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IntroductionThe human gut microbiota plays a crucial role in mental health through the gut-brain axis, impacting central nervous system functions, behavior, mood, and anxiety. Consequently, it is implicated in the development of neuropsychiatric disorders. This study aimed to assess and compare the gut microbiota profiles and populations of individuals with bipolar disorder and healthy individuals in Iran. MethodsFecal samples were collected from 60 participants, including 30 bipolar patients (BPs) and 30 healthy controls (HCs), following rigorous entry criteria. Real-time quantitative PCR was utilized to evaluate the abundance of 10 bacterial genera/species and five bacterial phyla.ResultsNotably, Actinobacteria and Lactobacillus exhibited the greatest fold change in BPs compared to HCs at the phylum and genus level, respectively, among the bacteria with significant population differences. Ruminococcus emerged as the most abundant genus in both groups, while Proteobacteria and Bacteroidetes showed the highest abundance in BPs and HCs, respectively, at the phylum level. Importantly, our investigation revealed a lower Firmicutes/Bacteroidetes ratio, potentially serving as a health indicator, in HCs compared to BPs.ConclusionThis study marks the first examination of an Iranian population and provides compelling evidence of significant differences in gut microbiota composition between BPs and HCs, suggesting a potential link between brain functions and the gut microbial profile and population. more...

Abstract Objective Neuropsychological findings in obsessive-compulsive disorder (OCD) are mainly clustered around the role of memory and executive functions. However, outcomes vary across different OCD populations. In addition, the extent to which each of these factors can distinguish patients with OCD (PwOCD) from healthy individuals remains uncertain and attracts great attention. The present study aims to investigate the above issues. Method This was a cross-sectional study of 182 individuals (90 PwOCD and 92 matched healthy controls). After screening for inclusion and exclusion criteria, the participants were administered neuropsychological tests including, the Wechsler Memory Scale-III (WMS-III), the Wisconsin Card Sorting Test (WCST), and the Stroop Color-Word Test (SCWT). Data were analyzed to test the study hypotheses using comparison of means and regression analysis methods. Results The results showed that PwOCD had poorer performance than the control group in Immediate Memory, General Memory, and Working Memory and also according to response inhibition indexes. The results also showed that General Memory and Reaction Time2 from the SCWT index could be predictive variables for discriminating between PwOCD and controls. Conclusion The findings of this study support the prior assumptions that PwOCD would have impaired memory dimensions and response inhibition, but did not support worse set-shifting performance. We also present an initial model for the predictive role of these neuropsychological variables in discriminating OCD from healthy individuals and increasing diagnostic accuracy. more...

Abstract Background The novel approaches to psychiatric classification assume that disorders, contrary to what was previously thought, are not completely separate phenomena. In this regard, in addition to symptom-based criteria, disturbances are also considered on the basis of lower level components. With this viewpoint, identifying common biochemical markers would be beneficial in adopting a comprehensive strategy for prevention, diagnosis and treatment. Main body One of the problematic areas in clinical settings is the coexistence of both obsessive–compulsive disorder (OCD) and bipolar disorder (BD) that is challenging and difficult to manage. In this study, using a system biologic approach we aimed to assess the interconnectedness of OCD and BD at different levels. Gene Set Enrichment Analysis (GSEA) method was used to identify the shared biological network between the two disorders. The results of the analysis revealed 34 common genes between the two disorders, the most important of which were CACNA1C, GRIA1, DRD2, NOS1, SLC18A1, HTR2A and DRD1. Dopaminergic synapse and cAMP signaling pathway as the pathways, dopamine binding and dopamine neurotransmitter receptor activity as the molecular functions, dendrite and axon part as the cellular component and cortex and striatum as the brain regions were the most significant commonalities. Short conclusion The results of this study highlight the role of multiple systems, especially the dopaminergic system in linking OCD and BD. The results can be used to estimate the disease course, prognosis, and treatment choice, particularly in the cases of comorbidity. Such perspectives, going beyond symptomatic level, help to identify common endophenotypes between the disorders and provide diagnostic and therapeutic approaches based on biological in addition to the symptomatic level. more...

Antiepileptic drugs (AEDs) have repeatedly shown inconsistent and almost contradictory effects on the neurocognitive system, from substantial impairments in processing speed to the noticeable improvement in working memory and executive functioning. Previous studies have provided a novel insight into the cognitive improvement by bumetanide as a potential antiepileptic drug. Through the current investigation, we evaluated the longitudinal effects of bumetanide, an NKCC1 co-transporter antagonist, on the brain microstructural organization as a probable underlying component for cognitive performance. Microstructure assessment was completed using SPM for the whole brain assay and Freesurfer/TRACULA for the automatic probabilistic tractography analysis. Primary cognitive operations including selective attention and processing speed, working memory capacity and spatial memory were evaluated in 12 patients with a confirmed diagnosis of refractory epilepsy. Participants treated with bumetanide (2 mg/ day) in two divided doses as an adjuvant therapy to their regular AEDs for 6 months, which followed by the re-assessment of their cognitive functions and microstructural organizations. Seizure frequency reduced in eight patients which accompanied by white matter reconstruction; fractional anisotropy (FA) increased in the cingulum-cingulate gyrus (CCG), anterior thalamic radiation (ATR), and temporal part of the superior longitudinal fasciculus (SLFt) in correlation with the clinical response. The voxel-based analysis in responder patients revealed increased FA in the left hippocampus, right cerebellum, and right medial temporal lobe, while mean diffusivity (MD) values reduced in the right occipital lobe and cerebellum. Microstructural changes in SLFt and ATR accompanied by a reduction in the error rate in the spatial memory test. These primary results have provided preliminary evidence for the effect of bumetanide on cognitive functioning through microstructural changes in patients with drug-resistant epilepsy. more...

Objective: Although the etiology of schizophrenia is unknown, it has a significant genetic component. ‎A number of studies have indicated that neuregulin-1 (NRG1) gene may play a role in the ‎pathogenesis of schizophrenia. In this study, we examined whether the rs2439272 of NRG1 ‎is associated with schizophrenia and its negative symptoms in an Iranian population.‎ Method: Rs2439272 was genotyped in 469 participants including 276 unrelated patients with schizophrenia and 193 healthy controls. The association of genetic risk with PANSS, and negative ‎symptoms was examined in the total, male and female samples. COCAPHASE and ‎CLUMP22 programs were used to compare the allele and genotype frequencies, and ‎general linear regression was used to analyze the quantitative dependent variables by the ‎selected variant.‎ Results: In this study, it was revealed that the G allele of rs2439272 might be an allele with the ‎increased risk of developing schizophrenia, especially in the male participants. In addition, ‎significant differences were found between the G allele and GG genotype frequencies and ‎PANSS, and negative symptoms in the total and male participants.‎ Conclusion: Our results supported the association between rs2439272 in NRG1 gene and risk of ‎schizophrenia and its negative symptoms in an Iranian population. more...

Objectives: There are a large number of primary researches on the prevalence of major depressive disorder (MDD) in Iran; however, their findings are varied considerably. A systematic review was performed in order to summarize the findings.Methods: Electronic and manual searches in international and Iranian journals were conducted to find relevant studies reporting MDD pre-valence. To maximize the sensitivity of the search, the references of relevant papers were also explored. We explored the potential sources of heterogeneity such as diagnostic tools, gender and other characteristics using meta-regression model. The com-bined mean prevalence rates were calculated for genders, studies using each type of instruments and for each province using meta-analysis method.Results: From 44 articles included in the systematic review, 24 reported current prevalence and 20 reported lifetime prevalence of MDD. The overall estimation of current prevalence of MDD was 4.1% (95% CI: 3.1-5.1). Women were 1.95 (95% CI: 1.55-2.45) times more likely to have MDD. The current prevalence of MDD in urban inhabitants was not significantly different from rural inhabitants. The analysis identified the variations in diagnostic tools as an important source of heterogeneity.Conclusions: Although there is not adequate information on MDD prevalence in some areas of Iran, the overall current prevalence of MDD in the country is high and females are at the greater risk of disease. more...

Objective: Neuropsychological findings in obsessive-compulsive disorder (OCD) are mainly clustered around the role of memory and executive functions. However, outcomes vary across different OCD populations. In addition, the extent to which each of these factors can distinguish patients with OCD (PwOCD) from healthy individuals remains uncertain and attracts great attention. The present study aims to investigate the above issues. Method: This was a cross-sectional study of 182 individuals (90 PwOCD and 92 matched healthy controls). After screening for inclusion and exclusion criteria, the participants were administered neuropsychological tests including, the Wechsler Memory Scale-III (WMS-III), the Wisconsin Card Sorting Test (WCST), and the Stroop Color-Word Test (SCWT). Data were analyzed to test the study hypotheses using comparison of means and regression analysis methods. Results: The results showed that PwOCD had poorer performance than the control group in Immediate Memory, General Memory, and Working Memory and also according to response inhibition indexes. The results also showed that General Memory and Reaction Time2 from the SCWT index could be predictive variables for discriminating between PwOCD and controls. Conclusion: The findings of this study support the prior assumptions that PwOCD would have impaired memory dimensions and response inhibition, but did not support worse set-shifting performance. We also present an initial model for the predictive role of these neuropsychological variables in discriminating OCD from healthy individuals and increasing diagnostic accuracy. [ABSTRACT FROM AUTHOR] more...

Background: The novel approaches to psychiatric classification assume that disorders, contrary to what was previously thought, are not completely separate phenomena. In this regard, in addition to symptom-based criteria, disturbances are also considered on the basis of lower level components. With this viewpoint, identifying common biochemical markers would be beneficial in adopting a comprehensive strategy for prevention, diagnosis and treatment. Main body: One of the problematic areas in clinical settings is the coexistence of both obsessive–compulsive disorder (OCD) and bipolar disorder (BD) that is challenging and difficult to manage. In this study, using a system biologic approach we aimed to assess the interconnectedness of OCD and BD at different levels. Gene Set Enrichment Analysis (GSEA) method was used to identify the shared biological network between the two disorders. The results of the analysis revealed 34 common genes between the two disorders, the most important of which were CACNA1C, GRIA1, DRD2, NOS1, SLC18A1, HTR2A and DRD1. Dopaminergic synapse and cAMP signaling pathway as the pathways, dopamine binding and dopamine neurotransmitter receptor activity as the molecular functions, dendrite and axon part as the cellular component and cortex and striatum as the brain regions were the most significant commonalities. Short conclusion: The results of this study highlight the role of multiple systems, especially the dopaminergic system in linking OCD and BD. The results can be used to estimate the disease course, prognosis, and treatment choice, particularly in the cases of comorbidity. Such perspectives, going beyond symptomatic level, help to identify common endophenotypes between the disorders and provide diagnostic and therapeutic approaches based on biological in addition to the symptomatic level. [ABSTRACT FROM AUTHOR] more...

Objective: Although the etiology of schizophrenia is unknown, it has a significant genetic component. A number of studies have indicated that neuregulin-1 (NRG1) gene may play a role in the pathogenesis of schizophrenia. In this study, we examined whether the rs2439272 of NRG1 is associated with schizophrenia and its negative symptoms in an Iranian population. Method: Rs2439272 was genotyped in 469 participants including 276 unrelated patients with schizophrenia and 193 healthy controls. The association of genetic risk with negative symptoms (by using panss) was examined in the total, male and female samples. COCAPHASE and CLUMP22 programs were used to compare the allele and genotype frequencies, and general linear regression was used to analyze the quantitative dependent variables by the selected variant. Results: In this study, it was revealed that the G allele of rs2439272 might be an allele with the increased risk of developing schizophrenia, especially in the male participants. In addition, significant differences were found between the G allele and GG genotype frequencies, and negative symptoms in the total and male participants. Conclusion: Our results supported the association between rs2439272 in NRG1 gene and risk of schizophrenia and its negative symptoms in an Iranian population. [ABSTRACT FROM AUTHOR] more...

Background: There are some reports on the effects of antidepressants on metabolic syndrome. However, our search in the previously published literature showed a lack of information on the comparison of the effects of different classes of antidepressants on lipid profile. Therefore, this study was aimed to compare the effects of fluoxetine and imipramine on serum total cholesterol (TC) and triglyceride (TG) as well as body weight (BW) in patients with major depressive disorder. Methods: Fifty one patients, 18 to 70 years of age, with major depressive disorder complied with the criteria of this preliminary, open-label clinical trial. Subjects received either imipramine (75-200 mg/day) or fluoxetine (20-40 mg/ day) for 8 weeks. Total cholesterol and TG levels, as well as BW were compared at baseline with those at weeks 4 and 8. Data was analyzed by SPSS software version 16.0. Results: In the fluoxetine group, TC levels decreased from 165.71 mg/dL to 156.71 mg/dL at week 4 (P = 0.07), and to 143.94 mg/dL at week 8 (P = 0.16); TG levels decreased from 129.35 mg/dL to 115.88 mg/dL at week 4 (P <0.001), and to 110.41 mg/dL at week 8 (P = 0.56). In the imipramine group, TC levels increased from 169.10 mg/dL to 178.69 mg/ dL at week 4 (P = 0.07), and to 208.69 mg/dL at week 8 (P < 0.001) while TG levels increased from 111.73 mg/dL to 128.83 mg/dL at week 4 (P = 0.005), and to 160.90 mg/dL at week 8 (P < 0.001). BW was significantly increased in the imipramine group at weeks 4 and 8. In the fluoxetine group, BW was non-significantly decreased from 75.69 ± 7.97 Kg (baseline) to 75.67 ± 8.01 Kg at week 4 (P = 0.88), and to 75.22 ± 8.67 Kg at week 8 (P = 0.20), while in the imipramine group, BW had significant increases from 72.53 ± 8.55 Kg (baseline) to 73.95 ± 8.61 mg/dL at week 4 (P < 0.001), and to 75.13 ± 8.34 mg/dL at week 8 (P < 0.001). Repeated measures ANOVA showed significant effects on both TC and TG levels as well as on BW in all patients receiving imipramine. However, in patients on fluoxetine, repeated measures ANOVA showed significant effects of this medication only on TC levels in males. Conclusions: Monitoring TC and TG and BW is recommended before starting imipramine in depressed patients with increased risk for cardiovascular disease. Fluoxetine may be the preferred agent in those with high or borderline high lipid levels. [ABSTRACT FROM AUTHOR] more...

Background: During the last two decades, mucheffort is put to better understand the etiology of schizophrenia. Studying negative symptoms such as endophenotypes is a plausible approach to elucidate the genetic basis of schizophrenia. Neuregulin-1 (NRG1) is a key candidate gene to develop schizophrenia and its negative symptoms. The NRG1 variant rs6988339 was previously characterized as a schizophrenia susceptibility locus in different Scottish populations. Objectives: The current study aimed to examine the association of rs6988339 with schizophrenia and its negative symptoms in an Iranian population. Methods: The current case-controlled study enrolled 469 subjects (276 unrelated schizophrenia patients and 193 healthy controls). The study investigated the association of rs6988339 with schizophrenia and its negative symptoms (assessed with the positive and negative syndrome scale; PANSS) in an Iranian population. Results: The obtained results showed that rs6988339 was a schizophrenia susceptibility locus in the Iranian population, the minor allele G was the risk allele and A the protective allele (P = 0.0007). Of the four subscales of the PANSS test, the negative score showed the strongest association with this variant (P = 0.001). Conclusions: The results further supported the implication of NRG1 in the pathogenesis of negative symptoms in schizophrenia. [ABSTRACT FROM AUTHOR] more...

Objectives: There are a large number of primary researches on the prevalence of major depressive disorder (MDD) in Iran; however, their findings are varied considerably. A systematic review was performed in order to summarize the findings., Methods: Electronic and manual searches in international and Iranian journals were conducted to find relevant studies reporting MDD prevalence. To maximize the sensitivity of the search, the references of relevant papers were also explored. We explored the potential sources of heterogeneity such as diagnostic tools, gender and other characteristics using meta-regression model. The combined mean prevalence rates were calculated for genders, studies using each type of instruments and for each province using meta-analysis method., Results: From 44 articles included in the systematic review, 24 reported current prevalence and 20 reported lifetime prevalence of MDD. The overall estimation of current prevalence of MDD was 4.1% (95% CI: 3.1-5.1). Women were 1.95 (95% CI: 1.55-2.45) times more likely to have MDD. The current prevalence of MDD in urban inhabitants was not significantly different from rural inhabitants. The analysis identified the variations in diagnostic tools as an important source of heterogeneity., Conclusions: Although there is not adequate information on MDD prevalence in some areas of Iran, the overall current prevalence of MDD in the country is high and females are at the greater risk of disease. more...