Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers.

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.

BDNF, DRD4, and HTR2A Gene Allele Frequency Distribution and Association with Mental Illnesses in the European Part of Russia.

The prevalence of mental disorders and how they are diagnosed represent some of the major problems in psychiatry. Modern genetic tools offer the potential to reduce the complications concerning diagnosis. However, the vast genetic diversity in the world population requires a closer investigation of any selected populations. In the current research, four polymorphisms, namely rs6265 in BDNF, rs10835210 in BDNF, rs6313 in HTR2A, and rs1800955 in DRD4, were analyzed in a case-control study of 2393 individuals (1639 patients with mental disorders (F20-F29, F30-F48) and 754 controls) from the European part of Russia using the TaqMan SNP genotyping method. Significant associations between rs6265 BDNF and rs1800955 DRD4 and mental impairments were detected when comparing the general group of patients with mental disorders (without separation into diagnoses) to the control group. Associations of rs6265 in BDNF, rs1800955 in DRD4, and rs6313 in HTR2A with schizophrenia in patients from the schizophrenia group separately compared to the control group were also found. The obtained results can extend the concept of a genetic basis for mental disorders in the Russian population and provide a basis for the future improvement in psychiatric diagnostics.

Alteration of Blood Immune Biomarkers in MCI Patients with Different APOE Genotypes after Cognitive Training: A 1 Year Follow-Up Cohort Study.

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function.

Modern Approaches to the Diagnosis of Cognitive Impairment and Alzheimer's Disease: A Narrative Literature Review.

BACKGROUND: The aging of the worlds population leads to an increase in the prevalence of age-related diseases, including cognitive impairment. At the stage of dementia, therapeutic interventions become usually ineffective. Therefore, researchers and clinical practitioners today are looking for methods that allow for early diagnosis of cognitive impairment, including techniques that are based on the use of biological markers. AIM: The aim of this literature review is to delve into scientific papers that are centered on modern laboratory tests for Alzheimers disease, including tests for biological markers at the early stages of cognitive impairment. METHODS: The authors have carried out a descriptive review of scientific papers published from 2015 to 2023. Studies that are included in the PubMed and Web of Science electronic databases were analyzed. A descriptive analysis was used to summarized the gleaned information. RESULTS: Blood and cerebrospinal fluid (CSF) biomarkers, as well as the advantages and disadvantages of their use, are reviewed. The most promising neurotrophic, neuroinflammatory, and genetic markers, including polygenic risk models, are also discussed. CONCLUSION: The use of biomarkers in clinical practice will contribute to the early diagnosis of cognitive impairment associated with Alzheimers disease. Genetic screening tests can improve the detection threshold of preclinical abnormalities in the absence of obvious symptoms of cognitive decline. The active use of biomarkers in clinical practice, in combination with genetic screening for the early diagnosis of cognitive impairment in Alzheimers disease, can improve the timeliness and effectiveness of medical interventions.

Intranasal neuropeptide Y is most effective in some aspects of acute stress compared to melatonin, oxytocin and orexin.

Objectives: In the current study, we compared the effects of a single intranasal administration of clomipramine with effects of four neuropeptides, melatonin, oxytocin, orexin, and neuropeptide Y, to compare them in an acute stress model. Methods: The anti-stress effect was evaluated in the sucrose preference and forced swimming tests. Serum corticosterone level in rats was measured to evaluate the stress response. Results: Neuropeptide Y reduced immobilization time in the Porsolt test and decreased corticosterone levels, but increased the anhedonia. Orexin had no positive effect on animal behavior, but decreased corticosterone levels. Oxytocin decreased immobilization time, maintained anhedonia at the level of control, but did not affect corticosterone levels. Melatonin demonstrated no positive effects in any of the tests. Conclusion: The intranasal administered neuropeptide Y could be a promising compound for the treatment of stress disorders.

Preparation of Protein Aerogel Particles for the Development of Innovative Drug Delivery Systems.

The research was oriented towards the preparation of aerogel particles based on egg white and whey protein isolate using various dispersion methods: dripping, spraying, and homogenization. Based on the results of analytical studies, the most appropriate samples were selected to obtain aerogels loaded with the drug. The results of the experimental research were used to study methods for obtaining nasal drug delivery systems based on aerogels. Protein aerogels were obtained by thermal gelation followed by supercritical drying. The obtained particles of protein aerogels have a specific surface area of up to 350 m2/g with a pore volume of up to 2.9 cm3/g, as well as a porosity of up to 95%. The results of experimental studies have shown that changing the dispersion method makes it possible to control the structural characteristics of protein aerogel particles. The results of the studies were applied to obtain innovative nasal drug delivery systems for the treatment of socially significant diseases. Analytical studies were conducted to determine the amount and state of adsorbed drugs in protein aerogel particles, as well as in vivo experiments on the distribution of clomipramine in blood plasma and brain tissue of rats to study the pharmacokinetics and bioavailability of the resulting drug-loaded protein aerogel.

Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders.

Mental disorders represent common brain diseases characterized by substantial impairments of social and cognitive functions. The neurobiological causes and mechanisms of psychopathologies still have not been definitively determined. Various forms of brain proteinopathies, which include a disruption of protein conformations and the formation of protein aggregates in brain tissues, may be a possible cause behind the development of psychiatric disorders. Proteinopathies are known to be the main cause of neurodegeneration, but much less attention is given to the role of protein impairments in psychiatric disorders' pathogenesis, such as depression and schizophrenia. For this reason, the aim of this review was to discuss the potential contribution of protein illnesses in the development of psychopathologies. The first part of the review describes the possible mechanisms of disruption to protein folding and aggregation in the cell: endoplasmic reticulum stress, dysfunction of chaperone proteins, altered mitochondrial function, and impaired autophagy processes. The second part of the review addresses the known proteins whose aggregation in brain tissue has been observed in psychiatric disorders (amyloid, tau protein, α-synuclein, DISC-1, disbindin-1, CRMP1, SNAP25, TRIOBP, NPAS3, GluA1, FABP, and ankyrin-G).

Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults.

Dementia has enormous implications for patients and the health care system. Genetic markers are promising for detecting the risk of cognitive impairment. We hypothesized that genetic variants associated with suicide risk might significantly increase the risk of cognitive decline because suicide in older adults is often a consequence of cognitive impairment. We investigated several single-nucleotide polymorphisms that were initially associated with suicide risk in dementia older adults and identified the APOE gene alleles. The study was performed with subjects over the age of 65: 112 patients with dementia and 146 healthy volunteers. The MMSE score was used to assess cognitive functions. Study participants were genotyped using real-time PCR (APOE: rs429358, rs7412; genes associated with suicide: rs9475195, rs7982251, rs2834789, rs358592, rs4918918, rs3781878, rs10903034, rs165774, rs16841143, rs11833579 rs10898553, rs7296262, rs3806263, and rs2462021). Genotype analysis revealed the significance of APOEε4, APOEε2, and rs4918918 (SORBS1) when comparing dementia and healthy control groups. The association of APOEε4, APOEε2, and rs10903034 (IFNLR1) with the overall MMSE score was indicated. The study found an association with dementia of rs4918918 (SORBS1) and rs10903034 (IFNLR1) previously associated with suicide and confirmed the association of APOEε4 and APOEε2 with dementia.