Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.
BACKGROUND
Altered expression of transcription factor specificity protein 4 (SP4) has been found in the postmortem brain of patients with psychiatric disorders including schizophrenia and bipolar disorder. Reduced levels of SP4 protein have recently been reported in peripheral blood mononuclear cells in first-episode psychosis. Also, SP4 levels are modulated by lithium treatment in cultured neurons. Phosphorylation of SP4 at S770 is increased in the cerebellum of bipolar disorder subjects and upon inhibition of NMDA receptor signaling in cultured neurons. The aim of this study was to investigate whether SP4 S770 phosphorylation is increased in lymphocytes of first-episode psychosis patients and the effect of lithium treatment on this phosphorylation.


METHODS
A cross-sectional study of S770 phosphorylation relative to total SP4 immunoreactivity using specific antibodies in peripheral blood mononuclear cells in first-episode psychosis patients (n = 14, treated with lithium or not) and matched healthy controls (n = 14) by immunoblot was designed. We also determined the effects of the prescribed drugs lithium, olanzapine or valproic acid on SP4 phosphorylation in rat primary cultured cerebellar granule neurons.


RESULTS
We found that SP4 S770 phosphorylation was significantly increased in lymphocytes in first-episode psychosis compared to controls and decreased in patients treated with lithium compared to patients who did not receive lithium. Moreover, incubation with lithium but not olanzapine or valproic acid reduced SP4 phosphorylation in rat cultured cerebellar granule neurons.


CONCLUSIONS
The findings presented here indicate that SP4 S770 phosphorylation is increased in lymphocytes in first-episode psychosis which may be reduced by lithium treatment in patients. Moreover, our study shows lithium treatment prevents this phosphorylation in vitro in neurons. This pilot study suggests that S770 SP4 phosphorylation could be a peripheral biomarker of psychosis, and may be regulated by lithium treatment in first-episode psychosis.
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Raquel
R
Pinacho
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America; Cell, Molecular and Developmental Biology Program, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Gregory
G
Saia
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Montserrat
M
Fusté
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Iria
I
Meléndez-Pérez
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Victoria
V
Villalta-Gil
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Josep Maria
JM
Haro
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Grace
G
Gill
Unitat de recerca, Fundació Sant Joan de Déu, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
Belén
B
Ramos
D000293:Adolescent; D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D000077152:Olanzapine; D010766:Phosphorylation / Q000187:drug effects; D010865:Pilot Projects; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000378:metabolism; D051706:Sp4 Transcription Factor / Q000097:blood*; D014635:Valproic Acid / Q000494:pharmacology; D055815:Young Adult
D014150:Antipsychotic Agents; C497124:SP4 protein, human; D051706:Sp4 Transcription Factor; D001569:Benzodiazepines; D012694:Serine; D014635:Valproic Acid; D008094:Lithium; D000077152:Olanzapine