Vesicle trafficking with snares: a perspective for autism.

Vesicle-mediated membrane traffic is the mechanism fundamental to many biological events, especially the release of neurotransmitters. The main proteins of the mechanism that mediates membrane fusion in vesicle-mediated membrane traffic are N-ethylmaleimide sensitive factor (NSF) supplemental protein (SNAP) receptor (SNAREs) proteins. SNAREs are classified into vesicle-associated SNAREs (vesicle-SNAREs/v-SNAREs) and target membrane-associated SNAREs (target-SNARE/t-SNAREs). Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by many symptoms, especially complications in social communication and stereotypical behaviours. Defects in synaptogenesis and neurotransmission, oxidative stress, and developmental defects in the early stages of development are defined in the pathogenesis of the disease. SNARE proteins are on the basis of synaptogenesis and neurotransmission. Although the formation mechanisms and underlying causes of the SNARE complex are not fully understood, expression differences, polymorphisms, abnormal expressions or dysfunctions of the proteins that make up the SNARE complex have been associated with many neurodevelopmental diseases, including autism. Further understanding of SNARE mechanisms is crucial both for understanding ASD and for developing new treatments. In this review, the formation mechanisms of the SNARE complex and the roles of various factors involved in this process are explained. In addition, a brief evaluation of clinical and basic studies on the SNARE complex in autism spectrum disorders was made.

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

AIM: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey. METHOD: A nation-wide, randomly selected, representative population of 5830 children (6-13 years-old) enrolled as a 2nd,3rd or 4th grade student in 30 cities were evaluated for presence of a psychiatric or mental disorder by a Sociodemographic Form, Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and DSM-IV-Based Screening Scale for Disruptive Behavior Disorders in Children and Adolescents scales. Impairment criterion was assessed via a 3 point-Likert scale by the parent and the teacher independently. RESULTS: Overall prevalence of any psychopathology was 37.6% without impairment criterion, and 17.1% with impairment criterion. Attention-deficit hyperactivity disorder was the most frequent diagnosis, followed by anxiety (19.5% and 16.7% without impairment, 12.4% and 5.3% with impairment, respectively). Lower education level and presence of a physical or psychiatric problem of the parents were independent predictors of any psychopathology of the offspring. CONCLUSION: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group.

Assessment of anxiety-depression levels and perceptions of quality of life in adolescents with dysmenorrhea.

BACKGROUND: This study aimed to assess the anxiety-depression levels and the perceptions of quality of life, as well as the factors affecting these variables, in adolescents with dysmenorrhea. METHODS: The participants included 60 adolescents with dysmenorrhea and 41 healthy adolescents between the ages of 12 and 18. This study used the Pediatric Quality of Life Inventory (PedsQL) for assessing the perceptions of quality of life, the State-Trait Anxiety Inventory (STAI) for measuring anxiety levels, and the Children's Depression Inventory (CDI) for measuring depression levels. RESULTS: It was determined that compared to healthy controls, the depression and anxiety scores were higher and the quality of life was impaired in adolescents with dysmenorrhea. In addition, it was shown that the depression and anxiety levels increased and the psychosocial health subscale scores of quality of life decreased with increasing dysmenorrhea severity. However, the likelihood of dysmenorrhea was found to be higher with increasing depression scores, while the anxiety levels had no effect on dysmenorrhea. CONCLUSION: In dysmenorrhea management, it is important to enhance awareness among pediatric clinicians and gynecologists regarding the associations between dysmenorrhea and mental problems.

Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder.

BACKGROUND: In our study, we aimed to evaluate the serum homocysteine levels, pyridoxine, folate and vitamin B12 levels in children with attention deficit hyperactivity disorders (ADHD). SUBJECTS AND METHODS: This study included 30 newly diagnosed drug-naive children with ADHD (23 males and 7 female, mean age 9.3±1.8 years) and 30 sex-and age matched healthy controls. The diagnosis of ADHD was made according to DSM-V criteria. Children and adolescents were administered the Schedule for Affective Disorders and Schizophrenia for School Aged Children, Present and Lifetime Version, the Conners' Parent Rating Scale-Revised, Long Form, the Conners' Teacher Rating Scale and the Wechsler Intelligence Scale for Children Revised (WISC-R) for all participants. Homocysteine, pyridoxine, folate and vitamin B12 levels were measured with enzyme-linked immunosorbent assay. RESULTS: Homocysteine, pyridoxine, folate and vitamin B12 levels were significantly lower in children with ADHD compared with their controls (p<0.05). A positive significant correlation was observed between the all WISC-R scores and vitamin B12 level in patients (r=0.408, p=0.025). CONCLUSIONS: The results obtained in this study showed that reduced homocysteine, pyridoxine, folate and vitamin B12 levels could be a risk factor in the etiology of ADHD.

Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder.

BACKGROUND: Defects in neurotransmission and synaptogenesis are noteworthy in the pathogenesis of ASD. Synapsin III (SYN III) is defined as a synaptic vesicle protein that plays an important role in synaptogenesis and regulation of neurotransmitter release and neurite outgrowth. Therefore, SYN III may associate with many neurodevelopmental diseases, including ASD. AIM: The aim of this study was to investigate whether the SYN III gene -631 C > G (rs133946) and -196 G > A (rs133945) polymorphisms are associated with susceptibility to ASD. METHODS: SYN III variants and the risk of ASD were investigated in 26 healthy children and 24 ASD children. SYN III gene variants were genotyped by PCR-RFLP methods. The differences in genotype and allele frequencies between the ASD and control groups were calculated using the chi-square (χ2). We analysed the SYN III gene using web-based tools. RESULTS: Our results suggest that the presence of the AA genotype of the SYN III -196 G > A (rs133945) polymorphism affects the characteristics and development of ASD in children (p = 0.012). SYN III -631 C > G (rs133946) polymorphism was not associated with ASD (p = 0.524). We have shown the prediction of gene-gene interaction that SYN III is co-expressed with 17 genes, physical interaction with 3 genes, and co-localization with 12 genes. The importance of different genes (SYN I, II, III, GABRD, NOS1AP, GNAO1) for ASD pathogenesis was revealed by GO analysis. CONCLUSION: Considering the role of SYN III and related genes, especially in the synaptic vesicle pathway and neurotransmission, its effect on ASD can be further investigated.

functional outcome in late adolescence/early adulthood of patients with autism spectrum disorder and its relationships with parental burnout and depression: A preliminary multi-center, cross-sectional study.

The aim of this study is to determine the functioning of adults with autism spectrum disorders (ASDs) diagnosed in childhood and depression and burnout levels among their parents. A total of 261 adults with ASDs and their parents were recruited for the study. Both parents completed the Beck Depression and Maslach Burnout Inventories and reported the functioning of their adult offspring with ASDs. Only 5.4 % of our sample reported "good" or "very good" outcomes. The most common psychiatric comorbidities were intellectual disabilities and attention-deficit/hyperactivity disorder. Maternal burnout and depression scores were significantly elevated compared to those of fathers. There is an undeniable urgent need for more research to identify the needs of adults and families suffering from ASD. Modifications for those with ASD may have to be made for support in workplaces, achieving driving licenses, using public transportation and attendance at tertiary education.

Effect of Impairment on the Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder in a National Survey: Nation-Wide Prevalence and Comorbidities of ADHD.

OBJECTIVE: This study aimed to determine the prevalence and comorbidities of attention-deficit hyperactivity disorder (ADHD) by evaluating a large-scale nation-wide sample of children. METHOD: The inclusion criterion was being enrolled as a 2nd, 3rd, or 4th-grade student. A semi-structured diagnostic interview (K-SADS-PL), DSM-IV-Based Screening Scale for Disruptive Behavior Disorders, and assessment of impairment (by both parents and teachers) were applied to 5,842 participants. RESULTS: The prevalence of ADHD was 19.5% without impairment and 12.4% with impairment. Both ADHD with and without impairment groups had similar psychiatric comorbidity rates except for oppositional defiant disorder (ODD) and conduct disorder (CD) diagnoses. Impairment in the ADHD group resulted in significantly higher ODD and CD diagnoses. CONCLUSION: Even when impairment is not described, other psychiatric disorders accompany the diagnosis of ADHD and may cause impairment in the future. Impairment in the diagnosis of ADHD significantly increases the likelihood of ODD and CD.

The Relationship Between Peer Bullying and Anxiety-Depression Levels in Children With Obesity.

Objective: It has been reported that there is a significant relationship between obesity and mental health problems, and the exposure to peer bullying plays a mediating role in this relationship. This study aimed to evaluate the risk of peer bullying in children with obesity and to investigate the relationship between bullying and anxiety and depression levels. Methods: A total of 64 patients aged between 8 and 16 years with obesity and 51 age- and gender-matched healthy children and adolescents without obesity were included in the study. Children in both groups were administered the Children's Depression Inventory (CDI) to determine their depression levels, the State-Trait Anxiety Inventory (STAI) to determine their anxiety levels, and the Revised Olweus Bully/Victim Questionnaire for Students to evaluate the bullying status. Results: Peer bullying rates, CDI, and STAI scores were significantly higher in children and adolescents in the obesity group compared with those in the control group (P < .05 for all). In the obesity group, depression and anxiety scores were found to be higher in children who were exposed to bullying compared with those who were not exposed to bullying (P < .05 for all). Obesity was found to increase the likelihood of peer bullying by 3.015 times (P = .018), and it was also found that the increase in the symptoms of trait anxiety and depression increased the likelihood of peer bullying (P = .01, P = .002, respectively). Discussion: In this study, it was shown that obesity is a risk factor for peer bullying, and both obesity and peer bullying negatively affect children's mental health. More detailed studies that explain the relationship between obesity, bullying, and mental problems will guide clinicians in obesity management.

Diagnostic Performance of Erythropoietin and Erythropoietin Receptors Levels in Children with Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a heterogeneous, highly heritable, a common childhood neurobehavioural disorder resulting from complex gene-gene and gene-environment interactions. The erythropoietin (Epo)/erythropoietin receptors (EpoR) system turned out to have additional important functions in nonhematopoietic tissue. In this study, we aimed to investigate the levels of Epo and and EpoR, and also their diagnostic values in children with ADHD. METHODS: A total of 70 children were included in the study, 35 drug-naive patients with ADHD (age: 6-12 years; male/female: 20/15) and 35 healthy controls (age: 6-12 years; male/female: 22/13). Serum Epo and EpoR levels was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. RESULTS: The results indicated that the levels of Epo decreased in patients with ADHD compared to control (p < 0.05). On the other hand, EpoR levels increased in these patients (p < 0.05). Furthermore, the ratio of Epo/EpoR was significantly lower in ADHD patients than controls (p < 0.05). Receiver operator characteristic curve analysis showed high diagnostic performance for Epo and EpoR, areas under curve were 0.980 and 1.000, respectively. CONCLUSION: This is the first report to investigate the association between serum Epo and EpoR levels in ADHD patients. Our results indicated that Epo may play a role in the etiology of ADHD, and Epo therapy may be beneficial in these disorders if given in addition to the routine treatment of children with ADHD. Furthermore, our results reveal possible diagnostic value of Epo and EpoR.

Vitamin D and vitamin D receptor levels in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: In this study, we aimed to evaluate vitamin D and vitamin D receptor levels in children with attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS: In this cross-sectional study, a total of 80 children including 40 ADHD patients (aged 6-12 years; 28 males and 12 females) and 40 age-, sex-, and season of blood collection-matched controls (aged 6-12 years; 25 males and 15 females) were enrolled. Serum vitamin D and vitamin D receptor levels and calcium, phosphorus, and alkaline phosphatase were measured. The vitamin D receptor levels in the serum were measured using the quantitative sandwich enzyme immunoassay technique. RESULTS: Serum vitamin D and vitamin D receptor levels were found to be significantly lower in children with ADHD compared to healthy controls. No significant differences were found in serum calcium, phosphorus, and alkaline phosphatase levels. No significant differences were found among the ADHD subtypes in terms of serum vitamin D, vitamin D receptor, calcium, phosphorus and alkaline phosphatase levels. CONCLUSION: This study suggests that children with ADHD have lower levels of vitamin D and vitamin D receptor. According to the authors' knowledge, this is the first study to describe vitamin D receptor levels in ADHD.

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD).

Estrogen has a crucial role in the regulation of reproductive and neuroendocrine function and exerts its effects through two classes of receptors, nuclear and membrane estrogen receptors (mERs). G protein-coupled estrogen receptor 1 (GPER) is a member of mERs, and despite limited research on the levels of GPER in patients with psychiatric diseases, a role of GPER in such conditions has been suggested. Here we evaluated serum estrogen and GPER levels in children with attention deficit hyperactivity disorder (ADHD) in relation to their age- and gender-matched healthy controls. A total of 82 children were included in the study, 47 drug- naïve patients with ADHD (age: 6-12 years; male/female: 34/13) and 35 healthy controls (age: 6-12 years; male/female: 19/16). The subgroups according to ADHD types were inattentive, hyperactive/impulsive, and combined. Serum estrogen was measured using an immunoassay system, while serum GPER was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Estrogen levels in children with ADHD were similar as in control group, while GPER levels were significantly lower in ADHD group compared to controls (p < 0.05). Logistic regression analysis showed a significant association between GPER levels and ADHD (p < 0.05), and no association between estrogen levels and ADHD (p > 0.05). No significant differences were found in GPER and estrogen levels between ADHD subgroups (p > 0.05). To the best of our knowledge, this study is the first to investigate estrogen and GPER levels in ADHD. Our preliminary findings suggest a relationship between serum GPER levels and ADHD, and this should be further investigated.

The Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in Children with Autism Spectrum Disorders.

OBJECTIVE: Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with an increasingly prevalent etiology, yet not fully understood. It has been thought that vitamin D, complex B vitamin levels and homocysteine are associated with environmental factors and are important in ASD. The aim of this study was to examine serum vitamin D, vitamin D receptor (VDR), homocysteine, vitamin B6, vitamin B12 and folate levels in ASD. METHODS: In this study, serum vitamin D and VDR, homocysteine, vitamins B6, B12 and folate levels were determined in 60 patients with ASD (aged 3 to 12 years) and in 45 age-gender matched healthy controls. In addition, calcium, phosphorus and alkaline phosphatase, which are associated with vitamin D metabolism, were measured from serum in both groups. ASD severity was evaluted by the Childhood Autism Rating Scale (CARS). RESULTS: Serum vitamin D and VDR were substantially reduced in patients with ASD in comparision to control group. However, homocysteine level was significantly higher and vitamin B6, vitamin B12 and folate were also reduced in patients with ASD. Total CARS score showed a positive association with homocysteine and a negative correlation with vitamins D,B6, B12, folate and VDR. CONCLUSION: This comprehensive study, which examines many parameters has shown that low serum levels of vitamins D, B6, B12, folate and VDR as well as high homocysteine are important in the etiopathogenesis of ASD. However, further studies are required to define the precise mechanism(s) of these parameters and their contributions to the etiology and treatment of ASD.

Prevalence of Childhood Affective disorders in Turkey: An epidemiological study.

AIM: To determine the prevalence of affective disorders in Turkey among a representative sample of Turkish population. METHODS: This study was conducted as a part of the "The Epidemiology of Childhood Psychopathology in Turkey" (EPICPAT-T) Study, which was designed by the Turkish Association of Child and Adolescent Mental Health. The inclusion criterion was being a student between the second and fourth grades in the schools assigned as study centers. The assessment tools used were the K-SADS-PL, and a sociodemographic form that was designed by the authors. Impairment was assessed via a 3 point-Likert type scale independently rated by a parent and a teacher. RESULTS: A total of 5842 participants were included in the analyses. The prevalence of affective disorders was 2.5 % without considering impairment and 1.6 % when impairment was taken into account. In our sample, the diagnosis of bipolar disorder was lacking, thus depressive disorders constituted all the cases. Among depressive disorders with impairment, major depressive disorder (MDD) (prevalence of 1.06%) was the most common, followed by dysthymia (prevalence of 0.2%), adjustment disorder with depressive features (prevalence of 0.17%), and depressive disorder-NOS (prevalence of 0.14%). There were no statistically significant gender differences for depression. Maternal psychopathology and paternal physical illness were predictors of affective disorders with pervasive impairment. CONCLUSION: MDD was the most common depressive disorder among Turkish children in this nationwide epidemiological study. This highlights the severe nature of depression and the importance of early interventions. Populations with maternal psychopathology and paternal physical illness may be the most appropriate targets for interventions to prevent and treat depression in children and adolescents.

Decreased levels of G protein-coupled estrogen receptor in children with autism spectrum disorders.

Sex hormones, specially estrogen, and it is receptors plays a critical role in the pathogenesis of psychiatric disorders including autism spectrum disorders (ASD). The aim of this study was to investigate the relationship between ASD and G protein-coupled estrogen receptor (GPER), a recently discovered estrogen receptors, and also to study the relation of serum GPER levels with the severity of autistic symptoms. The present study included 45 children with drug naive ASD diagnosed by DSM-V criteria, aged between 3 and 12 years and 40 age- and gender-matched healthy controls. The severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) total score. The GPER levels in the serum were measured using the quantitative sandwich enzyme immunoassay technique. The serum GPER level was significantly lower in the ASD patients than in the controls. There was a negative significant correlation between the GPER level and the CARS score. There were no significant correlations between GPER level with estradiol and age. In conclusion, this study demonstrated that the decreased serum GPER levels were associated with ASD and GPER may play an important role in the etiology of ASD.

Assessment of Psychopathology and Quality of Life in Children and Adolescents With Migraine.

AIM: The aims of this study were to investigate comorbid psychiatric disorders and to identify anxiety and depression levels and quality of life in children and adolescents with migraine; and to assess their relationship with migraine. METHOD: 35 patients aged 9-16 years were followed in our neurology clinic and their parents were included into the study. 35 age- and sex-matched patients were employed as the control group. In the subjects included, psychiatric disorders were assessed by using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version. All children and adolescents were assessed by using the Children's Depression Inventory, the State-Trait Anxiety Inventory and the Pediatric Quality of Life Inventory. In addition, the Pediatric Migraine Disability Assessment Tool and visual analog scale were used to identify the degree of disability and pain severity in patients with migraine. FINDINGS: In the psychiatric assessment of children and adolescents with migraine, it was found that a psychiatric diagnosis was made in 40% of patients; and depression scale scores were significantly higher than those of controls. Quality of life was found to be poorer in patients with migraine compared to controls. It was found that quality of life was negatively correlated with pain severity and degree of disability; while it was positively correlated with depression scores. DISCUSSION: In children and adolescents with migraine, treatment of psychiatric disorders in addition to migraine therapy can facilitate migraine management and may decrease the need for prophylactic therapy.

Assessment of Psychopathology, Quality of Life, and Parental Attitudes in Adolescents with Type 1 Diabetes Mellitus.

INTRODUCTION: The aim of the present study was to identify psychopathology, parental attitudes, perceptions of quality of life, and relationships between these factors in adolescents with type 1 diabetes mellitus (DM). METHODS: Fifty adolescents (12-18 years old) with type 1 diabetes mellitus and 50 healthy adolescents and their parents were recruited for the study. Clinical interviews with the diabetic adolescents were performed using "Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)." Both groups completed the "Depression Scale for Children," "State-Trait Anxiety Inventory," and "Health Related Quality of Life Scale for Children," while their parents completed the "Parental Attitude Research Instrument," "The Coping Strategy Indicator," and "Health Related Quality of Life Scale for Children-Parent Form." RESULTS: The psychological disorder ratio in diabetic adolescents was 68%. No significant difference was found regarding perceptions of quality of life between the diabetic group and control group. However, diabetic adolescents with psychological disorder had reduced perception of quality of life than those without psychological disorder. Among parental attitudes, an authoritarian attitude was found to be more common in the diabetic group. It was found that among coping strategies, parents in the diabetic group use avoidance more commonly. CONCLUSION: In the present study, a high rate of psychopathology was detected among adolescents with type 1 DM. In addition, no clear impairment in quality of life was reported in patients with type 1 DM; however, there was worsening in the perception of quality of life in the presence of psychiatric disorders accompanying diabetes. It was found that parents of diabetic children use inappropriate coping strategies and negative parental attitudes more often than those of healthy controls.