Study of the influence of disease duration on glutatione-dependent ensymes dynamics in patients with paranoid schizophrenia.

OBJECTIVE: Aim: The objective of the research was to conduct a comprehensive longitudinal analysis of the temporal dynamics of glutathione system functionality in individuals diagnosed with paranoid schizophrenia. Specifically, the research was focused on investigating variations in the profiles of glutathione-dependent enzymes, with meticulous consideration given to the duration of the illness. PATIENTS AND METHODS: Materials and Methods: The study group comprised 300 individuals officially diagnosed with 'Paranoid Schizophrenia,' subdivided into five subgroups, each consisting of 60 patients. The subgroups were defined as follows: Subgroup I included 60 patients with a disease duration ranging from 3 to 5 years; Subgroup II comprised 60 patients with a duration of 6 to 10 years; Subgroup III consisted of 60 patients with a duration of 11 to 15 years; Subgroup IV included 60 patients with a duration of 16 to 20 years; and Subgroup V encompassed 60 patients with a duration of 21 years and older. The comparison group comprised 20 patients diagnosed with "Primary psychotic episode". RESULTS: Results: The research demonstrates a consistent and noteworthy reduction in the enzymatic activities of glutathione peroxidase, glutathione reductase, and glutathione-S-transferase in various Subgroups of paranoid schizophrenia patients. The observed declines are particularly prominent within the first 3-5 years of the illness, show casing statistically significant reductions. Patients with prolonged illness durations, especially surpassing 21 years, display substantial reductions in all three enzymes, suggesting a cumulative enzymatic impact associated with prolonged illness. CONCLUSION: Conclusions: The identification of critical periods of inhibition in the glutathione protection chain, provides valuable information about potential therapeutic interventions for individuals with paranoid schizophrenia.

[EMDR in delusional disorder and substance use disorder: integrated treatment]. / EMDR bij een waanstoornis en stoornis in het gebruik van een middel: geïntegreerd behandelen.

Recently, a patient was admitted to our department, who reported personality disorder symptoms and a cannabis use disorder. Additionally, a delusional disorder, aggression regulation issues and PTSD were classified. After employing CBT for substance use, the Hero Without Violence module and EMDR, the treatment was completed. Integrated treatment in this patient proved successful regarding the PTSD, aggression regulation problems and SUD. With the described case, the authors hope to provide a clear description of the possibilities of integrated treatment for a patient with complex problems.

[Clinical systematics of chronic delusional psychoses in schizophrenia and schizophrenia-spectrum pathology]. / Klinicheskaya sistematika khronicheskikh bredovykh psikhozov pri shizofrenii i patologii shizofrenicheskogo spektra.

OBJECTIVE: To develop a systematics of chronic delusional psychoses in schizophrenia and pathology of the schizophrenic spectrum that takes into account psychopathological structure (the mechanism of delusional formation) and the trajectories of the disease course (the ratio of negative/positive dimensions). MATERIAL AND METHODS: The study sample was recruited from the large Moscow psychiatric hospital in 2019-2024 and included 126 patients (94 male, 32 female, mean age 36.5±12.1 years) hospitalized with ICD-10 diagnosis of paranoid schizophrenia (F20.00) or delusional disorder (F22). A clinical-psychopathological method was used. RESULTS: The study identifies three variants of paranoid domains, the typology of which takes into account both the psychopathological structure and the trajectories of their development, which determine the dominance of predominantly negative or positive symptoms throughout the disease: 1) psychosis with delusional interpretations and predominant orientation of symptoms towards the negative pole of the schizophrenia psychopathology (n=37, 29.4%); 2) psychosis with hallucinatory delusions and predominant direction of symptoms towards the positive pole of the schizophrenia psychopathology (n=50, 39.7%); and 3) «combined¼ hallucinatory-delusional psychosis with a simultaneous orientation of symptoms to the negative/positive poles of the schizophrenia psychopathology (n=39, 30.9%). Detailed phenomenological characteristics of each of the three presented variants are given. CONCLUSION: The developed three-component taxonomy confirms, on the model of chronic delusional psychoses appearing in schizophrenia and the pathology of the schizophrenia spectrum, the concept of simultaneous representation of two relatively independent domains determined by neurobiological processes in the schizophrenia psychopathology positive and negative disorders.

Antipsychotic use in a large community sample of patients with delusional disorder.

BACKGROUND: To examine clinical and sociodemographic differences between patients with delusional disorder; with and without diagnoses of an additional severe mental disorder (SMD) or cognitive impairment. METHODS: Population-based study including all individuals diagnosed with DD between 2005 and 2021 from a large catchment area in Madrid, Spain. Sociodemographic and clinical characteristics and the antipsychotic prescription patterns of the study population was described. Patients were divided into (i) patients with DD and no additional diagnosis of SMD or cognitive impairment (DD group), (ii) patients with DD and a diagnosis of an additional SMD (DD-SMD group), and (iii) patients with DD and cognitive impairment (DD-CI group). RESULTS: Of 1109 patients with a DD diagnosis (62.5 % female), 131 (11.8 %) patients were diagnosed with an additional SMD, and 69 (6.2 %) were diagnosed with cognitive impairment. DD-SMD patients were on average 10 years younger and had longer time between first mental healthcare contact and DD disorder than DD patients. DD-CI patients were on average 10 years older and had a higher proportion of females. Paliperidone (21.9 %) and aripiprazole (20.6 %) were the modal antipsychotic drugs chosen overall. DD-SMD patients were more likely to receive paliperidone and to be prescribed long-acting injectable medication; DD-CI were more likely to receive risperidone or quetiapine; and DD patients were more likely to receive olanzapine. CONCLUSIONS: Sociodemographic and clinical characteristics and choice of antipsychotic drug and delivery method for individuals with DD vary based on its comorbidity.

Is the Caudate, Putamen, and Globus Pallidus the Delusional Disorder's Trio? A Texture Analysis Study.

BACKGROUND: The neurobiological basis of delusional disorder is less explored through neuroimaging techniques than in other psychotic disorders. This study aims to provide information about the neural origins of delusional disorder (DD) by examining the neuroanatomical features of some basal nuclei with magnetic resonance imaging (MRI) texture analysis. MATERIALS AND METHODS: Twenty DD patients and 20 healthy individuals were included in the study. Globus pallidus, putamen, and caudate nuclei were selected individually with a region of interest (ROI) on the axial MRI images. The entire texture analysis algorithm applied to all selected ROIs was done with an in-house software. Nuclei on both sides were taken as separate samples. RESULTS: There were no significant differences between groups in terms of age and gender. The average "mean, median and maximum" values of all three nuclei were decreased in DD patients. The small putamen area and the differences detected in different tissue parameters for all three nuclei in delusional disorder patients indicate that they differ in delusional disorder from normal controls (p < 0.05). CONCLUSION: The differences detected in the texture parameters for all three nuclei indicate that there is something different in the DD from in the normal controls. Neuroimaging studies with larger samples and different techniques in the future may shed light on the etiology of delusional disorder.

[Electroencephalographic differences in patients with paranoid schizophrenia with or without a history of suicide attempts]. / Elektroentsefalograficheskie razlichiya u bol'nykh paranoidnoi shizofreniei s nalichiem ili otsutstviem suitsidal'nykh popytok v anamneze.

OBJECTIVE: To identify differences in electroencephalographic parameters in schizophrenia patients with and without a history of suicide attempts. MATERIAL AND METHODS: Eighty-seven inpatients (50 men and 37 women) with paranoid schizophrenia were examined. Suicidal attempts in the anamnesis of patients were verified by a psychiatrist on the basis of clinical interviewing. The severity of psychopathological symptoms was assessed using The Positive and Negative Syndrome Scale (PANSS) based on a five-factor model. Electroencephalogram (EEG) parameters were recorded and evaluated using a 16-channel encephalograph. A clinical and quantitative analysis of the recordings was carried out with the calculation of absolute spectral power indicators for theta, alpha and beta rhythms, as well as the severity of the activation reaction (Berger effect). RESULTS: Significantly higher rates of the PANSS depression factor were revealed in patients with a history of suicide attempts (p=0.016). Clinical analysis of EEG changes did not reveal any significant differences between the groups (p>0.05). The spectral analysis of the EEG showed significant differences only in the spectral power of the beta rhythm in the central (p=0.048) and occipital (p=0.021) leads with closed eyes, which was lower in the group with a history of suicide attempts. The degree of alpha rhythm depression in the occipital leads was also significantly lower in this group (p=0.016). The regression analysis showed that significant correlates of suicidal attempts in patients with paranoid schizophrenia are the PANSS depressive factor (t=2.784; p=0.016) and a deficiency in the activation response to EEG (t=-2.035; p=0.045). CONCLUSION: The results complement previous studies on the relationship between suicidal attempts, clinical symptoms and neurophysiological features of the functioning of the brain of patients with paranoid schizophrenia.

The efficacy of vortioxetine for the delusional disorder of cenesthopathy.

Cenesthopathy is a rare syndrome characterized by strange bodily and oral sensations and is classified as a delusional disorder, somatic type, according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Cenesthopathy has been considered difficult to treat. However, to improve cenesthopathy, many pharmacotherapeutic options are reported, including antidepressants and antipsychotics. In this case report, vortioxetine significantly alleviated the distress of oral cenesthopathy in a patient with cerebral ischemia and depression without any adverse effects. To the best of our knowledge, this is the first report on the efficacy of vortioxetine in treating cenesthopathy. Though it is unclear why vortioxetine was effective for cenesthopathy in our case, we stated two possibilities for improving his oral cenesthopathy. When treating oral cenesthopathy in elderly patients, clinicians consider to be one of the options to prescribe vortioxetine.

Clinical Characterization, Course, and Treatment of Othello Syndrome: A Case Series and Systematic Review of the Literature.

BACKGROUND: Othello syndrome (OS) is a condition characterized by a delusion of jealousy that one's spouse is having extramarital affairs. As in the eponymous Shakespearean tragedy, there is an unfortunate risk of violence. For patients with these symptoms, consultation-liaison psychiatrists may be asked to assist with evaluating the differential diagnosis, assessing safety, and developing treatment options. OBJECTIVE: This study's objective was to solidify current knowledge of the clinical presentations and management of OS through a systematic review of the literature and description of 2 new cases. METHODS: We conducted a literature search from the start of relevant databases through August 2023 to identify English language case reports of adults (≥18 years) with OS that described clinical evaluations, biological treatments, and outcomes. We extracted demographics, proposed etiologies, treatment choices and responses, duration of delusions, comorbid psychiatric symptoms, neuro-radiographic findings, and presence of physical violence. We reported clinical findings for 2 new cases. RESULTS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we screened 705 abstracts and conducted full-text reviews of 118 articles to identify 73 cases published from 1983 to 2023 meeting inclusion criteria. The mean age was 58.2 years with male predominance (M:F = 1.88). Etiologies included primary psychiatric disorders (16, 22%), other medical conditions (38, 52%), and medications or other substances (19, 26%). Delusional disorder, cerebrovascular accident, and dopaminergic agonists were the most common etiologies, respectively, in these groups. Antipsychotics were the most common treatment (57, 78%). Symptom remission was reported in 51 (70%) cases. The average duration of OS was 39.5 months. Of 32 cases reporting brain imaging insults, 12 of 20 (60%) showed right-sided lesions, and 8 of 20 (40%) showed left-sided lesions, with 9 of 32 (28%) located in the frontal lobes. The most commonly co-existing psychiatric symptom was depression (14, 19%). Violence was reported in 25 cases (34%). Our 2 new cases were consistent with these findings. CONCLUSIONS: OS may be a manifestation of several neuropsychiatric conditions, primarily delusional disorder, cerebrovascular accident, Alzheimer's dementia, and the use of dopaminergic agonists. One-third of cases include violent behaviors. It appears to respond to antipsychotic medications, but treatment is delayed more than 3 years on average. Available data have not localized OS to a specific brain region.

Conceptualizing a less paranoid schizophrenia.

Schizophrenia stands as one of the most studied and storied disorders in the history of clinical psychology; however, it remains a nexus of conflicting and competing conceptualizations. Patients endure great stigma, poor treatment outcomes, and condemnatory prognosis. Current conceptualizations suffer from unstable categorical borders, heterogeneity in presentation, outcome and etiology, and holes in etiological models. Taken in aggregate, research and clinical experience indicate that the class of psychopathologies oriented toward schizophrenia are best understood as spectra of phenomenological, cognitive, and behavioral modalities. These apparently taxonomic expressions are rooted in normal human personality traits as described in both psychodynamic and Five Factor personality models, and more accurately represent explicable distress reactions to biopsychosocial stress and trauma. Current categorical approaches are internally hampered by axiomatic bias and systemic inertia rooted in the foundational history of psychological inquiry; however, when such axioms are schematically decentralized, convergent cross-disciplinary evidence outlines a more robust explanatory construct. By reconceptualizing these disorders under a dimensional and cybernetic model, the aforementioned issues of instability and inaccuracy may be resolved, while simultaneously opening avenues for both early detection and intervention, as well as for more targeted and effective treatment approaches.

CLINICAL AND GENETIC FEATURES OF PERSONALIZED ANTIPSYCHOTIC THERAPY OF PATIENTS WITH PARANOID SCHIZOPHRENIA OF THE KAZAKH ETHNIC GROUP IN THE REPUBLIC OF KAZAKHSTAN.

The problems of schizophrenia therapy occupy a leading place in both foreign and domestic clinical psychiatry. The paper presents the results of a study to identify reliable biomarkers for predicting antipsychotic therapy of patients with paranoid schizophrenia of the Kazakh ethnic group in the Republic of Kazakhstan, conducted within the framework of the project: "National program for the introduction of personalized and preventive medicine in the Republic of Kazakhstan" IRN ОР12165486. The effectiveness and tolerability of antipsychotic drugs used in the treatment of paranoid schizophrenia in the Republic of Kazakhstan according to clinical treatment protocols are analyzed. Gender and age-specific dynamics in the clinic of paranoid schizophrenia in antipsychotic therapy in persons of Kazakh ethnicity are described. Certain genetic features of representatives of the Kazakh ethnic group have been identified, which can influence the effectiveness and tolerability of antipsychotic drugs, which determines the basis of an innovative approach to personalized therapy of paranoid schizophrenia in patients of the Kazakh ethnic group in the Republic of Kazakhstan.

MISATTRIBUTION OF EMOTIONAL OVER-AROUSAL TO NEUTRAL FACES IN ACUTE PARANOID SCHIZOPHRENIA PSYCHOSIS.

INTRODUCTION: Misattribution of motivational salience to non-salient (neutral) stimuli could be viewed as a hallmark of psychosis in schizophrenia. Studies have recently revealed increased subjective experience of emotional arousal (EA) to neutral social stimuli in paranoid schizophrenia psychosis, suggesting a misattribution of emotional salience to them. We examined this phenomenon directly by quantifying the level of EA subjectively attributed to low-arousal, neutral-valenced faces. SUBJECTS AND METHODS: A task for EA attribution to neutral (in the context of affective) facial expressions was applied to 44 actively psychotic paranoid schizophrenia inpatients and 44 well-matched healthy controls. RESULTS: Psychotic patients, compared with healthy controls, rated the neutral faces as more aroused (t (86) = 3.15, p =.001) thus misattributing emotional salience to them. DISCUSSION: This finding supports the hypothesis that over-assignment of EA to neutral faces could be viewed as a subclinical affective mechanism of the clinically manifested experience of delusional perception. CONCLUSION: The study provides the first direct empirical evidence for misattribution of emotional salience in terms of over-attribution of EA to neutral faces during acute paranoid schizophrenia psychosis.

SOCIAL COGNITION AND OXIDATIVE STRESS IN SCHIZOPHRENIA PATIENTS AND FIRST-DEGREE RELATIVES OF PATIENTS.

BACKGROUND: Misattribution of motivational salience to non-salient (neutral) stimuli could be viewed as a hallmark of psychosis in schizophrenia. Studies have recently revealed increased subjective experience of emotional arousal (EA) to neutral social stimuli in paranoid schizophrenia psychosis, suggesting a misattribution of emotional salience to them. We examined this phenomenon directly by quantifying the level of EA subjectively attributed to low-arousal, neutral-valenced faces. SUBJECTS AND METHODS: Patients with remitted schizophrenia (PG) (n=26), first-degree relatives of schizophrenic patients (RG) (n=25), and healthy controls (HCG) (n=36) were compared in terms of oxidative stress parameters -serum Superoxide Dismutase, Catalase, Glutathione Peroxidase (GPx), Nitrite, Nitrate, Malondialdehyde, and Total Glutathione levels-, social cognition measured by the Reading the Mind in the Eyes Test and working memory measured by the N-back Task. Groups were compared, assuming that HCG had a genetically lower risk of schizophrenia compared to PG and RG. RESULTS: HCG performed significantly better than PG and RG, who were genetically at high risk, in terms of social cognition (respectively p=0.000, p=0.014), working memory (respectively p=0.001, p=0.003), and had statistically lower Glutathione Peroxidase (GPX) level than the PG and RG (both p:0.000). After controlling for the effect of the general intellectual abilities measured by the Raven Standard Progressive Matrices Test and working memory the differences between groups on the Eyes Test disappeared (p=0.057). However, this value tended to be significant. CONCLUSION: It was concluded that social cognition and working memory and GPx level may be used as endophenotypes and social cognition, working memory, and general intellectual skills are different but strongly related constructs. Endophenotypes guide treatment targets even after the disease has developed. The results of our study showed that in addition to psychopharmacological treatments, interventions to reduce oxidative stress and approaches to improve cognitive skills will have a positive impact on the disease's progression.

Reshaping the diagnostic borders: Historical analysis of the diagnostic changes following the introduction of the schizophrenia concept.

BACKGROUND: Although the concept of schizophrenia is still widely presented as having replaced that of dementia praecox, studies have shown that the former was broader than the latter, resulting in a more complex diagnostic redistribution. However, this is poorly documented by quantitative approaches. AIMS: We sought to test the hypothesis that the use of the concept of schizophrenia had caused a diagnostic redistribution and to quantify it. METHOD: A retrospective study, based on admission register archives of the Strasbourg University Clinic of Psychiatry was conducted. The frequency of diagnoses given to patients were examined at two key time periods: one before (TP1) and one after (TP2) the introduction of the schizophrenia concept (established between 1926 and 1928). Eight main diagnoses related to schizophrenia were considered. RESULTS: Patients diagnosed with schizophrenia at TP2 mainly received the diagnoses of dementia praecox but also depression, hebephrenia, manic depressive illness, hysteria, paraphrenia, catatonia and mania at TP1. Dementia praecox and hebephrenia were the most relayed by schizophrenia. Bayesian sensitivity analyses confirmed the robustness of our data against distinct scenarios challenging our hypothesis. CONCLUSIONS: Our results confirm the broadening of the concept of schizophrenia compared to that of dementia praecox but also qualify the different concepts supposed to have been impacted. They provide unique quantitative data that define the contours of the diagnostic redistribution thus provoked. They also give relevant input in the current context where the need to rethink the DSM/ICD concept of schizophrenia is still debated.

Functional and clinical outcomes of delusional disorder and schizophrenia patients after first episode psychosis: a 4-year follow-up study.

BACKGROUND: Literature has typically associated delusional disorder with a poorer prognosis relative to schizophrenia, without considering the confounding effect of age despite the differential age of onset. This study therefore aims to investigate the diagnostic stability, clinical, functional, and neurocognitive differences of Chinese first-episode psychosis age-matched patients with delusional disorder and schizophrenia at four years. METHODS: 71 delusional disorder and 71 age-matched schizophrenia patients were followed up for four years after their initial episode. Their symptoms, insight in psychosis, side effects of medication, medication compliance, functioning, and neurocognitive performance were assessed at four years. RESULTS: At four years, 65% of DD patients maintained the same diagnosis, while the rest shifted to SZ. Only those without a diagnostic shift were included in the analysis. Delusional disorder patients (n = 46) experienced greater general psychopathology and poorer insight, but better attitude towards medication than schizophrenia patients (n = 71). Social and occupational functioning, quality of life, and cognitive functioning, however, were similar in delusional disorder and schizophrenia patients. CONCLUSIONS: Results indicate that delusional disorder is less diagnostically stable than schizophrenia. Their outcomes in a Chinese population were largely similar at four years after removing the confounding age factor, implying that delusional disorder and schizophrenia may not be as distinct as previously thought.

Statistical shape analysis of corpus callosum in delusional disorder.

Neurobiological foundations of delusional disorder (DD) have been studied less with neuroimaging techniques when compared to other psychotic disorders. The present study aimed to delineate the neural substrates of DD by investigating neuroanatomical characteristics of the corpus callosum (CC) with statistical shape analysis (SSA) conducted on magnetic resonance images (MRI). Twenty (female:male=1:1) DSM-5 DD patients and 20 age- and gender-matched healthy individuals were included. High-resolution 3D T1 Turbo Field Echo MRI images were scanned with a 1.5 T MR device. The landmarks that were selected to determine the shape differences in CC were identified based on previous studies. Furthermore, constructed landmarks were determined and employed to better assess regional shape differences. There was no significant difference in the CC area in the mid-sagittal images between the DD patients and controls. However, DD patients exhibited a pattern of structural CC changes in various regions. The study findings emphasizes the variable subregional nature of CC in DD patients. Future SSA studies with larger samples could shed further light on DD etiology, diagnosis, classification and treatment options.

[An effect of antipsychotic and anticholinergic treatment on cognitive function in patients with schizophrenia]. / Vliyanie antipsikhoticheskoi i antikholinergicheskoi terapii na kognitivnye funktsii u bol'nykh shizofreniei.

OBJECTIVE: To reveal the relationships between antipsychotic and anticholinergic drugs and cognitive functions in patients with schizophrenia. MATERIAL AND METHODS: The observational prospective study was conducted at the Bekhterev National Medical Center of Psychiatry and Neurology. The study involved 41 patients (22 men and 19 women) with paranoid schizophrenia, according to ICD 10 criteria, aged 30.12±8.24 years on stable antipsychotic monotherapy or in combination with anticholinergic drug (trihexiphenidyl). Cognitive functions were assessed using the «Brief Assessment of Cognitive Function in Patients with Schizophrenia¼ (BACS) scale, severity of mental state and extrapyramidal disturbances were measured using the «Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale for Assessment of Extrapyramidal Side Effects (SAS). All examination procedures were performed twice at weeks 2 and 8 of therapy. Patients were divided into 2 groups according to the type of antipsychotic therapy. Twelve patients received first generation antipsychotics (FGAs) (group 1), 29 patients received second generation antipsychotics (SGAs) (group 2). RESULTS: Patients receiving SGAs had a significant decrease in the overall SAS score at week 8 of therapy compared with data at week 2, and there was an improvement in cognitive function, unlike patients receiving FGAs. There were also changes on BACS tests the digit sequencing (V=51.5, p=0.007), token motor task (V=75.5, p=0.007) and Tower of London (V=52, p=0.027) only in patients of group 2. CONCLUSION: The improved tolerance to the drug, as well as cognitive measures, was shown in patients taking SGAs by week 8. Our study confirms the importance of adhering to the minimum effective dose of antipsychotic drugs for the treatment of schizophrenia to prevent cognitive impairment, and to give preference to SGAs in the choice of treatment.