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.

Magnetisation transfer imaging revealed microstructural changes related to apathy symptoms after ischaemic stroke.

OBJECTIVES: Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. METHODS: We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. RESULTS: Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p = 0.003). These associations were independent of depressive symptoms. CONCLUSION: Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

Changes in the brain directly following alcohol consumption-a study of healthy male individuals, with the use of proton magnetic resonance spectroscopy (1HMRS) and diffusion (DWI).

AIMS: To use proton magnetic resonance spectroscopy (1HMRS) and diffusion weighted imaging (DWI) to identify ethanol in the brain directly after consumption, and examine changes in brain metabolite levels and brain microstructure relative to the duration of time following exposure to alcohol. METHODS: The study involved 44 male volunteers (18-55 years). All brain changes were assessed in the frontal lobes, occipital lobes, basal ganglia and cerebellum, however the detailed analyses focused on the frontal lobes. All participants were examined four times, i.e. before and 0.5-hour, 1 hour and 2 hours after consumption of 150 mL pure vodka (60 g of ethanol). RESULTS: The highest ethanol levels were identified between 0.5 and 1 hour following alcohol intake. There were significant increases in the concentrations of lipids and lactates approximately one hour after alcohol consumption, and the concentration levels were found to normalise during the following two hours. Some statistically insignificant trends of changes were found for tCr, tCho, mI, GABA, Glc, Glx and tNAA. For the DWI and ADC (Apparent Diffusion Coefficient of water) values, the findings showed statistically insignificant decrease and increase, followed by a tendency towards normalisation. Similar associations in changes of metabolite concentrations and DWI and ADC values were found in the other locations investigated in the study. CONCLUSION: A single dose of alcohol as used in this experiment produces increases in lipids and lactates in brain tissues that appear reversible.

Sex differences in brain metabolite concentrations in healthy children - proton magnetic resonance spectroscopy study (1HMRS).

PURPOSE: The aim of this 1HMRS study was to define sex-related differences in metabolic spectrum between healthy children. Forty-nine girls and boys aged 6-15 years were examined. MATERIAL AND METHODS: Volume of interest was located in seven brain regions: frontal lobes, basal ganglia, hippocampi, and cerebellum. RESULTS: Statistical analysis of the results showed significantly higher (p < 0.05) myo-inositol concentrations relative to the total concentrations in the boys than the girls, as well as higher absolute N-acetyl aspartate concentrations in the left frontal lobes in girls. No other significant differences were shown, except for trends in differences. CONCLUSIONS: In clinical practice the diagnostic process first of all focuses on assessing concentrations of metabolites to relative cerebellum concentration. Thus, the findings of the present study allow the conclusion that when analysing the results of 1HMRS studies in children it is not necessary to take into account the child's gender.

Brain Maturation-Differences in Biochemical Composition of Fetal and Child's Brain.

INTRODUCTION: The aim of this study was to evaluate differences in 1H MRS spectra of the brain of fetuses and children from 6 to 11 years of age. MATERIAL AND METHODS: 21 healthy fetuses in the third trimester and 22 children were examined using the proton nuclear magnetic resonance. The relative metabolite concentrations to the sum of all metabolites were calculated. RESULTS: In the 1H MRS spectra of the brain from fetuses and children, there are the same characteristic peaks: N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI). NAA/Σ, NAA/Cr, and Cr/Σ concentrations are significantly higher and Cho/Σ, Cho/Cr, mI/Σ, and mI/Cr are significantly lower in children than in the fetuses. CONCLUSIONS: It was found that the brain metabolism changes from fetal life to childhood. The results of this study may provide a valuable basis for further research on brain maturation and "healthy aging."

Regional Differences in the Concentrations of Metabolites in the Brain of Healthy Children: A Proton Magnetic Resonance Spectroscopy (1HMRS) Study.

BACKGROUND: The aim of this 1HMRS study was to identify any potential regional differences in the metabolic spectrum in the brains of healthy children. MATERIAL/METHODS: Forty-nine healthy children aged 6-15 years (mean 11.6 years) were examined, including 21 girls and 28 boys. A 1.5T MR system (xi Signa HD 1.5T General Electric) was used in patient examinations. The VOI (Volume of Interest) was defined in 7 locations: the frontal lobe in the right and left hemispheres, the basal ganglia in the right and left hemispheres, hippocampus in the right and left hemispheres and cerebellum. SAGE 7.0 software was used for the analysis of data obtained from the 1HMRS study. Differences in the concentrations of metabolites in various regions of the brain in children were verified using the t-test for independent samples. RESULTS: There were significant differences in concentration levels between various brain regions for all the examined metabolites. NAA was the metabolite characterized by the greatest regional variation with significant differences being observed between all locations. Only in the case of Lip/Cr and the ratio of the Lip concentration to the sum of the concentrations of all the metabolites no significant differences could be observed. CONCLUISONS: The results of the study show that a child's brain is inhomogeneous. The results underline the need of the regional differences in the concentrations of metabolites being taken into account when comparing the results of 1HMRS studies in children.

From periphery immunity to central domain through clinical interview as a new insight on schizophrenia.

Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical and laboratory analysis was conducted, incorporating magnetic resonance spectroscopy with immunology markers, psychiatric scores, and biochemical data, on a cohort of 45 patients diagnosed with schizophrenia and 51 healthy controls. The aim was to delineate predictive markers for diagnosing schizophrenia. A logistic regression model was used, as utilized to analyze the impact of multivariate variables on the prevalence of schizophrenia. Utilization of a stepwise algorithm yielded a final model, optimized using Akaike's information criterion and a logit link function, which incorporated eight predictors (White Blood Cells, Reactive Lymphocytes, Red Blood Cells, Glucose, Insulin, Beck Depression score, Brain Taurine, Creatine and Phosphocreatine concentration). No single factor can reliably differentiate between healthy patients and those with schizophrenia. Therefore, it is valuable to simultaneously consider the values of multiple factors and classify patients using a multivariate model.

[Proton spectroscopy of the lower leg muscles before and after exercise]. / Spektroskopia protonowa miesni podudzia przed i po wysilku fizycznym.

The aim of this study was to at tempt to assess the suitability of proton spectroscopy (1HMRS) in deter mining the metabolic state of the lower leg muscles in healthy volunteers before and after intense exercise. 30 healthy volunteers participated in the study, performed on a 1.5T MR scanner using a point-resolved spectroscopy (PRESS) sequence. VOI (Volume of Interest) was localized in the tibialis anterior and soleus muscle lower leg. The data were processed using GE spectroscopy tools. We analyzed on all MR spectra the following metabo lits: intramyocellular lipids (IMCL), extramyocellular lipids (EMCL), carnitine (Ct), creatine (Cr), choline (Cho), trimethylamines (TMA), glucose (Glc), taurine (Tau) and lactate (Lac). We compared the resultant intensity ratios using t - test. Based on statistical analysis of results, there was no si gnificant difference between average value of relative (WSS) (p<0.05) before and after exercise for either the tibialis anterior muscle or soleus muscle. Only the division of the research group into subgroups showed statistical differences. For the tibialis anterior (TA) showed an increase in the TMA subgroup of male group, volunteers whom doing sport occasionally and non smoking. Ct decrease in subgroup volunteers whom exercise time was exactly 20 minutes. For soleus muscle (SOL) increase IMCL(CH2) in subgroup of volunteers whom exercise time was exactly 20 minuts and non smoking. In the subgroup of volunteers doing sports professionally Ct increase after exercise. 1HMRS allows noninvasive studies of muscle metabolism before and after exercises.

The Association of the Oral Microbiota with the Effects of Acid Stress Induced by an Increase of Brain Lactate in Schizophrenia Patients.

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood-brain barrier, leading to the brain acidity. This study aimed to examine the association of the oral microbiota with the effects of acid stress induced by an increase of brain lactate in schizophrenia patients. The study included patients with a diagnosis of acute polyphasic psychotic disorder meeting criteria for schizophrenia at 3-month follow-up. Results: Individuals with a significantly higher total score on the Positive and Negative Syndrome Scale had statistically significantly lower lactate concentrations compared to those with a lower total score and higher brain lactate. We observed a positive correlation between Actinomyces and lactate levels in the anterior cingulate cap and a negative correlation between bacteria associated with lactate metabolism and some clinical assessment scales. Conclusions: Shifts in the oral microbiota in favour of lactate-utilising bacterial genera may represent a compensatory mechanism in response to increased lactate production in the brain. Assessment of neuronal function mediated by ALA-LAC-dependent NMDA regulatory mechanisms may, thus, support new therapies for schizophrenia, for which acidosis has become a differentiating feature of individuals with schizophrenia endophenotypes.

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.

Olfactory Dysfunction in Patients With Relapsing-Remitting Multiple Sclerosis Treated With Disease-Modifying Therapies.

BACKGROUND: Olfactory dysfunction evaluated with time-consuming tests was more common in patients with multiple sclerosis (MS) than in controls and correlated with neurological deficit. The aim of the present study was to compare olfactory function between patients with relapsing-remitting MS (RRMS) and controls with short and simple screening tool-the Sniffin' Sticks Identification Test (SSIT)-and search for its association with clinical and radiological features of the disease. METHODS: The study included 30 controls and 30 patients with RRMS treated with disease-modifying therapies-injectables (interferon ß or glatiramer acetate, N = 18) and oral drugs (dimethyl fumarate or fingolimod, N = 12). Hyposmia was defined as a score of 6 points or fewer in the SSIT olfactory test. The data concerning number of previous relapses, disability in Expanded Disability Status Scale (EDSS), and recent brain magnetic resonance imaging (MRI) scan were collected. Moreover, thalamic volume and third ventricle width were recorded in every patient. Additionally, cognition and fatigue in patients were evaluated 24 months after olfactory assessment with the Symbol Digit Modalities Test (SDMT) and Fatigue Scale for Motor and Cognitive Functions (FSMC), respectively. RESULTS: Patients with RRMS had a higher risk of hyposmia than controls (66.7% vs 36.7%, OR = 1.82, 95% CI, 1.10-3.67, P = .02). Neither inflammatory (number of previous relapses or new brain MRI lesions) nor neurodegenerative (EDSS, SDMT, and FSMC scores; thalamic volume; third ventricle width) MS features did not correlate with SSIT score (P > .05). In patients treated with oral drugs, olfactory dysfunction correlated with FSMC cognitive subscale (r = -0.90, P = .006). CONCLUSIONS: Olfactory dysfunction is nearly twice as common in RRMS as in controls and correlates with fatigue level in patients treated with dimethyl fumarate or fingolimod.

Relationship of metabolic parameters with the course of the first episode of psychosis - preliminary research. / Zwiazek parametrów metabolicznych z przebiegiem pierwszego epizodu psychozy ­ badania wstepne.

OBJECTIVES: Cardiometabolic syndromes are the most common causes of complications shortening life expectancy in patients treated for mental disorders, especially schizophrenia. However, how much cardiometabolic risk is related to lifestyle, side-effects of treatment or psychosis is not clear. The aim of this study was a prospective assessment of metabolic changes in young, initially somatically healthy patients diagnosed with the first acute episode of psychosis with no prior pharmacological treatment. METHODS: The study involved 15 young patients (average age of 19.95 ± 6.88 years). Analyses (laboratory and clinical) were performed at the time of admission and after 3 and 12 weeks and included morphology, lipid profile, glucose, inflammation markers, blood pressure (BP), and body mass index (BMI). The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), and the cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). The duration of untreated psychosis (DUP) was also measured. RESULTS: There was a significant increase in BMI, dyslipidemia, inflammation, and systolic blood pressure after 12 weeks from the start of the treatment, while cortisol level decreased. A negative correlation was observed between PANSS-P (PANSS positivescale) measurements and total cholesterol, PANSS total and low-density lipoprotein, as well as DUPand MoCA. High-density lipoprotein (HDL) correlated positively with DUP, cortisol, monocytes, and white blood cells in the first week. CONCLUSIONS: The results of the study indicate a relationship between the development and treatment of the first acute episode of psychosis and the results of laboratory tests that are indicators of the development of metabolic stress in patients.

Determinants of Schizophrenia Endophenotypes Based on Neuroimaging and Biochemical Parameters.

Despite extensive research, there is no convincing evidence of a reliable diagnostic biomarker for schizophrenia beyond clinical observation. Disorders of glutamatergic neurotransmission associated with N-methyl-D-aspartate (NMDA) receptor insufficiency, neuroinflammation, and redox dysregulation are the principal common mechanism linking changes in the periphery with the brain, ultimately contributing to the emergence of negative symptoms of schizophrenia that underlie differential diagnosis. The aim of the study was to evaluate the influence of these systems via peripheral and cerebral biochemical indices in relation to the patient's clinical condition. Using neuroimaging diagnostics, we were able to define endophenotypes of schizophrenia based on objective laboratory data that form the basis of a personalized approach to diagnosis and treatment. The two distinguished endophenotypes differed in terms of the quality of life, specific schizophrenia symptoms, and glutamatergic neurotransmission metabolites in the anterior cingulate gyrus. Our results, as well as further studies of the excitatory or inhibitory balance of microcircuits, relating the redox systems on the periphery with the distant regions of the brain might allow for predicting potential biomarkers of neuropsychiatric diseases, including schizophrenia. To the best of our knowledge, our study is the first to identify an objective molecular biomarker of schizophrenia outcome.

Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study.

INTRODUCTION: In women undergoing breast-conserving surgery (BCS), 20-25% require a re-operation as a result of incomplete tumour resection. An intra-operative technique to assess tumour margins accurately would be a major advantage. A novel method for intraoperative margin assessment was developed by applying a thin flexible scintillating film to specimens-flexible autoradiography (FAR) imaging. A single-arm, multi-centre study was conducted to evaluate the feasibility of intraoperative [18F]FDG FAR for the assessment of tumour margins in BCS. METHODS: Eighty-eight patients with invasive breast cancer undergoing BCS received ≤ 300 MBq of [18F]FDG 60-180 min pre-operatively. Following surgical excision, intraoperative FAR imaging was performed using the LightPath® Imaging System. The first 16 patients were familiarisation patients; the remaining 72 patients were entered into the main study. FAR images were analysed post-operatively by three independent readers. Areas of increased signal intensity were marked, mean normalised radiances and tumour-to-tissue background (TBR) determined, agreement between histopathological margin status and FAR assessed and radiation dose to operating theatre staff measured. Subgroup analyses were performed for various covariates, with thresholds set based on ROC curves. RESULTS: Data analysis was performed on 66 patients. Intraoperative margin assessment using FAR was completed on 385 margins with 46.2% sensitivity, 81.7% specificity, 8.1% PPV, 97.7% NPV and an overall accuracy of 80.5%, detecting both invasive carcinoma and DCIS. A subgroup analysis based on [18F]FDG activity present at time of imaging revealed an increased sensitivity (71.4%), PPV (9.3%) and NPV (98.4%) in the high-activity cohort with mean tumour radiance and TBR of 126.7 ± 45.7 photons/s/cm2/sr/MBq and 2.1 ± 0.5, respectively. Staff radiation exposure was low (38.2 ± 38.1 µSv). CONCLUSION: [18F]FDG FAR is a feasible and safe technique for intraoperative tumour margin assessment. Further improvements in diagnostic performance require optimising the method for scintillator positioning and/or the use of targeted radiopharmaceuticals. TRIAL REGISTRATION: Identifier: NCT02666079. Date of registration: 28 January 2016. URL: https://clinicaltrials.gov/ct2/show/NCT02666079 . ISRCTN registry: Reference: ISRCTN17778965. Date of registration: 11 February 2016. URL: http://www.isrctn.com/ISRCTN17778965 .

[Presurgical functional brain examination MR (fMRI)]. / Przedoperacyjne badanie funkcjonalne mózgu MR (fMRI).

Neurosurgery in functionally relevant brain structures carries a high risk for surgery induced post-operative neurological deficits. Functional magnetic resonance imaging (fMRI) is one of the most commonly used functional neuroimaging techniques for pre-surgical brain mapping. Preoperative fMRI is optimal method to localize specific functions of the human brain that govern motor, sensory or language functions. fMRI facilitates the selection of the safest treatment and is very helpful to plane and to perform function preserving surgery in patients with brain tumors. This kind of examination is feasible for clinical routine neuroimaging and provides important diagnostic information noninvasively that is otherwise unavailable. fMRI examinations require also advanced software for data analysis.

[Myoinositol trends in HMRS brain spectrum of patients with hepatic encephalopathy]. / Ocena zachowania mioinozytolu w widmie metabolicznym mózgowia (HMRS) u pacjentów z encefalopatia watrobowa.

Hepatic encephalopathy (HE) comprises a complex set of neuropsychiatric abnormalities upon primary hepatic dysfunction. Ammonia and other nitrogen-based compounds are thought to be essential etiological factors when dysmetabolized in the liver, they provoke highly undesirable neuroglial transmission in the central nervous system (CNS). Proton MR spectroscopy (HMRS) is a noninvasive in vivo method of analyzing the metabolic spectrum of neuronal tissue and its pathological changes even before overt clinical symptoms occur and can be seen in morphological MR examination. Myoinositol (ml) is one of the metabolites that can be identified with HMRS. It is considered a glial marker, directly involved in compensation processes to overcome toxic effects of hepatic metabolites which had crossed the brain-blood barrier. Thus, ml may be a crucial prognostic factor for patients with HE. The goal of the present paper was to selectively investigate ml trends upon the MR brain spectrum. 36 male participants were enrolled in the study: 20 patients (mean age 58.2 years) with clinical symptoms suggestive of HE in the course of either chronic viral hepatitis or post-viral liver cirrhosis, and 16 men (mean age 51.3 years) with normal liver function (control group). Brain MR examinations were performed in all participants, followed by HMRS in single voxel spectroscopy (SVS) technique from occipital gray matter of right (Voxel 1) and left (Voxel 2) cerebral hemispheres. MR data were acquired with a 1.5 T GE Signa Excite scanner. ml peak height was normalized with respect to creatine. A statistically significant decrease in ml/Cr ratio has been appreciated in the MR spectra of HE patients. The mean ml/Cr ratio for HE patients was 0.75, and was 0.93 for the control group, and, for alpha = 0.05, the observed differences between ml/Cr ratio mean values appeared to be statistically significant.

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders.

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.

Evaluation of changes in biochemical composition of fetal brain between 18th and 40th gestational week in proton magnetic resonance spectroscopy.

INTRODUCTION: The aim of this study is to determine the right 1H MRS spectra of the brain in fetuses of different age, and then to define what metabolic changes occur between 18th and 40th weeks of pregnancy. METHODS: 1H MRS studies of 32 fetuses aged 18-40 gestational weeks were performed, in which the MRI excluded central nervous system malformations. The studied group included 11 fetuses aged 18-25 weeks (the second half of the second trimester), 14 fetuses aged 26-33 weeks (the first half of the third trimester), and seven fetuses aged 34-40 weeks (the second half of the third trimester). The relative ratios of metabolites concentrations to the sum of all metabolites were calculated. RESULTS: Increase in the concentrations of N-acetylaspartate (NAA), Cr, Cho, and myo-inositol (mI) with gestational age is statistically significant. Only increase in Glx is statistically insignificant. In the analyzed period of pregnancy also, an insignificant increase of NAA/Σ and Cr/Σ ratios and a decrease of mI/Σ, Cho/Σ and Glx/Σ ratios were noticed. CONCLUSIONS: Changes in the 1H MRS spectrum are visible with increasing age of the fetus. All studied substances in fetal brain change their concentrations during pregnancy, which may be associated with the synaptic and dendritic development as well as myelination. Knowledge about the chemical changes in the fetal brain can provide valuable information in studies of the mechanisms of pregnancy and fetal development, define steps of brain metabolic development and explain reasons of pathologies.

Microstructure changes of occipital white matter are responsible for visual problems in the 3-4-year-old very low birth weight children.

PURPOSE: The main aim of the study was to evaluate which factors affect the long-time visual function in preterm children, whether it is prematurity or retinopathy of prematurity or perhaps disturbances in the visual pathway. MATERIALS AND METHODS: Fifty-eight children with mean birth weight 1016 g (range 520-1500 g) were evaluated at mean age 48 months (range 42-54 months). All children underwent magnetic resonance imaging (MRI) studies, visual evoked potentials (VEPs), and the Developmental Test of Visual Perception (DTVP). The MRI evaluation included diffusion tensor imaging and fractional anisotropy (FA), and colored orientation maps were calculated for each subject. Based on the results of the VEP evaluation, children were divided into two groups: A-abnormal results of VEP (n = 16) and B-normal VEP results (comparison group, n = 42). RESULTS: FA values of inferior left and right occipital white matter (OWM) were lower in the group of children with abnormal VEP compared to the comparison group (0.34 ± 0.06 vs. 0.38 ± 0.06; P = 0.047; 0.31 ± 0.04 vs. 0.36 ± 0.06; P = 0.007, respectively). Furthermore, there were correlations between the latency (r = -0.35; P = 0.01) and amplitude (r = 0.31; P = 0.02) and FA in OWM. Children with abnormal VEP had lower DTVP scores as compared with children with normal VEP results (88 ± 18 vs. 95 ± 16 points, P = 0.048). Finally, a multivariate logistic regression revealed that FA of the inferior OWM was the only independent risk factor for the abnormal VEP (P = 0.04). CONCLUSION: Visual perception, VEPs, and white matter microstructural abnormalities in very low birth weight children at the age of 3-4 are significantly correlated.