Investigation of the serotonergic activity and the serotonin content in serum and platelet, and the possible role of the serotonin transporter in patients with depression

According to the monoamine hypothesis, the development of depression is associated with dysfunctions of the serotonergic system. Alterations in the serotonin transporter gene (5-HTTLPR), the serotonergic activity in the brain, and the content of serotonin (5-HT) have been related to depression and were examined separately by previous studies. This study investigates these parameters in 89 depressed patients and 89 healthy participants. We investigated the serotonergic activity measured by the loudness dependence of auditory evoked potentials (LDAEP). In addition to the examination of the serotonin content (serum and platelet), enzyme-linked immunosorbent assays (ELISA) were used and 5-HTTLPR genotypes were analyzed. We observed a lower serotonin content in patients compared to healthy participants. Further, we noticed a correlation between anxiety and depression-associated symptoms with serotonergic activity. Patients treated with SSRI/SNRI showed decreased contents of serum serotonin compared to patients without any psychotropic medication or other psychotropic medications. Since the serotonergic activity, peripheral serotonin content, and 5-HTTLPR were unrelated, the results suggest independent alterations of central and peripheral serotonergic systems in depression. In line with this finding, serotonergic activity was related to anxiety and depression symptoms. Furthermore, the applied medication seems to influence serum serotonin content in patients with depression

Prescription of sedative hypnotics in psychiatric and somatic inpatients

Benzodiazepines (BZD) and Z-drugs (ZD) are often prescribed to treat psychiatric disorders. Despite the risk of dependency and serious adverse events, they are increasingly prescribed to outpatients. Yet little is known about the prescription to inpatients. In this article, we analyze the BZD and ZD prescription patterns in the routine data of 913 psychiatric and somatic inpatients treated in Bochum, Germany. BZD were prescribed more often as regular medication in psychiatry and ZD in somatic hospitals. ZD were more often used on demand, by female patients, and combined with other substances. Both were frequently prescribed to older adults, especially as part of somatic treatment and in combination with opioids. Prescription of sedative hypnotics is frequent in psychiatric and somatic inpatients. Their use seems to be partially independent of recorded psychiatric indications

Analysis of cytokine levels, T regulatory cells and serotonin content in patients with depression

Alterations in peripheral serotonin concentrations and an imbalanced immune system have been reported in patients with depression. Cytokines and T regulatory (Treg) cells may play an important role in the development of depression. This study investigates the levels of cytokines and Treg cells, as well as the concentration of serotonin (5-HT) in the blood of 89 patients suffering from depression and 89 healthy participants between two acquisitions. We investigated the state of health before (T1) and after (T2) psychological and pharmacological therapy. Both cytokine (IL-6, IL-10, TNF-$\alpha$, and INF-$\gamma$) and 5-HT levels in the blood were measured by enzyme-linked immunosorbent assays. The levels of CD4$^{+}$CD25$^{+}$ Treg cells were determined by flow cytometric analysis. Patients with depression showed significantly higher serum levels of IL-6 and INF-$\gamma$, no altered serum levels of IL-10 and TNF-$\alpha$, and decreased platelet and serum 5-HT levels compared with healthy participants at the first acquisition. In addition, the symptoms of depression and anxiety, the TNF-$\alpha$ level, and the amount of CD4$^{+}$CD25$^{+}$ cells in the blood were decreased from the first to the second acquisition. Further, a correlation between IL-6 and platelet 5-HT has been observed in patients. An imbalance of the immune system in patients with depression and an association of the serotonergic system and cytokines were observed. These results indicate that the development of depression might be related to several interacting proteins, including cytokines and 5-HT, and the treatment affects imbalances of these factors

Genetic variation of the 5-HT1A rs6295, 5-HT2A rs6311, and CNR1 rs1049353 and an altered endocannabinoid system in depressed patients

$\bf Background$ The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention. $\bf Method$ In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5-HT2A rs6311, and 5-HT1A rs6295 by high-resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self-questionnaires. Fifty-nine patients participated in a second appointment to measure the concentration of AEA, 2-AG, and symptoms of depression and anxiety. $\bf Results$ We observed higher AEA and decreased 2-AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2-AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2-AG. Gender differences were found concerning increased 2-AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5-HT1A rs6295 and 5-HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients. $\bf Conclusion$ In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2-AG and AEA, and genetic variations of the 5-HT1A and 5-HT2A could play a role in patients with depression and may be involved in a depressive disorder

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers

$\bf Background$ The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 $\it (CNR1)$ gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the $\it FAAH$ gene on the serotonergic and endocannabinoid system in 59 healthy volunteers. $\bf Methods$ Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs $\textit {(rs1049353, rs344420)}$ was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method. $\bf Results$ Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the $\it CNR1$-A-allele-carriers, a reduced AEA (A-allele-carrier $\textit {M = 0.66}$, SD = $\it 0.24$; GG genotype $\textit {M = 0.72}$, SD = $\it 0.24$) and 2AG (A-allele-carriers $\textit {M = 0.70}$, SD = $\it 0.33$; GG genotype M = 1.03, SD = $\it 0.83$) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed. $\bf Conclusions$ Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression