Downregulation of miR-29a as a possible diagnostic biomarker for schizophrenia.

BACKGROUND: MicroRNAs (miRNAs) are epigenetic factors regulating many genes involved in brain development. Dysregulation of miRNA could result in dysregulation of genes which may contribute to diseases affecting the brain and behavior (e.g., schizophrenia). miR-29 family is a miRNA family contributing to brain maturation. miR-29 knockout in animal studies is reported to correlate with psychiatric disorders very similar to those seen in schizophrenia. In this study, we aimed to evaluate the miR-29a level in patients with schizophrenia and its potential value in the diagnosis of schizophrenia. MATERIALS AND METHODS: The serum sample of 42 patients with schizophrenia and 40 healthy subjects were obtained from the Azeri Recent onset/Acute phase psychosis Survey (ARAS) Cohort study. After preparations, the expression level of miR-29a was investigated by real-time PCR. The SPSS and GraphPad prism software were used to analyze the relation between miR-29a level and clinical parameters and its potential as a biomarker for the diagnosis of schizophrenia. RESULTS: Our study showed a significantly lower miR-29a level in patients compared to healthy controls (p = 0.0012). Furthermore, miR-29a level was significantly lower in some types of schizophrenia (p = 0.024). miR-29a level was not related to sex, age, or heredity (p > 0.05). miR-29a also showed 80% specificity and 71.43% sensitivity in the diagnosis of schizophrenia. CONCLUSION: Downregulation of miR-29a in schizophrenia is significantly related to the development of this illness. It might have the potential as a biomarker for schizophrenia.

MicroRNAs and pro-inflammatory cytokines as candidate biomarkers for recent-onset psychosis.

BACKGROUND: Recent studies on the schizophrenia spectrum and other psychotic disorders showed that alternation of immune system components, particularly microRNAs (miRNAs) and pro-inflammatory compounds, plays a significant role in developing the illness. The study aimed to evaluate serum expression of the miRNA-26a, miRNA-106a, and miRNA-125b as genetic factors and serum levels of IL-6, IL-1ß, and TNF-α as pro-inflammatory factors in an IranianAzeri population. METHODS: Forty patients with recent-onset non-affective psychosis and 40 healthy people as a control group were involved. Expression levels of miRNAs and serum levels of the cytokines were measured using RT-qPCR and ELISA, respectively. T-test, receiver operating characteristics (ROC), and spearman correlation coefficient were carried out data analysis. RESULTS: Findings showed higher levels of IL-6, IL-1ß, TNF-α, miR-26a, and miR-106a in the plasma of the patients' group compared with the control. miRNA-26a showed a statistically significant higher level (p < .003) compared to the control group, with AUC = 0.84 (95% CI: 0.77 to 0.93, P < .001) and cut-off point = 0.17 in comparison to other miRNAs as mentioned above; in this regard, it might be a suggestive biomarker for schizophrenia in the early stage of the illness. Moreover, miRNAs' expression level was not substantially associated with the level of any measured cytokines above. CONCLUSIONS: miR-26a might be a suggestive biomarker for schizophrenia in the early stage of the illness. Given that the relationship between other miRNAs and cytokines is not yet well understood; accordingly, there are encouragement and support for continued research in this fascinating field.

Global environmental risk factors of schizophrenia: a study protocol for systematic review and meta-analysis of cohort studies.

INTRODUCTION: Schizophrenia is a chronic, complex and severe psychiatric disorder affecting millions of people every year and inflicting different costs to the individual, family and community. A growing body of evidence has introduced several genetic and environmental factors and their interactions as aetiological factors of schizophrenia. The goal of this systematic review and meta-analysis is to present an updated representation of the global environmental risk factors of schizophrenia. METHOD AND ANALYSIS: This protocol is developed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guideline. We will systematically search the databases such as PubMed, Scopus, Web of Science, PsycINFO and Embase until 30 September 2022. We include Cohort studies that have reported one or more risk factors of schizophrenia. We will also search Google Scholar search engine and references lists of included articles. Extracting the relevant data and assessing the quality of the included studies will be independently performed by different authors of our team. The risk of bias for the included studies will be evaluated using Newcastle-Ottawa Scale. Subgroup analysis, meta-regression or sensitivity analysis will be our solution to deal with heterogeneity between studies. We will use a funnel diagram as well as Begg and Egger tests to check for possible publication bias. ETHICS AND DISSEMINATION: Ethical approval is not required because there will be no primary data collection or human involvement. The results of this study will be published in an international peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359327.

ARAS recent onset acute phase psychosis survey, a prospective observational cohort of first episode psychosis in Iran-the cohort profile.

The Middle East is underrepresented in psychosis research. The ARAS recent onset acute phase psychosis survey (ARAS) is a longitudinal cohort across multiple centers in Iran, established to investigate characteristics, determinants and early course of psychosis in a non-Western, Middle East context. Here, baseline characteristics of the ARAS cohort are reported. The ARAS cohort enrolled patients with recent onset psychosis from September 2018 to September 2021 in East Azerbaijan, Kermanshah and Tehran, including Iranian patients from different sociocultural contexts. The baseline assessment included demographics, socioeconomic status, clinical (positive, negative, depressive symptoms) and psychosocial (religiosity, social support, self-stigma) characteristics, cognitive functioning, metabolic profile, substance use and medication use measured by validated questionnaires. These assessments will be followed up after one and five years. A total of 500 patients with a first episode of psychosis were enrolled from three provinces in Iran. With 74.1% being male, the mean age (SD) of patients was 32.3 (9.7) years. Nearly a quarter of patients was diagnosed with schizophrenia and 36.8% with substance induced psychotic disorder. Amphetamine (24%) and opium (12%) use were common, cannabis use was not (5%). Only 6.1% of patients lived alone while 29% of patients was married and had children. The majority of them had achieved secondary educational level and 34% had a paid job. The most common antipsychotic treatment was risperidone. There was a wide range for scores of PANSS, with 9.4% having dominant negative symptoms. The most common prescribed medication was risperidone. Near to 40% of patients had noticeable signs of depression and prevalence of metabolic syndrome was 13.4%. The majority of patients (57.2%) had moderate and 5.4% reported to have severe disability. More than 30% reported to be highly religious. Patients had the highest satisfaction with people living with, and the lowest for finance and job.

Assessment of Neuropsychiatric Indicators in Children and Adolescents With Primary Brain Tumors and Other Brain Space-Occupying Lesions Before and After Surgery.

Objectives: Cognitive abilities might be impaired due to brain lesions in children and adolescents. This study aimed to investigate neuropsychiatric indicators in children and adolescents with primary brain tumors and other brain space-occupying lesions (SOLs) before and after the surgical procedure. Materials & Methods: The current pre-post study was conducted on 81 patients with brain SOLs aged under 18 years hospitalized in the Neurosurgery Ward of Imam Reza university hospital, Tabriz, Iran, within 20 December 2016 to 20 December 2017. The patients with metastatic brain tumors were excluded. Before and after the surgical procedure, Digit Span forward and backward task (to assess working memory), Stroop Task and Trail Making Task A and B (to assess attention), and Rey-Osterrieth Complex Figure Test (ROCF) (to assess visuospatial memory) were carried out. Then, the scores of the tests were compared to standard values and postsurgical scores. Results: The most prevalent type of brain SOLs was medulloblastoma, and the most prevalent region of involvement was the posterior fossa. The scores of all tests after the surgery were significantly improved, compared to those before the surgery (P<0.05). In the assessment of Digit Span forward and backward task scores, there was no significant difference between the scores of patients before the surgery and standard values (P>0.05). Regarding the scores of various stages of the ROCF, the scores of the immediate recall stage were significantly low (P<0.05). Regarding Trail Making Task A and B and Stroop Task before the surgery, only Trail Making Task A and B scores were significantly increased (P<0.05). The scores of Trail Making Task A were significantly higher in patients with medulloblastoma and anatomically in left temporal tumors, which indicated greater damage to the attention field (P<0.05). In addition, in cerebellar tumors, the scores of the immediate recall stage of the ROCF were significantly lower than in other brain tumors or SOLs (P<0.05). Conclusion: The visuospatial memory and attention of preoperative assessments were significantly impaired, compared to those of the healthy population (P<0.05). Working memory, visuospatial memory, and attention showed improvement, compared to those before the surgery. Deficits in the attention domain were greater in medulloblastoma.

Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia.

Schizophrenia (SCZ) is known as a complicated mental disease with an unknown etiology. The microdeletion of 22q11.2 is the most potent genetic risk factor. Researchers are still trying to find which genes in the deletion region are linked to SCZ. MIR185, encoding microRNA (miR)-185, is present in the minimal 1.5 megabase deletion. Nonetheless, the miR-185 expression profile and its corresponding target genes in animal models and patients with 22q11.2 deletion syndrome (22q11.2DS) imply that more study is required about miR-185 and its corresponding downstream pathways within idiopathic SCZ. The expression of hsa-miR-185-5p and its corresponding target gene, shisa family member 7 (SHISA7), sometimes called CKAMP59, were evaluated in the peripheral blood (PB) samples of Iranian Azeri patients with idiopathic SCZ and healthy subjects, matched by gender and age as control groups by quantitative polymerase chain reaction (qPCR). Fifty SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were enrolled. The expression of hsa-miR-185-5p in the PB samples from subjects with idiopathic SCZ was substantially lower than in that of control groups (posterior beta = -0.985, adjusted P-value < 0.0001). There was also a difference within the expression profile between female and male subgroups (posterior beta = -0.86, adjusted P-value = 0.046 and posterior beta = -1.015, adjusted P-value = 0.004, in turn). Nevertheless, no significant difference was present in the expression level of CKAMP59 between PB samples from patients and control groups (adjusted P-value > 0.999). The analysis of the receiver operating characteristic (ROC) curve suggested that hsa-miR-185-5p may correctly distinguish subjects with idiopathic SCZ from healthy people (the area under curve (AUC) value: 0.722). Furthermore, there was a strong positive correlation between the expression pattern of the abovementioned genes in patients with SCZ and healthy subjects (r = 0.870, P < 0.001 and r = 0.812, P < 0.001, respectively), indicating that this miR works as an enhancer. More research is needed to determine if the hsa-miR-185-5p has an enhancer activity. In summary, this is the first research to highlight the expression of the miR-185 and CKAMP59 genes in the PB from subjects with idiopathic SCZ. Our findings suggest that gene expression alterations mediated by miR-185 may play a role in the pathogenesis of idiopathic and 22q11.2DS SCZ. It is worth noting that, despite a substantial and clear relationship between CKAMP59 and hsa-miR-185-5p, indicating an interactive network, their involvement in the development of SCZ should be reconsidered based on the whole blood sample since the changed expression level of CKAMP59 was not significant. Further research with greater sample sizes and particular leukocyte subsets can greatly make these results stronger.

Expression Analysis of Ermin and Listerin E3 Ubiquitin Protein Ligase 1 Genes in the Periphery of Patients with Schizophrenia.

Schizophrenia (SCZ) is a severe mental disorder with an unknown etiology. Recent researches indicate that correct myelination and translational regulation play a role in the pathogeny of SCZ. This study evaluated the expression pattern of Ermin (ERMN) and Listerin E3 ubiquitin protein ligase 1 (LTN1) genes, which play a role in myelination and ribosome quality control, respectively. The expression of the ERMN and LTN1 genes in the peripheral blood (PB) of 50 SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were assessed using quantitative polymerase chain reaction. Additionally, we used a bioinformatics approach based on microarray dataset analysis to examine the expression of these two genes in olfactory epithelium (OE) specimens. The expression of ERMN demonstrated no significant differences in PB samples among SCZ patients and healthy controls (adjusted P-value = 0.101). The expression of LTN1 was significantly higher in PB samples obtained from female patients compared with sex-matched controls (posterior beta = 1.734, adjusted P-value < 0.0001). Significant correlations were found between expression of the mentioned genes in PB samples both among SCZ patients and among healthy controls (r = 0.485, P < 0.001 and r = 0.516, P < 0.001, respectively). According to our in silico findings, the ERMN expression levels in OE samples of SCZ were statistically higher than those in controls (log2FC = 1.93, adj.P.Val = 9.66E-15). On the contrary, LTN1 expression levels in OE samples were statistically lower in SCZ cases versus controls (log2FC = - 0.77, adj.P.Val = 2.14E-06). Besides, a significant correlation was found between the expression of the mentioned genes in OE samples (r = - 0.60, P < 0.001). In conclusion, the present study is the first evidence to highlight the expression of the ERMN and LTN1 genes in the periphery of SCZ patients. Our findings may provide light on the SCZ's pathogeny.

Escitalopram and progressive muscle relaxation training are both effective for the treatment of hot flashes in patients with breast cancer: a randomized controlled trial.

INTRODUCTION: Available treatments for hot flashes in patients with breast cancer are not always tolerable or effective for all patients. METHODS: Patients diagnosed to have primary breast cancer were randomly allocated to receive 10 mg of escitalopram, placebo, or progressive muscle relaxation therapy. Patients were asked to report the frequency and duration of hot flashes during day and night, at baseline and after ten weeks of treatment, and completed the menopause rating scale. RESULTS: Eighty-two patients were randomly assigned to receive escitalopram (n = 26), PMRT (n = 28), and placebo (n = 28). PMRT and escitalopram could effectively decrease number and duration of diurnal and nocturnal HFs in patients with breast cancer, with a better effect observed from escitalopram. They could both decrease the total score of MRS. CONCLUSION: Both escitalopram ad PMRT can reveal nocturnal and diurnal HFs in terms of frequency and duration in patients with breast cancer.

Virtual reality-based interventions for patients with paranoia: A systematic review.

BACKGROUND AND OBJECTIVE: Paranoia is an important psychiatric symptom with a remarkable effect on daily life. Virtual reality (VR)-based treatments are influential and safe for patients with paranoia. This study aimed to evaluate the effectiveness, and define the clinical and technical characteristics of available VR strategies for the treatment of patients with paranoia. MATERIALS AND METHODS: Studies published up to 25/11/2021 reporting VR-based interventions for the treatment of patients with paranoia were reviewed in five databases, including PubMed, Embase, Web of Science, PsycINFO, and Scopus. RESULTS: Out of 302 initial search results, eight were included in the present study based on the inclusion criteria. Six studies were randomized clinical trials with the interventions in the experimental group being based on VR, compared to routine interventions as controls. Two were before-after studies. The most commonly used hardware and software were head-mounted display and Unity3D, respectively. Interventions had a range of 1-16 sessions with follow-up durations of 0-6 months. All investigations showed positive results in the main target, including improved social participation, reduced level of anxiety, as well as diminished suspicious ideas and paranoid symptoms. CONCLUSIONS: Our findings demonstrated that VR-based interventions are effective treatments. Although the use of VR technology is limited for a variety of reasons, such as cost, it improves symptoms in patients with paranoia.

Automatic classification of schizophrenia patients using resting-state EEG signals.

Schizophrenia is one of the serious mental disorders, which can suspend the patient from all aspects of life. In this paper we introduced a new method based on the adaptive neuro fuzzy inference system (ANFIS) to classify recorded electroencephalogram (EEG) signals from 14 schizophrenia patients and 14 age-matched control participants. Sixteen EEG channels from 19 main channels that had the most discriminatory information were selected. Possible artifacts of these channels were eliminated with the second-order Butterworth filter. Four features, Shannon entropy, spectral entropy, approximate entropy, and the absolute value of the highest slope of autoregressive coefficients (AVLSAC) were extracted from each selected EEG channel in 5 frequency sub-bands, Delta, Theta, Alpha, Beta, and Gamma. Forty-six features were introduced among the 640 possible ones, and the results included accuracies of near 100%, 98.89%, and 95.59% for classifiers of ANFIS, support vector machine (SVM), and artificial neural network (ANN), respectively. Also, our results show that channels of alpha of O1, theta and delta of Fz and F8, and gamma of Fp1 have the most discriminatory information between the two groups. The performance of our proposed model was also compared with the recently published approaches. This study led to presenting a new decision support system (DSS) that can receive a person's EEG signal and separates the schizophrenia patient and healthy subjects with high accuracy.

Application of newly developed SARS-CoV2 serology test along with real-time PCR for early detection in health care workers and on-time plasma donation.

BACKGROUND: As the daily number of coronavirus infection disease 19 (COVID19) patients increases, the necessity of early diagnosis becomes more obvious. In this respect, we aimed to develop a serological test for specifically detecting anti-SARS-CoV2 antibodies. METHODS: We collected serum and saliva samples from 609 individuals who work at TBZMED affiliated hospitals in Tabriz, Iran, from April to June of 2020. Real-time PCR technique was used to detect SARS-CoV-2 genome using specific primers. An enzyme linked immunosorbent assay (ELISA) test was designed based on virus nucleocapsid (N), spike (S) and its receptor binding domain (RBD) protein, and the collected sera were subjected to IgM and/or IgG analysis. RESULT: Real-time PCR results showed that 66 people were infected with the SARS-CoV-2. Our designed ELISA kit showed 93.75% and 98% of sensitivity and specificity, respectively. In this study, 5.74% of participants had specific IgG against RBD, whereas the percentage for IgM positive individuals was 5.58%. Approximately the same results were observed for S protein. The number of positive participants for NP increased further, and the results of this antigen showed 7.38% for IgG and 7.06% for IgM. CONCLUSION: The ELISA test beside real-time PCR could provide a reliable serologic profile for the status of the disease progress and early detection of individuals. More importantly, it possesses the potential to identify the best candidates for plasma donation according to the antibody titers.

An Observational Cohort of First Episode Psychosis in Iran: The Azeri Recent Onset Acute Phase Psychosis Survey (ARAS Cohort) Study Protocol.

Background: Most of our knowledge about the etiology, course, treatment, and outcome of schizophrenia spectrum and other psychotic disorders stems from Western countries. Data from populations living in other geographical areas and low- and middle-income countries, with different genomes (ethnicity) and exposomes (e.g., culture and social support, drugs of abuse, religion), will add to our knowledge of this complex disorder. Methods: The Azeri Acute phase/Recent onset psychosis Survey (ARAS) has been initiated to study the course of the disorder in patients with recent-onset psychosis using validated diagnostic tools and a comprehensive outcome monitoring system, aiming to reveal indicators for understanding the risk and resilience factors and for choosing the best-personalized treatment strategy. All participants will be evaluated for clinical signs and symptoms as well as risk and resilience factors and will be followed up for 1, 3, and 5 years for outcomes in several domains. A hierarchical cluster method will be applied to identify the number of clusters for each outcome. Defined models will be applied to assess the predictive value of cognition on symptomatic and functional outcomes at follow-up. Discussion: The ARAS cohort will yield significant academic- (research and education) and care-related achievements. ARAS data and experience will have value both in being a useful model for other parts of this region and in an expansion of the currently available knowledge.

Turkish Version of the Test Your Memory (TYM-TR) as a Screening Tool in Memory Clinics.

INTRODUCTION: This study compared the Turkish version of Test Your Memory (TYM) MMSE (Mini-Mental State Examination) and CDT (Clock Drawing Test) in patients with neurocognitive disorder. METHODS: After a thorough medical workup, patients with a diagnosis of neurocognitive disorder were enrolled. A cross-sectional design was used to compare the TYM results with those of MMSE and CDT. RESULTS: This study was conducted on 100 patients, including 46 males and 54 females, aged 52 to 86. The majority of patients were diagnosed with vascular neurocognitive disorder. The z-score of TYM-TR was significantly lower in the domains of registration, recall, visuospatial, and total score. The same results were achieved when CDT was added to MMSE. The same pattern was observed separately for those who were diagnosed with a mild or major neurocognitive disorder. CONCLUSION: Patients' cognitive deficits might be more evident when measured by the TYM-TR compared to the MMSE.

Prevalence of drug use, alcohol consumption, cigarette smoking and measure of socioeconomic-related inequalities of drug use among Iranian people: findings from a national survey.

BACKGROUND: Drug use can lead to several psychological, medical and social complications. The current study aimed to measure and decomposes socioeconomic-related inequalities in drug use among adults in Iran. METHODS: This was a cross-sectional study The PERSIAN Cohort is the largest and most important cohort among 18 distinct areas of Iran. This study was conducted on 130,570 adults 35 years and older. A structured questionnaire was applied to collect data. The concentration index (C) was used to quantify and decompose socioeconomic inequalities in drug use. RESULTS: The prevalence experience of drug use was 11.9%. The estimated C for drug use was - 0.021. The corresponding value of the C for women and men were - 0.171 and - 0.134, respectively. The negative values of the C suggest that drug use is more concentrated among the population with low socioeconomic status in Iran (p < 0.001). For women, socioeconomic status (SES) (26.37%), province residence (- 22.38%) and age (9.76%) had the most significant contribution to socioeconomic inequality in drug use, respectively. For men, SES (80.04%), smoking (32.04%) and alcohol consumption (- 12.37%) were the main contributors to socioeconomic inequality in drug use. CONCLUSIONS: Our study indicated that drug use prevention programs in Iran should focus on socioeconomically disadvantaged population. Our finding could be useful for health policy maker to design and implement effective preventative programs to protect Iranian population against the drug use.

An epidemiological survey of psychiatric disorders in Iran: Kermanshah.

BACKGROUND: There is no population based study about prevalence of psychiatric conditions in Kermanshah. A screening study reported the rate of 39.1% for psychiatric disorders. METHODS: This is the second phase of a larger study. From those with a positive screening, 15% were randomly selected and interviewed face-to-face at home by trained clinical psychologists with Farsi version of the structured clinical interview for DSM-IV (SCID) I and II. RESULTS: The original sample was 2102 participants, from those 319 individuals were interviewed. Only 15 participants (4.7% of the positively screened sample) had a negative result. Major depressive disorder (8.3%), generalized anxiety disorder (4.7%), obsessive compulsive disorder (4.6%) and obsessive compulsive personality disorder (3.3%) were the most common disorders diagnosed within this sample. CONCLUSION: This population based study gives prevalence rates for psychiatric disorders in Kermanshah for the first time. Results can be the basis for health care policy makers and further studies.

Mental health status among female sex workers in Tabriz, Iran.

Female sex workers are a deprived part of Islamic communities. It is necessary for public health policy makers to have knowledge about their mental health status. This study aims to have an evaluation of mental health among female sex workers in Tabriz for the first time in northwest of Iran. In this cross-sectional study, 48 female sex workers who had accepted to be evaluated were included. Sociodemographic and general mental health statuses, using General Health Questionnaire (GHQ-28), were recorded. Those with GHQ-28 score more than 23/24 in the first session were thoroughly interviewed in a second session in order to find out their specific mental disorder, using Structured Clinical Interview for DSM-IV axis 1 and 2 Disorders (SCID 1 and 2). This study suggests that 62.5% of female sex workers suffer from a mental health problem which is in accordance with previous studies. Mood and anxiety disorder were two of the most common, and there were also records of personality disorders among participants of this survey. There were also high rates of addiction in female sex workers of this study. Based on findings of this study, high rates of mental disorders such as personality disorders, anxiety disorder, and mood disorder were detected among female sex workers in the northwest of Iran. Financial incentive was reported to be the primary motivation for choosing sex work as a source of income.