Schizophrenia is a multifactorial psychiatric disorder whose manifestation is driven by a complex interplay between genetic susceptibility and environmental adversity. Adverse prenatal exposures, including maternal infections, psychosocial stress, and fetal hypoxia, play a critical role in shaping neurobiological vulnerability during sensitive periods of neuroontogenesis. Maternal immune activation and chronic stress elicit a systemic inflammatory cascade characterized by the overproduction of pro-inflammatory cytokines (IL-6, IL-17, IL-1β, and TNF-α). These inflammatory mediators compromise the permeability of the fetal blood-brain barrier, trigger persistent microglial activation, and upregulate the kynurenine pathway of tryptophan metabolism, subsequently leading to aberrant synaptic pruning and NMDA receptor dysfunction. Concurrently, prenatal stress driven by excessive maternal glucocorticoids disrupts the regulatory loops of the hypothalamic-pituitary-adrenal axis, downregulates central glucocorticoid receptor expression, and impairs BDNF–TrkB-mediated neurotrophic support. Intrauterine hypoxia activates HIF-1α and the Notch signaling cascade, shifting neural stem cell differentiation toward astrogliogenesis while depleting cellular antioxidant defenses. A universal epigenetic predictor underlying these abnormalities is their consolidation through altered DNA methylation profiles and histone modifications, particularly within the regulatory regions of the GAD1 , BDNF , and RELN genes. These persistent changes culminate in postnatal structural abnormalities of the prefrontal cortex and hippocampus, as well as chronic GABAergic and glutamatergic neurotransmission deficits. In conclusion, heterogeneous prenatal triggers converge on distinct immune, endocrine, and epigenetic pathways to establish the morphofunctional substrate of vulnerability to schizophrenia, ultimately disrupting neural network maturation and the excitation-inhibition balance in the central nervous system.
Gambling disorder (GD) is a behavioral addiction characterized by high comorbidity, significant social and economic consequences. The neurobiological mechanisms underlying GD are similar to those observed in substance use disorders, which opens possibilities for pharmacological intervention. However, no medication has yet been approved for the treatment of GD, and the evidence base for existing agents remains limited. This review summarizes data on the pharmacological treatment of GD based on current systematic reviews and network meta-analyses, and discusses methodological limitations and clinical prospects for the use of various drug classes. This narrative literature review was conducted, encompassing clinical trials, case series, and open-label studies of opioid antagonists, antipsychotics, mood stabilizers, anticonvulsants, antidepressants, gabapentinoids, and other agents. The most compelling evidence was found for nalmefene and naltrexone, which produced statistically significant reductions in GD symptoms compared to placebo, particularly in patients with high craving. Antidepressants, olanzapine, and topiramate failed to outperform placebo in most studies. Mood stabilizers may be beneficial in cases of comorbid bipolar disorder, but the evidence remains very limited. N-acetylcysteine, memantine and gabapentinoids showed encouraging preliminary results; GLP-1 receptor agonists, ketamine, and psilocybin remain experimental. Thus, opioid antagonists may be considered a first-line (off-label) therapy for GD, complementing rather than replacing cognitive-behavioral therapy. Larger controlled trials and the identification of biomarkers for treatment personalization are needed.
Objective of the study. The article is devoted to the evaluation of the role of some clinical and personal factors of preference for virtual communication in persons with schizophrenia spectrum disorders. Material and methods. A total of 84 patients with diagnosed F.20 — F.25 disorders (ICD-10) were evaluated using psychometric techniques (SADS Social Avoidance and Distress Scale; Hostility Projective Test; Affiliation Motivation Test) and the author’s Virtual or Real Communication Preference Questionnaire. When analyzing the results, the indicators of score dispersion for the measured parameters, nonparametric criteria for independent and dependent samples, and methods of correlation and factor analysis were used. The results of the study indicate that the majority of patients in the examined group (75%) retain a preference for real communication over virtual communication, and virtual communication is more often preferable for patients with a higher total score for the severity of mental disorder symptoms. In the examined group of patients who prefer virtual communication, maladaptive personality traits are more clearly expressed: hostility, social anxiety, social distress, social avoidance, and fear of rejection; they also have a low level of affiliation motivation. The proposed method for assessing communication preferences allows predicting the risks of patients evading participation in rehabilitation activities conducted in the format of real or virtual communication, and can be useful in planning psychosocial rehabilitation activities.
Alcohol dependence (AD) and depressive disorders (DD) exhibit a high level of comorbidity, significantly complicating treatment and worsening the clinical prognosis. The search for drugs that target the common pathogenetic mechanisms of these comorbid conditions is relevant. One such drug is agomelatine: an MT1 and MT2 melatonin receptor agonist and a 5-HT2C serotonin receptor antagonist. The identification of pharmacogenetic markers of agomelatine efficacy is an important goal in personalized therapy for comorbid AD and DD, as individual treatment response remains difficult to predict. Objective: To identify pharmacogenetic markers of agomelatine efficacy in patients with AD and comorbid DD. Materials and Methods. The pharmacogenetic study was conducted based on a 12-week, double-blind, randomized, placebo-controlled trial (N=100) of agomelatine efficacy in outpatients with AD and comorbid depression. The primary efficacy indicator was treatment retention, defined as the time (weeks) until discontinuation for any reason. The study’s genetic panel included 10 polymorphic loci in 8 genes: pharmacological targets of agomelatine — the melatonin receptors MT1 ( MTNR1A ) and MT2 ( MTNR1B ) and the serotonin receptor 5-HT2C ( HTR2C) , the gene encoding the cytochrome P450 enzyme CYP1A2 , which controls agomelatine pharmacokinetics, and key genes of the dopamine system (DRD2, ANKK1 ) and the endogenous opioid system ( OPRM1 , OPRK1 ). An analysis of associations between individual genetic variants and their combinations with the risk of early treatment discontinuation was performed within the dominant model in the agomelatine and placebo groups using Cox regression models. Hazard ratio (HR) with confidence intervals (CI) were calculated. Results. In the group of patients receiving agomelatine, an increased risk of early discontinuation of therapy, taking into account gender and age adjustment, was associated with carriage of the minor allele T rs2119882 in the MTNR1A gene [HR=2.25; 95%CI: (1.02–5.00); p=0.045], as well as with combinations of this variant with carriage of the minor allele A rs1800497 in the ANKK1 gene [HR=2.5; 95%CI: (1.16–5.61), p=0.019], the major genotype GG rs6275 in the DRD2 gene [HR=2.13; 95%CI: (1.02–4.46), p=0.045], the major genotype GG rs 10830963 in the MTNR1B gene [HR=2.10; 95%CI: (1.04–4.23), p=0.039], minor allele A rs2069514 in the CYP1A2*1C gene [HR=2.32; 95%CI: (1.01–5.35), p=0.048]. There was also an independent marker of the risk of dropping out of the therapy program in the form of a combination of minor alleles C rs762551 in the CYP1A2*1F gene and C rs6318 in the HTR2C gene [HR=3.32; 95%CI: (1.04–6.42), p=0.042]. No associations were found in the placebo group. Conclusion. The results of this study suggest that the pharmacogenetic response to agomelatine is polygenic in nature and is determined by the interaction of genes regulating the pharmacodynamics of the drug, its pharmacokinetics, and the neurobiological mechanisms of AD (reward cascade). The results of the study also might create a possibility to develop a polygenic pharmacogenetic panel that can be used for personalized approach to treatment of the patients with AD and comorbid depression with agomelatine.
The review summarizes data on the prevalence and clinical manifestations of alcohol and psychoactive substance dependence syndrome in patients with post-traumatic stress disorder, including veterans and combatants. A narrative analysis of original studies, recent review data, and Russian clinical addiction concepts of drinking motivation and pathological craving was performed. The interpretation of the literature took into account ICD-11 diagnostic updates, including complex post-traumatic stress disorder (complex PTSD) as a distinct diagnostic category that combines the core PTSD symptoms with disturbances in self-organization: affective dysregulation, persistent negative self-concept, and interpersonal difficulties. Consideration of complex PTSD is clinically relevant for veteran and addiction-treatment samples, because this category may be associated with greater functional, social, and comorbid burden than PTSD without pronounced disturbances in self-organization. The prevalence of post-traumatic stress disorder among patients with dependence varies depending on the type of dependence, sample characteristics, and diagnostic instruments. Based on the literature, a preliminary scheme of clinically vulnerable clusters is proposed as a framework for further development of a screening model and subsequent empirical verification.
