No abstract

Environmental pressure affects the genotype throughout different epigenetic processes. There is currently ample evidence on the role of epigenetics in developing various mental disorders. A burden of environmental pressure, such as psychological trauma, and its influence on genotype can lead to a variety of psychopathologies. Thus, this study focuses on the epigenetic activity of the complex protein machinery operating on chromatin – the ATP-dependent chromatin remodeling complexes. Although there are several recent studies on the molecular structure, functions, and taxonomy of ATP-dependent chromatin remodeling complexes, the focus of this paper is to highlight the importance of those ‘protein machines’ in developing psychiatric disorders. Data were obtained from human preclinical and clinical studies. The results of this review indicate an importance of ATP-dependent chromatin remodeling complexes in the interaction between environmental factors, including traumatic events, and genetic vulnerability to stress. Several studies indicate that ATP-dependent chromatin remodeling complexes play a crucial role in the development and consolidation of memory, in neurodevelopmental processes, and in etiology depressive-like behavior. Thus, the activity of those ‘protein machines’ emerges as a key factor in the pathophysiology of various psychiatric diseases. It can also be concluded that the limitations of clinical studies may be explained by inappropriate laboratory methods and research paradigms due to the delayed timeframe of biochemical responses to environmental stimuli. Future research in this field may enable a better understanding of the pathophysiology of psychiatric diseases and contribute to the development of novel molecular treatment targets.

A large body of research attributes learning deficits in schizophrenia (SZ) to the systems involved in value representation (prefrontal cortex, PFC) and reinforcement learning (basal ganglia, BG) as well as to the compromised connectivity of these regions. In this study, we employed learning tasks hypothesized to probe the function and interaction of the PFC and BG in patients with SZ-spectrum disorders in comparison to healthy control (HC) subjects. In the Instructed Probabilistic Selection task (IPST), participants received false instruction about one of the stimuli used in the course of probabilistic learning which creates confirmation bias, whereby the instructed stimulus is overvalued in comparison to its real experienced value. The IPST was administered to 102 patients with SZ and 120 HC subjects. We have shown that SZ patients and HC subjects were equally influenced by false instruction in reinforcement learning (RL) probabilistic task (IPST) (p-value = 0.441); however, HC subjects had significantly higher learning rates associated with the process of overcoming cognitive bias in comparison to SZ patients (p-value = 0.018). The behavioral results of our study could be hypothesized to provide further evidence for impairments in the SZ-BG circuitry; however, this should be verified by neurofunctional imaging studies.

Accumulating evidence indicates that individuals with schizophrenia show poor dietary habits that might account for increased susceptibility to cardiovascular diseases in this population. However, it remains unknown whether this observation can be generalized over the whole population of individuals with schizophrenia. Therefore, in this study we aimed to investigate dietary habits, in terms of adherence to the Mediterranean diet (MD) in subjects with the deficit subtype of schizophrenia (SCZ-D), those with non-deficit subtype (SCZ-ND), and healthy controls (HCs). We recruited 45 individuals with SCZ-ND, 40 individuals with SCZ-D, and 60 HCs. Dietary habits were assessed using the Food Frequency Questionnaire-6 with a 12-month recall. Adherence to MD was decreased only in subjects with SCZ-D compared with HCs. Lower adherence to MD was associated with significantly higher levels of clinician-rated and self-reported negative symptoms (including alogia, avolition, and anhedonia). No significant correlations of adherence to MD with depressive symptoms were found. Lower adherence to MD was related to significantly higher body mass index in subjects with schizophrenia, but not in HCs. Our results indicate that poor adherence to MD is associated with a diagnosis of SCZ-D, higher severity of negative symptoms, and greater risk of developing overweight or obesity.

Schizophrenia spectrum disorders (SZ) are characterized by impairments in probabilistic reinforcement learning (RL), which is associated with dopaminergic circuitry encompassing the prefrontal cortex and basal ganglia. However, there are no studies examining dopaminergic genes with respect to probabilistic RL in SZ. Thus, the aim of our study was to examine the impact of dopaminergic genes on performance assessed by the Probabilistic Selection Task (PST) in patients with SZ in comparison to healthy control (HC) subjects. In our study, we included 138 SZ patients and 188 HC participants. Genetic analysis was performed with respect to the following genetic polymorphisms: rs4680 in COMT, rs907094 in DARP-32, rs2734839, rs936461, rs1800497, and rs6277 in DRD2, rs747302 and rs1800955 in DRD4 and rs28363170 and rs2975226 in DAT1 genes. The probabilistic RL task was completed by 59 SZ patients and 95 HC subjects. SZ patients performed significantly worse in acquiring reinforcement contingencies during the task in comparison to HCs. We found no significant association between genetic polymorphisms and RL among SZ patients; however, among HC participants with respect to the DAT1 rs28363170 polymorphism, individuals with 10-allele repeat genotypes performed better in comparison to 9-allele repeat carriers. The present study indicates the relevance of the DAT1 rs28363170 polymorphism in RL in HC participants.

Trauma, as well as chronic stress that characterizes a modern fast-paced lifestyle, contributes to numerous psychopathologies and psychological problems. Psychiatric patients with traumas, as well as healthy individuals who experienced traumas in the past, are often characterized by diminished cognitive abilities. In our protocol, we used an animal model to explore the influence of chronic trauma on cognitive abilities and behavior in the group of 20 rats (Rattus norvegicus). The experimental group was introduced to chronic (12 consecutive days) exposure to predator odor (bobcat urine). We measured the reinforcement learning of each individual before and after the exposition via the Probabilistic Selection Task (PST) and we used Social Interaction Test (SIT) to assess the behavioral changes of each individual before and after the trauma. In the experimental group, there was a significant decrease in reinforcement learning after exposure to a single trauma (Wilcoxon Test, p = 0.034) as well as after 11 days of chronic trauma (Wilcoxon-test, p = 0.01) in comparison to pre-trauma performance. The control group, which was not exposed to predator odor but underwent the same testing protocol, did not present significant deterioration in reinforcement learning. In cross-group comparisons, there was no difference between the experimental and control group in PST before odor protocol (U Mann-Whitney two-sided, p = 0.909). After exposure to chronic trauma, the experimental group deteriorated in PST performance compared to control (U Mann-Whitney Two-sided, p = 0.0005). In SIT, the experimental group spent less time in an Interaction Zone with an unfamiliar rat after trauma protocol (Wilcoxon two-sided test, p = 0.019). Major strengths of our models are: (1) protocol allows investigating reinforcement learning before and after exposition to chronic trauma, with the same group of rats, (2) translational scope, as the PST is displayed on touchscreen, similarly to human studies, (3) protocol delivers chronic trauma that impairs reward learning, but behaviorally does not induce full-blown anhedonia, thus rats performed voluntarily throughout all the procedures.

Fluctuating asymmetry (FA), a morphological marker of developmental stability, may be related to an individual's biological condition, e.g., health or fertility. The aim of this study was to test if the level of a woman's FA was related to her fertility and reproductive potential as measured by reproductive hormone levels. Fifty-three healthy, non-pregnant, naturally cycling women (mean age = 23.42, SD = 1.85 years), participated in the study, conducted in Wrocław (Poland) in May 2015. Early-follicular phase serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured. FA was calculated based on anthropometric measures of six bilateral body traits, and the composite FA index was used in statistical analyses. No relationship was observed between FA and the levels of FSH, LH, and AMH (p > .05), controlled for potential confounders. However, the level of E2 was positively correlated with FA (p < .05). Thus, in young women, FA was not related to hormones levels related to ovarian reserve, but more symmetrical women had lower E2 levels. As FA is an index of developmental stability, environmental, and genetic stress, the results of the study confirm previous research suggesting that developmental conditions may be related to women's endogenous estrogen levels.

Central endocannabinoid system (eCBS) is a neuromodulatory system that inhibits potentially harmful, excessive synaptic activation. Endocannabinoid receptors are abundant among brain structures pivotal in different mental disorders development (for example, hippocampus, amygdala, medial-prefrontal cortex, hypothalamus). Here, we review eCBS function in etiology of psychosis, emphasizing its role in dealing with environmental pressures such as traumatic life events. Moreover, we explore eCBS as a guard against hypothalamic-pituitary-adrenal axis over-activation, and discuss its possible role in etiology of different psychopathologies. Additionally, we review eCBS function in creating adaptive behavioral patterns, as we explore its involvement in the memory formation process, extinction learning and emotional response. We discuss eCBS in the context of possible biomarkers of trauma, and in preclinical psychiatric conditions, such as at-risk mental states and clinical high risk states for psychosis. Finally, we describe the role of eCBS in the cannabinoid self-medication-theory and extinction learning.