Reelin Signaling and Synaptic Plasticity in Schizophrenia.

Recent research emphasizes the significance of studying the quality of life of schizophrenia patients, considering the complex nature of the illness. Identifying neuronal markers for early diagnosis and treatment is crucial. Reelin (RELN) stands out among these markers, with genetic studies highlighting its role in mental health. Suppression of RELN expression may contribute to cognitive deficits by limiting dendritic proliferation, affecting neurogenesis, and leading to improper neuronal circuits. Although the physiological function of reelin is not fully understood, it plays a vital role in hippocampal cell stratification and neuroglia formation. This analysis explores reelin's importance in the nervous system, shedding light on its impact on mental disorders such as schizophrenia, paving the way for innovative therapeutic approaches, and at the same time, raises the following conclusions: increased methylation levels of the RELN gene in patients with a diagnosis of schizophrenia results in a multiple decrease in the expression of reelin, and monitoring of this indicator, i.e., methylation levels, can be used to monitor the severity of symptoms in the course of schizophrenia.

Brain-derived neurotrophic factor and matrix metalloproteinase-9 activity during rehabilitation therapy of schizophrenic patients - environmental pilot study.

INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the peripheral level of brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) during rehabilitation therapy, combined with neurofeedback in schizophrenic patients, and to investigate whether these biomarkers are related to psychopathological symptoms, changes in auditory evoked potentials (AEPs), and quantitative EEG (QEEGs) mapping. MATERIAL AND METHODS: The study involved two groups of patients diagnosed with paranoid schizophrenia in partial remission who participated in a 3-month structured rehabilitation programme combined with neurofeedback (REH group) and a standard support group (CON group). The following parameters were assessed: BDNF and MMP-9 serum levels, AEPs, QEEGs, and psychopathological symptoms (PANSS). RESULTS: A clinical improvement within the 3-month rehabilitation therapy course was correlated with the increase in BDNF and MMP-9 serum level. Despite the increase in BDNF and MMP-9 during the 3-month rehabilitation therapy, it was not possible to demonstrate any strong and significant correlation between the 2 examined neuropeptides. During the 3-month rehabilitation therapy, the theta waveform share reduction in QEEG, P50 latency reduction and amplitude increase correlated with PANSS Total and MMP-9 results. CONCLUSIONS: All clinical (PANSS Positive, Negative, General, Total) and biochemical results (BDNF, MMP-9) of the REH group changed significantly over the 3-month period. Positive symptoms improved only in the CON group.

Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment.

Schizophrenia is a chronic and relapsing disorder that is characterized not only by delusions and hallucinations but also mainly by the progressive development of cognitive and social deficits. These deficits are related to impaired synaptic plasticity and impaired neurotransmission in the nervous system. Currently, technological innovations and medical advances make it possible to use various self-regulatory methods to improve impaired synaptic plasticity. To evaluate the therapeutic effect of various rehabilitation methods, we reviewed methods that modify synaptic plasticity and improve the cognitive and executive processes of patients with a diagnosis of schizophrenia. PubMed, Scopus, and Google Scholar bibliographic databases were searched with the keywords mentioned below. A total of 555 records were identified. Modern methods of schizophrenia therapy with neuroplastic potential, including neurofeedback, transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, virtual reality therapy, and cognitive remediation therapy, were reviewed and analyzed. Since randomized controlled studies of long-term schizophrenia treatment do not exceed 2-3 years, and the pharmacological treatment itself has an incompletely estimated benefit-risk ratio, treatment methods based on other paradigms, including neuronal self-regulatory and neural plasticity mechanisms, should be considered. Methods available for monitoring neuroplastic effects in vivo (e.g., fMRI, neuropeptides in serum), as well as unfavorable parameters (e.g., features of the metabolic syndrome), enable individualized monitoring of the effectiveness of long-term treatment of schizophrenia.

Relationship of Neuropeptide S (NPS) with Neurocognitive, Clinical, and Electrophysiological Parameters of Patients during Structured Rehabilitation Therapy for Schizophrenia.

INTRODUCTION: Neuropeptide S is a biomarker related to various neuropsychiatric and neurocognitive functions. Since the need to improve cognitive functions in schizophrenia is unquestionable, it was valuable to investigate the possible relationships of plasma levels of NPS with neurocognitive, psychopathological and EEG parameters in patients with schizophrenia. AIM: Relationships between the serum NPS level and neurocognitive, clinical, and electrophysiological parameters were investigated in patients diagnosed with schizophrenia who underwent structured rehabilitation therapy. METHODS: Thirty-three men diagnosed with schizophrenia were randomized into two groups. The REH group (N16) consisted of patients who underwent structured rehabilitation therapy, the CON group (N17) continued its previous treatment. Additionally, the reference NPS serum results were checked in a group of healthy people (N15). In the study several tests assessing various neurocognitive functions were used: d2 Sustained-Attention Test (d2), Color Trails Test (CTT), Beck Cognitive Insight Scale (BCIS), Acceptance of Illness Scale (AIS), and General Self-Efficacy Scale (GSES). The clinical parameters were measured with Positive and Negative Syndrome Scale (PANSS) and electrophysiological parameters were analyzed with auditory evoked potentials (AEPs) and quantitative electroencephalography (QEEG). The NPS, neurocognitive, clinical, and electrophysiological results of REH and CON groups were recorded at the beginning (T1) and after a period of 3 months (T2). RESULTS: A decreased level of NPS was associated with the improvement in specific complex indices of d2 and BCIS neurocognitive tests, as well as the improvement in the clinical state (PANSS). No correlation was observed between the level of NPS and the results of AEPs and QEEG measurements. CONCLUSIONS: A decreased level of NPS is possibly related to the improvement in metacognition and social cognition domains, as well as to clinical improvement during the rehabilitation therapy of patients with schizophrenia.

Relationship of Neuropeptide S with Clinical and Metabolic Parameters of Patients during Rehabilitation Therapy for Schizophrenia.

Neuropeptide S (NPS) is a factor associated with the central regulation of body weight, stress, anxiety, learning, memory consolidation, wakefulness-sleep cycle, and anti-inflammatory and neuroplastic effects. Its stress-reducing, anti-anxiety, arousal without anxiety, and pro-cognitive effects represent an interesting option for the treatment of neuropsychiatric disorders. The purpose of the study was to examine the potential associations of NPS levels in the blood with clinical and metabolic parameters during the rehabilitation therapy of patients with schizophrenia. Thirty-three male subjects diagnosed with schizophrenia were randomly divided into two groups. The rehabilitation group (REH, N16) consisted of patients who were subjected to structured, 3-month intensive rehabilitation therapy, and the control group (CON, N17) consisted of patients who were subjected to a standard support mechanism. Both groups continued their pharmacological treatment as usual. The NPS concentration, as well as clinical and metabolic parameters, were compared in both groups. Additionally, a group of healthy (H) males (N15) was tested for NPS reference scores. To look for the specificity and selectivity of the NPS relationship with clinical results, various factor models of the positive and negative syndrome scale (PANSS) were analyzed, including the original PANSS 2/3 model, its modified four-factor version, the male-specific four-factor model, and two five-factorial models validated in large groups in clinical and multi-ethnic studies. Results and conclusions: (1) Structured rehabilitation therapy, compared to unstructured supportive therapy, significantly reduced the level of schizophrenia disorders defined by various factor models derived from PANSS. (2) The clinical improvement within the 3-month rehabilitation therapy course was correlated with a significant decrease in neuropeptide S (NPS) serum level. (3) The excitement/Hostility (E/H) factor, which included schizophrenic symptoms of the psychotic disorganization, was specific and selective for the reduction in serum NPS, which was stable across all analyzed factor models. (4) The long-term relationship between serum NPS and clinical factors was not accompanied by basic metabolic parameters.

Improving Clinical, Cognitive, and Psychosocial Dysfunctions in Patients with Schizophrenia: A Neurofeedback Randomized Control Trial.

Objectives: The aim of this study was to use neurofeedback (NF) training as the add-on therapy in patients with schizophrenia to improve their clinical, cognitive, and psychosocial condition. The study, thanks to the monitoring of various conditions, quantitative electroencephalogram (QEEG) and brain-derived neurotrophic factor (BDNF), was supposed to give an insight into mechanisms underlying NF training results. Methods: Forty-four male patients with schizophrenia, currently in a stable, incomplete remission, were recruited into two, 3-month rehabilitation programs, with standard rehabilitation as a control group (R) or with add-on NF training (NF). Pre- and posttherapy primary outcomes were compared: clinical (Positive and Negative Syndrome Scale (PANSS)), cognitive (Color Trails Test (CTT), d2 test), psychosocial functioning (General Self-Efficacy Scale (GSES), Beck Cognitive Insight Scale (BCIS), and Acceptance of Illness Scale (AIS)), quantitative electroencephalogram (QEEG), auditory event-related potentials (ERPs), and serum level of BDNF. Results. Both groups R and NF improved significantly in clinical ratings (Positive and Negative Syndrome Scale (PANSS)). In-between analyses unveiled some advantages of add-on NF therapy over standard rehabilitation. GSES scores improved significantly, giving the NF group of patients greater ability to cope with stressful or difficult social demands. Also, the serum-level BDNF increased significantly more in the NF group. Post hoc analyses indicated the possibility of creating a separate PANSS subsyndrome, specifically related to cognitive, psychosocial, and BDNF effects of NF therapy. Conclusions: Neurofeedback can be effectively used as the add-on therapy in schizophrenia rehabilitation programs. The method requires further research regarding its clinical specificity and understanding mechanisms of action.

[The Montreal Cognitive Assessment 7.2--Polish adaptation and research on equivalency]. / Montrealska Skala Oceny Funkcji Poznawczych MoCA 7.2.- polska adaptacja metody i badania nad równowaznoscia.

AIM: The Montreal Cognitive Assessment is a screening test for diagnosis of Mild Cognitive Impairment- MCI. Only one version of the method was available in Poland so far. In order to assess progression of cognitive impairment, or to diagnose effectiveness of therapy, two equivalent version of method are needed. English additional version 7.2. was translated and culturally adapted to sustain reliability of the assessment. Then equivalency of both Polish versions was investigated. This paper examines whether both Polish versions of MoCA are equivalent, and describes the process of its cultural adaptation. METHODS: 66 psychiatric patients (37 men, 29 women) with different levels of cognitive impairment were examined using both Polish versions of MoCA. Both versions were administered randomly to patients with no time interval in between. RESULTS: No significant differences (p=0,601) for total MoCA scores were found between first version of Polish MoCA, and alternate version. Equivalency measured by correlation coefficient Spearman's rho correlation coefficient (rho=0,926) proved to be high. CONCLUSIONS: Both Polish versions of MoCA are equivalent, and can be useful in repeated measurement of progress in cognitive impairment or in testing of the effectiveness of treatment.

[Venous thromboembolism as an adverse effect of antipsychotic treatment]. / Zylna choroba zakrzepowo-zatorowa jako dzialanie niepozadane leków przeciwpsychotycznych.

Many studies, suggest an association between the use of antipsychotics (APs) and occurrence of venous thromboembolism (VTE). Thromboembolism is often related to a significant r'iisk of disability or death. Despite many years of investigating the interrelationsbetween use of APs and VTE, they have not been specified yet. This paper aims to summarize reports on the VTE risk factors in patients using APs. Based on the analyzed clinical studies, meta-analyses and.data published by European Medicines Agency, it has been determined, that the main risk factors for VTE are duration of treatment and patient-related factors, such as gender, age, body mass, and physical activity. Current data do not allow to identify the prothrombotic potential for individual APs or indicate a higher risk for developing VTE in patients treated ' with newer atypical APs. Due to the complex pathogenesis of VTE it would benecessaryto perform large, comparative studies, allowing to identify precisely differences in prothrombotic potential of individual APs. It is necessary to specify products with the lowest VTE risk, what would be useful in the treatment of high-risk patients. All patients treated with APs should be assessed with the risk ofVTE and, if needed, appropriate prevention methods (including most of all the elimination of modifiable risk factors) should be implemented. Moreover, patients should be educated in scope of VTE prodromal symptoms. All patients with the higher VTE risk should be diagnosed as soon as possible and adequate treatment should be implemented.

[Toward the new classification of mental disorders--Polish psychiatrists' opinions about project of ICD-11]. / W kierunku nowej klasyfikacji zaburzen psychicznych --opinie polskich psychiatrów dotyczace projektu ICD-11.

AIM: The World Psychiatric Association (WPA) and the World Health Organization (WHO) initiated a series of national surveys regarding the revision of the chapter on Mental and Behavioural Disorders of the ICD-10. They are part of the global and systematic studies providing input into the new classification of mental disorders (ICD-11). METHOD: In Poland, the survey after translation and implementing was performed electronically in collaboration with the Polish Psychiatric Association (17 Jan - 22 Feb 2011). 206 psychiatrists presented their experiences and ideas regarding international and other classification systems. RESULTS: We present results from our national part of the survey. Psychiatrists called for simplifying the classification system, with less than 100 main categories in ICD-11. That would be beneficial for professionals, their clients and all other participants. Psychiatrists accepted both strict diagnostic criteria and flexible guidance in a classification manual. The independent severity axis should be implemented for all diagnoses. The functional status was considered to be a part of general diagnostic criteria. The dimensional scales were indicated as beneficial for the diagnostic process. Participants did not report any important problems with the cross-cultural applicability of existing classifications. The validity of some categories of ICD-10 was considered poor and their definitions should be reviewed, especially: schizotypal disorder, schizoaffective disorder, borderline personality disorder, dissociative/conversion disorders and some neurotic disorders. CONCLUSION: The survey, as a part of truly international process, was the occasion to strengthen Polish psychiatrists' contribution regarding developing the new international classification (ICD-11).

[Classification of mental disorders--a conceptual framework for the ICD-11]. / Klasyfikacja zaburzen psychicznych--koncepcyjne zalozenia ICD-11.

The World Psychiatric Association (WPA) and World Health Organization (WHO) are currently engaging in the revision of the International Classification of Diseases and Related Health Problems (ICD-10). Polish Psychiatric Association (PPA) is participating in that process and the first step was an international survey of Polish psychiatrists expressing their experiences and concepts about the new ICD-11. The mission is to produce an international classification that is up to the contemporary challenge, is ready for electronic health records, serves as a standard for scientific comparability and facilitates communication in psychiatry. This is the review of works currently underway, including PPA members' tasks and efforts, regarding ICD-10 revision.

[Psychophysiological analysis of bipolar disorder treatment with functional magnetic resonance imaging (fMRI), spectroscopic (1H-MRS) and volumetric MRI assessment of CNS: report of three cases]. / Analiza psychofizjologiczna terapii zaburzen afektywnych ocenianej za pomocq czynnosciowego rezonansu magnetycznego (fMRI), spektroskopii (1H-MRS) oraz wolumetrii osrodkowego ukladu nerwowego: opis trzech przypadków.

BACKGROUND: Neuroimaging studies, including MRI, have identified various abnormalities in patients with bipolar disorders. However those findings have been inconsistent with regard to different MRI techniques, clinical and neurocognitive assessments as well as treatment results. So far the functional magnetic resonance imaging (fMRI) studies haven't been performed in psychiatric patients in Poland. AIM: The aim of the present study was to use fMRI, as well as two other MRI techniques to examine their relationships with clinical and neurocognitive assessments and the effectiveness of psychiatric treatment of bipolar disorders. METHOD: In this preliminary report, three bipolar patients were tested and compared with one healthy subject by means of three MRI techniques: fMRI, prefrontal spectroscopy (1H-MRS) and volumetric MRI of hippocampus regions. Clinical (MADRS) and neurocognitive (Stroop-like) assessments were performed. RESULTS: Clinical, cognitive and MRI findings (fMRI, 1H-MRS, vMRI) were highly or moderately correlated. CONCLUSIONS: MRI techniques may effectively support both clinical and neurocognitive assessments of the ongoing treatment in bipolar patients.

[Core factors of schizophrenia structure based on PANSS and SAPS/SANS results. Discerning and head-to-head comparisson of PANSS and SASPS/SANS validity]. / Podstawowe wymiary zaburzen schizofrenicznych w oparciu o pomiar skalami PANSS i SAPS/SANS. Zróznicowanie i porównanie trafnosci pomiarowej PANSS i SAPS/SANS.

AIM: A lot of inconsistencies across dimensional studies of schizophrenia(s) are being unveiled. These problems are strongly related to the methodological aspects of collecting data and specific statistical analyses. Psychiatrists have developed lots of psychopathological models derived from analytic studies based on SAPS/SANS (the Scale for the Assessment of Positive Symptoms/the Scale for the Assessment of Negative Symptoms) and PANSS (The Positive and Negative Syndrome Scale). The unique validation of parallel two independent factor models was performed--ascribed to the same illness and based on different diagnostic scales--to investigate indirect methodological causes of clinical discrepancies. METHOD: 100 newly admitted patients (mean age--33.5, 18-45, males--64, females--36, hospitalised on average 5.15 times) with paranoid schizophrenia (according to ICD-10) were scored and analysed using PANSS and SAPS/SANS during psychotic exacerbation. All patients were treated with neuroleptics of various kinds with 410mg equivalents of chlorpromazine (atypicals:typicals --> 41:59). Factor analyses were applied to basic results (with principal component analysis, normalised varimax rotation). Investing the cross-model validity, canonical analysis was applied. RESULTS: Models of schizophrenia varied from 3 to 5 factors. PANSS model included: positive, negative, disorganisation, cognitive and depressive components and SAPS/SANS model was dominated by positive, negative and disorganisation factors. The SAPS/SANS accounted for merely 48% of the PANSS common variances. The SAPS/SANS combined measurement preferentially (67% of canonical variance) targeted positive-negative dichotomy. Respectively, PANSS shared positive-negative phenomenology in 35% of its own variance. The general concept of five-dimensionality in paranoid schizophrenia looks clinically more heuristic and statistically more stabilised.

Factor structure of paranoid schizophrenia: a prospective study.

Paranoid schizophrenics were scored and analyzed using PANSS and principal component method on admission (T1, 480 patients), after 4 weeks (T2, 223 patients), after 8 weeks (T3, 146 patients) and after 6 months of treatment (T4, 104 patients). Seven factor models accounted for 68-74% of the variances (including models of 104 patients present at all four stages). T1 and T2 models comprised 6-7 factors and were dominated by positive and excitement symptoms. The grandiosity factor could only be identified in T1. T3 and T4 models were reduced to 5 factors and incorporated a greater expression of depressive disorders and a relatively greater expression of negative and cognitive symptoms. Negative and cognitive dimensions were the most stable elements of all the models. The concept of the depressive factor appeared to be too restrictive to describe a whole variety of the affective dimension.