Honoring We the People
We the People is a higher thought and one’s serotonin system is part of all thoughts – high or otherwise. Today’s serotonin (5-HT) focus is homeostasis, with particular attention on the central nervous system. From the National Institutes of Health (PubMed), our We the People line-up includes four 2015 serotonin articles regarding: selective serotonin reuptake inhibitors (SSRIs) and obsessive-compulsive disorder (OCD), 5-HT3 receptors and OCD, prefrontal cortex (brain) and 5-HT2A receptors, and genetic research on suicide and the serotonin transporter gene (5-HTT, SERT).
We the People All!
I. Obsessive-Compulsive Disorder and the Serotonin System (SSRIs)
“This narrative review gathers together a range of international experts to critically appraise the existing trial-based evidence relating to the efficacy and tolerability of pharmacotherapy for obsessive compulsive disorder in adults. … Robust data supports the effectiveness of treatment with selective serotonin reuptake inhibitors (SSRIs) and clomipramine in the short-term and the longer-term treatment and for relapse prevention. Owing to better tolerability, SSRIs are acknowledged as the first-line pharmacological treatment of choice. For those patients for whom first line treatments have been ineffective, evidence supports the use of adjunctive antipsychotic medication, and some evidence supports the use of high-dose SSRIs.”
Obsessive-compulsive disorder (OCD): Practical strategies for pharmacological and somatic treatment in adults.
Fineberg NA, Reghunandanan S, Simpson HB, Phillips KA, Richter MA, Matthews K, Stein DJ, Sareen J, Brown A, Sookman D.
Psychiatry Res. 2015 Feb 10. pii: S0165-1781(14)00986-X. doi: 10.1016/j.psychres.2014.12.003. [Epub ahead of print]
PMID: 25681005 [PubMed - as supplied by publisher]
II. Obsessive-Compulsive Disorder and the Serotonin System (5-HT3 Receptors)
“The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. … The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. … Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. … Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn.”
Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature.
Serata D, Kotzalidis GD, Rapinesi C, Janiri D, Di Pietro S, Callovini G, Piacentino D, Gasperoni C, Brugnoli R, Ferri VR, Girardi N, Tatarelli R, Ferracuti S, Angeletti G, Girardi P, Del Casale A.
Hum Psychopharmacol. 2015 Feb 10. doi: 10.1002/hup.2461. [Epub ahead of print]
PMID: 25676060 [PubMed - as supplied by publisher]
III. Prefrontal Cortex (Brain), Dopamine and Serotonin-2A (5-HT2A)
“Modulation of dopamine (DA) released by serotonin-2 (5-HT2) receptors has been implicated in the mechanism of action of antipsychotic drugs. The mesocortical DA system has been implicated particularly in the cognitive deficits observed in schizophrenia. Agonism at 5-HT2A receptors in the prefrontal cortex (PFC) is associated with increases in cortical DA release. Evidence indicates that 5-HT2A receptors in the cortex regulate mesocortical DA release through stimulation of a "long-loop" feedback system from the PFC to the ventral tegmental area (VTA) and back. However, a causal role for VTA glutamate in the 5-HT2-induced increases in PFC DA has not been established. … These results demonstrate that stimulation of glutamate receptors in the VTA is necessary for 5-HT2 agonist-induced increases in cortical DA.”
Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release.
Pehek EA, Hernan AE.
Neuroscience. 2015 Jan 28;290C:159-164. doi: 10.1016/j.neuroscience.2015.01.029. [Epub ahead of print]
PMID: 25637799 [PubMed - as supplied by publisher]
IV. Major Depressive Disorder, Suicide and the Serotonin Transporter Gene (5-HTT, SERT)
“The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD). … Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. … These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.”
Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder.
Lee HY, Hong JP, Hwang JA, Lee HJ, Yoon HK, Lee BH, Kim YK.
Psychiatry Investig. 2015 Jan;12(1):136-41. doi: 10.4306/pi.2015.12.1.136. Epub 2015 Jan 12.
PMID: 25670956 [PubMed] Free PMC Article
Today’s Video: Serotonin: Suicide, Aggression and Impulsivity (7 of 8)
*Next Up: Tomorrow, Sunday 22 February, We the People, Publius and Homeostatic Cannabinoids.
Posted by Bryan W. Brickner