Şeref Şimşek

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.

Oxidative Stress and DNA Damage in Untreated First-Episode Psychosis in Adolescents.

Objective: Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents. Methods: This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM-IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined using the ELISA method and commercial ELISA kits. Results: The mean age was 14.5 ± 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 ± 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05). Conclusions: This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia.

Examining the levels of BDNF and cortisol in children and adolescent victims of sexual abuse—a preliminary study

BACKGROUND Previous reports have suggested the biological and psychological effects of trauma induced by cortisol and brain-derived neurotrophic factor (BDNF). The present study compared the levels of BDNF, cortisol, and adrenocorticotropic hormone (ACTH) in children and adolescent victims of sexual abuse to those without a trauma history. METHODS The study was conducted in the Department of Child Psychiatry at Dicle University. The study included 44 children (M/F: 12/32) aged between 8 and 17years who experienced sexual abuse with 42 age-and gender-matched children who did not have a history of trauma. Cortisol, ACTH, and BDNF levels were measured using ELISA. RESULTS Cortisol levels were higher and BDNF levels were significantly lower in the victims of sexual abuse compared to the control group. The mean time that elapsed from the initial sexual abuse occurrence until the date of examination was 22.7±21.7months. The evaluation of the relationship between this time span and cortisol levels revealed that cortisol levels decreased with increasing time after trauma. Cortisol and BDNF levels were lower in the victims who experienced multiple sexual assaults. CONCLUSIONS The results of the present study suggest that cortisol and BDNF could be biological molecular mediators of the effects of trauma on biological and psychological systems. This is the first report on the effects of cortisol and BDNF induced trauma in child and adolescent victims of sexual abuse.

Cortisol and Brain-Derived Neurotrophic Factor Levels Prior to Treatment in Children With Obsessive-Compulsive Disorder.

OBJECTIVE In this study, we investigated serum brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels between children with obsessive-compulsive disorder (OCD) prior to treatment and healthy controls. In addition, the study aimed to assess any correlations between OCD symptom severity and BDNF, ACTH, and cortisol levels. METHODS Twenty-nine children, aged from 7 to 17 years (male/female: 21/8) and diagnosed with OCD according to DSM-IV prior to treatment, were compared with 25 healthy control subjects (male/female: 16/9). The study was conducted between December 2012 and December 2013. The Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL), Childrens Yale-Brown Obsessive Compulsive Scale, and Childrens Depression Inventory (CDI) were administered to the children. BDNF, ACTH, and cortisol levels were detected using a prepared kit with the enzyme-linked immunosorbent assay method. RESULTS BDNF, ACTH, and cortisol levels in the OCD group were significantly higher when compared with the control group (P = .02, P = .03, and P = .046, respectively). No association was detected between the severity and duration of OCD symptoms and BDNF, ACTH, and cortisol levels. CDI scores in both groups were similar. The mean (SD) duration of OCD symptoms was 17.9 (18.5) months. CONCLUSIONS Our findings suggest that BDNF levels adaptively increase as a result of the damaging effects of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity on brain tissue in the early stages of OCD. HPA axis abnormalities and BDNF may play a role in the pathogenesis of the disease.

Serum cytokine profiles of Children with Obsessive-Compulsive Disorder shows the evidence of autoimmunity

Background: Previous reports have described an association between autoimmunity and primary obsessive compulsive disorder. This study aimed to investigate any differences in the levels of T helper 1, 2, and 17 effector cell cytokines between obsessive compulsive disorder patients and the control group. Methods: The study included 34 children (23 males, 11 females), aged between 7 and 17 years, with a diagnosis of obsessive compulsive disorder prior to receiving treatment. The control group consisted of age- and gender-matched children. Study participants were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, Children’s Yale Brown Obsession Compulsion Scale, and Children’s Depression Inventory. Cytokine serum concentrations were measured using the BD Cytometric Bead Array Human Th1/Th2/Th17 Cytokine Kit. Results: Interleukin-17A, tumor necrosis factor-α, and interleukin-2 levels were significantly higher in obsessive compulsive disorder patients, However, there was no correlation between T helper 1 and 17 cytokine profiles in the obsessive compulsive disorder group. The duration and severity of obsessive compulsive disorder symptoms were not significantly associated with interleukin-17A, interferon-gamma-γ, interleukin-10, interleukin-6, interleukin-4, and interleukin-2 levels. Interestingly, a negative correlation was found between tumor necrosis factor-α levels and Clinical Global Impression scores. Conclusions: These findings suggest, in some cases, obsessive compulsive disorder may develop on a background of autoimmunity, and interleukin-2, tumor necrosis factor-α, and interleukin-17A may play a role in these autoimmune processes. Therefore, we believe it is important to investigate for obsessive compulsive disorder symptoms in patients with autoimmune disease and, conversely, autoimmune diseases in obsessive compulsive disorder patients.

DNA damage and antioxidants in treatment naïve children with obsessive–compulsive disorder

The current study aimed to investigate whether serum antioxidant levels and DNA damage differ between the children and adolescents with Obsessive Compulsive Disorder (OCD) and healthy controls. The study included 31 children (Male/Female, 22/9; age range 7-17 years), with treatment naïve OCD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) and 28 age- and gender-matched healthy control subjects. Childrens Yale Brown Obsession Compulsion Scale (CY-BOC) was applied to the children. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all measured by the enzyme-linked immunosorbent assay method. GPx, CoQ and 8-OHdG levels were found to be significantly higher in the OCD group, compared to the control group (p=0.010, p=0.034, p=0.010, respectively); however, no significant difference was found in the SOD levels between two groups (p=0.10). There were no correlations between the CY-BOC scores, depression scores, duration of the disease and biochemical parameters (p>0.05, for all). Children with OCD were found to have higher antioxidant levels and oxidative DNA damage. The findings of this study support the role of oxidative stress in the pathogenesis of OCD. In this regard, any possible effect of adding antioxidants to conventional treatment can be investigated.

Elevated levels of tissue plasminogen activator and E-selectin in male children with autism spectrum disorder

Although the etiopathology of autism spectrum disorder (ASD) is not clear, immune dysfunction has been proposed as a mechanism for the pathophysiology of ASD. The purpose of this study is to examine serum levels of tissue plasminogen activator (t‐PA) and some adhesion molecules in children with ASD that have not been investigated previously in detail. The study group included 35 male children aged from 2 to 9 diagnosed with ASD according to DSM‐V criteria. Soluble platelet endothelial adhesion molecule‐1 (sPECAM‐1), P‐selectin, E‐selectin, and t‐PA in the serum were determined with enzyme‐linked immunosorbent assay. Autism behavior check list (ABC) is used for the assessment of ASD severity. The levels of t‐PA (P = 0.025) and E‐selectin (P = 0.007) was detected significantly higher in children with ASD than control group. Serum levels of sPECAM‐1 showed statistically significant negative correlation with sensory, body and object‐use, language, social, and self‐help and total scores in the patient group (r = −0.349, P = 0.04; r = −0.411, P = 0.01; r = −0.412, P = 0.01; r = −0.417, P = 0.01, and r = −0.531, P < 0.01, respectively). Serum levels of P‐selectin levels showed statistically significant negative correlation with ABC total score in the patient group (r = −0.378, P = 0.03). It may be suggested that t‐PA, E‐selectin, P‐selectin, and sPECAM‐1 a crucial role in inflammatory conditions in children with ASD. Autism Res 2016, 9: 1241–1247.

Lower Brain-Derived Neurotropic Factor Levels in Untreated Adolescents With First-Episode Psychosis.

Objective Brain-derived neurotropic factor (BDNF) is known to play a role in the pathogenesis of schizophrenia. However, the relationship between early onset schizophrenia and BDNF has not been extensively studied. The aim of the study was to compare the levels of BDNF between adolescent patients with first-episode psychosis (FEP) and the healthy control subjects. Method The study was conducted in the Department of Child Psychiatry at Dicle University. A total of 26 adolescent patients aged between 11 and 17 years who had not received previous therapy and whose conditions were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and 26 age- and sex-matched healthy adolescent control subjects were included. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and the Positive and Negative Symptom Scale were conducted with all participants. The clinical global impression was used to evaluate disease severity. The BDNF levels were measured in the serum by enzyme-linked immunosorbent assay method. Results The mean (SD) age was 14.6 (1.6) years in both FEP group (male/female, 11/15) and the control group (P > 0.05). The FEP group had significantly lower serum BDNF levels (2.0 ± 1.9 ng/mL) compared with the control group (3.4 ± 3.0 ng/mL, P = 0.03). There was no significant relationship between BDNF concentration and the Positive and Negative Symptom Scale (positive and negative scores) scores (r = −0.14, P = 0.74 and r = 0.49, P = 0.22, respectively). There was no significant relationship between the duration of untreated psychosis and serum BDNF levels (r = −0.22, P = 0.32). Conclusions High incidence of schizophrenia in patients with FEP suggests a relationship between BDNF levels and the pathogenesis of schizophrenia. We suggest that BDNF may be a useful neurobiological marker of early onset schizophrenia.

Cortisol and ACTH levels in drug-naive adolescents with first-episode early onset schizophrenia

The aim of this study was to investigate serum levels of cortisol and adrenocorticotropic hormone in adolescents with first‐episode early onset schizophrenia. A total of 23 adolescent patients, who did not receive prior therapy and who were diagnosed with psychosis according to DSM‐IV, were included. Kiddie‐Schedule for Affective Disorders and Schizophrenia‐Present and Lifetime Version, Positive and Negative Symptom Scale, and Clinical Global Impression Scale were conducted with the participants. No significant differences were found between the patients and the control subjects in serum cortisol and adrenocorticotropic hormone levels (P > .05). Our studys findings do not support the hypothesis of increased hypothalamic‐pituitary‐adrenal axis activity in first‐episode early onset schizophrenia.

The Levels of Cortisol and Oxidative Stress and DNA Damage in Child and Adolescent Victims of Sexual Abuse with or without Post-Traumatic Stress Disorder

Objective The aim of this study was to investigate whether cortisol and oxidative stress levels and DNA damage differ between individuals who developed PTSD or not following a sexual trauma. Methods The study included 61 children aged between 5 and 17 years who sustained sexual abuse (M/F: 18/43). The patients were divided into two groups: patients with PTSD and patients without PTSD based, based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Cortisol, glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q, 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all evaluated by the ELISA method. Results Our evaluation revealed a diagnosis of PTSD in 51% (n=31) of victims. There was no significant difference between the groups with or without PTSD in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels. There was no correlation between CAPS scores and GPx, SOD, coenzyme Q, and 8-OHdG levels between patients with or without PTSD. In patients with PTSD, both cortisol and 8-OHdG levels decreased with increasing time after trauma, and there was no significant correlation with cortisol and 8-OHdG levels in patients without PTSD. Conclusion Although the present study did not find any difference between the groups in terms of 8-OHdG concentrations, the decreases in both cortisol and 8-OHdG levels with increasing time after trauma is considered to indicate a relationship between cortisol and DNA damage.