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Abstract Background There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups. Methods The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used. Results DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC. Conclusions Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research.

In the face of increasing social, economic, and health consequences of alcohol use disorders (AUDs) and limited effects of available treatment options, the search for novel prevention and management methods continues to remain a timely and valid endeavor. This, however, requires a better grasp of the theoretical framework underlying addiction mechanisms. With the goal to extend the existing body of evidence on AUDs, we set out to investigate the effect of personality-related factors and depressive symptomatology on (i) impulsivity, (ii) cognitive response inhibition, and (iii) the links between the two measures of behavioral control (different facets of impulsivity and response inhibition) in a treatment-seeking AUD sample. To this end, 53 male (n = 45) and female (n = 8) inpatients at an alcohol rehabilitation center completed three self-report questionnaires: the International Personality Item Pool (IPIP-50), the Beck Depression Inventory Second Edition (BDI-II) and the Barratt Impulsiveness Scale (BIS-11) and performed one behavioral task—an alcohol go/no go task. Regression analyses revealed conscientiousness, intellect, and depression level to be important potential predictors of self-report impulsivity and processing speed in recovering drinkers. No significant links were observed between the two measures of behavioral control, thus complementing evidence that while they both encompass behavioral under-regulation, they may indeed represent distinct psychological constructs.

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.

This study compared cognitive domains between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), analyzing relationships between psychopathological dimensions and cognitive domains. A total of 29 DS patients, 45 NDS patients, and 39 HC subjects participated. Cognitive domains were measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale. Clinical groups performed poorer than HC groups in regards to speed of processing, attention/vigilance, working memory, verbal and visual learning and memory, reasoning and problem solving, and social cognition. DS patients scored poorer than NDS patients in terms of all cognitive domains and the overall score, except for reasoning and problem solving. Positive, negative, disorganization, and resistance symptoms were related to cognitive functions only in NDS patients. Our findings suggest that the MCCB battery is sensitive to detecting cognitive dysfunctions in both deficit and non-deficit schizophrenia.

Evidence suggests a role of the immune system in the pathogenesis of a number of mental conditions, including schizophrenia (SCH). In terms of physiology, aside from its crucial protective function, the complement cascade (CC) is a critical element of the regeneration processes, including neurogenesis. Few studies have attempted to define the function of the CC components in SCH. To shed more light on this topic, we compared the levels of complement activation products (CAP) (C3a, C5a and C5b-9) in the peripheral blood of 62 patients with chronic SCH and disease duration of ≥ 10 years with 25 healthy controls matched for age, sex, BMI and smoking status. Concentrations of all the investigated CAP were elevated in SCH patients. However, after controlling for potential confounding factors, significant correlations were observed between SCH and C3a (M = 724.98 ng/mL) and C5a (M = 6.06 ng/mL) levels. In addition, multivariate logistic regression showed that C3a and C5b-9 were significant predictors of SCH. There were no significant correlations between any CAP and SCH symptom severity or general psychopathology in SCH patients. However, two significant links emerged between C3a and C5b-9 and global functioning. Increased levels of both complement activation products in the patient group as compared to healthy controls raise questions concerning the role of the CC in the etiology of SCH and further demonstrate dysregulation of the immune system in SCH patients.

Abstract Background The approach-avoidance training program (AATP) has shown preliminary promise as an add-on to standard treatment for alcohol dependence. However, knowledge is lacking as to whether the effectiveness of AATP can be enhanced further when performed in a typical drinking situation. The main aim of this study is to investigate whether approach-avoidance training implemented in a virtual reality bar environment is superior to the classical joystick PC-version of the AATP. Methods The study will be implemented as a randomized controlled trial. A total of 204consecutively enrolled alcohol use disorder (AUD) patients, recruited from alcohol inpatient clinics in Germany, Poland and Denmark, will be randomized into one of three groups at the start of standard alcohol treatment: group A) stimuli-relevant AATP + treatment as usual (TAU); group B) stimuli-relevant AATP in virtual reality + TAU, and group C) TAU only (control group). Treatment outcomes will be assessed at pre-treatment, post-treatment and 3-month follow-up. Repeated-measures ANOVA will be applied to compare the trajectories of the groups over time on drinking, craving and impulsiveness outcomes. It is hypothesized that the two experimental groups will achieve better treatment outcomes compared to group C and that group B will achieve better outcomes than group A. Discussion This study is the first trial examining the effectiveness of stimuli-relevant AATP delivered in a VR environment. The use of VR has shown promise in enhancing the effectiveness of other psychological treatments and since AATP has already been shown effective as add-on treatment, it is of interest to investigate whether these effects can be further enhanced by implementing the program in more ecologically valid environments. If proven effective, the AATP-VR can, like the AATP, be implemented easily and cheaply as add-on treatment or continued care to enhance the effectiveness of current evidence-based treatment. Trial registration ClinicalTrials.gov ID: NCT04283305 Registration date: 24.02.20

Abstract Background The clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia. Methods Three SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity. Conclusions The results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.

Chronic subclinical inflammation is believed to be an important factor in the pathogenesis of schizophrenia. Meta-analyses confirm the presence of increased levels of peripheral inflammatory markers (IM) in schizophrenia and its prodromal stages. Peripheral cytokines may affect the brain microstructure through chronic activation of microglia. Disruptions in the integrity of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) are commonly seen in patients with schizophrenia spectrum disorders. We therefore attempted to verify in a cross-sectional study whether there is a correlation between levels of peripheral IM and the integrity of these brain regions in healthy controls, from prodromal states and first episode psychosis to long-term schizophrenia. The integrity of white matter was measured using diffusion tensor imaging. Despite a broad analysis of six IM (CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ), we did not find any correlations with the integrity of the SLF or ILF in any of the analyzed groups (after correction for multiple comparisons). In conclusion, our study does not support the existence of a link between disrupted levels of peripheral IM and reduced integrity of ILF and SLF in schizophrenia spectrum disorders. However, prospective studies are needed to verify this over a long period of time.

Physiotherapy in oncology is a process closely related to cancer treatment methods. Rehabilitation is based on physical activity in various forms involving the musculoskeletal system but also affects the emotional state. Physical activity influences physical and psychological well-being of people undergoing oncological treatment, in the course of which the most common psychiatric disorders are depression, substance use disorder, sleep disorders, fatigue syndrome, resulting in worsening of the quality of life. Difficulties in implementing physical exercise in cancer patients pose a challenge to treatment teams.

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

Some symptoms of schizophrenia might be present before full-blown psychosis, so white matter changes must be studied both in individuals with emerging psychosis and chronic schizophrenia. A total of 86 patients—12 ultra-high risk of psychosis (UHR), 20 first episode psychosis (FEP), 54 chronic schizophrenia (CS), and 33 healthy controls (HC)—underwent psychiatric examination and diffusion tensor imaging (DTI) in a 3-Tesla MRI scanner. We assessed fractional anisotropy (FA) and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILS). We found that CS patients had lower FA than FEP patients (p = 0.025) and HC (p = 0.088), and higher MD than HC (p = 0.037) in the right SLF. In the CS group, we found positive correlations of MD in both right ILF (rho = 0.39, p < 0.05) and SLF (rho = 0.43, p < 0.01) with disorganization symptoms, as well as negative correlation of FA in the right ILF with disorganization symptoms (rho = −0.43, p < 0.05). Among UHR individuals, we found significant negative correlations between MD in the left ILF and negative (r = −0.74, p < 0.05) and general symptoms (r = −0.77, p < 0.05). However promising, these findings should be treated as preliminary, and further research must verify whether they can be treated as potential biomarkers of psychosis.

The superior longitudinal fasciculus (SLF) is a white matter bundle that connects the frontal areas with the parietal areas. As part of the visuospatial attentional network, it may be involved in the development of schizophrenia. Deficit syndrome (DS) is characterized by primary and enduring negative symptoms. The present study assessed SLF integrity in DS and nondeficit schizophrenia (NDS) patients and examined possible relationships between it and psychopathology. Twenty-six DS patients, 42 NDS patients, and 36 healthy controls (HC) underwent psychiatric evaluation and diffusion tensor imaging (DTI). After post-processing, fractional anisotropy (FA) values within the SLF were analyzed. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. The PANSS proxy for the deficit syndrome was used to diagnose DS. NDS patients had lower FA values than HC. DS patients had greater negative symptoms than NDS patients. After differentiating clinical groups and HC, we found no significant correlations between DTI measures and psychopathological dimensions. These results suggest that changes in SLF integrity are related to schizophrenia, and frontoparietal dysconnection plays a role in its etiopathogenesis. We confirmed that DS patients have greater negative psychopathology than NDS patients. These results are preliminary; further studies are needed.

IntroductionThe co-existence of schizophrenia and metabolic syndrome is a widely described phenomenon that contributes to the worse functioning of patients in everyday life. A relatively new area of research is the relationship between metabolic syndrome (MS) and cognitive function in patients with schizophrenia. The aim of the study was to verify the relationship between the presence of metabolic syndrome and cognitive function of patients with schizophrenia and to assess the possibility of changing cognitive function by introducing appropriate dietary intervention.Materials and MethodsThe study involved 87 individuals diagnosed with schizophrenia according to ICD-10 criteria, aged 19 to 67 years (M = 41.67; SD = 11.87). Patients were in the remission phase of schizophrenia, all using antipsychotics for pharmacological treatment. From a group of 83 patients with schizophrenia and diagnosed metabolic syndrome (according to IDF criteria) 30 patients were randomly assigned to an experimental group—with dietary intervention, 29 patients—to group without dietary intervention, 24 patients with schizophrenia without metabolic syndrome was a comparison group. All groups were evaluated for cognitive function using Stroop Test, Trail Making Test (TMT), Verbal Fluency Test, Digit Span Backwards Test. In the experimental group a dietary intervention was applied, which was to provide the examined person with a 7-day dietary plan with reduced calorie content, in compliance with the Mediterranean diet.ResultsAfter the dietary intervention there was a significant improvement in the number of errors made in the third Stroop Test (p

This narrative review presents recent developments in virtual reality (VR)-based interventions for alcohol use disorders (AUDs). The latest advances in mental healthcare hail an imminent cyber revolution, ushering in novel treatment options, with immersive virtual technology at the very forefront of expected change. With an aim to (a) provide a background on VR use in mental healthcare of AUD patients, (b) summarize existing evidence on conventional approaches to the treatment of AUDs and a trending paradigm shift towards VR applications in their management, and (c) describe key issues and future directions in research on craving assessment and VR cue-induced therapy in AUDs, a search for experimental and meta-analytic evidence was performed in six databases: PubMed and EBSCO (Medline, ERIC, PsychINFO, Academic Search Ultimate, and Health Source: Nursing/Academic Edition). Pooled results were screened for eligibility, and relevant papers were selected for inclusion. The analysis revealed VR’s promising effects in the treatment of AUDs. Its remarkable potential to simulate cues underlying subsequent addictive behaviors makes its application in the assessment and treatment of AUDs an attractive alternative to researchers and clinicians alike. Nevertheless, more evidence is needed before virtual reality cue exposure therapy (VR-CET) can become a clinical standard of care.

There is a paucity of reports examining the relationship between the integrity of the corpus callosum (CC) and different aspects of cognitive functioning in patients with first-episode (FES) and chronic schizophrenia (CS) simultaneously; furthermore, what results exist are inconclusive. We used diffusion tensor imaging tractography to investigate differences in integrity in five regions of the CC between FES, CS, and healthy controls (HC). Additionally, we analyzed correlations between these regions’ integrity and working memory, planning, and speed of processing. Eighteen patients with FES, 55 patients with CS, and 30 HC took part in the study. We assessed cognitive functions with four tasks from Measurement and Treatment Research to Improve Cognition in Schizophrenia. Patients with CS showed lower fractional anisotropy (FA) in Region 5 (statistical trend) and higher mean diffusivity (MD) in Regions 4 and 5 than HC, and patients with FES had higher MD in Region 3 (statistical trend) than HC. Both clinical groups performed worse on working memory and speed of processing tasks than HC, and patients with CS scored worse than HC on independent planning, and worse than FES and HC on dependent planning. Moreover, in patients with CS, MD in Region 3 was correlated with verbal working memory. Our results suggest that patients with FES and CS are characterized by impaired integrity of the middle and posterior CC, respectively. We confirmed that both clinical groups have cognitive impairments. Moreover, the integrity of the middle CC may influence planning in patients with CS.

Deficit syndrome (DS) is a subtype of schizophrenia characterized by primary persistent negative symptoms. The corpus callosum (CC) appears to be related to psychopathology in schizophrenia. This study assessed white matter integrity in the CC using diffusion tensor imaging (DTI) in deficit and non-deficit schizophrenia (NDS) patients. We also investigated the psychopathological dimensions of schizophrenia and their relationship to CC integrity. Fifteen DS patients, 40 NDS patients, and 30 healthy controls (HC) underwent psychiatric evaluation and neuroimaging. We divided the CC into five regions and assessed their fractional anisotropy (FA) and mean diffusivity (MD). Psychopathology was assessed with the Positive and Negative Syndrome Scale. DS patients had lower FA than NDS patients and HC, and higher MD in Region 5 of the CC than did HC. NDS patients had higher MD in Region 4 of the CC. The patient groups differed in terms of negative symptoms. After differentiating clinical groups and HC, no significant correlations were observed between DTI measures and psychopathological symptoms. Our results suggest that DS and NDS are characterized by minor impairments of the posterior CC. We confirmed that DS patients have greater negative psychopathology than NDS patients. Our results are preliminary, and further studies are needed.

The phenomenon of stupefying by the use of available over-the-counter drugs (OTC) among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine (methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported. The test results cited by the authors clearly indicate that the use of OTC drugs, whose turnover is not controlled is a domain of females. The extent of use of drugs not prescribed by a doctor has remained for many years at a constant level. The most common poisonings with OTC drugs are caused by those that affect the respiratory system or exert analgesic or antipyretic effects. They are also used in attempted suicides, especially among females. Analyzing poisonings caused by OTC medications their seasonality has been observed. Their number increases during spring–autumn. A territorial differentiation in areas of OTC drug trade in terms of their quantities, with the predominance of southern regions is also noted. Intoxication with psychoactive substances causes the deterioration of relations between young people. In the reviewed studies there is no detailed information on the composition of non-prescription medicines. Moreover, young people have easy access to mushroom fungi, growing in nearby forests and meadows that may have hallucinogenic effects and are available in pharmacies and on the Internet. Med Pr 2017;68(3):413–422

Introduction: The immune system is undoubtedly involved in the pathogenesis of various psychiatric disorders, such as schizophrenia, bipolar disorder, or depression. Although its role is not fully understood, it appears that this area of research can help to understand the etiology of mental illness. One of the components of the human immune system is the complement system, which forms a part of the innate immune response. Physiologically, except for its essential protective role, it is a vital element in the regeneration processes, including neurogenesis. To date, few studies have tried to clarify the role of the complement cascade in mental disorders.Materials and Methods: We evaluated concentrations of C3a, C5a, and C5b-9 complement cascade components in the peripheral blood of 30 patients suffering from bipolar disorder (BD) for at least 10 years, in euthymia, who were not treated with lithium salts. In addition, we divided our study sample into BD type I (BD-I, 22 persons), and BD type II (BD-II, 8 patients). The control group consisted of 30 healthy volunteers matched for age, sex, BMI, and smoking habits.Results: Compared to healthy controls, BD patients had elevated concentrations of all the investigated components. Furthermore, in patients with BD-II, we observed higher concentrations of C5b-9 as compared to patients with BD-I. However, there was a significant effect of BD diagnosis only on the levels of C3a and C5a but not on the level of C5b-9 after adjustment for potential confounding factors.Conclusions: Increased concentrations of components C3a and C5a of the complement system in the investigated group as compared to healthy controls suggest involvement of the complement cascade in the pathogenesis of BD, and provides further evidence of immune system dysregulation in BD patients.

Progress in medical science has allowed the discovery of many factors affecting the pathogenesis of bipolar disorder, and among the most recent research directions are found regenerative and inflammatory processes. The role of regenerative processes remains particularly poorly explored, but available data encourage further research, which may explain the pathogenesis of bipolar disorder (BD). The aim of this study was to evaluate the mobilization of stem cells into peripheral blood, in patients with bipolar disorder during stable phase, not treated with lithium salts. The study included 30 unrelated individuals with the diagnosis of bipolar disorder, with disease duration of at least 10 years, not treated with lithium salts for at least five years prior to the study. The control group consisted of 30 healthy subjects, matched for age, sex, body mass index (BMI), origin, socio-demographic factors and nicotine use. Blood samples underwent cytometric analyses to assess concentrations of: Very Small Embryonic Like (VSEL) CD34+, VSEL AC133+, HSC CD34+, HSC AC133+. There were no significant differences in stem cell levels between patients with BD and healthy controls. However, the level of VSEL cells AC133 + was significantly higher in type I BD patients compared to healthy controls. Our results indicate a disturbance in regenerative processes in patients with bipolar disorder.

The metabolic syndrome (MS) is highly prevalent in schizophrenia patients, resulting from both pharmacotherapy and their lifestyle. To avoid its development, the analysis of patients’ eating behaviors followed by the necessary nutritional changes should become a routine element of treatment. The aim of this study is to investigate the effect of dietary habits on the course of schizophrenia and MS, cognitive performance, symptom severity, and subjective assessment of eating behaviors in schizophrenia patients. Total of 87 participants (63.2% women) aged 19 to 67 years (M = 41.67; SD = 12.87), of whom 60 met the IDF criteria for MS, completed the PANSS, the verbal fluency test, the Stroop Color-Word Test, and the digit span task, followed by a thorough nutritional interview. There were no significant differences in the dietary behaviors between investigated schizophrenia patients with and without comorbid MS. Interestingly, their eating habits compared quite favorably to those described in the literature. No associations were found between positive eating habits and other tested variables in patients with MS. They were, however, linked to lower PANSS scores in the entire sample. In addition, positive eating habits correlated with better cognitive performance and a more adequate subjective assessment of dietary habits. It would be amiss to assume that schizophrenia patients lack the ability to control their eating behaviors. Nutrition education may foster desirable dietary changes and improve the sense of agency, thus helping to reduce symptom severity and enhancing cognitive performance in this patient population.

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

Accumulating evidence indicates the potential effect of microbiota on the pathogenesis and course of schizophrenia. However, the effects of olanzapine, second-generation antipsychotics, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in schizophrenia patients treated with olanzapine during six weeks of their hospital stay. After a seven-day washout from all psychotropic medications, microbiota compositions were evaluated at baseline and after six weeks of hospitalization using 16S rRNA sequencing. The study was conducted in 20 inpatients, who followed the same hospital routine and received 5−20 mg daily doses of olanzapine. Olanzapine treatment was associated with clinical improvements in all patients and significant increases in body mass index in females, but not changes in gut microbiota compositions and predicted function. The severity of symptoms at the beginning of treatment varied in accordance with the predicted metabolic activity of the bacteria. The present findings indicate that the microbiota of schizophrenia patients is highly individual and has different taxonomical (Type 1, with a predominance of Prevotella, and Type 2 with a higher abundance of Bacteroides, Blautia and Clostridium) and functional clusters, and it does not change following six weeks of olanzapine therapy; in addition, the microbiota is not associated with either the weight gain observed in women or the effectiveness of olanzapine therapy.