The Moderating Role of the FKBP5 Gene Polymorphisms in the Relationship between Attachment Style, Perceived Stress and Psychotic-like Experiences in Non-Clinical Young Adults.

Numerous studies have reported that stressful life experiences increase the risk of psychosis and psychotic-like experiences (PLEs). Common variations of the FKBP5 gene have been reported to impact the risk of psychosis by moderating the effects of environmental exposures. Moreover, anxious and avoidant attachment styles have been shown to increase both the level of perceived stress and the risk for psychosis development. In the present cross-sectional study, we aimed to investigate whether variants of the FKBP5 gene moderate the effects of attachment styles and the level of perceived stress on the development of PLEs. A total of 535 non-clinical undergraduates were genotyped for six FKBP5 single nucleotide polymorphisms (SNPs) (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158). The Psychosis Attachment Measure (PAM), the Perceived Stress Scale-10 (PSS-10) and the Prodromal Questionnaire 16 (PQ-16) were administered to assess attachment styles, the level of perceived stress and PLEs, respectively. Anxious attachment style, lower levels of perceived self-efficacy and higher levels of perceived helplessness were associated with a significantly higher number of PLEs. The main effects of attachment style on the severity of PLEs were significant in models testing for the associations with perceived self-efficacy and three FKBP5 SNPs (rs1360780, rs9296158 and rs9470080). The main effect of rs38003733 on the number of PLEs was observed, with GG homozygotes reporting a significantly higher number of PLEs in comparison to T allele carriers. In individuals with dominant anxious attachment style, there was a significant effect of the interaction between the FKBP5 rs4713902 SNP and self-efficacy on the severity of PLEs. Among rs4713902 TT homozygotes, a low level of perceived self-efficacy was associated with higher severity of PLEs. In subjects with non-dominant anxious attachment, a low level of perceived self-efficacy was associated with a higher number of PLEs, regardless of the genotype. Our results indicate that the FKBP5 gene might moderate the relationship between attachment, perceived stress and PLEs.

Transcranial magnetic stimulation (TMS) in treatment of psychiatric disorders - review of current studies. / Przezczaszkowa stymulacja magnetyczna (TMS) w terapii zaburzen psychicznych ­ aktualny przeglad badan.

Current progress of basic and clinical science creates background for new therapeutic appliances of brain stimulation methods in disorders of central nervous system. This review describes present state of knowledge regarding practical aspects of one of those methods - transcranial magnetic stimulation, TMS. The review was based on contemporary literature on use of transcranial magnetic stimulation in various diseases, particularly including present recommendations and guidelines as well as systematic reviews, published after year 2000. TMS is a quite novel, non-invasive, well tolerated treatment method with alow amount of transient adverse effects and complications. Development of new therapeutic protocols makes it possible to introduce this procedure in new groups of patients, including a wide range of mental disorders such as depression, bipolar disorder, schizophrenia, also cognitive function disorders and posttraumatic stress disorder. In Poland it is still hardly available, though more and more clinical centers start to perform this kind of therapy, providing proper equipment and trained personnel.

The Impact of the FKBP5 Gene Polymorphisms on the Relationship between Traumatic Life Events and Psychotic-Like Experiences in Non-Clinical Adults.

Common variations of the FKBP5 gene are implicated in psychotic disorders, by modulating the hypothalamic-pituitary-adrenal axis reactivity to stress. It has been demonstrated that some of them might moderate the effects of childhood trauma on psychosis proneness. However, these associations have not been investigated with respect to traumatic life events (TLEs). Therefore, we aimed to explore whether the FKBP5 polymorphisms moderate the effects of TLEs on the level of psychotic-like experiences (PLEs). A total of 535 non-clinical adults were approached for participation, and genotyping of six FKBP5 polymorphisms (rs3800373, rs9470080, rs4713902, rs737054, rs1360780 and rs9296158) was performed. The Prodromal Questionnaire-16 (PQ-16) and the Traumatic Events Checklist (TEC) were administered to assess PLEs and TLEs, respectively. Among the rs1360780 CC homozygotes, a history of physical abuse was associated with significantly higher PQ-16 scores. This difference was not significant in the rs1360780 T allele carriers. Similarly, a history of physical abuse was associated with significantly higher PQ-16 scores in the rs9296158 GG homozygotes but not in the rs9296158 A allele carriers. Finally, emotional neglect was related to significantly higher PQ-16 scores in the rs737054 T allele carriers but not in the rs737054 CC homozygotes. The present study indicates that variation in the FKBP5 gene might moderate the effects of lifetime traumatic events on psychosis proneness.

Appetite regulating hormones in first-episode psychosis: A systematic review and meta-analysis.

We aimed to perform a systematic review and meta-analysis of appetite regulating hormones in patients with first-episode psychosis (FEP). Meta-analyses were conducted using random-effects models with Hedges' g as the effect size estimate. We identified 31 eligible studies, investigating the levels of 7 appetite regulating hormones (adiponectin, insulin, leptin, ghrelin, orexin, resistin and visfatin) in 1792 FEP patients and 1364 controls. The insulin levels in FEP patients were higher than in controls (g = 0.34, 95%CI: 0.19 - 0.49, p < 0.001), even considering only antipsychotic-naïve patients (g = 0.39, 95%CI: 0.12 - 0.66, p = 0.005). The severity of negative symptoms was positively associated with the effect size estimates (ß = 0.08, 95%CI: 0.01 - 0.16, p = 0.030). Moreover, we found lower levels of leptin in antipsychotic-naïve FEP patients (g = -0.62, 95%CI: -1.11 - 0.12, p = 0.015). Impaired appetite regulation, in terms of elevated insulin levels and decreased leptin levels, occurs in early psychosis, before antipsychotic treatment. Hyperinsulinemia might be related to negative symptoms.

Adiponectin levels in patients with bipolar disorder: A systematic review and meta-analysis.

Bipolar disorder (BD) is associated with high prevalence rates of obesity-related conditions and subclinical inflammation. Adiponectin is produced by adipose tissue and exerts anti-inflammatory activities. We aimed to perform a systematic review and meta-analysis of studies investigating adiponectin levels in BD patients and healthy controls. Electronic databases were searched from their inception until 15th Jan 2019. Random-effects models with the Hedges' g as the effect size (ES) estimate were used. We included 11 studies, representing 477 patients and 380 controls. Pooled data analysis revealed no significant differences in adiponectin levels between BD patients and controls (ES = 0.28, 95%CI: -0.34 - 0.90, p = 0.372). The levels of adiponectin were significantly higher during euthymia (ES = 1.09, 95%CI: 0.03-2.16, p = 0.044). The levels of adiponectin in depressed patients were lower, but this result did not reach statistical significance (ES = -0.90, 95%CI: -1.85 - 0.05, p = 0.063). Due to low number of studies, the subgroup analysis of manic patients was not performed; however, a severity of manic symptoms was not associated with the ES estimates. Longer illness duration and a higher percentage of BD type I (BD-I) patients were associated with higher ES estimates. A higher severity of depressive symptoms was associated with lower ES estimates. Heterogeneity was significant in all analyses. Results of the Egger's test were insignificant, showing no publication bias. Our results indicate that adiponectin might be a state marker of BD as it appears to be elevated in euthymia and decreased in depression. Illness progression and a diagnosis of BD-I might contribute to higher adiponectin levels.

Coping styles and symptomatic manifestation of first-episode psychosis: Focus on cognitive performance.

Cognitive deficits are widely observed in patients with psychosis and represent one of most important determinants of functional outcomes. It has been shown that patients with psychosis prefer maladaptive coping strategies over active coping styles. However, it remains unknown whether cognitive impairments are related to coping styles in psychotic disorders. Therefore, the aim of this study was to assess whether cognitive deficits observed in patients with first-episode psychosis (FEP) might impact the use of specific coping strategies. We recruited 40 FEP patients and 35 healthy controls. In our study, FEP patients were more likely to use maladaptive coping styles after adjustment for education level and medication effects. The use of maladaptive coping strategies was associated with greater impairments of visuospatial/constructional abilities and language skills in FEP patients. In addition, lower odds of using adaptive coping were related to higher levels of depressive symptoms in the group of patients. Adaptive coping was associated with better global cognitive performance in healthy controls. Our results indicate that cognitive impairments, especially worse performance of visuospatial/constructional abilities and language skills, might be related to the preference of maladaptive coping strategies. Lower odds of using adaptive coping styles might be associated with more severe depressive symptomatology.

Assessment of the Association Between Cigarette Smoking and Cognitive Performance in Patients With Schizophrenia-Spectrum Disorders: A Case-Control Study.

The prevalence of cigarette smoking is significantly higher in patients with schizophrenia compared to the general population. Schizophrenia is also characterized by cognitive impairments that can be detected in the premorbid phase of illness. However, studies addressing the association between cigarette smoking and cognition in patients with psychosis have provided mixed findings. Therefore, the aim of this study was to assess the relationship between tobacco smoking and cognitive performance in patients with schizophrenia. In this case-control study, we recruited 67 inpatients with schizophrenia (34 cigarette smokers) and 62 healthy controls (30 cigarette smokers) at two clinical sites (Wroclaw and Szczecin, Poland). Cognitive performance was examined using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Smoking dependence was determined using the Fagerström Test for Nicotine Dependence (FTND) and the pack-year index. Results show that, after adjustment for potential confounders, smokers with schizophrenia presented significantly lower scores on delayed memory tests compared to non-smokers with schizophrenia (F = 11.07, p = 0.002). In healthy controls, after adjustment for age, sex, and education level, smokers had significantly lower scores in immediate memory (47.1 ± 6.4 vs. 52.0 ± 4.0, F = 11.64, p = 0.001), visuospatial/constructional functions (34.8 ± 3.8 vs. 37.7 ± 1.8, F = 12.86, p = 0.001) and global cognition (177.0 ± 15.7 vs. 191.2 ± 14.0, F = 12.63, p = 0.001) compared to non-smokers. There were no significant correlations between FTND scores or pack-year index and cognitive performance neither in patient nor control group. Our results show that cigarette smoking is related to worse delayed memory performance in schizophrenia patients as well as deficits of immediate memory, visuospatial/constructional functions, and global cognition in controls. Longitudinal studies are required to establish causal interference between smoking and cognition in patients with schizophrenia.

Decreased use of active coping styles contributes to elevated allostatic load index in first-episode psychosis.

Accumulating evidence indicates that stress plays an important role in the development of psychotic disorders. Recent studies have revealed that patients with first-episode psychosis (FEP) present systemic biological dysregulations related to stress-exposure in terms of elevated allostatic load (AL) index. However, the mechanisms underlying this observation remain unknown. Therefore, in this study we aimed to investigate the AL index with respect to stress coping strategies in 36 FEP patients and 31 matched controls. We found significantly higher AL index in FEP patients compared to controls after co-varying for potential confounding factors. Patients with FEP were less likely to use active and task-focused coping. Lower odds of using these coping styles, planning as well as positive reinterpretation and growth were related to higher AL index in FEP patients, but not in controls. Depressive symptoms were associated with lower likelihood of using task-focused coping as well as positive reinterpretation and growth. Additionally, depressive symptoms were related to higher AL index. Finally, depressive symptoms mediated the effects of task-focused coping as well as positive reinterpretation and growth on the AL index. Our results confirm systemic biological dysregulation indexed as AL in FEP patients. Lower odds of using active coping styles might contribute to higher AL index via the mediating effect of depressive symptoms in patients with FEP. Longitudinal studies are required to establish causal inferences between coping styles, depressive symptoms and the AL index in early psychosis.

Vascular endothelial growth factor in patients with schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Accumulating evidence indicates that schizophrenia might be accompanied by abnormal vascularization. Vascular endothelial growth factor (VEGF) is one of key molecules involved in the development of vessels with vasodilatory activities. OBJECTIVES: We aimed to perform a systematic review and meta-analysis of studies investigating serum or plasma levels of VEGF in patients with schizophrenia and first-episode psychosis (FEP). METHODS: Electronic databases were searched from their inception until 18th Apr 2018. Meta-analysis was performed using random-effects models with Hedges' g as the effect size estimate. Quality assessment was performed using the Newcastle-Ottawa Scale. RESULTS: We included 15 eligible studies, representing 982 patients and 791 healthy controls. Main analysis revealed no significant differences in VEGF levels between patients and controls (g = 0.10, 95%CI = -0.24-0.45, p = .553). Subgroup analysis demonstrated unaltered levels of VEGF in FEP patients (g = 0.03, 95%CI = -0.53-0.59, p = .911), including antipsychotic-naïve individuals (g = 0.34, 95%CI = -0.07-0.74, p = .103). However, the levels of VEGF were significantly higher in medicated multiple-episode schizophrenia (MES) patients (g = 0.45, 95%CI = 0.03-0.87, p = .036) compared to controls. Heterogeneity across studies was significant in the majority of analyses, except for the analysis of antipsychotic-naïve FEP patients. Tests of asymmetry were insignificant, indicating a lack of publication bias. LIMITATIONS: Main limitations of our meta-analysis include inability to address medication effects exhaustively and relatively low number of studies in subgroup analyses. CONCLUSIONS: Our results indicate elevated levels of VEGF in MES patients that are unaltered in FEP individuals. Longitudinal studies are required to disentangle whether elevated levels of VEGF in MES patients reflect illness progression, comorbid physical health impairments or appear due to medication effects.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study.

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1ß, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1ß) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.

Areas of stigma and discrimination of mentally ill people among Internet respondents in Poland. / Obszary stygmatyzacji i dyskryminacji osób chorujacych psychicznie wsród respondentów internetowych w Polsce.

OBJECTIVES: The aim of this study was to investigate the public perception of mentally ill people, stigma of the mentally ill and distance towards them in Poland. METHODS: The study group was composed of 1,309 respondents who were interviewed using an authors' own survey, which was spread with the use of online media. RESULTS: The results indicate a high level of stigma of psychiatric patients in the subjective assessment of their appearance, intellect as well as respondents' sense of superiority over the patients. The stigma of a psychiatric patient is also resolutely demonstrated in the economic aspect, which results from respondents' unwillingness to employ, or even work with people affected by a disorder from the mental illness group. CONCLUSIONS: Undoubtedly, the fight against the phenomenon of stigma and discrimination against people affected by mental health problems is becoming one of the priorities in the field of mental health.

Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review.

Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults. In this article, we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes. In the majority of studies from this field, interacting effects of variation in genes encoding catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) have been explored. Almost consistently, these studies revealed that polymorphisms in COMT, BDNF, and FKBP5 genes might interact with early life stress and cannabis abuse or dependence, influencing various outcomes of schizophrenia spectrum disorders and BD. Other interactions still require further replication in larger clinical and non-clinical samples. In addition, future studies should address the direction of causality and potential mechanisms of the relationship between gene × environment interactions and various categories of outcomes in schizophrenia and BD.