MicroRNA dysregulation in manic and euthymic patients with bipolar disorder.

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.

Effect of Maternal Depression on Brain-derived Neurotrophic Factor Levels in Fetal Cord Blood.

OBJECTIVE: : We aimed to assess the association between cord blood brain-derived neurotrophic factor (BDNF) concentration and maternal depression during pregnancy. METHODS: : A total of 48 pregnant women, admitted for elective caesarean section to Department of Obstetrics and Gynecology, The Konya Research and Training Hospital and Konya Necmettin Erbakan University Meram Medical Faculty, were included in this study. The study group included 23 women diagnosed as having depression during pregnancy and the control group included 25 pregnant women who did not experience depression during pregnancy. RESULTS: : The groups had similar sociodemographic characteristics. Cord blood BDNF concentration was significantly lower in babies born to mothers with major depression as compared with those in the control group. We didn’t find any correlation between the umbilical cord blood BDNF levels and BDI scores. CONCLUSION: : The results suggest that the existence of major depression in pregnant women may negatively affect fetal circulating BDNF levels.

Liraglutide for psychiatric disorders: clinical evidence and challenges.

Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

The Diagnostic Value of Malondialdehyde, Superoxide Dismutase and Catalase Activity in Drug Naïve, First Episode, Non-Smoker Generalized Anxiety Disorder Patients.

OBJECTIVE: Generalized anxiety disorder (GAD) is a common anxiety disorder. Although lots of research done to reveal neurobiological basis of GAD, it is still unclear. Diagnosis of GAD depends on subjective complaints of patients, thus the need for a biological marker is constantly emerging. In this study, we aimed to investigate diagnostic value of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in GAD. METHODS: We evaluated MDA, SOD, and CAT levels in peripheral blood of 46 patients and 45 controls. MDA was measured with Ohkawa's methods, SOD was measured with Fridovich method, and CAT was measured with Beutler's method. RESULTS: MDA was significantly increased in patients than controls, medians 4.05 nmol/mg and 1.71 nmol/mg respectively, p＜0.001; SOD and CAT activity was significantly decreased in patients than controls, medians of SOD were 159.07 U/mg and 301.87 U/mg, p＜0.001 respectively, medians for CAT were 138.47 U/mg and 160.60 U/mg respectively. We found high correlation between Hamilton Anxiety Rating Scale and SOD, MDA r values were 0.723 and 0.715 respectively, p＜0.001 for both. Receiver operator characteristic (ROC) curve analysis showed high diagnostic performance for MDA and SOD, low diagnostic performance for CAT, areas under curve were 1.0, 1.0, and 0.648 respectively. CONCLUSION: Our results reveal possible diagnostic value of MDA, less likely of SOD but not CAT. Future studies should investigate diagnostic value of oxidants and antioxidantn enzymes in larger samples and include diagnostic value of these parameters.

Peripheral Signatures of Psychiatric Disorders: MicroRNAs.

MicroRNAs (miRNAs) are 22 nucleotide long RNA transcripts, their synthesis starts in nucleus and continues in cytoplasm. As being critical for post-transcriptional regulators of gene expression they have been investigated in psychiatric disorders. There are numerous studies performed in peripheral tissues for psychiatric disorders. Here in this article, we aimed to review some common miRNAs denoted significant in at least two studies and their relevance to psychiatric research. We focused on miR-320, miR-106, miR-34, miR-223, miR-107, and miR-134.

Increased Serum G Protein-coupled Estrogen Receptor 1 Levels and Its Diagnostic Value in Drug Naïve Patients with Major Depressive Disorder.

OBJECTIVE: The facts that depression is more prevalent in females than in males and females are exposed to depression more commonly during certain hormonal fluctuating periods indicate the role of sex hormones in physiopathology. Estrogen acts over estrogen receptors alpha and beta and recently identified G protein-coupled estrogen receptor 1 (GPER1). The present study aimed, for the first time, to evaluate serum GPER1 levels in drug-naïve major depressive disorder (MDD) patients. METHODS: The study included 56 newly diagnosed drug-naïve MDD patients aged between 18 and 50 years and 42 age- and gender-matched healthy volunteers. Medical history was obtained and physical examinations, laboratory tests, and the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) were performed. The serum GPER1 levels were measured. RESULTS: The HAM-D score was significantly higher in the MDD patients than in the controls. The GPER1 level was significantly higher in the MDD patients than in the controls. A positive correlation was found with GPER1 levels and depression scores. The receiver operating characteristic analysis revealed sensitivity, specificity, positive predictive value, and negative predictive value as 82.1%, 90.5%, 92.0%, and 79.2%, respectively, for the presence of depression, when the serum GPER1 value was ≥0.16. CONCLUSION: This study demonstrated significantly higher serum GPER1 levels in the MDD patients than in the controls, a positive correlation was found between GPER1 levels and depression scores and serum GPER1 level was valuable in predicting the presence of depression.

Dose Dependent Course of Hyperprolactinemic and Normoprolactinemic Galactorrhea Induced by Venlafaxine.

Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used for the treatment of depression. We report a case of galactorrhea in a patient with major depressive disorder after starting treatment with venlafaxine. In particular, we discuss the course of hyper and normoprolactinemic galactorrhea. We managed this side effect initially by dose reduction and further by switching to essitalopram. Physicians should be aware of endocrinologic side effects such as galactorrhea during the serotonin and noradrenaline reuptake inhibitor treatment.

Tardive Dyskinesia Associated with Bupropion.

Present report describes a 46 year old male patient with a diagnosis of major depression who developed tardive dyskinesia during bupropion therapy. Our patient had no history of neuroleptic use and his laboratory and neurologic examinations were normal. He had no family history of neurologic diseases. Although bupropion induced dyskinesia has been previously reported in the literature, it is rare and our case is the first case regarding tardive dyskinesia.

Evaluation of Malondialdehyde, Superoxide Dismutase and Catalase Activity in Fetal Cord Blood of Depressed Mothers.

OBJECTIVE: The umbilical cord consists of two arteries and one vein and it functions in the transport between the maternal and fetal circulation. Biochemical analysis of fetal cord blood (FCB) during delivery could be beneficial in terms of understanding the fetal environment. In this study, we aimed to investigate oxidative parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in FCB during delivery. METHODS: We collected FCB samples during caesarean section. Our study included 33 depressed mothers and 37 healthy controls. We investigated MDA, SOD, and CAT levels in FCB samples. RESULTS: We found no significant difference between groups in terms of MDA (p=0.625), SOD (p=0.940), and CAT (p=0.413) levels. CONCLUSION: Our study reveals probable protective effects of the placenta from oxidative stress. Future studies should include larger samples.

Impact of aggression, depression, and anxiety levels on quality of life in epilepsy patients.

The aim of this study was to investigate the impact of aggression levels on the quality of life (QoL) of epilepsy patients. This study was conducted on 66 volunteer control subjects, who were matched by age and sex to the patient group, which consisted of 66 patients who applied to the Psychiatry and Neurology clinics for outpatient treatment, were aged between 18 years and 65 years, and were diagnosed with epilepsy. A sociodemographic and clinical data form designed by us was distributed among the study participants, along with Buss-Perry Aggression Scale, Beck Anxiety Scale, Beck Depression Scale, and the Quality of Life Scale Short Form (SF-36). Compared with the control group, the patient group displayed higher scores in all subgroups of Buss-Perry Aggression Scale subscales at a statistically significant level (P<0.05). As per the SF-36 questionnaire, physical functioning, physical role disability, general health perception, social functioning, mental health perception, and pain subscales were statistically lower in the patient group (P<0.05). Significant links between Beck Depression Scale and Beck Anxiety Scale levels, as well as some subscales of QoL and aggression levels, were also determined. In conclusion, epilepsy patients experienced impaired QoL compared with the healthy control group and their QoL was further impaired due to increased levels of anxiety, depression, and aggression.

Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment.

OBJECTIVE: Human serum paraoxonase (PON1) prevents lipids from peroxidation and functions as an antioxidant mechanism. Malonyldialdehyde (MDA) is the final product of lipid peroxidation and can be used as an indicator of oxidative stress. The aim of this study was to investigate PON1, MDA, and arylesterase (ARY) levels in schizophrenic patients who are taking typical, atypical, or combined (typical and atypical) antipsychotic drug treatment, with respect to those of healthy controls. METHODS: We evaluated 41 patients (11 taking typical antipsychotics, 19 taking atypical antipsychotics, 11 taking combined antipsychotics) and 43 healthy controls. RESULTS: MDA levels were higher in schizophrenic patients taking typical antipsychotics compared with healthy controls (p=0.001). ARY levels were higher in patients taking atypical antipsychotics compared with healthy controls (p=0.005). PON1 activity was similar in all groups. CONCLUSION: Our results indicate that treatment with typical antipsychotic drugs could be related to increased MDA levels; and antipsychotic medication may increase PON1 levels in schizophrenic patients.

Arterial Stiffness in Patients Taking Second-generation Antipsychotics.

OBJECTIVE: That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. METHODS: Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. RESULTS: Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). CONCLUSION: This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients.

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case-control study.

Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1ß, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5' nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21-0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06-69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility.

Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine.

Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case-control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5'-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523-0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117-2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140-2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.

Investigation of Dysregulation of Several MicroRNAs in Peripheral Blood of Schizophrenia Patients.

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.

Serum levels of G protein-coupled estrogen receptor 1 (GPER1) in drug-naive patients with generalized anxiety disorder.

Sex hormones, particularly estrogen, are suggested to play a role in the physiopathology of generalized anxiety disorder (GAD). Estrogen functions through the estrogen receptors alpha and beta and the recently discovered G protein-coupled estrogen receptor 1 (GPER1). This study aimed, for the first time, to evaluate serum GPER1 levels in drug-naive patients with GAD. This study included 40 newly diagnosed drug-naive patients with GAD aged between 18 and 50 years and 40 age- and gender-matched healthy controls. Medical histories were obtained, and physical examinations and laboratory tests were conducted; the Hamilton Anxiety Rating Scale (HAM-A) was also used for all participants. Serum GPER1 levels were measured. The serum GPER1 level was significantly higher in the patients with GAD than in the controls. A positive significant correlation was observed between the GPER1 level and the HAM-A score. The receiver operating characteristic analysis revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 85.0%, 82.5%, 82.9%, and 84.6%, respectively, for the presence of anxiety when the serum GPER1 value was ≥0.14 (the area under the curve was 0.904.). In conclusion, this study demonstrated that GPER1 levels were associated with the anxiety levels of patients, and that the serum GPER1 level was a valuable predictor of the presence of anxiety independent of gender.

Depression in pregnancy is associated with decreased glutathione peroxidase activity in fetal cord blood.

The investigation of fetal cord blood (FCB) during child delivery has created a novel topic in the field of psychiatric research. The umbilical vein receives nutrients and oxygen from the mother's circulation and transports them to the fetal circulation. Investigating fetal cord blood during delivery is beneficial for understanding the fetal environment. Depression in pregnancy is associated with medical and emotional burdens. In this study, we aimed to investigate glutathione peroxidase (Gpx) and myeloperoxidase (MPO) activity in the FCB of depressed mothers and healthy controls. Our study included 45 depressed mothers and 59 healthy controls. The FCB samples were collected from the umbilical vein during delivery. We found that Gpx levels were significantly decreased in the FCB of depressed mothers than healthy controls, medians were 0.14 U/ml and 0.16 U/ml respectively, Z: -3.567 and p < 0.001. MPO levels were similar in both groups, medians were 1.0 U/L and 1.2 U/L respectively, Z: -1.837 and p:0.066. Depression in pregnancy may be associated with decreased antioxidant levels, and this condition may cause an oxidative load, which may lead to improper brain development. Future studies should be performed in larger samples to clarify our preliminary results.

Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.

Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms and haplotype GTTT (BsmI/TaqI/FokI/ApaI) are associated with an increased risk of ASD. Our findings support the hypothesis that 25(OH)D is involved in the pathophysiology of autism and that serum 25(OH)D levels may be affected by FokI polymorphisms in children with ASD. Our results should be considered as preliminary and needs confirmation by future studies.