Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease.

The integration of disparate data types provides a more complete picture of complex biological systems. Here we combine small-volume metabolomic and transcriptomic platforms to determine subtle chemical changes and to link metabolites and genes to biochemical pathways. Capillary electrophoresis–mass spectrometry (CE–MS) and whole-genome gene expression arrays, aided by integrative pathway analysis, were utilized to survey metabolomic/transcriptomic hippocampal neurochemistry. We measured changes in individual hippocampi from the mast cell mutant mouse strain, C57BL/6 Kit^W-sh/W-sh. These mice have a naturally occurring mutation in the white spotting locus that causes reduced c-Kit receptor expression and an inability of mast cells to differentiate from their hematopoietic progenitors. Compared with their littermates, the mast cell-deficient mice have profound deficits in spatial learning, memory, and neurogenesis. A total of 18 distinct metabolites were identified in the hippocampus that discriminated between the C57BL/6 Kit^W-sh/W-sh and control mice. The combined analysis of metabolite and gene expression changes revealed a number of altered pathways. Importantly, results from both platforms indicated that multiple pathways are impacted, including amino acid metabolism, increasing the confidence in each approach. Because the CE–MS and expression profiling are both amenable to small-volume analysis, this integrated analysis is applicable to a range of volume-limited biological systems.

The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer’s disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.

BACKGROUND: Studies suggest that the components of brain-evoked potentials (EPs) may serve as biomarkers of the post-traumatic stress disorder (PTSD) caused by participation in combat operations; however, to date, research remains fragmented, with no studies that have attempted to combine different paradigms. In addition, the mismatch negativity component has not been studied in a Russian sample of veterans with PTSD. AIM: To identify objective neurophysiological markers of combat-related PTSD using the method of auditory-evoked potentials in active and passive listening paradigms. METHODS: The study included a recording of auditory EPs in an oddball paradigm in three settings: 1) directed attention to auditory stimuli, 2) passive listening while viewing a neutral video sequence, and 3) viewing a video sequence associated with a traumatic event. Combatants diagnosed with PTSD (18 people) were compared with mentally healthy civilian volunteers (22 people). RESULTS: An increase in the latency period of the early components of auditory EP (N100 and P200), an increase in the amplitude of the P200 component to a deviant stimulus, and a decrease to a standard one in the active listening paradigm were established in the PTSD group. There were no significant differences in the parameters of the P300 component. The characteristics of mismatch negativity in the passive paradigm were revealed: an increase in the phenomenon amplitude, both when shown a video sequence associated with a traumatic event and when shown a neutral video sequence. A binary logistic regression model constructed using the selected parameters showed that the identified characteristics can potentially be considered as diagnostic markers of PTSD in combatants, as the classification accuracy stood at 87% (sensitivity — 81%, specificity — 91%). CONCLUSION: Potential neurophysiological markers of PTSD are the following: the amplitude and latency of early components of auditory EPs in the paradigm of directed attention to stimuli and the amplitude of mismatch negativity during passive attention.

Objective. To compare the content of β-amyloid (Aβ) peptides Aβ40, Aβ42, total and threonine phosphorylated 181 tau-protein in cerebrospinal fluid (CSF) of patients with the clinical diagnosis of Alzheimer’s disease (AD). Material and methods. The study was performed on 64 patients with a diagnosis of dementia and MMSE scores of 24 or lower. All patients underwent lumbar puncture. Aβ40, Aβ42, Aβ42/40 ratio, total tau, phosphorylated tau at threonine 181 were determined in the CSF using a multiplex assay according to the manufacturer’s protocol, the concentration was determined in pkg/ml. Results. The preliminary diagnosis of AD was made in 3 patients (5%). As a result of the study of protein content in the CSF, signs of AD were detected in 48 (75%) people. The findings suggest that the diagnosis of AD is made 10—14 times less frequently than it should be according to the World Health Organization data. The discrepancy between clinical diagnosis and laboratory findings is confirmed by our study. Conclusion. Differences in the therapy of dementias and the development of new drugs targeting specific links in the pathogenesis of different types of dementias require accurate and complete diagnosis of dementias, especially AD, as the most common type of dementia.

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.