Xia Li1, Yuan Fan1, Shifu Xiao1, Sufang Peng1, Xiaowei Dong2, Xianjie Zheng2, Chia-Chen Liu3, Huafang Li4, Zeping Xiao5. 1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China. 2. Brain Function Research Laboratory, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China. 3. Department of Neuroscience, Mayo Clinic, Jacksonville FL 32224, USA. 4. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China. Electronic address: lhlh_5@163.com. 5. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China. Electronic address: xiaozeping88@163.com.
Abstract
BACKGROUND: Platelet 5-hydroxytryptamin (serotonin, 5-HT) has been examined for its use as a peripheral biomarker for depression or other mental disorders; however, it remains unclear whether blood 5-HT levels can reflect the brain's levels of serotonin. METHODS: Platelet 5-HT levels in 45 drug-naïve, 32 citalopram-treated patients with major depression and 32 healthy control were assayed, Hamilton Depression scale (HAMD) and Hamilton Anxiety Scale (HAMA) were assessed. We then measured 5-HT in platelet, in platelet-poor plasma and in the nuclei of brain tissues obtained from chronic unpredictable mild stress (CUMS) rats with or without citalopram treatment, and from the controls rats that were treated with vehicle. Toward this end, we analyzed whether correlations exist between platelet and brain. RESULTS: No differences were observed among drug-naïve patients, citalopram-treated patients and health control according to gender and age (p>0.05). Drug-naïve depressed patients had highest scores in HAMD and HAMA among the three groups (F=223.3, p<0.01; F=70.7, p<0.01, respectively) Citalopram-treated patients had significantly lower platelet 5-HT levels,compared to control subjects (Mean 58.1±36.8ng/10(9) versus 558.0±199.4ng/10(9), p<0.01) and compared to drug-naïve patients (Mean 58.1 ±36.8ng/10(9) versus 646.4±259.0ng/10(9), p<0.01), while drug-naïve patients had similar 5-HT platelet concentrations as controls(p>0.05). Consistent with clinical results, in comparison with control (1473.4±391.0ng/10(9)) and drug-naive CUMS rats (1559.0±424.4ng/10(9)), the citalopram-treated CUMS rats (684.2±335.6ng/10(9)) demonstrated a significant reduction in platelet 5-HT levels (p<0.01), but there were no difference among the three groups in platelet-poor plasma 5-HT(F=0.11, p>0.05). Hippocampal 5-HT levels were higher among CUMS rats treated with saline (98.2±59.0ng/g) than vehicle animals (31.9±18.3ng/g, p<0.01) or citalopram-treated rats (42.1±33.9ng/g, p<0.05); however, 5-HT concentrations in prefrontal cortex and Raphe Nuclei were consistent among citalopram-treated or saline-treated CUMS rats(p>0.05). Furthermore, the levels of platelet 5-HT did not correlate with neuronal 5-HT levels (p>0.05). LIMITATIONS: Dosages was fix for citalopram-treat rats, and the citalopram-treated vehicle arm did not set up. CONCLUSIONS: Our study suggests that platelet 5-HT levels might respond to SSRI treatment, but this peripheral index is not a direct reflector of central 5-HT levels.
BACKGROUND: Platelet 5-hydroxytryptamin (serotonin, 5-HT) has been examined for its use as a peripheral biomarker for depression or other mental disorders; however, it remains unclear whether blood 5-HT levels can reflect the brain's levels of serotonin. METHODS: Platelet 5-HT levels in 45 drug-naïve, 32 citalopram-treated patients with major depression and 32 healthy control were assayed, Hamilton Depression scale (HAMD) and Hamilton Anxiety Scale (HAMA) were assessed. We then measured 5-HT in platelet, in platelet-poor plasma and in the nuclei of brain tissues obtained from chronic unpredictable mild stress (CUMS) rats with or without citalopram treatment, and from the controls rats that were treated with vehicle. Toward this end, we analyzed whether correlations exist between platelet and brain. RESULTS: No differences were observed among drug-naïve patients, citalopram-treated patients and health control according to gender and age (p>0.05). Drug-naïve depressed patients had highest scores in HAMD and HAMA among the three groups (F=223.3, p<0.01; F=70.7, p<0.01, respectively) Citalopram-treated patients had significantly lower platelet 5-HT levels,compared to control subjects (Mean 58.1±36.8ng/10(9) versus 558.0±199.4ng/10(9), p<0.01) and compared to drug-naïve patients (Mean 58.1 ±36.8ng/10(9) versus 646.4±259.0ng/10(9), p<0.01), while drug-naïve patients had similar 5-HT platelet concentrations as controls(p>0.05). Consistent with clinical results, in comparison with control (1473.4±391.0ng/10(9)) and drug-naive CUMS rats (1559.0±424.4ng/10(9)), the citalopram-treated CUMS rats (684.2±335.6ng/10(9)) demonstrated a significant reduction in platelet 5-HT levels (p<0.01), but there were no difference among the three groups in platelet-poor plasma 5-HT(F=0.11, p>0.05). Hippocampal 5-HT levels were higher among CUMS rats treated with saline (98.2±59.0ng/g) than vehicle animals (31.9±18.3ng/g, p<0.01) or citalopram-treated rats (42.1±33.9ng/g, p<0.05); however, 5-HT concentrations in prefrontal cortex and Raphe Nuclei were consistent among citalopram-treated or saline-treated CUMS rats(p>0.05). Furthermore, the levels of platelet 5-HT did not correlate with neuronal 5-HT levels (p>0.05). LIMITATIONS: Dosages was fix for citalopram-treat rats, and the citalopram-treated vehicle arm did not set up. CONCLUSIONS: Our study suggests that platelet 5-HT levels might respond to SSRI treatment, but this peripheral index is not a direct reflector of central 5-HT levels.