Specificity proteins 1 and 4 in peripheral blood mononuclear cells in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial

  • Èlia Vila
  • Elena Huerta-Ramos
  • Christian Núñez
  • Judith UsallEmail author
  • Belén RamosEmail author
Original Paper


Accumulating evidence suggests that Specificity Protein 1 (SP1) and 4 (SP4) transcription factors are involved in the pathophysiology of schizophrenia. The therapeutic use of selective oestrogen modulators such as raloxifene added to antipsychotic drugs in the treatment of postmenopausal women with schizophrenia has been investigated in a few clinical trials, which reported an improvement in negative, positive, and general psychopathological symptoms. We aimed to investigate the possible association between peripheral SP protein levels and symptom improvement in postmenopausal women with schizophrenia treated with adjuvant raloxifene. In a subgroup of 14 postmenopausal women with schizophrenia from a 24-week, randomized, parallel, double-blind, placebo-controlled clinical trial (NCT015736370), we investigated changes in SP1 and SP4 protein levels in peripheral blood mononuclear cells. Participants were randomized to either 60 mg/day adjunctive raloxifene or placebo. Psychopathological symptoms were assessed at baseline and at week 24 with the Positive and Negative Syndrome Scale (PANSS). The expression of SP proteins was evaluated by immunoblot, and changes in PANSS scores and protein levels were compared at baseline and after 24 weeks of treatment. An improvement in symptoms was observed in the intervention group, but not in placebo group. Post-treatment protein levels of SP4, but not SP1, correlated with improvements in general and total PANSS subscales in the raloxifene intervention group. A reduction in SP4 levels was found after raloxifene treatment. These results suggest that SP4 may be involved in raloxifene symptom improvement in postmenopausal women and could be a potential candidate for future studies investigating blood-based biomarkers for raloxifene effectiveness.


Raloxifene Schizophrenia Blood biomarkers SP4 transcription factor Postmenopause, symptoms 



We thank Dr. Rose of Rose Translation Services (UK) for the English editing of this manuscript.


This work was supported by the Stanley Medical Research Institute (10T-1392) to JU and a Miguel Servet grant (MS16/00153- CP16/00153) to BR financed and integrated into the National R + D + I and funded by the Instituto de Salud Carlos III (Spanish Ministry of Health)—General Branch Evaluation and Promotion of Health Research—and the European Regional Development Fund (ERDF). The funding bodies had no further role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflicts of interest.

Supplementary material

406_2018_938_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 35 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Psiquiatria MolecularInstitut de Recerca Sant Joan de DéuEsplugues de LlobregatSpain
  2. 2.Intervencions en Salut MentalInstitut de Recerca Sant Joan de DéuEsplugues de LlobregatSpain
  3. 3.Parc Sanitari Sant Joan de DéuSant Boi de LlobregatSpain
  4. 4.Instituto de Salud Carlos III, Centro de Investigación en Red de Salud Mental (CIBERSAM)MadridSpain
  5. 5.Catalan Group in Women’s Mental Health Research (GTRDSM)BarcelonaSpain
  6. 6.Dept. de Bioquímica i Biologia Molecular, Facultat de MedicinaUniversitat Autònoma de BarcelonaBellaterraSpain

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