Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.

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Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.

Willner’s “chronic mild stress” (CMS) model is a globally recognized and most commonly used depression model. A depression model induced by ultrasonic exposure of variable frequencies has been created in our laboratory. This article compares two models of the depressive-like state according to three validity criteria. Face validity has been demonstrated in sucrose preference test, Porsolt test, social interest, open field and the Morris water maze. Rats after ultrasound impact have more pronounced anhedonia and social isolation. The construct validity has been proven due to increased levels of corticosterone, epinephrine and norepinephrine and reduced levels of dopamine and some of its metabolites in rat plasma after ultrasound exposure. Predictive validity has been described previously, where the therapeutic effects of various classes of antidepressants have been shown. Our study has demonstrated that the ultrasound-induced depression model is suitable, such as the generally accepted CMS protocol, and meets all required validity criteria. The model presented in this article might help to study pathogenetic mechanisms of depressive disorders, as well as to test promising methods of depression treatment.

Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

Fetal development is susceptible to environmental factors. One such factor is exposure to stress during pregnancy. The present study aimed to investigate the effects of chronic prenatal stress (PS) on the development and behavior of rat offspring during infancy and juvenile ages. Existing approaches to modeling prenatal stress on animals do not correlate with the main type of stress in pregnant women, namely psychological stress. We used a new stress paradigm in the experiment, namely, stress induced by exposure to variable frequency ultrasound (US), which acted on pregnant Wistar rats on gestational days 1–21. This type of stress in rodents can be comparable to psychological stress in humans. We assessed physical development, reflex maturation, motor ability development, anxious behavior, response to social novelty, and social play behavior in male and female offspring. Additionally, we investigated maternal behavior and the effect of neonatal handling (NH) on behavior. Prenatal stress did not affect postnatal developmental characteristics in rat pups, but prenatally stressed rats had higher body weight in early and adult age than controls. Prenatal exposure to a stressor increased anxiety in the open-field test (OF), changed social preferences in the social novelty test (SN), and impaired social play behavior in males. Neonatal handling reduced anxiety and restored social behavior, but evoked hyperactive behavior in rat pups. Maternal behavior did not change. Our study demonstrated for the first time that exposure to variable frequency ultrasound during pregnancy influences offspring development and impairs behavior, correlating with the effects of other types of stress during pregnancy in rodents. This supports the idea of using this exposure to model prenatal stress.

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p < 0.001). And IL-6 was evaluated in the schizophrenia group (p < 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia.

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.