THE ROLE OF ADENYLATE-CYCLASE ACTIVITY IN PLATELETS OF PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER

Abstract

Introduction Blood platelets can be considered a reliable peripheral model of presynaptic serotonergic neurons, as they are endowed with a 5-HT reuptake transporter similar to that present in the brain cells (Marazziti et al., 2004). The biological basis of the patophysiology of obsessive-compulsive disorder (OCD) is centered on serotonergic system, although evidences of both dopaminergic and adrenergic systems involvement are consistent (Westenberg et al., 2007). A possible role of second messengers, such as cyclic adenosine monophosphate (cAMP) signaling, in the development of OCD has been recently postulated, although evidences are meager and, in some cases, contradictory (McDougle et al., 1999). The aim of the present study was to explore and to compare the adenylate cyclase (AC) activity either in basal conditions, either after the stimulation by isoprenaline (ISO) in platelets of OCD patients and healthy control subjects. Also, AC activity was measured both in the absence and in the presence of α- and β- adrenoreceptor antagonists. Materials and methods Forty patients (20 men and 20 women, aged between 23 and 34 years; mean±SD: 26.5 ± 4.8) were included in the study. All of them met Diagnostic and Statistic Manual of Mental Disorders 5th edition (DSM-5) criteria for OCD, were not currently depressed, nor had any history of mood disorders or any other comorbid conditions. This group was compared to a similar one, composed by 40 healthy volunteers patients (20 men and 20 women, aged between 21 and 32 years; mean±SD: 24.6 ± 6.3), all of them without familiar or personal history of major psychiatric disorders. The severity of OC symptoms was evaluated by means of the Yale Brown Obsessive-Compulsive Scale (Y-BOCS). Thirty (30) ml of blood were collected from fasting subjects between 8.00-10.00 a.m. to avoid circadian rhythm interference. Results The platelet basal AC activity was similar in OCD patients and healthy subjects. The addition of 10 μM ISO enhanced significantly (p Discussion No difference in the basal AC activity in platelet membranes of healthy subjects and OCD patients was found. The addition of 10 µM ISO to platelet membranes provoked a significant stimulation of the enzyme activity of the same magnitude in the two groups. Our findings suggests that, at our experimental conditions, there is an inhibitory component of ISO effect on platelet AC, due to the agonist interaction with α2 receptors, at its higher concentrations (> 1 μM). These data suggest the presence of a condition of supersensitive β-receptors in platelets of OCD patients that, perhaps, could reflect (or provoke) alterations of the intracellular signaling system mediated by the cAMP and of the related kinases. In conclusion, the results of the present study suggest that abnormal second messenger pathways in OCD may be also related to cathecolamine system disturbances, which might open new therapeutic strategies especially in resistant patients who do not respond to serotonergic medications.