Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia.

BACKGROUND: Schizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC. AIM: To investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia. MATERIAL AND METHODS: The participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing. RESULTS: Moderate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1-CCR3) and between CpGmean and MD of CCR1 in SCH. Weaker positive correlations were found for CpGmean with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH. CONCLUSIONS: The methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations.

Serum Inflammatory Markers and Integrity of the Superior Longitudinal Fasciculus and the Inferior Longitudinal Fasciculus in Schizophrenia, from Prodromal Stages to Chronic Psychosis-A Cross-Sectional Study.

Chronic subclinical inflammation is believed to be an important factor in the pathogenesis of schizophrenia. Meta-analyses confirm the presence of increased levels of peripheral inflammatory markers (IM) in schizophrenia and its prodromal stages. Peripheral cytokines may affect the brain microstructure through chronic activation of microglia. Disruptions in the integrity of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) are commonly seen in patients with schizophrenia spectrum disorders. We therefore attempted to verify in a cross-sectional study whether there is a correlation between levels of peripheral IM and the integrity of these brain regions in healthy controls, from prodromal states and first episode psychosis to long-term schizophrenia. The integrity of white matter was measured using diffusion tensor imaging. Despite a broad analysis of six IM (CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ), we did not find any correlations with the integrity of the SLF or ILF in any of the analyzed groups (after correction for multiple comparisons). In conclusion, our study does not support the existence of a link between disrupted levels of peripheral IM and reduced integrity of ILF and SLF in schizophrenia spectrum disorders. However, prospective studies are needed to verify this over a long period of time.

Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis.

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies.

Psychopathology and Integrity of the Superior Longitudinal Fasciculus in Deficit and Nondeficit Schizophrenia.

The superior longitudinal fasciculus (SLF) is a white matter bundle that connects the frontal areas with the parietal areas. As part of the visuospatial attentional network, it may be involved in the development of schizophrenia. Deficit syndrome (DS) is characterized by primary and enduring negative symptoms. The present study assessed SLF integrity in DS and nondeficit schizophrenia (NDS) patients and examined possible relationships between it and psychopathology. Twenty-six DS patients, 42 NDS patients, and 36 healthy controls (HC) underwent psychiatric evaluation and diffusion tensor imaging (DTI). After post-processing, fractional anisotropy (FA) values within the SLF were analyzed. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. The PANSS proxy for the deficit syndrome was used to diagnose DS. NDS patients had lower FA values than HC. DS patients had greater negative symptoms than NDS patients. After differentiating clinical groups and HC, we found no significant correlations between DTI measures and psychopathological dimensions. These results suggest that changes in SLF integrity are related to schizophrenia, and frontoparietal dysconnection plays a role in its etiopathogenesis. We confirmed that DS patients have greater negative psychopathology than NDS patients. These results are preliminary; further studies are needed.

Serum inflammatory markers and their associations with white matter integrity of the corpus callosum in schizophrenia patients and healthy controls.

Schizophrenia is associated with disrupted integrity of white matter microstructure of a variety of brain regions, especially the corpus callosum (CC). Chronic subclinical inflammation is considered to be one of the factors involved in the pathogenesis of this disease, and increased levels of peripheral inflammatory markers are often observed in schizophrenia patients. Therefore, we decided to investigate whether the integrity of the corpus callosum is correlated with levels of these markers. A total of 50 patients with stable chronic schizophrenia (SCH) and 30 controls (CON) were enrolled in the study. All participants underwent psychiatric evaluation, neuroimaging, and blood sampling including the measurement of serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL - 10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and C-reactive protein (CRP). Additional potentially related factors, such as age, gender, BMI, smoking, disease duration, and treatment were included in the analysis. Significantly higher IL-6 and IFN-γ levels were observed in SCH compared to CON. In SCH, IFN-γ was positively correlated with mean diffusivity of region 2 of the CC. In CON, IL-6 was inversely correlated with fractional anisotropy of region 1 of the CC. These results support the potential influence of peripheral inflammatory markers on the integrity of the CC in schizophrenia, but require verification in longitudinal studies.

Relationship of Corpus Callosum Integrity with Working Memory, Planning, and Speed of Processing in Patients with First-Episode and Chronic Schizophrenia.

There is a paucity of reports examining the relationship between the integrity of the corpus callosum (CC) and different aspects of cognitive functioning in patients with first-episode (FES) and chronic schizophrenia (CS) simultaneously; furthermore, what results exist are inconclusive. We used diffusion tensor imaging tractography to investigate differences in integrity in five regions of the CC between FES, CS, and healthy controls (HC). Additionally, we analyzed correlations between these regions' integrity and working memory, planning, and speed of processing. Eighteen patients with FES, 55 patients with CS, and 30 HC took part in the study. We assessed cognitive functions with four tasks from Measurement and Treatment Research to Improve Cognition in Schizophrenia. Patients with CS showed lower fractional anisotropy (FA) in Region 5 (statistical trend) and higher mean diffusivity (MD) in Regions 4 and 5 than HC, and patients with FES had higher MD in Region 3 (statistical trend) than HC. Both clinical groups performed worse on working memory and speed of processing tasks than HC, and patients with CS scored worse than HC on independent planning, and worse than FES and HC on dependent planning. Moreover, in patients with CS, MD in Region 3 was correlated with verbal working memory. Our results suggest that patients with FES and CS are characterized by impaired integrity of the middle and posterior CC, respectively. We confirmed that both clinical groups have cognitive impairments. Moreover, the integrity of the middle CC may influence planning in patients with CS.

White Matter Integrity of the Corpus Callosum and Psychopathological Dimensions in Deficit and Non-Deficit Schizophrenia Patients.

Deficit syndrome (DS) is a subtype of schizophrenia characterized by primary persistent negative symptoms. The corpus callosum (CC) appears to be related to psychopathology in schizophrenia. This study assessed white matter integrity in the CC using diffusion tensor imaging (DTI) in deficit and non-deficit schizophrenia (NDS) patients. We also investigated the psychopathological dimensions of schizophrenia and their relationship to CC integrity. Fifteen DS patients, 40 NDS patients, and 30 healthy controls (HC) underwent psychiatric evaluation and neuroimaging. We divided the CC into five regions and assessed their fractional anisotropy (FA) and mean diffusivity (MD). Psychopathology was assessed with the Positive and Negative Syndrome Scale. DS patients had lower FA than NDS patients and HC, and higher MD in Region 5 of the CC than did HC. NDS patients had higher MD in Region 4 of the CC. The patient groups differed in terms of negative symptoms. After differentiating clinical groups and HC, no significant correlations were observed between DTI measures and psychopathological symptoms. Our results suggest that DS and NDS are characterized by minor impairments of the posterior CC. We confirmed that DS patients have greater negative psychopathology than NDS patients. Our results are preliminary, and further studies are needed.

The relationship between cingulum bundle integrity and different aspects of executive functions in chronic schizophrenia.

BACKGROUND: Evidence suggests that disruption in the cingulum bundle (CB) may influence executive dysfunctions in schizophrenia, but findings are still inconsistent. Using diffusion tensor imaging tractography, we investigated the differences in fiber integrity between schizophrenia patients and healthy controls together with the association between fiber integrity and executive functions. METHODS: Thirty-two patients with chronic schizophrenia and 24 healthy controls took part in the study. Both groups were matched for age, sex, and years of education. Assessment of cognitive functions was performed using the Berg Card Sorting Test (BCST), the Color Trail Test (CTT), and the Stroop Color-Word Test (SCWT). RESULTS: Results showed group differences, bilaterally (left and right) in fractional anisotropy (FA) of the CB, where patients showed less anisotropy than controls. Moreover, normal asymmetry (left FA > right FA) in the CB in schizophrenia was found. There were no group differences in mean diffusivity (MD). Patients had a similar but reduced profile of executive functions compared to healthy controls. However, when premorbid IQ was controlled for, the differences were no longer statistically significant. In schizophrenia patients, a negative correlation was found between FA of the left CB and perseverative errors in the BCST. CONCLUSIONS: These findings provide evidence that CB disruption appears in schizophrenia patients and might account for impairments of executive processes, including concept formation.

[Intracranial remote epidural haematoma as a complication after resection of an occipital lobe metastatic tumour from a testicular embryonal carcinoma ­ a case report].

We present the case of a patient who suffered from intracranial epidural haematoma in the left fronto -temporo -parietal region as a complication after left parieto -occipital craniotomy and a resection of a metastatic lesion from a testicular embryonal carcinoma to the left occipital lobe. We also discuss possible causes of this complication.