Chronic Psychiatric Disorders Research Articles

Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis.

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.

Altered PLCβ/IP3/Ca2+ Signaling Pathway Activated by GPRCs in Olfactory Neuronal Precursor Cells Derived from Patients Diagnosed with Schizophrenia.

Background: Schizophrenia (SZ) is a multifactorial chronic psychiatric disorder with a worldwide prevalence of 1%. Altered expression of PLCβ occurs in SZ patients, suggesting alterations in the PLCβ/IP3/Ca2+ signaling pathway. This cascade regulates critical cellular processes in all cell types, including the neuronal lineage; however, there is scarce evidence regarding the functionality of this transduction signaling in neuronal cells derived from SZ patients. Objective: We evaluated the functionality of the PLCβ/IP3/Ca2+ pathway in olfactory neuronal precursor cells (hONPCs) obtained from SZ patients. Methods: Cryopreserved hONPCs isolated from SZ patients and healthy subjects (HS) were thawed. The cellular types in subcultures were corroborated by immunodetection of the multipotency and lineage markers SOX-2, Musashi-1, nestin, and β-III tubulin. The PLCβ/IP3/Ca2+ pathway was activated by GPCR (Gq) ligands (ATP, UTP, serotonin, and epinephrine). In addition, PLCβ and IP3R were directly stimulated by perfusing cells with the activators m-3M3FBS and ADA, respectively. Cytosolic Ca2+ was measured by microfluorometry and by Ca2+ imaging. The amount and subcellular distribution of the PLCβ1 and PLCβ3 isoforms were evaluated by confocal immunofluorescence. IP3 concentration was measured by ELISA. Results: The results show that the increase of cytosolic Ca2+ triggered by GPCR ligands or directly through either PLCβ or IP3R activation was significantly lower in SZ-derived hONPCs, regarding HS-derived cells. Moreover, the relative amount of the PLCβ1 and PLCβ3 isoforms and IP3 production stimulated with m-3M3FBS were reduced in SZ-derived cells. Conclusions: Our results suggest an overall functional impairment in the PLCβ/IP3/Ca2+ signaling pathway in SZ-derived hONPCs.

TRATAMENTO FARMACOLÓGICO DA ESQUIZOFRENIA: PASSADO, PRESENTE E FUTURO

Schizophrenia is a chronic and severe psychiatric disorder characterised by the manifestation of positive and negative symptoms and/or cognitive dysfunction. Treatment typically includes psychotherapy, sociotherapy and pharmacological therapy, which consists of the use of typical and atypical antipsychotic drugs, as well as dopaminergic system stabilisers. Although they do not provide a cure, these treatments can reduce the intensity and frequency of symptoms, resulting in improved quality of life and a quicker reintegration into social life. Thus, the aim of the present study was to conduct a narrative literature review on the clinical evolution of antipsychotic use throughout history, as well as to discuss potential new drugs that are still in clinical research. Studies have shown that typical antipsychotics are effective in treating positive symptoms but have no impact on negative symptoms and can even exacerbate or provoke them. Additionally, they produce highly limiting side effects, such as movement disorders. Atypical antipsychotics, on the other hand, are capable of reducing both positive and negative symptoms, and they also present fewer side effects related to the extrapyramidal motor system. However, they tend to cause metabolic disturbances. Conversely, dopaminergic system stabilisers also treat both positive and negative symptoms, with side effects that are generally better tolerated, along with a lower propensity to cause weight gain and motor disturbances. It is worth noting that many patients are unable to tolerate the various adverse reactions of the available antipsychotics. Moreover, some patients are or become refractory to their therapeutic effects. Consequently, there is currently a focus on developing new agents that have different pharmacological targets. Some of these potential new drugs have shown efficacy in refractory patients, representing a potential paradigm shift in the treatment of the disorder.

The importance of oxidative stress in the pathogenesis and treatment of bipolar affective disorder: a review of the literature

Introduction: Bipolar affective disorder (BD), also known as manic-depressive illness, is a chronic and recurrent psychiatric disorder characterised by significant mood disturbances. It is one of the leading causes of disability worldwide and is associated with a high risk of suicide. Recent studies highlight the role of oxidative stress (OS) in the pathogenesis of BD. The body's pro/antioxidant imbalance adversely affects cellular and molecular processes. Aim: The aim of this review is to synthesise the current state of knowledge on the role of OS in the aetiology and course of BD, including key biomarkers and potential therapeutic interventions. Methods: A review of the scientific literature was conducted, including articles published between 2000 and 2024. Searches were conducted in PubMed, Scopus and Web of Science databases, using the following keywords: 'bipolar disorder', 'oxidative stress', 'antioxidants', 'biomarkers', 'mitochondrial dysfunction', 'redox homeostasis', 'treatment'. Results: Results indicate that patients with BD have elevated levels of OS markers, including increased lipid peroxidation, altered antioxidant enzyme activity and impaired redox homeostasis. Treatment with lithium and other mood stabilisers may modulate levels of OS markers, which is one potential mechanism of drug action. However, inconclusive data suggest the need for further research to clarify the relationship between OS and BD. Conclusions: OS plays an important role in the pathophysiology of BD, offering potential directions for therapeutic interventions. Understanding the complex interactions between OS and BD may lead to the development of more targeted therapies aimed at reducing oxidative damage and improving patient health. Keywords: oxidative stress, bipolar affective disorder, redox, lipid peroxidation, protein damage, antioxidants, lithium

Machine learning with multiple modalities of brain magnetic resonance imaging data to identify the presence of bipolar disorder

BackgroundBipolar disorder (BD) is a chronic psychiatric mood disorder that is solely diagnosed based on clinical symptoms. These symptoms often overlap with other psychiatric disorders. Efforts to use machine learning (ML) to create predictive models for BD based on data from brain imaging are expanding but have often been limited using only a single modality and the exclusion of the cerebellum, which may be relevant in BD. MethodsIn this study, we sought to improve ML classification of BD by combining information from structural, functional, and diffusion-weighted imaging. Participants (108 BD I, 78 control) with BD type I and matched controls were recruited into an imaging study. This dataset was randomly divided into training and testing sets. For each of the three modalities, a separate ML model was selected, trained, and then used to generate a prediction of the class of each test subject. Majority voting was used to combine results from the three models to make a final prediction of whether a subject had BD. An independent replication sample was used to evaluate the ability of the ML classification to generalize to data collected at other sites. ResultsCombining the three machine learning models through majority voting resulted in an accuracy of 89.5 % for classification of the test subjects as being in the BD or control group. Bootstrapping resulted in a 95 % confidence interval of 78.9 %–97.4 % for test accuracy. Performance was reduced when only using 2 of the 3 modalities. Analysis of feature importance revealed that the cerebellum and nodes of the emotional control network were among the most important regions for classification. The machine learning model performed at chance on the independent replication sample. ConclusionBD I could be identified with high accuracy in our relatively small sample by combining structural, functional, and diffusion-weighted imaging data within a single site but not generalize well to an independent replication sample. Future studies using harmonized imaging protocols may facilitate generalization of ML models.

Care burden and associated factors among caregivers of patients with bipolar type I disorder

BackgroundFamily caregivers play a significant role in providing care for these people at home and need new evidence on the outcomes of their caregiving. Caregiving for people with chronic psychiatric disorders, especially Bipolar type I Disorder (BD-I), is a major challenge in the healthcare system. This study aimed to examine the relationship between caregiver burden, resilience and optimism in family caregivers of patients with BD-I.MethodsThis study used a cross-sectional design and involved 209 family caregivers of people with BD-I by convenience sampling method. Data were collected using the Zarit Burden Inventory (ZBI), Connor-Davidson Resilience Scale (CD-RISC), and Revised Life Orientation Test (LOT-R). The participants were selected from the list of family caregivers covered by the Ibn Sina Hospital’s health clinic in Mashhad, Iran. The data were analyzed using descriptive statistics and multiple regression analysis with a significance level of 0.05.ResultsThe average ages of the caregivers and their patients were 45.43 (13.34) and 36.7 (14.05), respectively. The average caregiver burden score was 41.92 (19.18), which was moderate (31 to 60). The predictors of caregiver burden in this study were caregiver-related factors such as optimism (p < 0.001, β = 0.25) and employment status (housewife: p = 0.038, β = 0.43; self-employed: p = 0.007, β = 0.12; retired: p < 0.001, β = 0.23), and patient-related factors such as the presence of psychotic symptoms (p < 0.001, β = 0.33), daily caregiving hours (p < 0.001, β = 0.16), history of suicide attempts (p = 0.035, β = 0.43), and alcohol consumption (p < 0.001, β = 0.85). These variables explained 58.3% of the variance in caregiver burden scores.ConclusionThe study concluded that family caregivers of people with BD-I had moderate levels of caregiver burden and low resilience, influenced by various factors related to themselves and their patients. Psychological education interventions within the framework of mental health support systems are recommended to reduce caregiver burden in these people.

Psychosocial impact of hoarding symptoms in college students and the potential for early intervention

Objective: Hoarding disorder is a chronic and progressive psychiatric disorder that often begins in adolescence and early adulthood. The purpose of this study was to investigate the impact of hoarding severity on college students’ psychosocial functioning and possible methods of early intervention. Participants: Undergraduate students (N = 363) at a large public university in the United States. Methods: Participants completed a self-report battery that included their parental history of clutter, perceptions about possible interventions for clutter, and standardized measures of hoarding severity, psychiatric symptoms, and psychosocial functioning. Results: Hoarding symptom severity predicted significant unique variance in emotional support and companionship, even when controlling for comorbid psychiatric symptoms. The main reasons endorsed by participants for disorganization of their objects despite adequate storage space were “lack of time” (37%), “easily distracted” (26%), and “procrastination” (34%). Conclusions: Emerging adults may benefit from early intervention focused on time management, attentional control, and consistent motivation.

The Role of Personality Traits, Cognitive Performances, and Perceived Social Support on Job Satisfaction Among Individuals with Chronic Psychiatric Disorders

Background: This study was conducted due to the importance of job satisfaction in chronic psychiatric patients and the lack of sufficient information about the associated variables. Objectives: The study aimed to assess the role of personality traits, cognitive performances, and perceived social support on job satisfaction among individuals with chronic psychiatric disorders employed in supportive-productive workshops in Semnan. Methods: This cross-sectional study was conducted using a quantitative and descriptive-correlational regression method. It included 152 individuals (both male and female) with chronic psychiatric disorders employed in supportive-productive workshops in Semnan city in 2022. Participants were randomly selected through a lottery method. Data were gathered using the NEO Five-Factor Inventory by Costa and McCrae (1985), the Field and Roth Job Satisfaction questionnaire (1951), Zimet's (1988) scale for perceived social support, and the Montreal Cognitive Assessment (1996). Data analysis was performed using regression analysis with SPSS version 24. Results: The regression analysis illustrated that although neuroticism, agreeableness, extraversion, conscientiousness, perceived social support, and cognitive performances had a significant predictive role on job satisfaction among patients with chronic psychiatric disorders, perceived social support and conscientiousness had the most significant effect, while cognitive performances had the least significant effect on predicting job satisfaction (P &lt; 0.05). Conclusions: It is recommended that authorities pay special attention to the perceived social support from society and family, as well as cognitive rehabilitation focusing on attention and concentration for individuals with chronic psychiatric disorders.

GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection

Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.

Contacts with environmental biodiversity affect human health: links revealed during the initial waves of the COVID-19 pandemic

The gradual decrease in the prevalence of serious infectious diseases over the last century has been followed by increase in so called “modern” diseases, including allergies, chronic inflammatory conditions, psychiatric, and metabolic disorders. Between 2019 and 2022, public awareness of the threat of infectious diseases in humans was renewed by the global pandemic of a new type of a coronavirus, the SARS-COV-2. This public interest opened improved possibilities to test hypotheses on the factors associated with inter-individual variation in susceptibility to infectious and “modern” diseases. Based on the Hygiene hypothesis and Biodiversity hypothesis, we predicted that contacts with natural environment and wildlife in childhood and/or in adulthood can improve general health and decrease the risks of severe COVID-19 progression or prevalence of the “modern” diseases, namely the allergies. Here we report the results of an online, self-evaluating questionnaire survey conducted in the Czech Republic, where we contrasted selected health issues, and linked them to the living environment, including the level of contacts with biodiversity. In a sample of 1188 respondents, we revealed a significant association of time spent in nature or contacts with biodiversity with physical and mental health, or incidence of allergies. This is unlike the COVID-19 progression, which was related to age, physical health, smoking, allergies, and interaction of age with smoking, but not to contacts with the natural environmental diversity. Our findings regarding to physical and mental health and allergies are in agreement with the Biodiversity hypothesis of allergy and, linking human and environmental health, they urge for One Health approach application.

Intermittent Theta Burst Stimulation Combined with Cognitive Training to Improve Negative Symptoms and Cognitive Impairment in Schizophrenia: A Pilot Study.

Schizophrenia is a chronic psychiatric disorder severely affecting patients' functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms cannot be treated pharmacologically and represent consistent predictors of the illness's prognosis. Cognitive remediation (CR) interventions have been applied to target these symptoms. Brain stimulation also provides promising yet preliminary results in reducing negative symptoms, whereas its effect on cognitive impairment remains heterogeneous. Here, we combined intermittent theta burst stimulation (iTBS) with CR to improve negative symptoms and cognitive impairment in schizophrenia spectrum patients. One hundred eligible patients were invited, and twenty-one participated. We randomized them into four groups, manipulating the stimulation condition (real vs. sham) and CR (no training vs. training). We delivered fifteen iTBS sessions over the left dorsolateral prefrontal cortex for three weeks, followed (or not) by 50 min of training. Consensus-based clinical and cognitive assessment was administered at baseline and after the treatment, plus at three follow-ups occurring one, three, and six months after the intervention. Mixed-model analyses were run on cognitive and negative symptom scores. The preliminary findings highlighted a marginal modulation of iTBS on negative symptoms, whereas CR improved isolated cognitive functions. We herein discuss the limitations and strengths of the methodological approach.

Implications of the Gut Microbiota for Brain Function and Behavior in Schizophrenia.

Schizophrenia is a severe, chronic psychiatric disorder characterized by delusions, hallucinations, cognitive impairments, and emotional dysregulation. This psychiatric illness is often resistant to treatment. This literature review aims to analyze the relationship between this complex psychological disorder and the gut microbiota found within the human body. The brain and gut are interconnected, and emerging research suggests a link between gut dysbiosis and schizophrenia. Gut dysbiosis refers to an imbalance or disruption in the composition and function of the gut microbiome. The studies comparing the gut microbiota of patients with schizophrenia to those without highlight significant differences at the phylum and genus levels, providing evidence of gut microbiome alteration. The lack of diversity of microbiota in schizophrenia patients can be altered and improved to a healthier microbiome by way of dietary intervention. Interventions that target the gut-brain axis, such as dietary probiotics or prebiotics, may help alleviate certain symptoms of schizophrenia and help improve patients' well-being. Understanding the complex interplay between gut microbiome health and schizophrenia may allow for the development of targeted interventions that alter the gut microbiome of patients with schizophrenia and, in turn, mitigate their symptoms and improve their quality of life.

Psychiatric Co-morbidity with Obsessive Compulsive Disorder

Background: Obsessive-compulsive disorder is a chronic psychiatric disorder. It is associated with substantial psychiatric comorbidity. Major Depressive disorder &amp; mixed anxiety and depressive disorder are the most common psychiatric co-morbidities.Objective: To evaluate the psychiatric co-morbidity with obsessive-compulsive disorder.Materials and Methods: It was a descriptive and cross-sectional clinical study. It was conducted in the Outpatient Department of Psychiatry, Khwaja Yunus Ali Medical College, Sirajganj from January 2021 to December 2022. Total 100 patients were taken. All the selected patients were interviewed in detail by using ICD-10. Analysis was done according to the Statistical Package for Social Science (SPSS) for windows version 25.Results: This study shows obsessive compulsive disorder is more common in young to middle age (21 to 40 years) and mean age of onset of illness was 28.31±10.21 years. Maximum (57%) were female and 43% were male. Depressive disorder, mixed anxiety and depressive disorder were most common psychiatric comorbidity (63% and 22%) in patient with OCD followed by panic disorder in 7% patients, social phobia in 5% patients, generalized anxiety disorder in 5% patients, substance abuse in 5% patients, schizophrenia in 5% patients, bipolar affective disorder in 2% patients and tic disorder in 1% patients.Conclusion: This study demonstrates a high prevalence of psychiatric comorbidities in individuals diagnosed with OCD. The most prevalent co-occurring disorders are depressive disorder &amp; mixed anxiety and depressive disorder. KYAMC Journal Volume: 14, No: 04, January 2024: 206-209.

A novel blood-based epigenetic biosignature in first-episode schizophrenia patients through automated machine learning

Schizophrenia (SCZ) is a chronic, severe, and complex psychiatric disorder that affects all aspects of personal functioning. While SCZ has a very strong biological component, there are still no objective diagnostic tests. Lately, special attention has been given to epigenetic biomarkers in SCZ. In this study, we introduce a three-step, automated machine learning (AutoML)-based, data-driven, biomarker discovery pipeline approach, using genome-wide DNA methylation datasets and laboratory validation, to deliver a highly performing, blood-based epigenetic biosignature of diagnostic clinical value in SCZ. Publicly available blood methylomes from SCZ patients and healthy individuals were analyzed via AutoML, to identify SCZ-specific biomarkers. The methylation of the identified genes was then analyzed by targeted qMSP assays in blood gDNA of 30 first-episode drug-naïve SCZ patients and 30 healthy controls (CTRL). Finally, AutoML was used to produce an optimized disease-specific biosignature based on patient methylation data combined with demographics. AutoML identified a SCZ-specific set of novel gene methylation biomarkers including IGF2BP1, CENPI, and PSME4. Functional analysis investigated correlations with SCZ pathology. Methylation levels of IGF2BP1 and PSME4, but not CENPI were found to differ, IGF2BP1 being higher and PSME4 lower in the SCZ group as compared to the CTRL group. Additional AutoML classification analysis of our experimental patient data led to a five-feature biosignature including all three genes, as well as age and sex, that discriminated SCZ patients from healthy individuals [AUC 0.755 (0.636, 0.862) and average precision 0.758 (0.690, 0.825)]. In conclusion, this three-step pipeline enabled the discovery of three novel genes and an epigenetic biosignature bearing potential value as promising SCZ blood-based diagnostics.

Level of insight in Egyptian patients having obsessive compulsive disorder: a comparative study

Background and objectivesObsessive–compulsive disorder (OCD) is a chronic psychiatric disorder defined by the existence of obsessions and/or compulsive behaviors or mental acts persistently and affects around 1–3% of the population in the world. Multiple studies demonstrated the link of the insight level to how severe was OCD and existence of resistance to both medications and psychotherapy in individuals with OCD. Studying the characteristics associated with poor insight is very important for management of treatment-resistant OCD and development of new therapeutic approaches. The purpose of this work was to assess the level of the insight in Egyptian patients with OCD, identify clinical correlates that could anticipate the degree of insight, and assess the validity and reliability of brown assessment of belief scale after being translated to Arabic version.MethodsA comparative cross-sectional study of 96 individuals (male and female aged from 18 to 60) diagnosed with OCD based on the Arabic version of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The study excluded any individuals with any coexisting neuro-psychiatric conditions and a history of major medical disease. Severity of OCD was assessed through the Arabic version of the Yale–Brown Obsessive–Compulsive Scale (YBOCS). Subsequently, participants performed the Brown Assessment of Beliefs Scale (BABS) after being translated into Arabic and assessed for reliability, validity and applicability of the translated form.ResultsPatients with OCD presented with poor insight were associated with more untreated time interval, longer disease duration and more severity that was dramatically differed (p ≤ 0.05, ≤ 0.001, ≤ 0.05 respectively). Also, there was a substantial notable correlation among BABS and YBOCS obsession, compulsion, and total score.ConclusionsThe existence of good insight in patients diagnosed with OCD was associated with lower severity and less duration of illness compared to patients with poor insight. Also, the more time waited before the intervention the worst the patient scores on the insight scale.

Causal associations between chronic viral hepatitis and psychiatric disorders: a Mendelian randomization study.

There may be an interaction between viral hepatitis and psychiatric disorders during disease progression. Herein, we conducted Mendelian randomization (MR) to explore the causal associations and mediators between viral hepatitis and psychiatric disorders. Genome-wide association studies summary data for viral hepatitis [including chronic hepatitis B (CHB) and chronic hepatitis C (CHC)] and psychiatric disorders (including depression, anxiety, schizophrenia, obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder) were obtained. Two-sample MR was performed to assess the causal associations between viral hepatitis and psychiatric disorders. Further, a mediation analysis was conducted to evaluate the potential mediators. Inverse-variance weighted, MR-Egger, and weighted median were used as the main methods, while a sensitivity analysis was performed to evaluate pleiotropy and heterogeneity. There was no causal effect of CHB/CHC on psychiatric disorders, as well as psychiatric disorders on CHB. However, schizophrenia presented a causal effect on increased CHC risk [odds ratio (OR)=1.378, 95%CI: 1.012-1.876]. Further, a mediation analysis identified coffee consumption and body mass index as mediators in the effect of schizophrenia on CHC, mediating 3.75% (95%CI: 0.76%-7.04%) and 0.94% (95%CI: 0.00%-1.70%) proportion, respectively. We revealed that schizophrenia patients faced a high risk of CHC, and insufficient coffee consumption and underweight could mediate the causal effect of schizophrenia on CHC. The prevention of hepatitis C might be a beneficial strategy for patients with schizophrenia. The right amount of nutrition supplements and coffee consumption might be part of a beneficial lifestyle in preventing the high CHC risk in patients with schizophrenia.

Impact of Bottom-up Cognitive Remediation on Functioning in Schizophrenia

In patients with schizophrenia, a chronic psychiatric disorder, cognitive impairments have a significant impact on functioning as well as symptoms. Cognitive remediation (cognitive remediation) interventions are a treatment approach that aims to improve cognitive functioning in patients with schizophrenia. These interventions can be categorized as "bottom-up" approaches that directly target cognitive functions and "top-down" approaches that indirectly affect cognitive functions. In this study, the contribution of bottom-up cognitive remediation interventions to functioning in schizophrenia was examined. The study provides evidence that bottom-up cognitive remediation interventions can improve cognitive functioning, social functioning and quality of life in patients with schizophrenia. When the literature is reviewed, it is observed that there is no research or programs about bottom-up cognitive remediation interventions in Türkiye. It is recommended that programs for bottom-up cognitive remediation interventions should be developed and utilized in Türkiye and they should be incorporated with the current therapy and rehabilitation approaches. It is important to benefit from technological opportunities, to increase the duration and intensity of interventions, to consider the issue of motivation and to ensure the integration of interventions into daily life, in creation of future bottom-up cognitive remediation intervention programs, in order to increase effectiveness, sustainability and cost-efficiency.

Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.

Although the world is acquitting from the throes of COVID-19 and returning to the regularity of life, its effects on physical and mental health are prominently evident in the post-pandemic era. The pandemic subjected us to inadequate sleep and physical activities, stress, irregular eating patterns, and work hours beyond the regular rest-activity cycle. Thus, perturbing the synchrony of the regular circadianclock functions led to chronic psychiatric and neurological disorders and poor immunological response in several COVID-19 survivors. Understanding the links between the host immune system and viral replication machinery from a clock-infection biology perspective promises novel avenues of intervention. Behavioral improvements in our daily lifestyle can reduce the severity and expedite the convalescent stage of COVID-19 by maintaining consistent eating, sleep, and physical activity schedules. Including dietary supplements and nutraceuticals with prophylactic value aids in combating COVID-19, as their deficiency can lead to a higher risk of infection, vulnerability, and severity of COVID-19. Thus, besides developing therapeutic measures, perpetual healthy practices could also contribute to combating the upcoming pandemics. This review highlights the impact of the COVID-19 pandemic on biological rhythms, sleep-wake cycles, physical activities, and eating patterns and how those disruptions possibly contribute to the response, severity, and outcome of SARS-CoV-2 infection.

Inflammation, Immunonutritive, and Cardiovascular Risk Biomarkers in Men With Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a significant public health issue associated with serious health risks. This study aims to reveal the relationship between AUD and inflammatory, immunonutritive, and cardiovascular risk markers by evaluating hemogram and biochemistry parameters together in AUD. The data of 54 male patients with AUD and 45 male controls were included in the study. Sociodemographic-clinical data of the participants and Alcohol Use Disorders Identification Test (AUDIT) results were obtained from medical records. Systemic immune inflammation index (SII) was obtained with the platelet x neutrophil/lymphocyte formula; systemic immune response index (SIRI) was obtained with the monocyte x neutrophil/lymphocyte formula, plasma atherogenicity index (AIP) was obtained with the ratio of triglyceride to High-density Lipoprotein (HDL) cholesterol. C-Reactive Protein (CRP) albumin-lymphocyte (CALLY) index was obtained with the albumin x lymphocyte/CRP x 104 formula. Aspartate aminotransferase (AST), Gamma Glutamyl Transferase (GGT) activities, neutrophil, CRP, ferritin, SII, and SIRI levels were significantly higher in those with AUD compared to controls. Laboratory results of those with AUD were consistent with atherogenic dyslipidemia; higher triglyceride and total cholesterol levels and AIP values were found compared to controls. The amount of alcohol consumed was a predictor for high SII, SIRI, and AIP levels. The CALLY index, which evaluates immune function, inflammation, and nutritional status together, was significantly lower in patients compared to controls. The amount of alcohol use and the total AUDIT score were predictors for a low CALLY index. The results of this study support that AUD is a chronic inflammatory psychiatric disorder. We suggest that new inflammatory, immunonutritive, and cardiovascular biomarkersSII, SIRI, AIP, and CALLY index could be promising clinical tools to evaluate the severity, potential complications, and treatment response of AUD.

Proteomic analysis of central amygdala systems regulated by the glucocorticoid receptor antagonist mifepristone in the context of alcohol dependence

Alcohol use disorder (AUD) is a chronic psychiatric disorder characterized by escalated alcohol use and emergence of negative emotional states during withdrawal. Studies show a dysregulation of glucocorticoid signaling in AUD, affecting the hypothalamic-pituitary-adrenal (HPA) axis and the central amygdala (CeA). Excessive activation of glucocorticoid receptors (GRs) is hypothesized to promote cognitive dysfunction, negative emotional states, and escalated drinking. Previous work demonstrates a functional increase in GR activity in the CeA during alcohol withdrawal in alcohol-dependent animal models. Importantly, the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment. We hypothesized that male and female rats will show sex differences in their CeA protein expression and that alcohol-induced reductions in brain anti-stress signaling (e.g., endocannabinoid system) will be normalized by mifepristone treatment. Male and female Wistar rats were exposed to chronic intermittent ethanol vapor (CIEV) or air (control) for 10 weeks. In week 7, half of each group received subcutaneous placebo pellets while the other half received mifepristone pellets (150mg, 21-day slow release). At the end of Week 10, the rats were sacrificed during acute (6-hour) CIEV withdrawal (and identical time in control groups). The CeA was analyzed using proteomics and ingenuity pathway analysis (IPA). In males, a total of 3050 proteins were detected in the CeA. Of these, 142 proteins were altered by alcohol (but not mifepristone), whereas an additional 253 proteins were altered by alcohol and “normalized” by mifepristone. In females, among the 2632 detected proteins, 46 were affected by alcohol (but not mifepristone), and 25 were altered by alcohol and restored by mifepristone. IPA revealed significant changes in canonical pathways, including the endocannabinoid neuronal synapse pathway and oxidative phosphorylation, affected by alcohol but normalized by mifepristone. Future studies will incorporate alcohol self-administration procedures in male and female rats to functionally examine proteins within these pathways as promising “druggable” targets that offer novel therapeutic avenues for AUD. Supported by NIH-NIAAA R01AA025996, P60AA009803, T32AA007577. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.