Association between Female Reproductive Factors and Risk of Dementia.

Women have an over 50% greater risk of dementia than men, which is a main topic of much research. This review aims to investigate the impact of a woman's reproductive history on dementia risk. The consequences of stillbirth are long-term health and psychosocial problems for women. Because of the awareness of an endangered pregnancy, many parents experience deep anxiety and stress in subsequent pregnancies. There are contradictory conclusions from research about abortion and the risk of dementia correlation. When it comes to the late age of first birth, which is said to be above 35 years old, it was observed that older mothers have a decreased risk of dementia compared to those who gave birth in their 20s; however, being a child of the older mother is connected with a higher risk of developing dementia. Using hormonal contraception can result in decreased risk of dementia as estrogen stimulates microglia-related Aß removal and reduces tau hyperphosphorylation. The influence of postmenopausal hormonal therapy and the duration of the reproductive period on developing dementia remains unclear. Although female disorders like endometriosis and polycystic ovary syndrome are reported to increase the risk of dementia, the research on this topic is very limited, especially when it comes to endometriosis, and needs further investigation. Interestingly, there is no conclusion on whether hypertensive disorders of pregnancy increase the risk of dementia, but most articles seem to confirm this theory.

Artificial light and neurodegeneration: does light pollution impact the development of Alzheimer's disease?

Two multidimensional problems of recent times - Alzheimer's disease and light pollution - seem to be more interrelated than previously expected. A series of studies in years explore the pathogenesis and the course of Alzheimer's disease, yet the mechanisms underlying this pathology remain not fully discovered and understood. Artificial lights which accompany civilization on a daily basis appear to have more detrimental effects on both environment and human health than previously anticipated. Circadian rhythm is affected by inappropriate lighting conditions in particular. The consequences are dysregulation of the sleep-wake cycle, gene expression, neuronal restructuring, brain's electricity, blood flow, metabolites' turnover, and gut microbiota as well. All these phenomena may contribute to neurodegeneration and consequently Alzheimer's disease. There is an increasing number of research underlining the complexity of the correlation between light pollution and Alzheimer's disease; however, additional studies to enhance the key tenets are required for a better understanding of this relationship.

The Amyloid Cascade Hypothesis in Alzheimer's Disease: Should We Change Our Thinking?

Old age increases the risk of Alzheimer's disease (AD), the most common neurodegenerative disease, a devastating disorder of the human mind and the leading cause of dementia. Worldwide, 50 million people have the disease, and it is estimated that there will be 150 million by 2050. Today, healthcare for AD patients consumes 1% of the global economy. According to the amyloid cascade hypothesis, AD begins in the brain by accumulating and aggregating Aß peptides and forming ß-amyloid fibrils (Aß42). However, in clinical trials, reducing Aß peptide production and amyloid formation in the brain did not slow cognitive decline or improve daily life in AD patients. Prevention studies in cognitively unimpaired people at high risk or genetically destined to develop AD also have not slowed cognitive decline. These observations argue against the amyloid hypothesis of AD etiology, its development, and disease mechanisms. Here, we look at other avenues in the research of AD, such as the presenilin hypothesis, synaptic glutamate signaling, and the role of astrocytes and the glutamate transporter EAAT2 in the development of AD.

Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19.

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.

The Effect of Frailty Syndrome on the Quality of Life of Individuals with Parkinson's Disease: A Pilot Observational and Multicenter Study on the Polish Population.

Parkinson's disease (PD) is a neurodegenerative disorder involving decreased dopamine release and atrophy of dopaminergic neurons of the substantia nigra. Frailty syndrome (FS) is common in older adults, which, in combination with PD symptoms, can substantially affect the quality of life (QOL). This study aimed to assess the prevalence of FS among PD patients and to identify variables affecting their QOL with particular attention to FS. The study included 296 patients (n = 173 women) with a mean age of 70.3 ± 5.7 years suffering from PD for an average of 8.2 ± 5.6 years. Patients were classified as at least stage II according to the Hoehn and Yahr scale. The following standardized questionnaires were used in the study: Schwab and England Activities of Daily Living (SE-ADL), Parkinson's Disease Questionnaire (PDQ-39), Beck Depression Inventory (BDI), Unified Parkinson's Disease Rating Scale (UPDRS), and Tilburg Frailty Indicator (TFI). FS was found in 96% (n = 283) of the PD patients studied. No depression occurred in 30% (n = 89) of subjects, moderate depression in 48% (n = 141) of subjects, and severe depression in 22% (n = 66) of subjects. The mean score of the PDQ-39 questionnaire in PD subjects with FS was 41.6 pts (min-max: 5.2-81.5 pts; SD = 17.4 pts), which was statistically significantly higher than in subjects without FS (p < 0.05). FS has been shown to be present in most of the subjects with PD. FS occurs more frequently with a longer PD period, which is associated with reduced physical capacity and QOL. Physical activity improves QOL and reduces disease progression. FS, similar to PD, is a common cause of disability in older adults and their dependency. Predictors such as depression, advanced stage of the disease, higher education, and low professional and economic status significantly affect the QOL level of PD patients. However, the results obtained among the Polish population of PD patients do not confirm the impact of FS on the QOL, so there is a need to conduct further research on this subject.

Clinical Correlates of the NR3C1 Gene Methylation at Various Stages of Psychosis.

BACKGROUND: Dysregulation of epigenetic processes might account for alterations of the hypothalamic-pituitary-adrenal axis observed in patients with schizophrenia. Therefore, in this study, we aimed to investigate methylation of the glucocorticoid receptor (NR3C1) gene in patients with schizophrenia-spectrum disorders, individuals at familial high risk of schizophrenia (FHR-P), and healthy controls with respect to clinical manifestation and a history of psychosocial stressors. METHODS: We recruited 40 first-episode psychosis patients, 45 acutely relapsed schizophrenia (SCZ-AR) patients, 39 FHR-P individuals, and 56 healthy controls. The level of methylation at 9 CpG sites of the NR3C1 gene was determined using pyrosequencing. RESULTS: The level of NR3C1 methylation was significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients compared with other subgroups of participants. Individuals with FHR-P and healthy controls had similar levels of NR3C1 methylation. A history of adverse childhood experiences was associated with significantly lower NR3C1 methylation in all subgroups of participants. Higher methylation of the NR3C1 gene was related to worse performance of attention and immediate memory as well as lower level of general functioning in patients with psychosis. CONCLUSIONS: Patients with schizophrenia-spectrum disorders show altered levels of NR3C1 methylation that are significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients. Higher methylation of the NR3C1 gene might be related to cognitive impairment observed in this clinical population. The association between a history of adverse childhood experiences and lower NR3C1 methylation is not specific to patients with psychosis. Longitudinal studies are needed to establish causal mechanisms underlying these observations.

Metabolic Dysregulation and Psychosocial Stress in Patients with Schizophrenia Spectrum Disorders: A Case-Control Study.

Patients with schizophrenia spectrum disorders have a reduced life expectancy, which is largely the consequence of a high co-occurrence of cardiovascular diseases. To date, several intrinsic and environmental factors underlying this phenomenon have been found. However, the association with psychosocial stress has not been extensively addressed. In this study, we tested the relationship between a history of adverse childhood experiences (ACEs), lifetime stressors, perceived stress and metabolic parameters in patients with schizophrenia spectrum disorders and in healthy controls. The participants included 85 inpatients with schizophrenia spectrum disorders and 56 healthy controls. Serum levels of glucose, insulin, low- and high-density lipoproteins (LDL and HDL), triglycerides, total cholesterol and high-sensitivity C-reactive protein (hsCRP) were determined. After adjustment for potential confounding factors, patients had significantly higher levels of glucose (F = 4.856, p = 0.030), triglycerides (F = 4.720, p = 0.032) and hsCRP (F = 7.499, p = 0.007) as well as significantly lower levels of HDL (F = 5.300, p = 0.023) compared to healthy controls. There were also significant effects of interactions between diagnosis and a history of ACEs on the levels of insulin (F = 4.497, p = 0.036) and homeostatic model assessment of insulin resistance (HOMA-IR) (F = 3.987, p = 0.048). More specifically, the levels of insulin and HOMA-IR were significantly higher in the subgroup of patients with schizophrenia spectrum disorders and a positive history of ACEs compared to other subgroups of participants. No significant associations between lifetime stressors and perceived stress with metabolic parameters were found. Our findings indicate that a history of ACEs might be associated with insulin resistance in patients with schizophrenia spectrum disorders. Therapeutic strategies targeting early-life stress should be considered with early interventions that aim to manage cardiometabolic comorbidity in patients with schizophrenia spectrum disorders.

Deep brain stimulation: new possibilities for the treatment of mental disorders. / Gleboka stymulacja mózgu (Deep Brain Stimulation) ­ nowe mozliwosci leczenia zaburzen psychicznych.

Deep brain stimulation (DBS) is a treatment method that is currently getting more and more attention from psychiatrists. It has proven to be efficacious and safe in the treatment of neurological disorders, mainly Parkinson's disease (PD), dystonia and essential tremor. DBS has very often contributed to successful treatment in cases that had proved resistant to all other methods of treatment. Nowadays treatment-resistant obsessive-compulsive disorder (OCD) is the main psychiatric indication for DBS. Many studies have focused on assessing the efficacy and safety of this method in different mental disorders, including depressive disorders, Alzheimer's disease, anorexia nervosa, Tourette syndrome, substance addiction or aggressive behaviors. Single cases of successful treatment in bipolar disorder, schizophrenia and post-traumatic stress disorder have also emerged in recent years. In this review the current state of knowledge on the applicability of DBS in psychiatry is presented, based on the available systematic reviews, clinical trials and case studies, as well as on neurophysiological and neuroimaging data.

Deep brain stimulation in obsessive-compulsive disorder - case report of two patients. / Gleboka stymulacja mózgu w zaburzeniu obsesyjno-kompulsyjnym ­ dwa przypadki kliniczne.

Obsessive-compulsive disorder (OCD) occurs in 2-3% of the general population. Due to its chronicity and high resistance to standard treatment, alternative clinical management based on neuroscientific findings has been sought. Deep brain stimulation (DBS) is a modern and dynamic approach in the treatment of OCD giving hope to patients who are resistant to current pharmacotherapy and psychotherapy based treatments. This paper presents two cases of patients diagnosed with refractory OCD who received DBS therapy with concurrent pharmacotherapy and cognitive behavioral psychotherapy (CBT). Both patients underwent a neurosurgical procedure to implant electrodes into the anterior limb of the internal capsule (ALIC) and nucleus accumbens (NAc). Before and after the start of neurostimulation, patients underwent a clinical evaluation which consisted of a psychiatric examination and psychometric measurements (Y-BOCS, HAMA, HDRS, GAF, SOFAS). During the follow-up period, a blind attempt to switch off the neurostimulation was made. During the 6-month follow-up period, a significant reduction in the obsessive-compulsive, depressive and anxiety symptoms was achieved as well as an improvement in global patient functioning. The tolerance of DBS was found to be very good and no significant side effects were observed. The obtained results provide the basis for the implementation of this method in patients with OCD who are resistant to current treatment.

Allostatic load index and its clinical correlates at various stages of psychosis.

Accumulating evidence indicates systemic biological dysregulations in patients with psychosis that have been conceptualized as the "allostatic load" (AL) index. We aimed to investigate the AL index in 37 subjects at familial high risk of psychosis (FHRP), 42 first-episode psychosis (FEP) patients, 25 acutely relapsed schizophrenia (SCZ-AR) patients and 42 healthy controls (HCs), taking into account psychopathology and cognitive impairment. The AL index was calculated based on 15 biomarkers (cardiovascular markers, anthropometric measures, inflammatory markers, glucose homeostasis parameters, lipids and steroids). Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The AL index was significantly higher in patients with psychosis and FHR-P individuals compared to HCs. Patients with FEP and FHR-P individuals had similar AL index. Moreover, the AL index was significantly higher in SCZ-AR patients compared to other groups of participants. Higher AL index was associated with more severe general psychopathology and depressive symptoms, lower scores of attention (total score, digit span and digit coding tasks) and semantic fluency, as well as worse general functioning in patients with psychosis. There was a significant negative correlation between the AL index and the scores of attention (total score and digit coding task) in FHR-P individuals. No significant correlations between the AL index and cognition were found in HCs. Our results indicate that biological dysregulations, captured by the AL index, appear already in FHR-P individuals and progress with psychotic exacerbations. Elevated AL index might contribute to cognitive impairments in FHR-P individuals and patients with psychosis.

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.

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.

Polymorphisms in immune-inflammatory response genes and the risk of deficit schizophrenia.

Polymorphisms in immune-inflammatory response genes are believed to impact schizophrenia susceptibility. However, it remains unknown whether immunogenetic factors play a role in the etiology of deficit schizophrenia (D-SCZ). Therefore, we genotyped four polymorphisms in genes encoding two immune system regulatory proteins (CTLA-4 rs231775 and CD28 rs3116496), interleukin-6 (IL6 rs1800795) and transforming growth factor-ß (TGFB1 rs1800470) in 513 schizophrenia patients and 374 controls. The CD28 rs3116496-CC genotype and C-allele were significantly more frequent in the whole group of patients and D-SCZ patients compared to controls. Our results indicate that the CD28 rs3116496 polymorphism might impact the risk of schizophrenia, especially D-SCZ.

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets.

Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity. Animal model studies have provided evidence that cytokines might impact cognitive performance through direct and indirect effects on long-term potentiation, neurogenesis and synaptic plasticity. Therefore, it has been hypothesized that cytokine alterations might contribute to cognitive impairment that is widely observed in MDD and persists beyond episodes of acute relapse in the majority of patients. Although several studies have provided that peripheral cytokine alterations might be related to cognitive deficits in patients with MDD, the quality of evidence still leaves much to be desired due to methodological heterogeneity and limitations. In this article, we provide an overview of studies investigating the association between peripheral cytokine alterations and cognitive performance in MDD, discuss underlying mechanisms and neural substrates. Finally, we propose possible treatment targets related to cytokine alterations taking into account existing evidence for antidepressant efficacy of anti-inflammatory pharmacological treatment modalities.

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.

AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. RESULTS: IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. CONCLUSIONS: Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.