Biochemical and pharmacological characterization of the serotonin transporter in human peripheral blood lymphocytes

Barkan, Tamar; Genevieve, David; Levy, Galit Katarivas; Weizman, Abraham; Rehavi, Moshe

doi:10.1016/s0924-977x(03)00107-x

Cited by 36 publications

(23 citation statements)

References 30 publications

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“…These antidepressants act directly on relevant peripheral immunocompetent cells to decrease release of inflammatory mediators [25]. Lymphocytes possess the serotonin transporter on their surface [8]; thus, there are "binding sites" that recognize the SSRIs and TCAs on lymphocytes. However, the precise pathway(s) from binding of the antidepressants at the surface of the lymphocyte to their immunomodulatory actions is not clear.…”

Section: Discussionmentioning

confidence: 99%

Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive-immune disorders

Taler

Bar

Korob

et al. 2008

International Immunopharmacology

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Section: Discussionmentioning

confidence: 99%

Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive-immune disorders

Taler

Bar

Korob

et al. 2008

International Immunopharmacology

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“…It has been suggested that lymphocytes also possess a serotonergic storage system that can be affected by SSRIs [78]. Some studies found that resting lymphocytes express SERT [79], while others suggest significant transporter expression on activated cells, indicating that activated lymphocytes might remove serotonin from the blood to the lymphatic system [80].…”

Section: The Serotonin Transportermentioning

confidence: 99%

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Maurer‐Spurej

2005

CMLS, Cell. Mol. Life Sci.

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Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.

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“…with similar pharmacological properties to 5-HTT in brain (Barkan et al 2004). These cells also express many components of the neuronal signal transduction cascade in their cytosol (Stieler et al 2001).…”

Section: Discussionmentioning

confidence: 94%

“…We also evaluated whether the CREB biomarkers have potential for predicting antidepressant response. As an in vitro model system, T-lymphocytes possess the desirable feature of expressing functional serotonin transporter (5-HTT) activity with similar pharmacological properties to 5-HTT in brain (Barkan et al 2004). The primary hypotheses were that baseline CREB variables and also change in CREB variables during treatment would differ among groupshealthy controls, responding patients and non-responding patients.…”

Section: Introductionmentioning

confidence: 99%

T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs

Lim

Kim

Carroll

et al. 2013

International Journal of Neuropsychopharmacology

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Response to drug treatment of major depression is variable and biomarkers of response are needed. Cyclic AMP response element binding protein (CREB) is considered a key mediator of antidepressant drug effect. We studied CREB in T-lymphocytes as a potential predictor of response to a selective serotonin reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot and electrophoretic mobility shift assays, at baseline and after 6 wk treatment. Thirty-four healthy controls were also studied. The rate of response was 36 of 69 cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed group compared to controls (p = 0.044 and p<0.001, respectively). Baseline tCREB values in responders were significantly reduced in comparison to non-responders and to controls. After 6 wk treatment, median values of change of all CREB measures were greater in responders (36) than in non-responders (33; p<0.001 for tCREB, p = 0.003 for pCREB, and p=0.072 for CRE-DNA binding). Similar but less robust changes in CREB variables distinguished remitters from non-remitters. The optimum value of baseline tCREB predicted response with a positive predicted value of 0.778 [21/27; 95% confidence intervals (CI) 0.621-0.935], negative predictive value of 0.643 (27/42; 95% CI 0.498-0.788) and accuracy of 0.695 (48/69; 95% CI 0.586-0.804). Patients with low baseline tCREB had a significantly greater rate of response (78%) than patients with high baseline tCREB (36%), p < 0.001. Moreover, the greatest changes in tCREB with treatment were observed in subjects who did respond. This preliminary study suggests that T-lymphocytic CREB biomarkers are reduced in depressed patients and may assist in the prediction of response to SSRI drugs in depression.

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Biochemical and pharmacological characterization of the serotonin transporter in human peripheral blood lymphocytes

Cited by 36 publications

References 30 publications

Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive-immune disorders

Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive-immune disorders

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs

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