The inconsistent results about cortisol levels in individuals with autism spectrum disorder (ASD) may be suggestive of other factors like gene polymorphisms rather than the disorder itself. We aimed to investigate the rs1360780 polymorphism in the FK506 binding protein 5 (FKBP5) gene and its relation to ASD and cortisol levels. Eighty-nine children with ASD ranging in age from two to fifteen years were selected for the study group, and eighty-six healthy children were selected for the control group. Blood samples were collected between 10 and 12 am in the morning. Enzyme linked immunosorbent assay and polymerase chain reaction were used to assay serum cortisol levels and genotyping, respectively. The mean cortisol levels for the study and the control groups were 8.5±3.6 μg/dL and 6.1±3.5 μg/dL, respectively. Cortisol levels were significantly higher in the study group compared to the control group (p<0.001). There was no statistically significant difference in terms of allele and genotype frequencies between the groups (p>0.05). Carrying the C allele was found possibly to increase the cortisol levels in the study group. This is the first clinical study to evaluate the association between rs1360780 polymorphism in the FKBP5 gene and serum cortisol levels in children with ASD compared to those of healthy participants. Since the prevalence of ASD is gradually increasing in recent years, possible endocrine and related genetic factors should be borne in mind while examining this population.

Objective: The goal of our study is to determine the level of Internet addiction (IA) in adolescents by utilizing the IA scale. Methods: We employed two tools: the IA test (IAT) and the beck depression inventory (BDI), complemented by a sociodemographic information form, to assess IA and depression levels. Results: A total of 201 participants were included. A positive correlation was found between daily Internet usage time and IAT scores (r = 0.388, p < 0.001) and between BDI scores and IAT scores (r = 0.161, p = 0.013). Females had a lower mean IAT score (63.56 +/- 28.08) (p < 0.001). The BDI scores varied significantly across the groups (p = 0.004). The mean BDI scores were higher in the severe addiction group (13.53 +/- 7.15) compared to the moderate (11.04 +/- 6.62), mild (10.11 +/- 5.38), and normal usage groups (9.28 +/- 5.54). A significant difference was found in gender distribution across the groups (p = 0.001). The presence of suicidal ideation differed significantly across the groups (p = 0.002). The presence of depression showed a significant difference (p = 0.038). Conclusions: Our study reveals a significant correlation between increased Internet usage and heightened levels of IA and depression among adolescents, with notable gender differences in IA severity.

Objetivo: Determinar el nivel de adicción a internet en adolescentes utilizando una escala de adicción a internet. Método: Nuestro estudio involucró a 201 estudiantes con adicción a internet. Empleamos dos herramientas, la IAT (internet addiction test) y el BDI (beck depression inventory), que se complementaron con un formulario de información sociodemográfica, para evaluar los niveles de adicción a internet y de depresión. Resultados: Se encontró una correlación positiva entre el tiempo diario de uso de internet y las puntuaciones del IAT (r = 0.388; p < 0.001), así como entre las puntuaciones del BDI y del IAT (r = 0.161; p = 0.013). Las mujeres tuvieron una puntuación media más baja en el IAT (p < 0.001). Las puntuaciones del BDI variaron significativamente entre los grupos (p = 0.004). Las puntuaciones medias del BDI fueron más altas en el grupo de adicción grave en comparación con los grupos de adicción moderada y de uso normal. Se encontró una diferencia significativa en la distribución por sexo entre los grupos (p = 0.001). La presencia de ideación suicida difirió significativamente entre los grupos (p = 0.002). La presencia de depresión mostró una diferencia significativa (p = 0.038). Conclusiones: Nuestro estudio revela una correlación significativa entre mayor uso de internet y niveles elevados de adicción y depresión en adolescentes, con diferencias de sexo notables en la gravedad de la adicción.

Background and Objectives: It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2–3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods: Forty-three ASD children aged 2–9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results: The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD (p < 0.05), there was no significant difference (p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters (p > 0.05). Conclusions: We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD.

INTRODUCTION: Brain tissue continues to develop throughout childhood and during adolescence. Trauma experienced during these periods has been reported to have particularly serious consequences. With a few exceptions, most studies reported elevated cortisol levels in non-stressed circumstances in the child and adolescent victims of sexual abuse compared to controls1 . Prolonged exposure to elevated cortisol levels has been shown to cause an increase in reactive oxygen species (ROS) at the cellular level and increased oxidative stress2 . The aim of the present study was to evaluate cortisol levels, oxidative stress, and DNA damage in child and adolescent victims of sexual abuse versus healthy controls who did not have a history of trauma. MATERIALS AND METHODS: The study was conducted in the Department of Child Psychiatry at Dicle University. Study data were collected between May 2012 and November 2012. The study included a total of 38 children (10 males and 28 females) aged between 9 and 17 years who had experienced childhood sexual abuse and 38 age- and gender-matched children as the control group. Children who reached an intelligence score below 70 points, who had a significant neurological or medical disorder, who received oral contraceptives, had previous or current cortisol therapy or used vitamins, and those who had morbid obesity or active infection were excluded in order to prevent interference with the biochemical parameters. In addition, patients with a history of psychiatric disorder before the latest trauma and those with a history of alcohol or substance abuse were excluded from the CSA group. Parents of all participants signed consent forms regarding their voluntary participation in the study. Approval for the study was obtained from the Non-Interventional Clinical Research Ethics Committee at Dicle University Faculty of Medicine. Sociodemographic features of the participants were obtained and a clinical data form was completed. This was followed by the collection of 2 ml venous blood samples for biochemical tests. The blood samples were obtained in the morning between 10.00 and 12.00 am. Cortisol, glutathione peroxidase (GPx), Coenzyme Q, 8-Hydroxy-2- Deoxyguanosine (8-OHdG), and Superoxide dismutase (SOD) were tested using the ELISA method and commercial kits. The statistical analysis was performed using the SPSS 15.0 software package. RESULTS: The mean age was 13.4±2.5 years (range 9-17 years) among the victims of sexual abuse. In the control group, the mean age was 13.5±2.6 years (range 9-17 years). There were ten males and 28 females in the CSA and control groups. The duration of education was lower in the victims of CSA and their parents compared to the control group. The number of siblings was higher. There was no significant difference between the groups in terms of their family history of psychiatric disorder and smoking/substance abuse. There was also no significant difference between the groups in terms of age at menarche and menstrual cycle. Regarding the parameters related to sexual abuse, 61% (n=23) of the victims experienced sexual abuse involving penetration. Of those victims, 55% (n=21) experienced a single assault and 45% (n=17) experienced multiple assaults. Of the victims, 24% (n=9) experienced familial sexual abuse (incestuous) and 76% experienced sexual abuse committed by non-related persons. Cortisol levels were significantly higher in the CSA group compared to the control group (p<0.01). There was no significant difference between the groups in terms of the levels of oxidative stress parameters (GPx, SOD, and coenzyme Q). Likewise, 8-OHdG levels as an indicator of DNA oxidation were not significantly different between the groups (Table 2). The mean time elapsed since the first sexual abuse until the date of examination was 20.6±22.4 months (3-95 months). The evaluation of the relationship between this time span and cortisol levels revealed that cortisol levels decreased as the time interval increased (r=-0.279, p=0.04). Similarly, 8-OHdG level decreased as the time elapsed since the sexual abuse increased (r=-0.252. p=0.04). In the CSA group, there was no significant relationship between the sexual abuse involving penetration and the levels of GPx, SOD, coenzyme Q, and 8-OHdG. The coenzyme Q level was lower in the victims who sustained multiple assaults than the victims of a single assault (p=0.04). Cortisol and SOD levels were lower in the victims of familial sexual abuse (p=0.03 and p=0.04, respectively). DISCUSSION: Studies conducted during childhood and adolescence on the victims of CSA report elevated cortisol levels; conversely, when studies on CSA victims are conducted after a significant amount of time has elapsed, cortisol levels are reported lower. This decrease in cortisol levels over time is referred to as attenuation hypothesis3 . Consistent with the literature data, the present study reported higher cortisol levels in the CSA group. Furthermore, cortisol levels decreased as time since the sexual abuse increased. In the present study, there was no significant difference between the control group and CSA group in terms of oxidative stress and DNA damage. In a recent study, increased oxidative stress has been shown in rats that were exposed to stress. In another study, oxidative stress was suggested to play a critical role in the development and exacerbation of post-traumatic stress disorder (PTSD). Consistent with the current results, a study conducted on 14 patients with PTSD reported no significant difference in terms of GPx and SOD levels when compared to the control group4 . Both cortisol and 8-OHdG levels were found to be decreased as the time since sexual abuse increased. Although we did not find any difference between the groups in terms of 8-OHdG concentrations, this finding was considered to be a reflection of the relationship between cortisol and DNA damage. In addition, the decrease in cortisol levels over time was suggested to be reflective of an adaptive process preventing harmful effects of prolonged exposure to high cortisol levels on brain structures such as the hippocampus and frontal cortex5 . In conclusion, no significant difference was found in children and adolescents who experienced sexual trauma in terms of oxidative stress level and DNA damage. Furthermore, some factors related to the trauma, such as sexual abuse within the family and multiple assaults, were found to have affected the level of oxidative stress. Because this is the first study that has been conducted in child and adolescent victims of sexual abuse, longitudinal studies on a larger scale are needed to confirm the results of the current study.

INTRODUCTION: Previous studies of first-episode psychosis (FEP) have revealed widespread loss of cortical tissue. Although tissue loss occurs in all brain sites, ventricular enlargement and fronto-temporal tissue loss are less pronounced in FEP in contrast to chronic patients. These changes in tissue morphology are the first evidence for the disease. In a study involving 15 adolescent and young adult patients, those with FEP were found to have significantly lower plasma BDNF levels compared to healthy controls1 . In untreated patients with FEP, low hippocampal volume was correlated with low BDNF levels. The aim of the present study was to compare BDNF levels between adolescent patients with FEP and matched healthy controls. Furthermore, the present study evaluated the relationship between symptom severity and BDNF levels. MEDHODS: Study Sample: The study was conducted in the Department of Pediatric Psychiatry at Dicle University Training and Research Hospital. The study data were collected between February 2012 and February 2013. A total of 26 adolescent patients aged between 11 and 17 years who had not received prior therapy and who were diagnosed with psychosis according to the DSM 4 (acute psychosis, schizophreniform disorder) and 26 age- and gender-matched healthy adolescent control subjects aged between 11 and 17 years who did not have a medical or neurological disorder were included in the study. The parents of the patients provided informed consent for all study participants. The Non-interventional Clinical Research Ethics Committee at Dicle University Faculty of Medicine reviewed and approved the study protocol. Study Procedures: Sociodemographic features of the participants were recorded and a clinical data form was completed. A structured psychiatric interview (K-SADS-PL and PANSS) was conducted with the participants. The clinical global impression (CGI) was used to evaluate disease severity. Finally, a 2 ml venous blood sample was obtained for biochemical tests. Forms and Scales: Sociodemographic Data and Clinical Data Form: This form contains questions regarding age, gender, education level, as well as the age, education level and occupation of the parents, consanguinity between parents, number of siblings, birth order among siblings, history of psychiatric disorder among family members and relatives, family history of alcohol/substance abuse, height and weight. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (K-SADS-PL): The original scale was developed by Kaufman et al. This scale was adapted to the Turkish language by Gökler et al. in 2004. The K-SADS-PL is administered during an interview with the parents and children, and the final evaluation is performed using input from all data sources. The scale evaluates the presence of psychopathological conditions in children and adolescents. The Positive and Negative Symptom Scale (PANSS): This scale is a semi-structured interview tool developed by Kay et al. in 1987, and the scale was evaluated for its validity and reliability by Kostakoğlu et al. in 1999. The scale consists of 30 items evaluating positive and negative symptoms and providing information about the general psychopathological condition. The Clinical Global Impression Scale (CGI): The Clinical Global Impression Scale (CGI) is a standardized evaluation tool used to rate disease severity, disease course over time, and drug effects according to the clinical condition of the patient and the severity of side effects. CGI-I is rated on a 7-point scale from 1 (normal) to 7 (severe disease). Measurement of BDNF: The blood samples were collected into gel tubes between 09:00 and 12:00. After withdrawal, blood samples were left at room temperature for 15 minutes to facilitate clotting. Blood samples were centrifuged at 5000rpm for six minutes. The serum was transferred to 1.5ml polypropylene tubes and stored at -80ºC for later analysis. Mature BDNF was measured using a human BDNF ELISA Kit (Hangzhou Eastbiopharm CO. LTD China). To minimize assay variance, all BDNF measurements were conducted on the same day. All experiments were performed in duplicate. The tests were performed according to the manufacturer’s instructions. The optical density of each well was measured using an automated microplate reader. Statistical Analysis: All statistical analysis was performed using the SPSS 15.0 software package. A p value <0.05 was considered statistically significant. RESULTS: The mean age was 14.6±1.6 years among adolescents in the FEP group (range: 11-17 years; M/F: 11/15) and the mean age was 14.6±1.6 years in the control group (range: 11-17, M/F: 10/16). There was no significant difference between the groups in terms of age and gender, employment status of the parents, and family history of alcohol or substance abuse. Past medical history of the family members and first-degree relatives of ten patients in the FEP group was remarkable for psychiatric disorder, while there was no history of psychiatric disorder in the control group (p=0.01). The rate of consanguineous marriages was significantly higher in the FEP group relative to the control subjects (p=0.03). There was no significant difference between the groups in terms of smoking history. The education level of the participants, the age and education level of the parents, the number of siblings, the birth order among siblings, height, weight, and BMI values are presented in Table 1. The mean PANSS positive score was 20.6±7.4, the mean PANSS negative score was 29.0±9.9, and the mean PANSS general psychopathology score was 33.9±5.7. The mean CGI score was 4.7±0.9. The mean age at disease onset was 13.6±1.7 years. The mean duration of untreated psychosis was 14.6±15.2 months. The CGI score increased with increasing duration of untreated psychosis (r=0.48, p=0.04). The serum BDNF concentration was significantly lower in the patient group (p=0.03). There was no significant relationship between PANSS and CGI scores and serum BDNF. There was no significant relationship between the duration of untreated psychosis and BDNF levels. DISCUSSION: The most important finding of the current study is that adolescent patients with FEP had significantly lower serum BDNF levels compared to healthy controls. Our finding is consistent with reports regarding adult patients with FEP. It is widely accepted that schizophrenia is a neurodevelopmental disorder. It has been suggested that schizophrenia occurs as a result of profound synaptic and dendritic destruction in the adolescent period and the secondary development of abnormal connections. Previous studies have reported an association between decreased plasticity and neurogenesis in the hippocampus and decreased BDNF2 . In addition, changes in serum BDNF levels reflect abnormal functioning of the dopaminergic system, which results in both positive and negative psychotic symptoms in the first episode of psychosis. Another important finding is the absence of a significant relationship between disease symptoms, disease severity, and BDNF levels. The association between BDNF levels and positive and negative symptoms is controversial. Some studies have reported no significant correlation between BDNF levels and schizophrenia symptoms. Two studies demonstrated a negative correlation between BDNF levels and both positive and negative symptoms. Another study reported a negative correlation between serum BDNF and positive symptoms. One study found a positive correlation between BDNF levels and positive symptoms3 . In conclusion, the present study found lower BDNF levels among adolescent patients with FEP compared to healthy controls, and there was no relationship between clinical symptoms and BDNF levels. The diagnosis of schizophrenia in patients with first-episode psychosis during the follow-up period suggests a relationship between BDNF and the pathogenesis of schizophrenia. We propose that BDNF may be an important neurobiological marker for EOS. Large-scale, multi-center follow-up studies are required in order to generalize the findings of the present study, which was the first study to be conducted in adolescent patients.

INTRODUCTION: Among other effects, oxidative stress also impairs normal brain functions through the inhibition of neurogenesis, altering neuronal transmission, and inducing mitochondrial dysfunction1 . Human and animals studies demonstrated that oxidative stress is related to anxiety. In an animal model of PTSD, inflammation and oxidative stress were reported to play a critical role in the development and exacerbation of PTSD2 . There are also studies that did not report a significant difference between patients with PTSD and the control group in terms of oxidative stress3 . It was reported that oxidative stress could be a critical molecular linkage between the hypothalamic– pituitary–adrenal (HPA) axis dysfunction and mental disorders. It was also reported that the stress-induced increase in cortisol levels accelerates glucose metabolism and production of reactive oxygen species. The aim of the present study is to evaluate children and adolescents who develop PTSD after experiencing sexual abuse versus those who did not develop PTSD in terms of the level of oxidative stress and DNA damage. METHOD: Study Sample: The study was conducted in the Department of Child Psychiatry at Dicle University. The study data were collected between July 2013 and February 2014. A total of 61 children, aged between 5 and 17 years (18 males and 43 females), participated in the study. The patients were divided into two groups, patients with PTSD and patients without PTSD, based on the results of a structured psychiatric interview. Children who achieved an intelligence score below 70 points, those with a significant neurological or medical disorder, those who received oral contraceptives, previous or current cortisol therapy, vitamins, and those with morbid obesity or active infection were excluded from the study in order to prevent interference with the biochemical parameters. The parents provided informed consent in order for their children to participate in the study. Approval was obtained for the study from the Non-interventional Clinical Researches Ethics Committee at Dicle University Faculty of Medicine. Scales: Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL): The schedule (K-SADSPL) was originally developed by Kaufman et al. It was adapted to the Turkish language by Gökler et al. in 2004. K-SADS-PL is administered during an interview with the parents and children, and the final evaluation is performed using input from all data sources. Clinician-Administered Post-Traumatic Stress Disorder Scale for Children and Adolescents (CAPS-CA): CAPS-CA is a semi-structured interview developed to evaluate the frequency and severity of present and past PTSD in children and adolescents according to DSM-III and DSM-4 diagnostic criteria. It was adapted from the Clinician-Administered Post-Traumatic Stress Disorder Scale (CAPS) by Nader et al. in 1996. The scale evaluates 17 symptoms of post-traumatic stress disorder based on DSM-4 and eight items related to PTSD. It was adapted to the Turkish language by Karakaya et al. in 2007. The Children’s Depression Inventory (CDI): The Children’s Depression Inventory developed by Kovacs based on the Beck Depression scale was used in the study. However, questions specific to the childhood period such as school success and relationship with friends were added. The scale was adapted to the Turkish language by Öy and contains 27 items, each of which is scored as 0, 1, or 2 points depending on the severity of the symptom. Biochemical Analysis: The blood samples were obtained in the morning between 10:00 and 12:00 AM. Cortisol, glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q, 8-Hydroxy-2-Deoxyguanosine (8-OHdG) levels were evaluated using the ELISA method and ready-to-use ELISA kits. Statistical Analysis: The statistical analysis was performed using SPSS 15.0 software package. A p value< 0.05 was considered statistically significant. RESULTS: The mean age was 13.3±2.4 years (range: 5-17 years) among the victims of sexual abuse. Our evaluation revealed a diagnosis of PTSD in 51% (n=31) of victims. There was no significant difference between patients with or without PTSD in terms of gender, smoking status, and menstrual cycle, the latter being assessed for adolescent patients. There was also no significant difference between the groups in terms of age, age of the mother/father, and education level of the parents. Regarding the parameters related to sexual abuse, 48% (n=29) of the victims experienced sexual abuse involving penetration. Of the victims, 46% (n=28) experienced single assault and 54% (n=33) experienced multiple assaults. 21% (n=13) of victims experienced sexual abuse within the family (incestuous), and 79% (n=48) experienced sexual abuse committed by non-related persons. There was no significant difference between patients with or without PTSD in terms of relationship with the abuse and presence of penetration (p=0.34 and p=0.68, respectively). There was no significant difference between the groups with or without PTSD in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels (Table 1). Likewise, there was no significant difference between the groups with or without depression in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels (p=0.43, p=0.46, p=0.38, p=0.53, and p=0.48, respectively). There was no correlation between CAPS scores and GPx, SOD, coenzyme Q, and 8-OHdG levels between patients with or without PTSD. The mean time that elapsed since the first sexual abuse until the date of examination was 23.9±24.1 months (range: 1-115 months). In the PTSD group, cortisol levels decreased with increasing time after trauma, and there was no significant correlation with the cortisol levels in patients without PTSD (r=-0.46, p=0.01 and r=-0.07, p=0.73, respectively). Similarly, 8-OHdG levels in the PTSD group decreased with increasing time after trauma, and there was no significant correlation with 8-OHdG levels in patients without PTSD (r=-0.42, p=0.03 and r=-0.04, p=0.85, respectively). DISCUSSION: In the present study, there was no significant difference between patients with or without PTSD in terms of oxidative stress and DNA damage. Furthermore, no relationship was found between the severity of the symptoms of PTSD and oxidative stress and DNA damage. In their studies, Tezcan et al. and Čeprnja et al. did not report any association between PTSD and oxidative stress3 . However, healthy volunteers having no past history of trauma were selected as the control group in their study. In addition, the type of trauma in their study was different compared to the present study. In contrast to our findings, human and animal studies showed an association between oxidative stress and anxiety. In an animal model of PTSD, inflammation and oxidative stress were reported to play a critical role in the development and exacerbation of PTSD2 . In the present study, cortisol and 8-OHdG levels decreased with increasing time after trauma in the PTSD group. Although we did not find any difference between the groups in terms of 8-OHdG concentrations, this finding was considered to be a reflection of the relationship between cortisol and DNA damage. In conclusion, there was no significant difference between children and adolescents with or without PTSD after sexual abuse in terms of the level of oxidative stress and DNA damage. However, cortisol and 8-OHdG levels decreased with increasing time after trauma in the PTSD group. Although we did not find any difference between the groups in terms of 8-OHdG concentrations, this finding was considered to be a reflection of the relationship between cortisol and DNA damage. This is the first study conducted in this age group.

INTRODUCTION: Glucocorticoids act through glucocorticoid receptors (GR) found in high concentrations in the amygdala and the hippocampus. In GR-mediated molecular activation, the brain-derived neurotropic factor (BDNF)-mediated signal pathway is required for memory consolidation. BDNF expression in the central nervous system is modified by various brain traumas including stress, ischemia, epileptic seizures, and hypoglycemia. Glucocorticoids play a role in the regulation of BDNF. In the rat hippocampus, stimulation of mineralocorticoid receptors (MR) increases the level of BDNF, while stimulation of glucocorticoid receptors (GR) decreases the BDNF levels1 . As mentioned above, trauma affects growth factors and the HPA axis. There are limited studies in the literature that have investigated the relationship between cortisol and BDNF levels in child and adolescent victims of sexual abuse. The present study compares the levels of BDNF, cortisol, and ACTH between child and adolescent victims of sexual abuse with those who have no trauma history. METHOD: Study Sample: The study was conducted in the Department of Child Psychiatry at Dicle University. The study included a total of 44 children (M/F: 12/32) between the ages of 8 and 17 years who had experienced child sexual abuse and 42 age- and gender-matched children (M/F: 12/30) as control group. The study data were collected between December 2011 and April 2012. Children who achieved an intelligence score below 70 points, who had significant neurological or medical disorders, who received oral contraceptives, had previous or current cortisol therapy, vitamins, and those who showed morbid obesity or active infection were excluded in order to prevent interference with the biochemical parameters. The patients were evaluated by two psychiatrists. The parents provided informed consent in order for their children to participate in the study. Approval for the study was obtained from the Non-Interventional Clinical Research Ethics Committee at Dicle University Faculty of Medicine. Sociodemographic features of the participants were obtained and a clinical data form was completed. This was followed by collection of a 2 ml venous blood sample for biochemical tests. Sociodemographic Data and Clinical Data Form: This form included questions about age, gender, education level, age of the parents, number of siblings, history of psychiatric disorders or substance abuse in the relatives, height, weight, and body mass index (BMI), type of abuse, duration and frequency of abuse, relationship with the abuser, and abuse history. Biochemical Analysis: The blood samples were obtained in the morning between 10:00 and 12:00 AM. Cortisol, ACTH, and BDNF levels were evaluated using the ELISA. Statistical Analysis: The statistical analysis was performed using SPSS 15.0 software package. A p-value below 0.05 was considered statistically significant. RESULTS: The mean age was 13.1±2.7 years (range: 8-17 years) among the victims of sexual abuse. In the control group, the mean age was 13.8±2.9 years (range: 8-17 years). The sexual abuse group consisted of 12 males and 32 females, and the control group consisted of 12 males and 30 females. The duration of education was lower and the mean number of siblings was higher in the victims of sexual abuse and their parents compared to the control group (p=0.02, p0.05). There was no significant difference between the groups in terms of height, weight, and BMI (p>0.05). Regarding the parameters related to sexual abuse, 64% (n=28) of the victims had experienced sexual abuse involving penetration. Of the victims, 52% (n=23) had experienced a single assault and 48% (n=21) multiple assaults. 23% (n=10) had experienced sexual abuse within the family (incestuous) and 77% (n=34) sexual abuse committed by non-related persons. Of all cases, 82% (n=36) were smokers and 18% (n=8) were non-smokers. Cortisol levels were significantly higher in the sexual abuse group compared to the control group (p<0.001). Albeit statistically insignificant, ACTH levels were higher in the sexual abuse group compared to the control group (p=0.10). Consistent with these findings, the ACTH/Cortisol ratio was lower (p<0.001). BDNF levels were significantly lower in the sexual abuse group compared to the control group (p=0.04). The mean time that elapsed from the first sexual abuse until the date of examination was 22.72±21.72 months (range: 2-120 months). The evaluation of the relationship between this time span and cortisol levels revealed that cortisol levels decreased as this time interval increased (r=-0.271, p=0.03). In the sexual abuse group, there was no relationship between the presence of penetration and cortisol, ACTH, and BDNF levels. Cortisol and BDNF levels were lower in the victims of multiple sexual assaults (p=0.03 and p=0.04, respectively). Cortisol and ACTH levels were lower in the victims of sexual abuse within the family; however, BDNF did not show a significant difference (p=0.03, p=0.049, p=0.11). DISCUSSION: One of the most important findings of the present study was that high cortisol levels were observed in the sexual abuse group. Furthermore, cortisol levels decreased as time elapsed, while trauma increased. The majority of the studies conducted on child and adolescent victims of trauma were found to have elevated non-stress cortisol levels. However, a meta-analysis of retrospective studies in patients that experienced chronic stress was found them to have decreased non-stress cortisol levels. This decrease in cortisol levels over time is referred to as the “attenuation hypothesis”. The second most important finding of the present study was lower BDNF levels observed in the sexual abuse group. In human studies, BDNF levels were lower in depressed women who were survivors of childhood physical abuse. BDNF levels were also lower in bipolar patients who had a history of trauma in childhood. The inverse relationship between memory performance and childhood sexual abuse was found to be associated with apolipoprotein E gene alleles. There are studies that implicated BDNF in the relationship between trauma and schizophrenia, bipolar disorder, PTSD, and depression2 . In animal studies, stress was suggested to be associated with changes in the functions and structure of the hippocampus through decreased neurogenesis, increased glucocorticoids, and/or decreased BDNF. In general, studies conducted on patients with PTSD have found lower BDNF levels compared to the control group3 . There are also studies suggesting no change or even an increase in BDNF levels. In the sexual abuse group, the presence of penetration had no effect on cortisol and BDNF levels. However, both cortisol and BDNF levels were lower in victims that experienced multiple sexual assaults. Cortisol levels were lower in victims of sexual abuse within the family. The effects of stress on cognitive functions and psychopathological processes are related to gender, type of stress, frequency, controllability, and predictability. In conclusion, the present study found elevated cortisol levels and decreased BDNF levels in child and adolescent victims of sexual abuse. Interestingly, cortisol levels decreased with increasing time after trauma. Furthermore, some factors related to trauma such as sexual abuse within the family and multiple assaults were found to have affected cortisol and BDNF levels. The results of the present study suggest that cortisol and BDNF could be biological molecular mediators of trauma on biological and psychological systems. While this is the first report on the effects of cortisol and BDNF-induced trauma in child and adolescent victims of sexual abuse, longitudinal studies with larger samples size are required to validate the findings of the current study.

INTRODUCTION: Current evidence indicates the role of cortisol in psychosis; however, the relationship between psychological symptoms and cortisol is not clear. It has been reported that cortisol has an indirect effect on the pathophysiology of psychosis. Studies on untreated patients with first-episode psychosis have mostly found HPA axis hyperactivity. Brain maturation continues during adolescence and is vulnerable to stress1 . To our knowledge, there is no study that evaluated cortisol and ACTH levels in adolescent patients with FEP. The aim of the present study was to evaluate cortisol and ACTH levels as indicators of the HPA axis activity in adolescent patients who were included in the study with a diagnosis of FEP and diagnosed with EOS after a follow-up period of six months. Furthermore, the present study evaluated the presence of a relationship between psychosis symptom severity and cortisol and ACTH levels. METHOD: Study Sample: The study was conducted in the Department of Child Psychiatry at Dicle University. The study data were collected between March 2013 and January 2014. A total of 23 adolescent patients aged between 11-17 years, who did not receive prior therapy and who were diagnosed with psychosis according to DSM-4 criteria, and 23 age- and gender-matched healthy adolescent controls aged between 11-17 years, who did not have a medical or neurological disorder, were included in the study. The parents of the patients provided informed consent for their voluntary participation in the study. Approval was obtained for the study from the Non-interventional Clinical Research Ethics Committee at Dicle University Faculty of Medicine. Study Procedures: Sociodemographic features of the participants were obtained and a clinical data form was completed. A structured psychiatric interview (K-SADS-PL and PANSS) was conducted with the participants. The clinical global impression (CGI) scale was used to evaluate disease severity. Finally, a 2 ml venous blood sample was obtained for biochemical tests. Forms and Scales: Sociodemographic Data and Clinical Data Form: This form contains questions about age, gender, education level, and age, education level and occupation of the parents, consanguinity between parents, number of siblings, birth order among siblings, history of a psychiatric disorder in family members and relatives, family history of alcohol/substance abuse, height, and weight. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (K-SADS-PL): The original scale was developed by Kaufman et al. It was adapted to the Turkish language by Gökler et al. in 2004. K-SADS-PL is administered during an interview with the parents and children, and the final evaluation is performed using input from all data sources. The scale evaluates the presence of psychopathological conditions in children and adolescents. The Positive and Negative Symptom Scale (PANSS): This scale is a semi-structured interview tool developed by Kay et al. in 1987, evaluated for its validity and reliability by Kostakoğlu et al. in 1999. The scale consists of 30 items evaluating positive and negative symptoms and providing information about general status of psychopathological condition. The Clinical Global Impression Scale (CGI): The Clinical Global Impression Scale is a standardized evaluation tool used to rate disease severity, disease course over time, drug effects considering the clinical condition of the patient, and severity of side effects. CGI-I is rated on a 7-point scale from 1 (normal) to 7 (most severe patients). Biochemical Analysis: The blood samples were obtained in the morning between 09:00 and 12:00. The samples were collected in gel tubes. After withdrawal, blood samples were allowed to rest for 15 minutes for clotting. Then, blood samples were centrifuged at 5000 rpm for six minutes. The sera were transferred to 1.5 ml polypropylene tubes and stored at -80°C until analysis. Cortisol and ACTH levels were evaluated using the ELISA method and ready-to-use kits. Statistical Analysis: The statistical analysis was performed using SPSS 15.0 software package. A p value <0.05 was considered statistically significant. RESULTS: The mean age was 14.5±1.4 years among adolescents in the FEP group (range: 8-17 years; M/F: 11/15) and 14.7±1.5 years in the control group (range: 11-17, M/F: 8/15). There was no significant difference between the groups in terms of age and gender, employment status of the parents, and family history of alcohol or substance abuse. Past medical history of the family members and first-degree relatives of seven patients (30%) in the FEP group was remarkable for psychiatric disorders, while there was no history of psychiatric disorders in the control group (p=0.02). The rate of consanguineous marriages was significantly higher in the FEP group (p=0.02). In the FEP group, the rate of consanguineous marriage in the parents was higher among male patients (p=0.045). In addition, the history of psychiatric disorders in the family members and first-degree relatives was more common among male patients, although the difference was not statistically significant (p=0.20). There was no significant difference between the groups in terms of smoking. Education level of the participants in terms of years, age of the parents, number of siblings, and BMI values are presented in Table 1. There was no significant difference between the patients and the control group in terms of cortisol and ACTH levels. There was no significant relationship between PANSS and CGI scores and cortisol and ACTH levels. Cortisol and ACTH levels were significantly higher in male patients with FEP compared to male patients in the control group (p=0.04 and p=0.02, respectively). There was no difference in these measures in females. The data pertaining to biochemical analyzes are presented in Table 2. The clinical features of the patients in the FEP group are presented in Table 3. DISCUSSION: The most important finding of the present study is the detection of higher cortisol and ACTH levels in male patients with FEP. In addition, the rate of consanguineous marriage in the parents was higher in male patients, suggesting a genetic loading. The importance of the vulnerability-stress model increases in the etiology and pathogenesis of psychosis. According to this model, predisposing biological factors increase the vulnerability of an individual to stress and predispose to the development of psychosis under distressing environmental conditions. The increase in cortisol levels has been suggested to occur before disease onset and predispose to disease development. The patients with psychosis are also known to exhibit intolerance and sensitivity to stressful stimulations. Trauma sustained in early periods of life causes hippocampal damage, and this in turn causes increased sensitivity to the development of psychosis2 . There was no significant difference between the patients and the control group in terms of cortisol and ACTH levels. Of four studies that measured cortisol levels in the serum similar to our study, two found elevated cortisol levels in the FEP group, while the other two studies found no difference. Of seven studies that measured cortisol levels in the plasma, none found a significant difference. Cortisol levels were elevated in almost all patients above 29.5 years of age3 . Another finding of the present study is the lack of a significant relationship between psychosis symptom severity and cortisol and ACTH levels. Almost all studies having similar design to our study have failed to demonstrate a significant relationship. However, one study reported a negative correlation between plasma cortisol level and PANSS positive score, and another study reported a positive correlation between PANSS negative score and cortisol levels. In conclusion, although there was no significant difference between patients in the FEP group and healthy controls in terms of cortisol and ACTH levels, cortisol and ACTH levels were higher in male patients in the FEP group. In addition, the rate of consanguineous marriage was higher among the parents of patients with FEP. The increase in cortisol levels has been suggested to occur before disease onset and predispose to disease development. We consider that individuals with genetic loading regarding psychosis must be more closely monitored for the activity of the HPA axis.

Several studies demonstrated biological effects of cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) on human metabolism and central nervous system. Our study investigated the serum levels of tPA along with BDNF and cortisol in children with autism spectrum disorder (ASD). Thirty three male children with ASD ranging in age from 2 to 15 years were selected for the study group and 27 age-matched healthy male children were selected for the control group. The ASD severity was determined by the score on the Autism Behavior Checklist (ABC). The mean cortisol levels for the study group and the control group were 79.1 ± 30.2 ng/ml and 60.0 ± 25.1 ng/ml, respectively. The mean BDNF levels for the study group and the control group were 5.9 ± 2.8 ng/ml and 3.7 ± 1.8 ng/ml, respectively. The mean tPA levels for the study group and the control group were 32.9 ± 18.5 ng/ml and 25.5 ± 15.1 ng/ml, respectively. Cortisol, BDNF and tPA levels were significantly higher in the study group compared to the control group (p < 0.001). There was no statistically significant effect in terms of age, ABC total and subscale scores on serum cortisol, BDNF and tPA levels in the study group (p > 0.05). It may be suggested that elevations may indicate a role in the pathogenesis of ASD or it may be the case that ASD may alter the levels or pathways of these metabolic factors. LAY SUMMARY: The underlying mechanism or a specific metabolic target relevant to autism spectrum disorder (ASD) has not yet been identified. Cortisol, brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) have biological effects on neuroplasticity but little is known about the role of cortisol and tPA-BDNF pathway in ASD. In the present study focused on male children with ASD, we have found higher blood levels of cortisol, BDNF and tPA than their healthy peers. This is the first clinical study to evaluate the serum tPA levels along with BDNF and cortisol in ASD. The results suggest that several neurotrophic and other related markers should be born in mind while examining children with ASD.

INTRODUCTION: Cortisol levels decrease or show no change in PTSD, although there are some exceptional cases. In the model proposed by Yehuda, PTSD was associated with increased adrenergic response and/or lack of a sufficient amount of cortisol in the circulation following trauma. In general, studies conducted on patients with PTSD have found lower BDNF levels compared to the control groups. A study of patients with PTSD and healthy controls who did not have a history of trauma found lower BDNF levels in patients with PTSD1 . Another study compared BDNF levels between patients with or without PTSD after trauma and reported lower BDNF levels in patients with PTSD2 . To our knowledge, there are no studies in the literature that evaluated cortisol and BDNF levels in adolescent and child victims of sexual abuse. The aim of the present study was to compare BDNF, cortisol, and ACTH levels in a special group of patients comprised of children and adolescent patients with or without PTSD after experiencing sexual assault, which is a catastrophic form of trauma. METHOD: Study Sample: The study was conducted in the Department of Child Psychiatry at Dicle University. The study data were collected between January 2013 and May 2013. The study included 55 children aged between 6 and 17 years, 13 of which were males and 42 were females. The patients were divided into two groups, with or without PTSD, based on the results of a structured psychiatric interview. Children who had mental retardation, history of head trauma, and those who received oral contraceptives, previous or current cortisol therapy or vitamins, and patients who had morbid obesity, chronic systemic disorders, and active infection were excluded in order to prevent interference with biochemical parameters. Two psychiatrists evaluated the patients, and parents provided informed consent in order for their children to participate in the study. Approval was obtained for the study from the Non-Interventional Clinical Research Ethics Committee at Dicle University Faculty of Medicine. Study Procedures: Sociodemographic features of the participants were obtained and a clinical data form was completed. This was followed by a structured psychiatric interview (K-SADS-PL and CAPS-CA) and administration of the self-reported Children’s Depression Inventory (CDI). Finally, a 2 ml venous blood sample was obtained for biochemical tests. Scales: Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL): The schedule (K-SADSPL) was originally developed by Kaufman et al. It was adapted to the Turkish language by Gökler et al. in 2004. K-SADS-PL is administered during an interview with the parents and children, and the final evaluation is performed using input from all data sources. Clinician-Administered Post-Traumatic Stress Disorder Scale for Children and Adolescents (CAPS-CA): CAPS-CA is a semi-structured interview developed to evaluate the frequency and severity of present and past PTSD in children and adolescents according to DSM-III and DSM-4 diagnostic criteria. It was adapted from the Clinician-Administered Post-Traumatic Stress Disorder Scale (CAPS) by Nader et al. in 1996. The scale evaluates 17 symptoms of post-traumatic stress disorder based on DSM-4 and eight tables related to PTSD. It was adapted to the Turkish language by Karakaya et al. in 2007. The Children’s Depression Inventory (CDI): The Children’s Depression Inventory developed by Kovacs based on the Beck Depression scale was used in this study. However, questions specific to the childhood period such as school success and relationship with friends were added. The scale was adapted to the Turkish language by Öy and contains 27 items: Each item is scored as 0, 1, or 2 points depending on the severity of the symptom. Biochemical Analysis: Blood samples were obtained in the morning between 10:00 and 12:00 am. Cortisol, ACTH, and BDNF levels were evaluated using ELISA method and ready-to-use ELISA kits. Statistical Analysis: The statistical analysis was performed using SPSS 15.0 software package. A p-value below 0.05 was considered statistically significant. RESULTS: The mean age was 14.16±2.62 years (range: 6-17 years) among the victims of sexual abuse. Of these victims, 27 (49%) were diagnosed with PTSD. There was no significant difference between patients with or without PTSD in terms of gender, place of living, school success, employment status of the parents, smoking, and menstrual cycle for adolescents. Regarding the parameters related to sexual abuse, 60% (n=33) of the victims experienced sexual abuse involving penetration. Of the victims, 56% (n=31) experienced a single incident of assault and 44% (n=24) experienced multiple assaults. Of the victims, 24% (n=13) experienced sexual abuse within the family (incestuous) and 76% (n=42) experienced sexual abuse committed by non-related persons. There was no significant difference between patients with or without PTSD in terms of relationship with the abuse and presence of penetration (p=0.30 and p=0.70, respectively). However, the rate of PTSD was higher in patients who experienced multiple sexual assaults compared to the victims of a single assault (p<0.001). There was no significant difference between patients with or without PTSD in terms of cortisol, ACTH, and BDNF levels. Likewise, there was no significant difference between patients with or without depression in terms of cortisol, ACTH, and BDNF levels. There were no correlations between CAPS scores and cortisol, ACTH, and BDNF levels between patients with or without PTSD. The mean time that had elapsed since the first sexual abuse until the date of examination was 21.5±22.4 months (3-110 months). In the PTSD group, cortisol levels decreased with increasing time after trauma, and there was no significant correlation with the cortisol levels in patients without PTSD (r=-0.46, p=0.01 and r=-0.07, p=0.73, respectively). There was no correlation between time that had elapsed since trauma and BDNF levels. DISCUSSION: In the current study, the presence of PTSD had no influence on cortisol and ACTH levels in children who had experienced sexual abuse, and cortisol levels decreased with increasing time after trauma in the PTSD group. The studies conducted on patients with PTSD often reported increased levels of CRH in the CSF and a decrease or no change in cortisol levels. Plasma, saliva, and urinary cortisol and plasma ACTH levels were found to be similar between patients with or without PTSD after trauma. Plasma cortisol levels decreased in the two groups, and it was reported that cortisol levels did not predict the development of PTSD. There are findings suggesting that low cortisol levels after exposure to trauma might have increased the risk of developing PTSD. There are also studies suggesting that no relationship between cortisol levels and the development of PTSD exists. In the present study, cortisol levels decreased as the time elapsed since the trauma increased in the PTSD group. It is therefore assumed that these individuals will have lower than normal cortisol levels in adulthood. In the present study, presence of PTSD had no effect on BDNF levels in child victims of sexual abuse, and there was no correlation between BDNF levels and the time that had elapsed since the trauma. In general, studies conducted on patients with PTSD have found lower BDNF levels compared to the control group1,2. BDNF levels were compared between patients with or without PTSD after trauma, and BDNF levels were lower in patients with PTSD (2). In the study by Hauck et al., serum BDNF levels were higher in patients who experienced sexual assault in the last one year compared to the control group; however, BDNF levels did not differ significantly among those who experienced trauma beyond the last one year3 . In conclusion, there was no significant difference between children and adolescents with or without PTSD in terms of cortisol, ACTH, and BDNF levels. However, the decrease in cortisol levels with increasing time after trauma in PTSD group points to the possible role of cortisol in the pathophysiology of the disease. Longitudinal studies on a larger sample are required in order to confirm the findings of the current study that was conducted in children and adolescent patients.

INTRODUCTION: Oxidative stress has been implicated in the psychopathology of schizophrenia, with abnormal activity of antioxidant enzymes, decreased antioxidant levels and increased lipid peroxidation all being demonstrated in patients with schizophrenia1 . There are, however, discrepancies between studies. Studies of adolescents with First-Episode Psychosis (FEP) showed lower total antioxidant (TAS) and glutathione (GSH) levels, and a relationship has been suggested between GDH deficiency and the loss of cortical gray matter over two years2 . The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis in adolescents. Furthermore, the study investigates the presence of a relationship between the severity of psychotic symptoms and oxidative stress and DNA damage. METHOD: Study Sample: The study was conducted in the Department of Child Psychiatry at Dicle University, using data that was collected between February and November 2014. The study included 20 adolescent patients aged between 11 and 17 years, all of whom had been diagnosed with psychosis according to DSM-4 criteria and who had received no previous psychiatric therapy, as the patient group, and 20 age-matched healthy adolescents with no medical or neurological disorders as the control group. Patients with an intelligence score of less than 70 points, those with marked neurological and medical problems, taking oral contraceptives, having undergone previous or current cortisol therapy or taking vitamins, those with morbid obesity, active infections or a history of substance abuse within the last 6 months were excluded from the study due to possible interference with the biochemical parameters. The parents of the patients provided informed consent for all study participants. The study was reviewed and approved by the Non-Interventional Clinical Research Ethics Committee at Dicle University, issue date 13.02.2012, number 395. Study Procedures: The sociodemographic features of the participants were obtained and a clinical data form was completed. Structured psychiatric interviews were conducted with the patients (K-SADS-PL and PANSS), with the Clinical Global Impressions (CGI) scale used to evaluate disease severity. Finally, a 2 mL venous blood sample was obtained for biochemical tests. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL): This scale was originally developed by Kaufman et al. and was adapted into the Turkish language by Gökler et al. in 2004. K-SADS-PL is administered during an interview with the parents and the child, and the final evaluation is made using input from all data sources. Positive and Negative Symptom Scale (PANSS): This is a semi-structured interview tool developed by Kay et al. in 1987, evaluated for its reliability and validity by Kostakoğlu et al. in 1999. The scale consists of 30 items evaluating positive and negative symptoms and providing information about the general status of the psychopathological condition. Clinical Global Impression Scale (CGI): The Clinical Global Impression Scale is a standardized evaluation tool used to rate disease severity, disease course over time and drug effects, considering the clinical condition of the patient and the severity of side effects. CGI-I is rated on a 7-point scale from 1 (normal) to 7 (most severe patients). Biochemical Analysis: The blood samples were obtained in the morning between 09:00am and 12:00 noon and were collected into gel tubes. After withdrawal, the blood samples were allowed to rest for 15 minutes to clot, after which they were centrifuged at 5000rpm for 6 minutes. The sera were transferred to 1.5 mL polypropylene tubes and stored at -80°C until the analysis. GPx, SOD, CoQ and 8-OHdG levels were evaluated using the ELISA. Statistical Analysis: The statistical analysis was performed using the SPSS 15.0 software package. A p value < 0.05 was considered statistically significant. RESULTS: The mean age was 14.5±1.6 years in the FEP group (M/F: 8/12) and 14.4±1.5 years in the control group (M/F: 8/12). There was no difference between the groups in terms of age and gender, and no difference in terms of employment status of the parents and family history of alcohol and substance abuse. Of patients in the FEP group, eight (40%) had a history of psychiatric disorders in the immediate family and first-degree relatives, while no patient in the control group had such a family history (p<0.01). The rate of consanguineous marriage between the parents was significantly higher in the FEP group (p<0.01), while there was no difference between the groups in terms of smoking status. The mean PANSS positive score was 19.4±6.8, the mean PANSS negative score was 28.1±9.5, and the mean PANSS general psychopathology score was 31.6±5.5. The mean CGI score was 4.6±1.0, while the mean age of disease onset was 14.1±1.9 years. The mean duration of psychosis before treatment was 13.1±14.3 months. There was no difference between the patient and the control group in terms of SOD, GPx or 8-OHdG values; and no significant relationship was identified between the PANSS and CGI scores of the patient group and the SOD, GPx, CoQ and 8-OHdG values. DISCUSSION: One of the most important findings of the present study is the lack of any significant difference between patients with FEP and the healthy controls in terms of oxidative stress. Studies of both adolescent and adult patients with FEP have reported deficiencies mostly in antioxidant defense mechanisms (enzymatic, non-enzymatic) and have implicated oxidative stress in the pathophysiology of schizophrenia (particularly with regard to negative symptomatology and cognitive functioning). The study of 102 children and adolescents by Micó et al. reported a decrease in total antioxidant defense glutathione levels and an increase in GPx activity, catalase and SOD activity2 , while the study of 48 children and adolescents by Fraguas et al. found a relationship between the decrease in glutathione levels and the loss of cortical gray matter in two years1 . The study of 105 children and adolescents by Martínez-Cengotitabengoa et al. reported lower total antioxidant and glutathione levels and a direct relationship between antioxidant defense capacity and global cognition at baseline and after a two-year follow-up period. The present study of patients with EOS found no difference in terms of oxidative stress, and therefore does not support study results that suggest a role of oxidative stress in the psychopathology of schizophrenia. Studies of adult patients with schizophrenia reported changes in antioxidant enzyme levels, although there are discrepancies between studies. The GPx level was reported to be higher in a study of patients with first-episode schizophrenia, while another study reported lower GPx levels. The SOD level was reported to be lower in one study conducted of patients with treated and untreated schizophrenia, while another study reported higher SOD levels. Another important finding of the present study is the lack of difference between the groups in terms of DNA damage. To the best of our knowledge, there has been no study to date evaluating DNA damage in adolescent patients with FEP, although studies of adult patients with FEP and schizophrenia have reported increased DNA damage, and this finding was interpreted as a molecular connection between schizophrenia and an accelerated aging process. An increase in 8-OHdG levels, indicating oxidative DNA damage, and telomere shortening, indicating direct DNA damage, has in the past been reported in patients with schizophrenia. This finding was considered to be an indication of the lack of oxidative DNA damage in early disease periods in patients with EOS and for an association of DNA damage with a chronic disease course. In conclusion, there was no difference between the patients with FEP and the control group in terms of oxidative stress and DNA damage; and furthermore, no relationship was identified between symptom severity, oxidative stress, and DNA damage. Future studies should evaluate more comprehensively the factors that contribute to the development of oxidative stress, as the present study revealed no change in the levels of oxidative stress in the early periods of disease, and there are studies that have reported higher oxidative stress in later disease stages.

The inconsistent results about cortisol levels in individuals with autism spectrum disorder (ASD) may be suggestive of other factors like gen polymorphisms rather than the disorder itself. So we aimed to investigate the rs1360780 polymorphism in FK506 binding protein 5 (FKBP5) gene and its relation to ASD and cortisol levels comparing with that of healthy participants. We have included two main groups as study and control groups in the present study. Eighty nine children with ASD ranging in age from 2 to 15 years were selected for the study group and age-matched 86 healthy children were selected for the control group. Cortisol levels were found to be significantly higher in the study group. However there was no statistically significant difference in terms of allele and genotype frequencies between the groups. Carrying the C allele of FKBP5 seems to increase the cortisol levels in the study group. This is the first clinical study to evaluate the association between rs1360780 polymorphism in FKBP5 gene and serum cortisol levels in children with ASD. Since the prevalence of ASD is gradually increasing in recent years, several endocrine and related genetic factors should be born in mind while examining this population.

Abstract Introductıon We aimed to determine the serum levels of transactive response of DNA-binding protein 43 (TDP-43) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), which are ubiquitin-proteasome pathway related molecules and have not been investigated so far, in children with attention-deficit/hyperactivity disorder (ADHD). Methods The study group was composed of thirty children aged between 6 and 10. They were diagnosed with ADHD according to DSM-IV criteria. They were the subjects who applied to Dicle University, Faculty of Medicine, and Department of Child Psychiatry in Diyarbakır, Turkey. Children with ADHD were assessed via Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale and Stroop test. Serum TDP-43 and UCH-L1 levels were analysed with enzyme-linked immunosorbent assay. Results The TDP-43 and UCH-L1 serum levels of children with ADHD were found to be statistically significantly higher than those of controls. On the other hand, we found that serum levels of TDP-43 correlated with interference effect and hyperactivity–impulsivity in children with ADHD. Conclusıon Imbalances in serum UCH-L1 and TDP-43 levels, and the correlation of TDP-43 levels with clinical parameters in children with ADHD may suggest that ubiquitin-proteasome pathway alterations are associated with ADHD. Deterioration of this pathway may cause intracellular TDP-43 aggregation.

Anorexia nervosa (AN) is an eating disorder, which is characterized by the avoidance of eating in a way that threatens the physical integrity of an individual, and trying to lose weight. It is known that the risk of mortality is high in AN. Death occurs as a results of medical complications and/or suicide. On the other hand, the exact time point of mortality becoming a risk during the progression of the disease progression is not defined. Certain predictors have been defined for mortality in AN. In this study, our aim was to present a case of a 15-year old female patient, who had died due to medical complications related to AN.

OBJECTIVEIn this study, it was aimed to understand the underlying possible immunopathogenesis of first episode, early onset schizophrenia (EOS) through profiling the T helper 1 (Th1) cell cytokines TNF-α, IFN-γ, and IL-2, Th2 cell cytokines IL-4 and IL-10, Th17 cell cytokine IL-17A, and inflammatory cytokine IL-6.METHODSThe study included a total of 30 children, admitted to child psychiatry outpatient clinic aged between 10 and 17 years of age, who had not received prior therapy and were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) as the patient group, and 26 age- and gender-matched children as the control group. Structured psychiatric interviews (K-SADS-PL and PANSS) were conducted with all participants. The BD Cytokine Bead Array Human Th1/Th2/Th17 Cytokine Kit is used for the measurement of serum cytokines, for example, IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ.RESULTSThere was no significant difference between groups in terms of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels (p > 0.05). However, there was a significant correlation between IL-10 and IL-4 with negative symptoms of EOS (r = -0.65, p = 0.02 and r = 0.67, p = 0.02, respectively).CONCLUSIONIL4 and IL-10 levels have a relationship with negative symptoms of disease. Therefore, this study might suggest that immunological processes might have a role in the disease pathophysiology.

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.

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.

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 study's findings do not support the hypothesis of increased hypothalamic‐pituitary‐adrenal axis activity in first‐episode early onset schizophrenia.

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. Children's 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.