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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

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Abstract

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.

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Acknowledgements

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

Funding

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.

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Authors and Affiliations

  1. Psiquiatria Molecular, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain

    Èlia Vila & Belén Ramos

  2. Intervencions en Salut Mental, Institut de Recerca Sant Joan de Déu, Santa Rosa 39-57, 08950, Esplugues de Llobregat, Spain

    Elena Huerta-Ramos, Christian Núñez & Judith Usall

  3. Parc Sanitari Sant Joan de Déu, Doctor Antoni Pujadas 42, 08830, Sant Boi de Llobregat, Spain

    Elena Huerta-Ramos, Christian Núñez, Judith Usall & Belén Ramos

  4. Instituto de Salud Carlos III, Centro de Investigación en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Elena Huerta-Ramos, Judith Usall & Belén Ramos

  5. Catalan Group in Women’s Mental Health Research (GTRDSM), Barcelona, Spain

    Elena Huerta-Ramos, Christian Núñez & Judith Usall

  6. Dept. de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Belén Ramos

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  1. Èlia Vila
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Correspondence to Judith Usall or Belén Ramos.

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Vila, È., Huerta-Ramos, E., Núñez, C. et al. 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. Eur Arch Psychiatry Clin Neurosci 269, 941–948 (2019). https://doi.org/10.1007/s00406-018-0938-7

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  • DOI: https://doi.org/10.1007/s00406-018-0938-7

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