Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis.

We assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis.

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.

Reduced expression of SP1 and SP4 transcription factors in peripheral blood mononuclear cells in first-episode psychosis.

Alterations of transcription factor specificity protein 4 (SP4) and 1 (SP1) have been linked to different neuropsychiatric diseases. Reduced SP4 and SP1 protein levels in the prefrontal cortex have been associated with bipolar disorder and schizophrenia, respectively, suggesting that both factors could be involved in the pathogenesis of disorders with psychotic features. The aim of this study was to investigate whether the reduction of SP1, SP4 and SP3 protein and mRNA expression in peripheral blood mononuclear cells in the early stages of psychosis may act as a potential biomarker of these disorders. A cross-sectional study of first-episode psychosis patients (n = 14) compared to gender- and age-matched healthy controls (n = 14) was designed. Patients were recruited through the adult mental health services of Parc Sanitari Sant Joan de Déu. Protein and gene expression levels of SP1, SP4 and SP3 were assessed in peripheral blood mononuclear cells of patients with first-episode psychosis and healthy control subjects. We report that protein levels of SP1 and SP4, but not SP3, are significantly reduced in patients compared to controls. In contrast, we did not observe any differences in expression levels for SP1, SP4 or SP3 genes between patient and control groups. In patients, SP4 protein levels were significantly associated with SP1 protein levels. No association was found, however, between protein and gene expression levels for each factor. Our study shows reduced SP1 and SP4 protein levels in first-episode psychosis in lymphocytes, suggesting that these transcription factors are potential peripheral biomarkers of psychotic spectrum disorders in the early stages.

Functional similarity of facial emotion processing between people with a first episode of psychosis and healthy subjects.

BACKGROUND: Neurofunctional and behavioral abnormalities in facial emotion processing (FEmoP) have been consistently found in schizophrenia patients, but studies assessing brain functioning in early phases are scarce and the variety of experimental paradigms in current literature make comparisons difficult. The present work focuses on assessing FEmoP in people experiencing a psychotic episode for the first time with different experimental paradigm approaches. METHODS: Twenty-two patients with a first psychotic episode (FPe) (13 males) took part in a functional magnetic resonance imaging study (1.5T) examining neural responses to explicit and implicit processing of fearful and happy facial expressions presented at two different intensities: 50% and 100%. Their brain activation was compared to that of 31 healthy subjects (15 males). RESULTS: Control subjects show differential patterns of brain activation regarding the task demands (implicit or explicit processing), the emotional content (happy or fear) and the intensities of the emotion (50% or 100%); such differences are not found in participants with a first psychotic episode (FPe). No interaction or group effects are seen between control and FPe participants with any of the emotional tasks assessed, although FPe subjects show worse behavioral performance. CONCLUSIONS: No brain areas recruited for FEmoP emerge as significantly different between people with a FPe and healthy subjects, independently on the demands of the task, the emotion processed, or the intensity of the emotion; but FPe participants show a limited recruitment of differential brain regions that could be associated with poor emotional processing in the short term. Our results outline the need of investigating the underlying processes that lead FPe participants to worse FEmoP performance.