Monday, November 28, 2011

Research on Serotonin Levels in Autoimmunity

Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE
HH Hofstetter,* R Mössner,† KP Lesch,† RA Linker,*‡ KV Toyka,* and R Gold*‡ (2005)

"These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses."


Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature


"In the present case, we see that treatment of co-morbid depression with an SSRI led to complete remission of arthritis in a 60-year-old individual. Postulated mechanisms through which antidepressants mediate this effect include their agonistic action on 5-HT2A receptors or inhibition of the signaling of Toll-like receptors that are responsible for mediating innate immunity. The relation between mediators of inflammation and biologic substrates of mood seem to be bidirectional."


Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis.
Sigvard Kopp and Per Alstergren

Department of Clinical Oral Physiology, Institute of Odontology, Karolinska Institutet, Box 4064, 141 04 Huddinge, Sweden.

"RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001)." Effect of Clonazepam on Raynaud's Phenomenon and Fingertip Ulcers in Scleroderma
Murat Colakoğlu, MD
Associate Professor in Nephrology, Departmen of Nephrology, School of Medicine, Pamukkale University, Denizli, Turkey
Veli Cobankara, MD
Associate Professor in Rheumatology, Department of Rheumatology, School of Medicine, Pamukkale University
Tekin Akpolat, MD

"Clonazepam, unlike many other benzodiazepines, appears to have serotonergic effects, which may contribute to its psychotropic and antimyoclonic properties. While the therapeutic action remains unclear, clonazepam's serotonergic effects may be responsible for the beneficial effect on Raynaud's phenomenon and fingertip ulcers.

Raynaud's phenomenon and erythromelalgia are both vascular acrosyndromes. Serotonin has been involved in the pathogenesis of both Raynaud's phenomenon and erythromelalgia."


Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
A Kling1, M Seddighzadeh2, L Ärlestig3, L Alfredsson4,5, S Rantapää-Dahlqvist3, L Padyukov2
Accepted 1 November 2007

"In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease."



Association between the use of serotonin receptor 2A–blocking antidepressants and joint disorders
Anders Kling1,*, Marit Danell-Boman1, Hans Stenlund2, Rune Dahlqvist1
Article first published online: 29 SEP 2009

"In the Swedish material, the 5-HT2A antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT2A–blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT2A–blocking antidepressants and 0.6% for the SSRIs (P < 0.001)." Ann Rheum Dis 2006;65:816-819 doi:10.1136/ard.2005.042473 Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis
A Kling1, S Rantapää-Dahlqvist2, H Stenlund3, T Mjörndal1

"The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease"

5-Hydroxytryptamine and tryptamine pathways in scleroderma
A. STACHOW, S. JABLONSKA, A. SKIENDZIELEWSKA (2006)

"These results suggest impaired transformation of serotonin into 5-hydroxyindoleacetic acid. A disproportionately high ratio of total indoles to indoleacetic acid suggests the presence of excess of tryptamine. The results of the study may indicate that in scleroderma metabolism of biogenic amines derived from tryptophan is abnormal, probably as a result of impaired activity of monoamine oxidase."


Intraplatelet and urinary serotonin concentrations in systemic lupus erythematosus with reference to its clinical manifestations
Kanai H, Tsuchida A, Yano S, Naruse T.
Third Department of Internal Medicine, Gunma University School of Medicine, Japan

"Active SLE showed a significantly higher urinary 5-HT concentration, 0.37 +/- 0.15 nmol/ml/mg Cr, than normal controls, 0.21 +/- 0.08 nmol/ml/mg Cr (p less than 0.01). Serial measurements of intraplatelet and urinary 5-HT levels in five patients with SLE revealed a significant correlation between clinical activity and intraplatelet and urinary 5-HT levels. "


Serum Factors Releasing Serotonin from Normal Platelets: Relation to the Manifestations of Systemic Lupus Erythematosus
MARK H. GINSBERG, M.D.; and MICHAEL O'MALLEY, B.S.

"In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients."


Headache, Raynaud’s syndrome and serotonin receptor agonists in systemic lupus erythematosus


Analysis of 5HT3Ra gene expression by real time PCR in Systemic Lupus
Erythematosus (SLE) patients

Mohammad Sabery Anvar, Ghasem Ahangari, Mohiedin Jafari, Shahin Dokht Samangouei, Raheleh Torabi
,Mohammad Taghi Sadeghi Kohpaieh

"We found over expression of 5HT3Ra in patients in comparison with healthy individuals group. Interestingly, some nucleotide changes have been found in 5HT3Ra gene in patients but not found sequential nucleotide changes in healthy individuals group. This study supposed that over expression of 5HT3Ra gene in SLE patients lead to over activation of immune cells that derived from over stimulation of them from serotonin blood serum that finally lead to autoimmune reactions that terminated in SLE."

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.
Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA.
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874.

Alteration of serotonin transporter density and activity in fibromyalgia
by Laura Bazzichi, Gino Giannaccini, Laura Betti, Giovanni Mascia, Laura Fabbrini,

The Expanded Biology of Serotonin
Annual Review of Medicine
Vol. 60: 355-366 (Volume publication date February 2009)
DOI: 10.1146/annurev.med.60.042307.110802

"Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new “expanded serotonin biology” and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.'
Miles Berger,1 John A. Gray,1,2 and Bryan L. Roth


Ablation of Serotonin 5-HT2B Receptors in Mice Leads to Abnormal Cardiac Structure and Function
Circulation. 2001;103:2973-2979
doi: 10.1161/01.CIR.103.24.2973

"Conclusions—Mutation of 5-HT2B receptor leads to a cardiomyopathy without hypertrophy and a disruption of intercalated disks. 5-HT2B receptor is required for cytoskeleton assembly to membrane structures by its regulation of N-cadherin expression. These results constitute, for the first time, strong genetic evidence that serotonin, via the 5-HT2B receptor, regulates cardiac structure and function."
(Circulation. 2001;103:2973.)




Recent advances in understanding serotonin regulation of cardiovascular function
Francine Côté1, Cécile Fligny1, Yves Fromes2, Jacques Mallet1, , Guilan Vodjdani1

"Recent studies have provided evidence that, in the absence of peripheral serotonin synthesis, blood serotonin (which is almost exclusively stored in platelets) is markedly reduced, and that this drop leads to heart failure. This implies that the level of circulating serotonin is a key factor in maintaining normal cardiovascular activity. These findings offer new prospects for the use of serotonin in therapies for cardiovascular diseases."


Int J Cardiol. 1988 Jun;19(3):335-9.
Plasma free and intraplatelet serotonin in patients with Raynaud's phenomenon.

"Serotonin was significantly higher in plasma (P less than 0.005) and in platelets (P less than 0.005) from Raynaud's patients than from normal controls. Moreover, plasma circulating serotonin could differentiate primary from secondary Raynaud's phenomenon, with significantly higher levels (P less than 0.05) for patients with an underlying connective tissue disease. Our data indicate a role for serotonin in Raynaud's phenomenon."
Biondi ML, Marasini B, Bianchi E, Agostoni A.
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Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome
SM Connolly, SR Quimby, WL Griffing, RK Winkelmann

"These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading."

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