Dataset Information

Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.

ABSTRACT:

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.

SUBMITTER: Pinacho R

PROVIDER: S-EPMC4411105 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.

Pinacho Raquel R Saia Gregory G Fusté Montserrat M Meléndez-Pérez Iria I Villalta-Gil Victoria V Haro Josep Maria JM Gill Grace G Ramos Belén B

PloS one 20150427 4

<h4>Background</h4>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 subject ...[more]

PMID: 25915526

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Project description:BackgroundThough olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions.MethodFEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined.ResultsIndividuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles.ConclusionsThese findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.

Dataset Information

Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.

Background

Methods

Results

Conclusions

Publications

Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.

Similar Datasets

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