine).80 It was further suggested that this blunted GH response to clonidine was Inhibitors,research,lifescience,medical a trait marker that persists in depressed patients following their recovery.81 -82 However,

as challenge with different α2-adrenoceptor-selective agents resulted in a normal GH response, an intrinsic abnormality in the GH system was also suggested as opposed to decreased a2-adrenoceptor sensitivity.83 Alterations in thyroid function have been Inhibitors,research,lifescience,medical repeatedly linked to depression and the administration of triiodothyronine (T3 ) seems to be an effective adjunctive treatment for many patients.84,85 The relationship between thyroid hormones and neurotransmitters have mainly focused on the noradrenergic and serotonergic systems and it was shown that thyroid hormone application increases cortical serotonin release86 and may act as a cotransmitter to Inhibitors,research,lifescience,medical NE in the adrenergic nervous system.87 However, the exact mechanism of this interaction is not clear. Especially intriguing was the observation that 5-HT function was especially reduced in patients without hypothalamus-pituitary-thyroid

axis abnormalities, which suggests that mechanisms that are not serotonergic might be involved in the reduced secretion of thyroid-stimulating hormone (TSH).84 A further hint Inhibitors,research,lifescience,medical on the influence of hormones comes from the fact that the immediate postpartum period is a time of highly increased Adenylyl cyclase risk for the onset or relapse of depression.88 Several results underline the influence of estrogen and progesterone,89 thyroid hormones,90 or alterations in the HPA axis,91 but the direct mechanisms have not been clarified. In addition, recurrent depressive symptoms can be limited to the premenstrual period and more enduring depression is typically exacerbated premenstrually. These findings on possible disturbances in sex hormones could give an explanation for the increased incidence in women. Neuroimmune mediators The clinical course of depression is that of a variable disease with long periods of recovery between periods of depression in many patients, but it can also involve closely spaced episodes that finally lead to a severe and unremitting course.