Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia.

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients' self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

Benefits and Meaning of Lipids Profile in Relation to Oxidative Balance and Brain Morphology in Schizophrenia.

Schizophrenia is characterized by complex metabolic dysregulations and their consequences. Until now, numerous theories have explained its pathogenesis, using a spectrum of available technologies. We focused our interest on lipid profile-periphery high-density cholesterol level and lipoproteins in the human brain and compared magnetic resonance imaging (MRI) scans of patients with schizophrenia and the healthy group. Detailed analysis of biochemical parameters was performed using magnetic resonance spectroscopy. Our study aimed to reveal correlations between periphery high-density lipoproteins levels and lipoproteins in the brain, depicted in MRI scans, and parameters of peripheral oxidative stress expressed as paraoxonase. Patients with schizophrenia have decreased levels of high-density lipoproteins, low paraoxonase activity, and slightly raised sodium in the blood. Positive significant correlations between serum high-density cholesterol and anterior cingulate cortex, unique brain area for schizophrenia pathophysiology, MR spectroscopy signals, and diffusion have been revealed. To our knowledge, this is the first study to describe the effect of an anterior cingulate disorder on high-density cholesterol levels on the development of schizophrenia.

Immunological routine laboratory parameters at admission influence the improvement of positive symptoms in schizophrenia patients after pharmacological treatment.

Introduction: The standard care of schizophrenia patients is based on the assessment of their psychotic behavior, using interview-based, subjective scales that measure symptoms severity. We aimed at defining easily accessible and inexpensive blood-derived clinical diagnostic parameters that might serve as objective markers in the prediction of the effects of pharmacological treatment of schizophrenia patients. Methods: A total of 40 patients with schizophrenia diagnosis according to ICD 10 during psychotic decompensation were included in the study. Blood-based biochemical parameters, BMI and interview-based medical scales of symptom severity were determined - all at admission and after 12 weeks of standard pharmacological treatment. Results: The drops in scale values were correlated with clinical parameters. All scale changes after treatment were dependent on the value of the given scale at admission, with higher initial values leading to larger drops of the values after treatment. Models based on those correlations were significantly improved when immune and metabolism parameters were included. C4 complement and C-reactive protein (CRP) level at admission were predictive of changes in Positive and Negative Syndrome Scale (PANSS) subscales related to significant disruption of thought processes, reality testing and disorganization. The pharmacological treatment-driven changes in scales representing negative symptoms were correlated with markers of the patients' thyroid status and metabolism. Discussion: We show that objective markers can be obtained by testing immune and metabolic parameters from the patients' blood and may be added at a low cost to the standard care of schizophrenia patients in order to predict the outcome of pharmacological treatment.

Redefining the Cut-Off Ranges for TSH Based on the Clinical Picture, Results of Neuroimaging and Laboratory Tests in Unsupervised Cluster Analysis as Individualized Diagnosis of Early Schizophrenia.

Thyroid abnormalities, including mild forms of hypothyroidism and hyperthyroidism, are reported as risk factors for the development of a number of neuropsychiatric disorders, including schizophrenia. The diagnostic process still takes into account the extreme ranges of the accepted reference values for serum TSH since the concentration of free thyroxine in the serum does not change by definition. TSH mU/L cut-off values in psychiatric patients are currently clinically considered in the case of extremely high serum TSH levels (>4.0 mU/L). The results obtained in this study suggest that the clinically significant value has a lower TSH cut-off point with an upper limit of 2-2.5 mU/L. The criteria for the differential diagnosis of patients with schizophrenia, however, mainly take into account statutory reference ranges without a background related to the history of thyroid diseases in the family. The results indicate the need to lower the upper cut-off values for TSH among patients with early psychosis, which is related to the potential clinical significance of the obtained values both in the field of clinical evaluation and neuroimaging and laboratory evaluation parameters. The cut-off points obtained with the prior available knowledge coincided with the values established in the unsupervised clustering method, which further confirms the legitimacy of their use in the individualized diagnosis strategy of schizophrenia.

Predictive factors of complications post intracranial meningioma surgery leading to early unplanned reoperations - a single center study.

INTRODUCTION: Complications occurring after neurosurgical procedures which lead to reoperations are associated with poor treatment outcomes. The aim of our study was to establish predictive factors of unplanned early reoperations after intracranial meningioma removal. MATERIALS AND METHODS: We retrospectively analyzed 177 patients who underwent craniotomy due to an intracranial meningioma. Early reoperation was de ned as reoperation during the same hospital stay. We used a χ2 test for proportional values and t-test and Mann-Whitney U tests as appropriate for continuous variables. To determine the potential predictors of early reoperation we used univariate and multivariate logistic regression analyses. RESULTS: A total of 13 (7.34%) patients underwent unplanned early reoperation. These patients underwent retrosigmoid craniotomies (25.00% vs. 6.40%; p = 0.047), suffered from ischemic heart disease (66.67% vs. 6.64%; p <0.01) and atrial fibrillation (60.00% vs. 6.25%; p <0.01), were receiving heparin (50.00% vs. 6.74%; p <0.01) and anticoagulants (66.67% vs. 6.21%; p <0.01) significantly more often than the general study population. In multivariate logistic regression analysis anticoagulant use (OR: 31.463; 95% CI: 1.139-868.604; p = 0.04) and retrosigmoid craniotomy (OR: 6.642; 95% CI: 1.139-38.73; p = 0.034) remained independently associated with a higher risk of early reoperation. CONCLUSIONS: Patients who underwent retrosigmoid craniotomy, those with a history of ischemic heart disease or atrial fibrillation and those who take heparin or anticoagulants are more likely to require early reoperation. Retrosigmoid craniotomy and anticoagulant use are independent risk factors for early reoperation.

Emergency Reoperations in Cranial Neurosurgery.

BACKGROUND: Complications after neurosurgical procedures that lead to reoperation are associated with poor outcome and economic costs. Therefore the aim of our study was to establish predictors of reoperation due to complications after cranial neurosurgery. METHODS: We retrospectively analyzed 875 patients who underwent a cranial neurosurgical procedure. We used univariate and multivariate logistic regression analysis to determine the possible predictors of reoperation. RESULTS: A total of 78 (8.91%) patients underwent emergency reoperation. Those patients more often were operated due to brain tumor (50.65% vs. 38.43%; P = 0.036) and least often due to head trauma (22.08% vs. 32.99%; P = 0.049). Reoperated patients more often underwent frontal craniotomy (26.47% vs. 13.46%; P < 0.01) and least often had burr hole surgery (7.35% vs. 19.21%; P = 0.016). Patients who did not require reoperation were more often operated during a weekend (5.29% vs. 16.99%; P < 0.01). After adjustment for confounders, weekend surgeries (OR: 0.309; 95% CI: 0.111-0.861; P = 0.025) remained independently associated with reduced risk of reoperation and frontal craniotomy (OR: 1.355; 95% CI: 1.005-1.354; P = 0.046) and lower mean cell hemaglobin concentration (OR: 2.227; 95% CI: 1.230-4.033; P < 0.01) remained independently associated with higher risk of reoperation. CONCLUSIONS: Brain tumor surgery and frontal craniotomy are associated with a higher risk of emergency reoperation. Patients with head trauma, operated on during a weekend, and those who underwent burr hole surgery are less likely to be reoperated. Frontal craniotomy and lower mean cell hemoglobin concentration are independently associated with a higher risk of reoperation and operation during a weekend with lower risk of reoperation.