Exploración de la función dopaminérgica en la depresión unipolar y bipolar

Abstract

Numerous studies suggest that the dopaminergic function is impaired at least in a subgroup of depressed patients, especially in bipolar patients. Neuroendocrine tests are one technique used to explore dopaminergic function in psychiatry and the most studied dopamine agonist is apomorphine (a dopamine agonist D1 / D2). Most of studies involving Apomorphine Test to evaluate the response to prolactin and growth hormone in unipolar and bipolar depressed patients have shown conflicting results. The objective of this study is to assess with the Apomorphine Test if dopaminergic function is altered in unipolar and bipolar depression. To that end I will be based on the development of three studies. In the first study a reduced sample of subjects in a homogeneous selection of type II bipolar patients was included. The purpose of this study was to assess the sensitivity of dopamine receptors in 19 patients admitted with major depression: 10 depressed bipolar type II, 9 unipolar depressed, compared with 15 healthy controls. We evaluated the multihormonal responses to the dopamine agonist Apomorphine (APO, 0.75 mg SC) in order to obtain an index of dopaminergic neurotransmission at the post synaptic level. In addition we assess in the same subjects, prolactin (PRL) response to 8AM and 11PM protirelin challenges (TRH, 200μg IV) and cortisol response to Dexamethasone suppression Test (DST,1 mg orally). Bipolar depressed patients showed a percentage of frenación to prolactin (PFP) significantly lower than healthy subjects (p = 0.0003) and unipolar depressed patients (p = 0.04). The main objective of the second study was to confirm the results obtained with Apomorphine Test found in the previous study, in a more extensive population and including mainly bipolar patients type I. The study population consists of 54 depressed bipolar patients, 80 depressed unipolar patients and 36 healthy subjects. Bipolar patients showed lower prolactin suppression to Apomorphine Test than unipolar patients and healthy subjects (both comparisons: p <0.00001). The results of TRH Test from the first study and the results of DST Test from the two studies ruled out that the results obtained with Apomorphine Test were not due to an alteration of lactotroph cells induced by TRH, or an overactivity of the corticotroph axis. The third study was conducted with a subpopulation of the second study in which a serial analysis of prolactin were added. The study population was 68 unipolar depressed patients, 39 bipolar depressed patients, compared with 24 healthy controls. Bipolar patients showed lower prolactin suppression to the Apomorphine Test than unipolar patients (p< 0.005) and healthy subjects (p<0.001). Nyctohemeral profiles of PRL were strictly comparable between unipolar and bipolar patients, and no statistically significant difference in PRL circadian mesor and amplitude could be demonstrated between patients and control subjects. Furthermore, APO-induced PRL suppression was not correlated with circadian PRL values. In conclusion, the results of the three studies showed that bipolar depressed patients have a altered post synaptic receptor sensitivity D2 in the tuberoinfundibular dopamine level, as assessed by the prolactin response to Apomorphine Test. This alteration is not in unipolar depressed patients so that , if the data were confirmed in subsequent studies, the test Apomorphine may have significant value as a biomarker of bipolar depression.

Date of Award	8 Jul 2016
Original language	Spanish
Supervisor	Diego Jose Palao Vidal (Director)