Furthermore, the shift to higher iodothyronine levels in euthyroid depressed inpatients, both in the morning35 and in the evening36 may contribute to the blunting of TSH response to TRH.37,38 The presence of a blunted TRH test or an abnormal TSH indicates the need for a biological treatment, while the initial status of these tests
has no predictive value in the choice of given antidepressants. However, patients with the lowest pretreatment evening TSH secretion (basal and after 11 PM TRH stimulation) have been found to have the lowest rate of antidepressant response.39 The reduced TSH values is a “state” Inhibitors,research,lifescience,medical marker of depression since its normalization is associated with remission.39 Conversely, persistence of blunted responses (ie, 8 AM-TSH and/or 11 PM-TSH and/or TSH) during remission could selleckchem represent a “vulnerability” marker of depression. Investigation Inhibitors,research,lifescience,medical of the noradrenergic (NA) system. One of the most consistently reported abnormal findings in depression is a blunted growth hormone
Inhibitors,research,lifescience,medical (GH) response to acute administration of clonidine, a partial α2-adrenoreceptor agonist, in drug-free patients. This abnormality suggests subsensitive postsynaptic α2-adrenoreceptors at the hypothalamic level, via growth hormone-releasing hormone release, linked to an erratic release of norepinephrine.40 This finding has led to a reformulation of the original NA depletion hypothesis of depression into the “noradrenergic dysregulation Inhibitors,research,lifescience,medical hypothesis,”40 which emphasizes a primary subsensitivity or downregulation in nerve terminal α2-adrenoreceptors, leading to impaired negative feedback on the presynaptic neuron, which in turn may induce a disinhibition of NA output and exaggerated NA release in response to any activation of
the catecholaminergic system. However, blunted GH response to clonidine does not appear specific to depression but rather to the “anxiety Inhibitors,research,lifescience,medical spectrum,” since this blunting has also been observed in generalized anxiety disorder,41 panic disorder,42,43 and social phobia.44 It PAK6 has also been argued that deficiencies in noradrenergic function could lead to differential response to noradrenaline and serotonin reuptake inhibitors.45 In a study by Coote et al46 the decreased GH response, before treatment, was correlated with subsequent good clinical response to desipramine (a “noradrenergic” antidepressant). In a recent study, Correa et al47 reported that amitriptyline, which primarily increases noradrenergic function, was more efficacious than fluoxetine in depressed patients showing blunted GH to clonidine at baseline (amitriptyline is at least 100 times most potent than fluoxetine in the inhibition of the noradrenaline transporter48). Taken together, these results suggest that the noradrenergic function might influence response to antidepressant treatment.