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Schmidt EF, Warner-Schmidt JL, Otopalik BG, Pickett SB, Greengard P, Heintz N. Identification of the Cortical Neurons that Mediate Antidepressant Responses. Cell. 2012 May 25 ; 149(5):1152-63. Pubmed Abstract

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Comment by:  Lei ZhangDavid M. BenedekCarol S. FullertonRobert J. Ursano
Submitted 29 May 2012
Posted 29 May 2012

P11 (S100A10) in cortical neurons' response to antidepressants: A new story for p11
The potential role of p11 (S100A10) in the pathogenesis of psychiatric illness is gaining increasing interest in the neuroscience community. Recent studies suggest that p11 may be important in a number of disorders including posttraumatic disorder (PTSD) and depression (Su et al., 2009; Zhang et al., 2011; Zhang et al., 2008; Svenningsson and Greengard, 2007; Verma et al., 2007; Warner-Schmidt et al., 2009). P11 has been considered as a potential biomarker or therapeutic target for the treatment of depression and PTSD (Su et al., 2009; Zhang et al., 2011; Svenningsson and Greengard, 2007). However, the neuronal cell target or targets for p11-involved treatment in the central nervous system (CNS) remain unknown. In the current study, the authors find that corticostriatal projection neurons are the critical cells for the response to antidepressants in the CNS, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy. They also demonstrate that in corticostriatal pyramidal cells, p11 and serotonin receptor 4 are abundantly expressed, suggesting their strong and specific responses to chronic antidepressant treatment. As antidepressants are also a mainstay of PTSD treatment, their findings suggest that p11 may also mark treatment response in this disorder. Therefore, their findings of p11 action at the neuronal cellular level will facilitate the understanding of the pathology and drug development of stress-related mental disorders such as depression and PTSD.


1. Su, T.P., et al. Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders. Journal of psychiatric research 43, 1078-1085 (2009). Abstract

2. Zhang, L., et al. P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide. Journal of psychiatric research 45, 435-441 (2011). Abstract

3. Zhang, L., et al. p11 is up-regulated in the forebrain of stressed rats by glucocorticoid acting via two specific glucocorticoid response elements in the p11 promoter. Neuroscience 153, 1126-1134 (2008). Abstract

4. Svenningsson, P. and Greengard, P. p11 (S100A10)--an inducible adaptor protein that modulates neuronal functions. Current opinion in pharmacology 7, 27-32 (2007). Abstract

5. Verma, R., et al. Investigating the role of p11 (S100A10) sequence variation in susceptibility to major depression. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 144B, 1079-1082 (2007). Abstract

6. Warner-Schmidt, J.L., et al. Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation. Journal of neuroscience 29, 1937-1946 (2009). Abstract

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