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Hasan Kandemir,1 Mehmet Emin Erdal,2 Salih Selek,3 Özlem İzci Ay,2 İbrahim Fatih Karababa,4 Mustafa Ertan Ay,2 Sultan Basmaci Kandemir,5 Şenay Görücü Yılmaz,2 Suat Ekinci,6 Bahar Taşdelen,7 Hüseyin Bayazit41Department of Child and Adolescent Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, Turkey; 2Department of Medical Biology and Genetics, Faculty of Medicine, Mersin University, Mersin, Turkey; 3Harris County Psychiatric Center, University of Texas Health Science Center at Houston, TX, USA; 4Department of Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, Turkey; 5Department of Psychiatry, Balikligöl State Hospital, Sanliurfa, Turkey; 6Department of Psychiatry, Balikli Rum Hospital, Istanbul, Turkey; 7Department of Biostatistics, Faculty of Medicine, Mersin University, Mersin, TurkeyAim: Obsessive–compulsive disorder (OCD) is a disorder characterized by the presence of obsessions and/or compulsions. Although disorder etiology and pathogenesis remains unknown, several theories about OCD development have been proposed, and many researchers believe that it is caused by both genetic and environmental factors. In the current study, our aim was to investigate miRNA levels in OCD.Methods: In the current study, we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p, and miR155a-5p levels in child and adolescent OCD patients. The research sample consisted of a group of 23 OCD patients and 40 healthy volunteer controls.Results: There was no significant difference in age and sex between the two groups (P>0.05).The levels of miR22-3p, miR24-3p, miR106b-5p, miR125b-5p, and miR155a-5p were significantly increased in the OCD subjects (P≤0.05). There were no statistically significant differences in miR18a-5p or miR107 levels between groups (P≥0.05).Conclusion: There could be a close relationship between levels of circulating miRNAs and OCD. If we could understand how the signaling pathways arranged by miRNAs impact on central nervous system development, function, and pathology, this understanding could improve our knowledge about OCD etiology and treatment.Keywords: OCD, micro RNA, miRNA, psychiatry, child psychiatry

Objective: Screening tests are recommended to identify genetic defects, chromosomal aneuploidies, and structural birth defects. Sonographic and maternal serum-based options are available for the risk assessment of aneuploidy in the first and/or second trimester. Also, invasive diagnostic methods, such as amniocentesis, are used for prenatal diagnosis, but these methods carry a tangible risk to the fetus. However, in recent years, circulating fetal nucleic acids have a promising moleculer tool in the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies. In this study, we aimed to explore the usability of microRNAs (miRNAs) in this process of prenatal diagnosis., Methods: Fourteen pregnant patients who were found to be carrying fetuses with congenital anomalies were designated as the patient group; 16 pregnant women identified as being at risk of carrying children with such anomalies-but whose fetuses were later found to be anomaly-free-were assigned to control group 1; and 13 pregnant women who had been screened and who had not been identified as being at risk made up control group 2. An analysis of miRNA expression, isolated from maternal plasma and amniotic fluid samples, was performed by quantitative real-time polymerase chain reaction., Results: It was found that hsa-miR-629-5p, hsa-miR-320c, hsa-miR-21-5p, hsa-let-7c-5p, hsa-miR-98-5p, hsa-miR-486-5p, hsa-miR-4732-5p, and hsa-miR-181a-5p levels increased in the patient group's maternal plasma compared to that of the control group., Conclusion: In light of these data, we believe that miRNAs may have an important role in the noninvasive prenatal diagnosis of fetal birth defects, especially Down syndrome.

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers., Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis., Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987., Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene., Competing Interests: The authors report no conflicts of interest.

Objective: The proto-oncogene Bax (Bcl-2-associated X protein) and related protein Bcl-2 (B-cell chronic lymphocytic leukemia/lymphoma-2) genes are triggers of apoptosis in Alzheimer's disease (AD). The balance of these proteins has an important role in the death or life of a neuronal cell, and the functional polymorphisms in genes expressing these proteins have been found to promote apoptosis. To investigate the role of Bax and Bcl-2 genes in AD, we examined the presence of the 2 polymorphisms in peripheral blood. To our knowledge, this is the first clinical association study of these 2 functional SNPs using the peripheral blood of patients with AD., Methods: Bax (rs4645878) and Bcl-2 (rs2279115) in Alzheimer's patients (N = 132) and healthy controls (N = 109), aged 65 to 85 years, were analyzed by qPCR (Quantitative Polymerase Chain Reaction) using TaqMan probe technology. Statistical analyses were done using SPSS, 11.5. The differences between groups were analyzed using an independent-samples t test. The relationships between genotypes and alleles were analyzed using chi-square or likelihood ratio test. The Hardy-Weinberg balance was checked for the patient and control groups. A p-value of less than 0.05 was taken as significant., Results: Sporadic AD patients and non-demented age matched control subjects were genotyped in this case-control study. No statistically significant relationship was found between the patients and controls for allele or genotype frequencies (p>0.05)., Conclusion: Our data suggest that these two polymorphisms do not contribute to AD in the population from the Mersin region of the Eastern Mediterranean. Further studies with larger sample sizes must be conducted to ascertain the association between the 2 polymorphisms.

Background: Bipolar disorder (BPD) is a major psychiatric disorder with an unclear pathophysiology. Peripheral blood samples are easily drawn, making them are good candidates for diagnosing diseases. MicroRNAs are small non-coding RNA transcripts that regulate gene expression by binding to the 3'- UTR of mRNAs and directing their degradation. The aim of this study was to use blood plasma to investigate microRNA dysregulations in bipolar manic and euthymic patients., Subjects and Methods: Blood samples were collected from 58 patients with bipolar I disorder (19 manic, 39 euthymic) and 51 healthy controls., Results: Four microRNAs (miR-29a-3p, p = 0.035; miR-106b-5p, p = 0.014; miR-107, p = 0.011; and miR-125a-3p, p = 0.014) were upregulated in the entire bipolar group, compared to the healthy controls. Seven microRNAs (miR-9-5p, p = 0.032; miR-29a-3p, p = 0.001; miR-106a-5p, p = 0.034; miR-106b-5p, p = 0.003; miR-107, p < 0.001; miR-125a-3p, p = 0.016; and miR-125b-5p, p = 0.004) were more upregulated in bipolar manic patients compared to the healthy controls, and two microRNAs (miR-106a-5p, p = 0.013, and miR-107, p = 0.021) showed statistically significant upregulation in the manic patients compared to the euthymic patients., Conclusions: Our results showed greater miRNA dysregulation in the manic patients than in the euthymic patients. Two microRNAs could be more selective for bipolar manic episodes. Future studies should include depressive patients along with euthymic and manic patients., (Copyright © 2019. Published by Elsevier B.V.)

Aim: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL)., Materials and Methods: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs 2DL1-4 and 2DS1-5 genes using polymerase chain reaction with sequence-specific primers., Results: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene-gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes., Conclusion: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases.

Background: Polycythemia vera (PV) and essential thrombocytosis (ET) are hematological disorders characterized by excessive production of mature and functional blood cells. These cellular disorders are thought to be associated with impaired apoptosis, which is one of the major cellular death mechanisms in hematopoietic cells., Objectives: In this study, our objective was to examine the association between potential polymorphisms of the Bcl 2, Bax, Fas and Fas Ligand genes involved in apoptosis and the occurrence of PV and ET., Material and Methods: A total of 93 patients diagnosed with PV (n = 38) or ET (n = 55) at the Department of Hematology were included in this study, and 93 healthy individuals served as controls. DNA isolation was performed in blood samples obtained from both groups of subjects to determine the Bcl 2, Bax, Fas, and Fas L genotypes using the real-time PCR method., Results: No statistically significant differences between controls and patients were found in terms of Fas -670 G > A (rs1800682), Fas -1377 G > A (rs2234767), Fas L IVS2 -124 A > G (rs5030772), Bax -248 G > A (rs4645878) and Bcl 2 -938 C > A (rs2279115) polymorphisms, genotypes, and allele frequency (p > 0.05)., Conclusions: The results show that polymorphisms in the Bcl 2, Bax, Fas, and Fas Ligand genes involved in the apoptotic pathways may not play a role in the pathogenesis of PV and ET.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent complex psychiatric disorders in children as well as adults. ADHD impacts not only the affected individuals but also their families and social and professional networks. The clinical and diagnostic criteria for ADHD remain imprecise, in part, due to lack of robust biomarkers. ADHD comprises multiple subsets of diseases that present a shared set of downstream clinical findings, while displaying extensive molecular heterogeneity. This calls for innovation in diagnostic strategies that can help establish an ADHD diagnosis unequivocally as well as guiding precision medicine in this common mental health disorder. No study has examined, to the best of our knowledge, the upstream regulation of miRNAs that impact the downstream final ADHD phenotype. The latter focus on putative genetic biomarkers that regulate the regulators and can be tested empirically, for example, through genetic association analyses of the biogenesis pathways for miRNAs that impact the ADHD phenotype. Hence, we report here polymorphic variation in 10 miRNA biogenesis pathway candidate genes, including RNASEN, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, and GEMIN4, in a large sample from the Eastern Mediterranean region (N = 355; 191 cases and 164 controls). We found that AGO1 rs595961 was significantly associated with ADHD susceptibility (p < 0.05). While polymorphic variation in other miRNA biogenesis pathway genes did not display a significant association in the present sample, the observations reported herein on miRNA biogenesis variation offer a new avenue of research for innovation in biomarker discovery concerning ADHD and other complex psychiatric diseases with major global health burden.

Objective: The prevalence of schizophrenia is 1%, and it is a debilitating disorder that often results in a shortened lifespan. Peripheral blood samples are good candidates to investigate because they can be easily drawn, and they are widely studied in psychiatric disorders. MicroRNAs are small non-coding RNA transcripts. They regulate the expression of genes by binding to the 3'-untranslated region (UTR) of mRNAs and pointing them to degrade. In this study, we aimed to investigate the expression of miR-9-5p, miR-29a-3p, miR-106-5p, miR-106b-5p, miR-107, miR-125a-3p, and miR-125b-3p in schizophrenia patients and healthy controls., Methods: We collected blood samples from 16 patients with schizophrenia and 16 healthy controls. MicroRNAs were measured with reverse transcriptase polymerase chain reaction., Results: Schizophrenia patients showed statistically significant upregulation of five microRNAs: miR9-5p (p=0.002), miR29a-3p (p＜0.001), miR106b-5p (p=0.002), miR125a-3p (p＜0.001), and miR125b-3p (p=0.018)., Conclusion: Our results increased the value of the miR106 and miR29 families as potentially and consistently dysregulated in psychiatric disorders. Our results should be considered preliminary, and they need confirmation in future studies with larger sample sizes.

Purpose: MicroRNAs (miRNA) play a paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. However, their interaction with radiofrequencies is still unknown. The aim of this study was to investigate the long-term effects of radiofrequency radiation emitted from a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue., Materials and Methods: The study was carried out on 16 Wistar Albino adult male rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8). Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation for 24 hours a day for 12 months (one year). The same procedure was applied to the rats in the sham group except the Wi-Fi system was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in detail., Results: The results revealed that long-term exposure of 2.4 GHz Wi-Fi radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p* = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3 times and miR- 106b-5p expression is 3.65 times lower in the exposure group than in the control group. However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in brain were not altered., Conclusion: Long-term exposure of 2.4 GHz RF may lead to adverse effects such as neurodegenerative diseases originated from the alteration of some miRNA expression and more studies should be devoted to the effects of RF radiation on miRNA expression levels.

Aims: Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase (MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A (rs2236225), reduced folate carrier (RFC1) A80G (rs1051266), and cystathionine β-synthase (CBS) 844ins68., Results: The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring (p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS (p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant., Conclusion: Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies.

Purpose: We still do not have any information on the interaction between radiofrequency radiation (RF) and miRNA, which play paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. The purpose of this study was to bridge this gap by investigating effects of long-term 900 MHz mobile phone exposure on some of the miRNA in brain tissue., Materials and Methods: The study was carried out on 14 Wistar Albino adult male rats by dividing them into two groups: Sham (n = 7) and exposure (n = 7). Rats in the exposure group were exposed to 900 MHz RF radiation for 3 h per day (7 days a week) for 12 months (one year). The same procedure was applied to the rats in the sham group except the generator was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106b-5p, rno-miR-107 and rno-miR-125a-3p in brain were investigated in detail., Results: Results revealed that long-term exposure of 900 MHz RF radiation only decreased rno-miR107 (adjP* = 0.045) value where the whole body (rms) SAR value was 0.0369 W/kg. However, our results indicated that other microRNA evaluated in this study was not altered by 900 MHz RF radiation., Conclusion: 900 MHz RF radiation can alter some of the miRNA, which, in turn, may lead to adverse effects. Therefore, further studies should be performed.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood disorders, although disorders etiology and pathogenesis remains unknown, several theories about ADHD development have been proposed and many researchers believe that it is caused by both genetic and environmental factors. In this study we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p and miR155a-5p levels in child and adolescent ADHD patients. The research sample consisted a group of 52 ADHD patients, and 52 healthy volunteer controls. There was no significant difference in age and sex between the two groups (p>0.05). miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107 levels were statistically significantly decreased in ADHD patients(p<0.05). miRNA 155a-5p levels were increased in patients group (p<0.05). The positive predictive value (PPV) and negative predictive value of miR107 was estimated for the cutoff point of 0.4480. PPV was 70% and NPV was 86.5% for the taken cut off point. There could be a close relationship between levels of circulating miRNAs and ADHD. If we could understand how the signaling pathways arranged by miRNAs, impact on CNS development, function and pathology this can improve our knowledge about ADHD etiology and treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the interaction of treatment-related hemodynamic changes with genotype status for Synaptosomal associated protein 25 (SNAP-25) gene in participants with attention deficit hyperactivity disorder (ADHD) on and off single dose short-acting methylphenidate treatment with functional near-infrared spectroscopy (fNIRS)., Method: A total of 15 right-handed adults and 16 right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten milligrams of short-acting methylphenidate was administered in a crossover design., Results: Participants with SNAP-25 DdeI T/T genotype had decreased right deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb] change. When the combinations of these genotypes were taken into account, the participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb]., Conclusions: These results suggested that SNAP-25 polymorphism might be associated with methylphenidate induced brain hemodynamic changes in ADHD participants.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist., (2008 Wiley-Liss, Inc.)

The aim of this study is to evaluate the potential radioprotective effects of N-acetylcysteine (NAC) against genotoxicity and cytotoxicity. The effect of WR-2721, as a representative of clinically used radioprotector, was compared with that of NAC, using the chromosomal aberration (CA) and micronucleus (MN) test systems in the irradiated rat's femoral bone marrow cells. We also investigated the mitotic index (MI), and the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The rats (n = 16) were divided randomly and equally into four groups: Control (C), Radiation (R), R+NAC (received irradiation and 1000 mg/kg NAC) and R+WR-2721 (received irradiation and 200 mg/kg WR-2721) rats. All the irradiated groups received whole-body gamma irradiation as a single dose of 6 Gy. Group R showed higher CA and MN formation when compared to C. Group R showed higher frequency of MN formation when compared to both R+NAC and R+WR-2721. The mean MI and PCE/NCE ratios were lower in Group R when compared to those of Group C. The mean MI and PCE/NCE ratios of both R+NAC and R+WR-2721 groups were lower when compared to those of Group C. The MI in Group R was lower when compared to that of both R+NAC and R+WR-2721 groups. In this study, the results give clues about the beneficial effects of NAC against radiation-induced genotoxicity and cytotoxicity in rat bone marrow and its effect may be comparable to that observed for WR-2721.

In this study, the extent of measles outbreak was investigated in the Idil and Cizre counties of Sirnak Province. New cases determined in patients who applied to primary care clinics and those detected during home visits were evaluated. In 2001, a total of 2,143 cases reported in Sirnak Province were signified as a probable outbreak. Three hundred and thirty-three patients in Cizre and 219 patients in Idil applied to the primary care clinics. Of the cases, in Cizre 8.4% (n=28) and in Idil 6.4% (n=14) were infants aged nine months and younger who had not yet been vaccinated. Totally, 17 new cases (8 in Cizre and 9 in Idil) in the exanthema phase were determined during home visits and these were considered as outbreak cases. Virus isolation was achieved in 12 cases. All isolates were sent to the Centers for Disease Control (CDC) for genotyping and classified as D6 group. In conclusion, measles epidemics are still seen in our country. Therefore, measles outbreaks necessitate intensive intervention by physicians who are employed in primary health care services.