Mehmet Akif Camkurt

Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls

Major depression is the most common psychiatric disorder. The diagnosis of depression depends on a patients subjective complaints, and the nature of the heterogeneous disorder. Thus, there is no known biomarker for depression to date. Previous research has indicated that microRNAs are dysregulated in bipolar disorder and schizophrenia. We aimed to investigate microRNA dysregulation in plasma samples of patients with major depression. Venous blood samples of 50 depressed patients and 41 healthy controls were collected and the quantification of microRNAs was established using qRT-PCR. We found miR-320a significantly downregulated and miR-451a significantly upregulated in depressed patients. We also found miR-17-5p and miR-223-3p upregulated, but not as significantly as miR-451a. Merging our results with previous published data shows that the blood miR-320 family may be a potential microRNA family dysregulated in major depression. Research should be performed on miR-320-related pathways and their relationship to depression. Additionally, miR-451a could serve as a candidate biomarker for depression based on the acting mechanism of ketamine. Studies targeting miR-451a levels before and after treatment could be helpful.

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.

Diagnostic performance of increased prolidase activity in schizophrenia.

We investigated whether prolidase activity has a diagnostic test value in schizophrenia and assessed the relation between prolidase activity and sociodemographic-clinical characteristics of patients with schizophrenia. Fifty patients with schizophrenia (diagnosed as schizophrenia according to DSM-V criteria) and 50 healthy volunteers were included in this study. Case and control groups had a similar distribution in age, sex, body mass index (BMI), and smoking status. Serum prolidase activity was measured in both groups and was determined to be significantly higher in the patient group (509.706±41.918) compared to the control group (335.4±13.6; t=6.231; p=0.0001). A cut-off point of 392.65U/L prolidase was determined for diagnostic measures from the plotted ROC curve. The area under the ROC curve was 1.000, which was significant (p<0.0001). Higher values were assigned as the disease state. Both positive predictive value (PPV) and negative predictive value (NPV) were 100% at the cut-off point of 392.650U/L. The prolidase levels of the control group were all below the cut-off point. There were no statistically significant differences between the two groups with regard to age, gender, or BMI (p>0.05), and no correlation was found between mean prolidase activity and age of onset of the disease, family history, disease duration, number of hospitalizations, subtypes of schizophrenia, PANSS scores or sub-scores, CGI-S scores, S-A scale scores, and the antipsychotic treatment (p>0.05). The results of this study indicate that serum prolidase activity may be a useful diagnostic test for schizophrenia; however, further studies are needed to verify this.

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.

Probable preventive effects of placenta from oxidative stress; Evaluation of total antioxidant status, total oxidant status and oxidative stress index in fetal cord blood during the delivery.

Depression in pregnancy may have negative effects on birth outcomes. It may also effect the intrauterine environment of the fetus. The umbilical cord is the conduit between the fetus and placenta, and functions in the transport between fetus and mother. Investigating biochemical parameters in fetal cord blood (FCB) during delivery may be helpful to understanding to what the fetus is exposed to, at least in the last trimester. In this study, we aimed to investigate total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in the FCB of depressed mothers and healthy controls during delivery. Our study included 33 depressed mothers and 37 healthy controls. TAS, TOS, and OSI were measured according to Erels method. We found that TAS, TOS, and OSI levels were similar in patients and healthy controls; however, the birth weights of depressed patients were significantly lower than those of healthy controls. Our results suggest that the placental barrier may prevent from oxidative stress. Future studies should include blood samples collected simultaneously from mothers during delivery.

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.

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.