The Role of Thrombocyte Serotonin System and Some Thrombocyte Characteristics in Treatment of Depressive Patients with Cardiovascular Diseases

Abstract

IntroductionAmong the known neurotransmitters, serotonin, norepinephrine and dopamine play the important roles in the development of psychiatric disturbances. The research so far has shown that this is not the matter of concentrations themselves, but of disbalance of concentrations between the neurotransmitter systems in CNS (central nervous system). There is proof that there is a decrease of serotonin, epinephrine and dopamine functions in patients suffering from the recurring depressive episodes, while there is a hyperactivity of norepinephrine and dopamine system in patients suffering from the bipolar affective disorder [1]. There is still a dilemma if there were a hypo or hyperactivity of serotonin system in generalized anxiety disorder [2,3]. The agonists of 5HT1A receptors reduce the symptoms of panic disorders, while the activation of 5HT2C receptors induces a panic attack [4]. Hypersensitivity of postsynaptic serotonin receptors plays an important role in obsessive-compulsive disorders [5]. Destabilization of serotonin system has been noted also in posttraumatic stress disorders. This fact had been confirmed by the efficiency of SIPPS in its treatment [6]. Dysfunction of serotonin system is also present in some personality disorders, urge-control disturbances, feeding disorders and dementia. It seems that the negative symptoms in schizophrenia are due to a dysfunction of serotonin system. In suicidal tendencies, the role of serotonin system is of the greatest importance and numerous post-mortem investigations had revealed lower concentrations of serotonin and its main metabolite 5-hydroxyindolacetate acid (5-HIAA) in brainstem, nuclei raphe, putamen and hypothalamus [7]. Some research show that lower levels of thrombocyte serotonin are connected with suicidal behaviour of depressive patients [8]. Numerous investigations have shown that, among the patients who had suffered a myocardial infarction or other diseases of cardiovascular system we can find depressive symptoms in the frame of depressive reaction, but also a real depression in its fully-blown clinical form. Depression slows the recovery in those patients but, even more importantly, some indices had been found in patients suffering from depression that it could be directly connected with an increased risk for the development of cardiovascular diseases and complications during recovery. Thrombocyte serotonin is a strong vasoconstrictor and the research has shown that the treatment with selective inhibitors of serotonin uptake (SIPPS) causes lowering of its concentration, thus reducing its role in increasing the cardiovascular risk and causing the complications of recovery. Also, the treatment of depressive patients with SIPPS lowers the values of MPV (mean platelet volume, mean thrombocyte cell volume), which had been recognized as an independent risk factor for the development of myocardial infarction and stroke.Serotonin system in thrombocytesEnterochromafine cells are the only cells besides 5HT neurons, that synthetize serotonin. They release it into the blood stream, from where it, bound to its transporter, goes mostly into the thrombocytes. Serotonin system in thrombocytes is very similar to the one in neurons. It is a part of the mechanism of thrombocyte response, which is actually a process of shape change and aggregation of thrombocytes [9,10]. Thrombocytes contain about 99% of total serotonin in circulation, so in physiological conditions, plasma levels of serotonin reflect the concentration of serotonin in thrombocytes. Human throm- bocytes contain averagely 150 to 600 ng of serotonin/109 thrombocytes [11]. Serotonin system of thrombocytes is made of: serotonin transmembrane carrier ( transporter), serotonin receptor, enzyme monoaminooxidase and serotonin stored in delta granules. Serotonin enters the thrombocytes and aggregates through actions of two carriers [12]. Protein 5-HT carrier (5HTt) is located at the membrane of thrombocyte and enables the intake of serotonin and other endogenous amines, for example dopamine, from plasma to the cytoplasmic fluid of thrombocytes [13]. …