Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness
FRONTIERS IN ENDOCRINOLOGY
Authors: Mazereel, Victor; Detraux, Johan; Vancampfort, Davy; van Winkel, Ruud; De Hert, Marc
Abstract
People with serious mental illness (SMI), including schizophrenia, bipolar disorder, and major depressive disorder, have a higher mortality rate and shortened life expectancy. This is mainly attributable to physical diseases, particularly cardiovascular diseases (CVDs). Important risk factors for CVDs are obesity and other metabolic abnormalities, which are especially prevalent in people with SMI. Several factors contribute to this increased risk, including unhealthy lifestyles. Psychotropic medication independently further increases this risk. In this review we want to examine the relationship between obesity and other components of the metabolic syndrome and psychotropic medication in people with SMI.
Triple reuptake inhibition of serotonin, norepinephrine, and dopamine increases the tonic activation of alpha(2)-adrenoceptors in the rat hippocampus and dopamine levels in the nucleus accumbens
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Authors: Jiang, Jojo L.; El Mansari, Mostafa; Blier, Pierre
Abstract
Clinical studies have shown the therapeutic efficacy of an increase in dopamine (DA) transmission in treatment of major depressive disorder (MDD). In the present study, we investigated whether blockade of DA transporters in addition to serotonin (5-HT) and norepinephrine (NE) produced additional adaptations of monoaminergic systems. In vivo electrophysiological recordings were carried out in male anesthetized rats. Vehicle, the 5-HT reuptake inhibitor escitalopram, the NE/DA reuptake blocker nomifensine and their combination (triple reuptake inhibition; TRI) were delivered for 2 or 14 days. Firing activity of NE, 5-HT and DA neurons was assessed. Tonic activation of 5-HT1A receptors and alpha(1)- and alpha(2)-adrenoceptors was determined in the hippocampus and extracellular DA levels in the nucleus accumbens (NAc). Unlike escitalopram, nomifensine and TRI administration increased the tonic activation of alpha(2)-adrenoceptors in the hippocampus despite decreasing NE neuronal firing activity after 2 and 14 days of administration. The firing activity of 5-HT neurons was increased after prolonged nomifensine and TRI regimens, while addition of nomifensine to escitalopram prevented the early 2-day suppression of firing by 5-HT reuptake inhibition. The tonic activation of 5-HT1A receptors was enhanced only with escitalopram. Whereas escitalopram and nomifensine decreased firing activity of DA neurons after a 2-day administration, their combination normalized it to baseline level after 14 days; this was accompanied by a robust increase in extracellular DA levels in the NAc. In summary, these results indicate that TRI increases NE and DA but not 5-HT transmission, suggesting a differential efficacy profile in MDD patients.