Chronic Neuropsychiatric Disorder Research Articles

Clinical and Sociodemographic Correlations with Neurological Soft Signs in Hospitalized Patients with Schizophrenia: A Preliminary Longitudinal Study.

Schizophrenia is a severe, chronic neuropsychiatric disorder characterized by symptoms that profoundly impact behavior, cognition, perception, and emotions, leading to a reduced quality of life and physical impairment. Given the complexity of schizophrenia, there is a pressing need for clinical markers and tools to predict its course, enhance disease staging, facilitate early intervention, improve differential diagnosis, and tailor individualized treatment approaches. Previous studies focused on the relationship between neurological soft signs (NSS) and factors such as age, illness duration, and symptomatology, indicating NSS as state markers improving in parallel with psychotic symptom remission or predicting treatment resistance. However, there is a lack of consensus on NSS assessment tools, hindering routine clinical monitoring despite diagnostic and prognostic potential. The present longitudinal study involved 81 psychiatric inpatients diagnosed with schizophrenia. Patients were assessed at three time points: baseline, 1 month, and 6 months. The examination included the use of scales to evaluate psychotic and neurological symptoms, as well as the identification of adverse extrapyramidal reactions caused by neuroleptic treatment. The progression of NSS was correlated to both the symptomatology and the sociodemographic data of the patients. The main findings from the present investigation revealed a statistical correlation between NSS and psychopathological symptoms, especially with negative symptoms of schizophrenia. However, it is important to note that neuroleptic side effects only had a limited impact on NSS. Therefore, instead of being linked to extrapyramidal symptoms caused by neuroleptics, NSS appears to be more frequently related with symptoms of schizophrenia. Our findings provide further support for their strong association with the course of schizophrenia, independent of treatment side effects, thus emphasizing their potential as reliable assessment tools in both research and clinical settings.

Fármacos antipsicóticos de segunda generación y su impacto en el tejido adiposo

Schizophrenia is a chronic neuropsychiatric disorder that affects 21 million people worldwide. Currently, second-generation or atypical antipsychotics (SGAs) are the first-line medications for the treatment of this disease. However, despite its high efficacy in counteracting the neuropsychiatric symptoms of schizophrenia, recent clinical investigations in patients treated with SGAs show an increase in the prevalence of pivotal metabolic alterations, including increased body weight, hyperglycemia and dyslipidemia. Although the molecular mechanisms responsible for these side effects are not fully understood, cumulative evidences associate SGA administration with alterations in the different adipose tissue depots of white, brown and beige adipocytes. In this review, we have recapitulated the current knowledge in this area with a particular focus on the molecular aspects of the adipocyte biology, including differentiation, lipid metabolism, thermogenic function and browning processes. Keywords: antipsychotics; schizophrenia; adipose tissue; thermogenesis; browning; lipid; metabolism

Plasma miRNAs as potential biomarkers for schizophrenia in a Jordanian cohort

BackgroundSchizophrenia (SZ), a complex and chronic neuropsychiatric disorder affecting approximately 1 % of the general population, presents diagnostic challenges due to the absence of reliable biomarkers, and relying mainly on clinical observations. MicroRNAs (miRNAs) signatures in a wide range of diseases, including psychiatric disorders, hold immense potential for serving as biomarkers. This study aimed to analyze the expression levels of specific microRNAs (miRNAs) namely miR-29b-3p, miR-106b-5p, and miR-199a-3p and explore their diagnostic potential for SZ in Jordanian patients. MethodsSmall RNAs (miRNAs) were extracted from plasma samples of 30 SZ patients and 35 healthy controls. RNA was reverse transcribed and quantified by real-time polymerase chain reaction (qRT-PCR). The expression levels of three miRNAs (miR-29b-3p, miR-106b-5p and miR-199a-3p) were analyzed. Receiver operating characteristic (ROC) curves analysis was performed to evaluate diagnostic value of these miRNAs. Target genes prediction, functional enrichment and pathway analyses were done using miRWalk and Metascape. STRING database was used to construct protein-protein network and identify hub genes. ResultsNotably, miR-106b-5p and miR-199a-3p were significantly upregulated (p < 0.0001), while miRNA-29b-3p was downregulated (p < 0.0001) in SZ patients compared to controls. The diagnostic potential was assessed through ROC curves, revealing substantial diagnostic value for miR-199a-3p (AUC: 0.979) followed by miR-106b-5p (AUC: 0.774), with limited diagnostic efficacy for miR-29b-3p. Additionally, bioinformatic analyses for the predicted target genes of the diagnostically significant miRNAs uncovered Gene Ontology (GO) terms related to neurological development, including morphogenesis, which is involved in neuron differentiation, brain development, head development, and neuron projection morphogenesis. These findings highlight a potential connection between the identified miRNAs and SZ pathophysiology in the studied Jordanian population. Furthermore, a protein-protein interaction network from the target genes identified in association with neurological development in the Gene Ontology (GO) terms deepens our comprehension of the molecular landscape of the regulated target genes. ConclusionsThis comprehensive exploration highlights the promising role of miRNAs in unraveling intricate molecular pathways associated with SZ in the Jordanian cohort and suggests that plasma miRNAs could serve as reliable biomarkers for SZ diagnosis and disease progression. Remarkably, this study represents the first investigation into the role of circulating miRNA expression among Jordanian patients with SZ, providing valuable insights into the diagnostic landscape of this disorder.

An EEG Study on β-γ Phase-Amplitude Coupling-Based Functional Brain Network in Epilepsy Patients.

Epilepsy, a chronic neuropsychiatric brain disorder characterized with recurrent seizures, is closely associated with abnormal neural communications within the brain. Despite that the phase-amplitude coupling (PAC) has been suggested to offer a new way to observe neural interactions during epilepsy, however, few studies pay attention to alterations of the epileptic functional brain network based on PAC, especially on the β-γ PAC. Therefore, we use scalp electroencephalography (EEG) data of epileptic patients and the β-γ PAC modulation index (MI) to construct functional brain networks to examine variations of neural interactions during different epileptic phases. Statistically, the findings show that between-channel MI values in the post-ictal period significantly increase compared to that in the pre-ictal period, and the between-channel MI value has a close association with the information of phase and amplitude provided by the channels. Importantly, in both the phase-amplitude and amplitude-phase functional brain networks, the average node degree is remarkably higher in the post-ictal period than that in the pre-ictal period, whereas the characteristic path length in the ictal and post-ictal periods is significantly lower than that in the pre-ictal period. Besides, the average betweenness centrality in the post-ictal period is remarkably higher than that in the ictal period. Interestingly, the positive correlations between within-channel MI values and between-channel MI values can be observed during the pre-ictal, ictal and post-ictal periods. These findings suggest that the β-γ PAC-based functional brain network may provide a novel perspective to understanding alterations of neural interactions during the epileptic evolution, and may contribute to effectively controlling the spread of epileptic seizures.

Female sex and burden of depressive symptoms predict insufficient response to telemedical treatment in adult attention-deficit/hyperactivity disorder: results from a naturalistic patient cohort during the COVID-19 pandemic.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence. However, data on telemedical treatment outcomes in adult patients with ADHD is scarce. We report here the sub-cohort analysis of a naturalistic cohort of adult patients (N = 254) recruited between April 2020-April 2021, comparing the effects of telemedical treatment on participants either clinically diagnosed with depression (N = 54) or ADHD (N = 67). Participants were asked to fill out the WHO-5 repetitively during >12 weeks of telemedical treatment. Furthermore scores of WHO-5, SCL-90R and BDI-II, psychopathology, psychosocial functioning, sociodemographic data, medical records and a feedback survey were analyzed for both groups and compared. Participants with ADHD were further stratified according to the development of well-being during the study period in order to identify factors associated with a satisfactory treatment outcome. Participants with depression reported a significant improvement of well-being during the course of the study, while no such effect could be seen in participants with ADHD on a group level. Despite the good outcome, participants with depression were more severely affected at baseline, with significantly worse psychopathology and a more precarious labor and financial situation. A detailed analysis of ADHD participants without clinical improvement revealed significantly higher BDI-II scores than for ADHD participants with a satisfactory outcome (p = 0.03, Mann-Whitney-U-Test), suggesting successful treatment was hampered by the combination of ADHD and depressive symptoms. Furthermore, female sex among ADHD patients was correlated with an unfavorable treatment outcome during the course of the study (p = 0.001, Spearman correlation) as well as living with children (p = 0.02, Spearman correlation). Besides screening for depressive symptoms before telemedical treatment, future research should address the specific needs of female ADHD patients as these patients may be at a particularly high risk of being overburdened with family work.

When Do Korsakoff Patients Justify Immoral Behaviors? The Influence of Premorbid Delinquency and Self-Other Perspectives in Moral Decision-Making and Moral Reasoning.

Korsakoff's syndrome (KS) is a chronic neuropsychiatric disorder caused by a vitamin B1 deficiency. KS is characterized by profound amnesia and often accompanied by poor executive functioning, decreased social-cognitive abilities, and difficulties in behavioral regulation. As moral behaviors and attitudes may provide insight in socio-behavioral interactions, the current study aimed to evaluate everyday moral maturity by administering self- versus other-oriented moral dilemmas in a group of KS patients (n = 20) and healthy controls (n = 20). Responses were scored according to the Kohlberg stages of moral reasoning. Furthermore, we assessed premorbid delinquency and current neurocognitive functioning as possible relevant factors. Our results show that KS patients were prone to lower levels of moral maturity when confronted with moral dilemmas relating to themselves, compared to dilemmas relating to (un)personal others in KS patients, while healthy subjects showed an opposite pattern. Moral immaturity could find its origin already before the onset of the KS diagnosis, as suggested by the elevated premorbid levels of delinquent behavior and correlation between premorbid delinquency and moral maturity in KS. Lower moral maturity could therefore be a possible predisposing factor to both delinquency and later development of Korsakoff's syndrome.

Detecting schizophrenia with 3D structural brain MRI using deep learning

Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.

CSMD1 rs10503253 increases schizophrenia risk in a Tunisian population-group

ObjectivesSchizophrenia is a complex and chronic neuropsychiatric disorder. Recent genome-wide association studies have identified several at risk genetic variants, including two single nucleotide polymorphisms, namely the rs10503253 and the rs1270942 respectively located in the CSMD1 and the CFB loci. The present case-control study was designed to assess potential associations between the two variants and the risk of developing schizophrenia and disease severity. Further we demonstrate the relationship between these variants and clinical characteristics in a population-group from Tunisia. Patients and methodsIn total, 216 patients diagnosed with schizophrenia along with176 healthy controls were included in this case–control study. The molecular analysis of the two polymorphisms was performed using tetra the Primer Amplification Refractory Mutation System–Polymerase Chain method. The statistical analysis was done using Compare V2.1 software, and correlations between genetic results and clinical characteristics were examined by Kruskal-Wallis testing. ResultsThe frequency of the rs10503253A allele was found significantly higher among patients with schizophrenia as compared to healthy controls and associated with high negative PANSS scores. While no association was found concerning the implication of the rs1270942 variant in schizophrenia risk, a positive correlation with high positive PANSS scores was further observed. ConclusionThe present finding confirms the previously reported association between the Cub and Sushi multiple Domain 1 rs10503253A allele and the risk to develop schizophrenia and identified the rs1270942 variant as a potential disease risk modifier. Such observations may be important for the definition of the susceptible immunogenetic background in North African individuals at risk to develop mental disorders.

Self-Reported Pain and Pain Observations in People with Korsakoff's Syndrome: A Pilot Study.

Korsakoff's syndrome (KS) is a chronic neuropsychiatric disorder. The large majority of people with KS experience multiple comorbid health problems, including cardiovascular disease, malignancy, and diabetes mellitus. To our knowledge pain has not been investigated in this population. The aim of this study was to investigate self-reported pain as well as pain behavior observations reported by nursing staff. In total, 38 people diagnosed with KS residing in a long-term care facility for KS participated in this research. The Visual Analogue Scale (VAS), Pain Assessment in Impaired Cognition (PAIC-15), Rotterdam Elderly Pain Observation Scale (REPOS), and the McGill Pain Questionnaire-Dutch Language Version (MPQ-DLV) were used to index self-rated and observational pain in KS. People with KS reported significantly lower pain levels than their healthcare professionals reported for them. The highest pain scores were found on the PAIC-15, specifically on the emotional expression scale. Of importance, the patient pain reports did not correlate with the healthcare pain reports. Moreover, there was a high correlation between neuropsychiatric symptoms and observational pain reports. Specifically, agitation and observational pain reports strongly correlated. In conclusion, people with KS report less pain than their healthcare professionals indicate for them. Moreover, there is a close relationship between neuropsychiatric symptoms and observation-reported pain in people with KS. Our results suggest that pain is possibly underreported by people with KS and should be taken into consideration in treating neuropsychiatric symptoms of KS as a possible underlying cause.

Experimental Models of Gulf War Illness, a Chronic Neuropsychiatric Disorder in Veterans.

Gulf War illness (GWI) is a chronic multifaceted condition with debilitating pain and fatigue, as well as sleep, behavioral, and cognitive impairments in war veterans. Currently, there is no effective treatment or cure for GWI; therefore, there is a critical need to develop experimental models to help better understand its mechanisms and interventions related to GWI-associated neuropsychiatric disorders. Chemical neurotoxicity appears to be one cause of GWI, and its symptoms manifest as disruptions in neuronal function. However, the mechanisms underlying such incapacitating neurologic and psychiatric symptoms are poorly understood. The etiology of GWI is complex, and many factors including chemical exposure, psychological trauma, and environmental stressors have been associated with its development. Attempts have been made to create GWI-like symptomatic models, including through chronic induction in mice and rats. Here, we present a brief protocol of GWI in rats and mice, which exhibit robust neuropsychiatric signs and neuropathologic changes reminiscent of GWI. This article provides a guide to working protocols, application of therapeutic drugs, outcomes, troubleshooting, and data analysis. Our broad profiling of GWI-like symptoms in rodents reveals features of progressive morphologic and long-lasting neuropsychiatric features. Together, the GWI model in rodents shows striking consistency in recapitulating major hallmark features of GWI in veterans. These models help identify mechanisms and interventions for GWI. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Experimental induction of Gulf War illness in rats Support Protocol 1: Monitoring of Gulf War illness signs and neuroimaging analysis in rats Basic Protocol 2: Experimental induction of Gulf War illness in mice Support Protocol 2: Monitoring of Gulf War illness signs and neuropathology analysis in mice.

A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome.

Tourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition. The gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day. Our results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment. Children with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Potential Plasma Metabolic Biomarkers of Tourette Syndrome Discovery Based on Integrated Nontargeted and Targeted Metabolomics Screening Plasma Metabolic Biomarkers of TS.

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by abnormal movements, phonations, and tics, but an accurate TS diagnosis remains challenging and indeed depends on its description of clinical symptoms. Our study was conducted to discover and verify some metabolite biomarkers based on nontargeted and targeted metabolomics. We conducted untargeted ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) for preliminary screening of potential biomarkers on 30 TS patients and 10 healthy controls and then performed validation experiments based on targeted ultrahigh-performance liquid chromatography triple quadrupole-MS (UHPLC/MS/MS) on 35 TS patients and 14 healthy controls. 1775 differentially expressed metabolites were identified by partial least squares discriminant analysis (PLS-DA), fold-change analysis, T-test, and hierarchical clustering analysis (adjusted p value <0.05 and |logFC| > 1). TS plasma samples were found to be differentiated from healthy samples in our approach. Furthermore, aspartate and asparagine metabolism pathways were considered to be a significant enrichment pathway in TS progression based on metabolite pathway enrichment analysis. For the 8 metabolites involved in this pathway that we detected, we then performed validation experiments based on targeted UHPLC/MS/MS. The t-test, Mann-Whitney U test, and receiver operating characteristic (ROC) curve analysis were used to determine potential biomarkers. Ultimately, L-arginine and L-pipecolic acid were validated as significantly differentiated metabolites (p < 0.05), with an AUC of 70.0% and 80.3%, respectively. L-pipecolic acid was defined as a potential biomarker for TS diagnosis by the combined application of nontargeted and targeted metabolomic analysis.

Clinical characteristics of lurasidone-treated patients in Spain using Natural Language Processing – A real-world data study with Electronic Health Records

IntroductionSchizophrenia is a chronic neuropsychiatric disorder which affects over 20 million people worldwide. Atypical antipsychotics are the first-line choice for the treatment of schizophrenia due to improved tolerability and diminished risk of extrapyramidal symptoms. Lurasidone is an atypical antipsychotic approved in Spain for the treatment of schizophrenia in September 2019. An RWD-based picture of lurasidone use is necessary to better understand its impact in routine clinical practice.ObjectivesTo set up a methodology based on Natural Language Processing (NLP) and machine learning for the analysis of the free-text information contained in the EHRs of patients treated with lurasidone in Spain.MethodsA multicenter, retrospective study based on RWD collected in EHRs of lurasidone users will be conducted in hospitals from the Spanish National Healthcare System. Information extracted from the free text in EHRs using NLP will be treated and analyzed as big data.ResultsA study database for lurasidone-treated patients in Spain has been instituted using the EHRead® technology ( Figure 1), which applies machine learning and deep learning to extract, analyze, and interpret the free-text information written in their de-identified EHRs. Sociodemographic and clinical variables in EHRs from September 2019 until the most recent data available are being collected to describe the target patient population and address treatment-related outcomes.ConclusionsNLP of free text in EHRs of lurasidone-treated patients renders a real-world picture of lurasidone usage in Spain. Studies using artificial intelligence techniques represent a novel source of information regarding psychiatric disorders and their clinical management.DisclosureI. Gabarda is employee at Angelini Pharma España, S.L.U. and C. de la Pinta is employee at Medsavana.

P547. Elevated and Uncoupled Glutamate and Glial Biomarkers in Patients With Schizophrenia and Treatment Resistant Schizophrenia

Schizophrenia (SCZ) is a severe and chronic neuropsychiatric disorder that is often subcategorized into 3 treatment-response-subgroups: 1) Patients with improved positive symptom response (PSr) following conventional, non-clozapine, antipsychotic treatment (APT) (i.e., treatment responders; TR), 2) patients with improved-PSr solely to clozapine treatment (i.e., clozapine responders; ClzR+), and 3) patients with no or suboptimal improved-PSr to APTs, including clozapine treatment (i.e., clozapine resistant; ClzR-).

An insight into neurotoxicity effects associated with Organophosphate exposure

Organophosphates comprise several groups of chemicals derived from phosphonic, phosphinic and phosphoric acids. The chemicals cause four major neurotoxic disorders: cholinergic syndrome, chronic organophosphate-induced neuropsychiatric disorder (COPIND), intermediate syndrome and organophosphate-induced delayed polyneuropathy (OPIDP). In the cholinergic syndrome, organophosphates exert their toxic effect through the inhibition of acetylcholinesterase. Patients with cholinergic syndrome experience several symptoms including sweating, lacrimation, salivation and rhinorrhea and respiratory difficulties. The primary symptoms in the intermediate syndrome are respiratory and proximal limb muscle weakness. In contrast, psychiatric conditions, such as depression and anxiety, have been reported in patients with COPIND. In OPIDP, patients experience acute cramping pain inside their calves and itchiness in the hands and feet, paresthesia and distal unresponsiveness.

An insight into neurotoxicity effects associated with Organophosphate exposure

Organophosphates comprise several groups of chemicals derived from phosphonic, phosphinic and phosphoric acids. The chemicals cause four major neurotoxic disorders: cholinergic syndrome, chronic organophosphate-induced neuropsychiatric disorder (COPIND), intermediate syndrome and organophosphate-induced delayed polyneuropathy (OPIDP). In the cholinergic syndrome, organophosphates exert their toxic effect through the inhibition of acetylcholinesterase. Patients with cholinergic syndrome experience several symptoms including sweating, lacrimation, salivation and rhinorrhea and respiratory difficulties. The primary symptoms in the intermediate syndrome are respiratory and proximal limb muscle weakness. In contrast, psychiatric conditions, such as depression and anxiety, have been reported in patients with COPIND. In OPIDP, patients experience acute cramping pain inside their calves and itchiness in the hands and feet, paresthesia and distal unresponsiveness.

Cholinergic Functioning, Cognition, and Anticholinergic Medication Burden in Schizophrenia.

Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which cognitive deficits persist, despite treatment. This review provides a summary of the clinical evidence linking ACh abnormalities to SZ-associated cognitive deficits, an overview of ACh-based pro-cognitive strategies attempted in SZ, and a survey of recent studies that describe the impact of anticholinergic medication burden on cognitive outcomes in SZ. Methodological challenges that currently limit more substantial investigation of ACh in SZ patients and future directions are also discussed.

Response to Fluvoxamine in the Obsessive-Compulsive Disorder Patients: Bayesian Ordinal Quantile Regression.

Background:Obsessive-Compulsive Disorder (OCD) is a chronic neuropsychiatric disorder associated with unpleasant thoughts or mental images, making the patient repeat physical or mental behaviors to relieve discomfort. 40-60% of patients do not respond to Serotonin Reuptake Inhibitors, including fluvoxamine therapy.Introduction:The aim of the study is to identify the predictors of fluvoxamine therapy in OCD patients by Bayesian Ordinal Quantile Regression Model.Methods:This study was performed on 109 patients with OCD. Three methods, including Bayesian ordinal quantile, probit, and logistic regression models, were applied to identify predictors of response to fluvoxamine. The accuracy and weighted kappa were used to evaluate these models.Results:Our result showed that rs3780413 (mean=-0.69, sd=0.39) and cleaning dimension (mean=-0.61, sd=0.20) had reverse effects on response to fluvoxamine therapy in Bayesian ordinal probit and logistic regression models. In the 75th quantile regression model, marital status (mean=1.62, sd=0.47) and family history (mean=1.33, sd=0.61) had a direct effect, and cleaning (mean=-1.10, sd=0.37) and somatic (mean=-0.58, sd=0.27) dimensions had reverse effects on response to fluvoxamine therapy.Conclusion:Response to fluvoxamine is a multifactorial problem and can be different in the levels of socio-demographic, genetic, and clinical predictors. Marital status, familial history, cleaning, and somatic dimensions are associated with response to fluvoxamine therapy.

Taurine prevents MK-801-induced shoal dispersion and altered cortisol responses in zebrafish

Schizophrenia is a chronic neuropsychiatric disorder characterized by a shortened lifespan and significant impaired social and vocational functioning. Schizophrenic patients can present hypothalamic-pituitary-adrenal (HPA) axis dysfunctions and cortisol dysregulation, which play an important role on the etiology onset, exacerbation, and relapsing of symptoms. Based on its intrinsic neuroprotective properties, taurine is considered a promising substance with beneficial role on various brain disorders, including schizophrenia. Here, we evaluated the effects of taurine on shoaling behavior and whole-body cortisol levels in zebrafish treated with dizocilpine (MK-801), which elicits schizophrenia-like phenotypes in animal models. Briefly, zebrafish shoals (4 fish per shoal) were exposed to dechlorinated water or taurine (42, 150, or 400 mg/L) for 60 min. Then, saline (PBS, pH 7.4 or 2.0 mg/kg MK-801) were intraperitoneally injected and zebrafish behavior was recorded 15 min later. In general, MK-801 disrupted shoaling behavior and reduced whole-body cortisol levels in zebrafish. All taurine pretreatments prevented MK-801-induced increase in shoal area, while 400 mg/L taurine prevented the MK-801-induced alterations in neuroendocrine responses. Moreover, all taurine-pretreated groups showed increased geotaxis, supporting a modulatory role in the overall dispersion pattern of the shoal. Collectively, our novel findings show a potential protective effect of taurine on MK-801-induced shoal dispersion and altered neuroendocrine responses, fostering the use of zebrafish models to assess schizophrenia-like phenotypes.