Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Objective: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. Methods: Plasma levels of S100B, tumor necrosis factor alpha (TNF-α), interferon gamma, interleukin (IL)-1β, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). Results: Concentrations of both S100B and TNF-α were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-α concentrations. Conclusion: Our findings showing an increase in peripheral concentrations of S100B and TNF-α provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders.

OBJECTIVE:: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. METHODS:: Plasma levels of S100B, tumor necrosis factor alpha (TNF-α), interferon gamma, interleukin (IL)-1ß, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). RESULTS:: Concentrations of both S100B and TNF-α were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-α concentrations. CONCLUSION:: Our findings showing an increase in peripheral concentrations of S100B and TNF-α provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.

Assessment of sleep problems and related risk factors observed in Turkish children with Autism spectrum disorders.

Sleep problems are common and difficult to manage in children with autism spectrum disorders (ASD). Another major adverse impact of sleep problems is that they exacerbate behavioral problems. To assess sleep problems and possible behavioral risk factors in detail, we aimed to compare sleep habits of children with ASD, with healthy children. The relationship between sleep difficulties and concomitant behavioral problems such as repetitive behaviors, hyperactivity, and social withdrawal were also examined. Hundred and seventeen children and adolescents including 64 with the diagnosis of ASD and 53 healthy subjects were enrolled in the study. Diagnostic Interview for ASD was performed according to DSM-IV-TR. Socio-demographical data form and childhood autism rating scale were filled by researchers. Aberrant behavior checklist (ABC), child behavior checklist and pediatric sleep questionnaire (PSQ) were completed by the parents of the children. Children with ASD had higher frequency of sleep problems, snoring, breathing problems, behavioral problems compared with healthy children (for all parameters; P < 0.001). A positive correlation was identified between the total score of PSQ and the total score of ABC (P < 0.05, Spearman correlation coefficient: 0.347). Sleep latency was prolonged in children with ASD compared with healthy subjects (P < 0.001). In accordance with the current literature, children with ASD were subject to sleep problems significantly more than the control group. Identified risk factors for sleep problems in ASD children were behavioral factors such as stereotypies, self-mutilation, hyperactivity, and social withdrawal. Autism Res 2016, 9: 536-542. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Immune system changes after sexual abuse in adolescents.

BACKGROUND: The immunological changes in diseases such as rheumatoid arthritis and multiple sclerosis have been found to be similar to the immunological changes in adults with post-traumatic stress disorder (PTSD). The biological consequences of and immunological disruptions associated with psychological trauma in sexually abused adolescents were investigated in this study. METHODS: Number of peripheral blood cells, intracellular cytokine level and cytotoxic activity of natural killer cells were measured on routine blood examination samples in adolescents aged 13-18 referred to the outpatient unit for forensic evaluation. Forty-three adolescents (patients with present/lifetime PTSD [PTSD-P/PTSD-L] associated with a history of childhood sexual abuse, n = 33; and 10 controls) were evaluated. RESULTS: Eosinophil percentage was high (P < 0.05), whereas stimulated intracellular interferon-γ was low (P < 0.05) in adolescents with PTSD-L compared with the control group. In PTSD-P patients exposed to repeated sexual abuse, CD3(+) HLA-DR(+) T-lymphocyte count was low (P < 0.05) compared with those with one-time sexual abuse. CONCLUSION: The increase in some immune system parameters and the decrease in several others, suggests a dysregulation of the immune system related to trauma in adolescents. Dysregulation of the immune system is known to cause autoimmune and chronic disease.

Early induction of ADAMTS 1, -4, -5 and -9 in IL-stimulated mouse astrocytes.

AIM: Astrocytes and extracellular matrix molecules have important roles in regulating synaptic functions between neurons in the central nervous system. However, under pathological conditions, these constituents are activated to form glial scar that is thought to be harmful for neuronal regeneration. The aim of this study was to evaluate the expression pattern of ADAMTS1, -4, -5 and -9 in IL-1 stimulated astrocyte cultures obtained from postnatal day zero mouse brains. MATERIAL AND METHODS: Real time PCR analyses were performed. RESULTS: An overexpression of ADAMTS1, -4, -5 and -9 at the 3-h time point after IL-1 stimulation was found. IL-1 stimulation induced aggrecaneses and this effect was time dependent. Maximum increase was detected at 3-h (six fold increase). Interestingly the expression of ADAMTS1 and -4 appeared to be at the highest expression level but the ADAMTS5 and ADAMTS9 expression level was much weaker (three times and two times respectively). CONCLUSION: To the best of our knowledge, this is the first report demonstrating induction of ADAMTS in IL-1 induced astrocytes. Aggrecanases may play a role in tissue destruction in the progression of central nervous system (CNS) injury and they are differentially expressed in mouse CNS, suggesting a critical role in the pathogenesis of CNS injury. This can be a very crucial aetiologic factor for some neuropsychiatric disorders.

Clinical, psychological and maternal characteristics in early functional constipation.

BACKGROUND: This cross-sectional study investigated the clinical features of functional constipation (FC) at preschool age, as well as emotional and behavioral characteristics of the children, psychological symptom level and parental attitudes of the mothers, and compared these with that of non-referred typically developing controls with normal intestinal habits. METHODS: Participants included 65 children with FC (mean age, 43.6 ± 15.4 months; range, 25-72 months), 59 healthy controls (mean age, 46.9 ± 14.5 months; range, 25-72 months) and the mothers of the children. The Childhood Behavior Checklist, Symptom Checklist 90 and Parental Attitude Research Instrument were filled in by the mothers. RESULTS: Participants with FC had higher problem scores than the comparison children in a variety of emotional and behavioral parameters. Approximately half exhibited internalizing and one-third had externalizing problems in the clinical range. The mothers of the patient group had higher levels of psychological distress, overprotective parenting and strict discipline. On multiple logistic regression analysis child psychopathology, maternal education level and maternal distress were independently associated with FC. CONCLUSION: Behavior problems are common in children with FC from an early age. Low level of education and high psychological distress of the mothers seem to be important risk factors for constipation and should be assessed carefully in the management of these cases.

An examination of the symptoms of anxiety and parental attitude in children with hemophilia.

BACKGROUND/AIM: Hemophilia is an inherited disease with serious repercussions. Psychiatric symptoms are frequently seen in children and adolescents with hemophilia. The aim of this study was to assess symptoms of anxiety in children with hemophilia and parental attitude towards children with hemophilia. MATERIALS AND METHODS: 42 boys were assessed according to child and adolescent psychiatry. Anxiety symptoms and parental attitude were obtained by the State-Trait Anxiety Scale, the Self-Report for Childhood Anxiety Related Disorders (SCARED) and the Parent Attitude Research Instrument (PARI). RESULTS: The mean age was 11.6 ± 2.5 (range; 7-16). State anxiety scores (44.02 ± 6.9) were higher than trait anxiety scores (32.7 + 7.5). The most interesting results were high scores related to overprotective mothering (47.9 ± 9.7) and the application of strict discipline (39.4 ± 9.1). The total SCARED scores obtained were (23.25 ± 11.3). CONCLUSION: Assuring a high quality of life is important for children and adolescents with chronic illness. Quality of life is negatively affected by psychiatric symptoms (e.g. anxiety symptoms, depression, intra-familial stress symptoms) in children with hemophilia. This study suggests that high anxiety scores and problems related to parental attitude can be seen in children and adolescents with hemophilia. These problems caused by parental attitude and anxiety symptoms should be considered in the treatment of hemophilia.

Atomoxetine Induced Hypothermia: A Case Report.

Adverse drug reactions are common in drugs used during childhood and adolescence. Atomoxetine, a selective reuptake inhibitor, was introduced as a safe non-stimulant alternative treatment for attention deficit hyperactivity disorder. Described common side effects of atomoxetine include: headache, abdominal pain, decreased appetite, fatigue, nausea, vomiting and dizziness. In our case, we present an adolescent male who developed hypothermia under atomoxetine treatment. To our knowledge, this is the first report of a causal connection between atomoxetine intake and hypothermia. Because hypothermia is a life-threatening condition and can be treated when interfered immediately, clinicians should be aware of this adverse effect of atomoxetine.

Long Acting Risperidone in an Adolescent with Conduct Disorder: A Case Report.

Adolescent conduct disorder (CD) is generally hard to manage clinically, as this population often refuses to take oral medications. Families and acquaintances of these adolescents usually suffer from extreme psychological, financial and social difficulties. Oral antipsychotics are the primary drugs of choice clinically, after behavioral treatments. Here we report a case with attention deficit hyperactivity disorder and conduct disorder who refuses to take any medications, was not eligible for behavioral treatments and was treated successfully with long acting risperidone.

A prospective observational study of attention-deficit/hyperactivity disorder in Central and Eastern Europe and Turkey: Symptom severity and treatment options in a paediatric population.

Abstract Objective. This study investigates the relationship between treatment regimen, symptom severity, comorbidities and health outcomes of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) in Central and Eastern Europe (CEE). Methods. Males and females aged 6-17 years with ADHD symptoms participated in this 12-month, prospective, observational, non-randomised study. Symptoms and comorbidities were assessed using the Child and Adolescent Symptom Inventory-4 Parent Checklists (CSI-4; ASI-4, categories L/O), and the Clinical Global Impressions-ADHD-Severity scale (CGI-ADHD-S). Baseline data are presented. Results. The study included 566 patients from Czech Republic, Hungary, Romania, Slovakia and Turkey. Psychiatrists made all diagnoses using The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV), World Health Organization International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), and "other" criteria (73, 27 and 0.4%, respectively). Patients were grouped into two cohorts based on whether they were prescribed psycho- and/or pharmacotherapy (n=443) or not (n=123). Patients receiving prescribed treatment were older and demonstrated higher symptom severity scores than those receiving no or "other" treatment. Most patients were prescribed conventional treatment for ADHD at baseline. Conclusions. Continued assessment of this population may aid the treatment and outcomes of ADHD in CEE.

Group A beta hemolytic streptococcal infections and obsessive-compulsive symptoms in a Turkish pediatric population.

The purpose of the present study was to evaluate obsessive-compulsive disease (OCD) in Turkish Children who had group A beta hemolytic streptococcal (GABHS) infections and those who had not. Thirty-one children and adolescents (the study group) were compared with 28 children and adolescents. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores were rated between study group and control group. The mean score, obsession and compulsion scores of CY-BOCS in the study group were significantly higher than they were in the control group (P < 0.05). The GABHS infections should be assessed in the etiology of OCD in children. Considering GABHS infections may help the treatment of OCD.

[Parental attitudes at the beginning of child's stuttering]. / Kekemelik baslangicinda ebeveyn tutumlarinin degerlendirilmesi.

OBJECTIVES: Stuttering is a communication disorder that frequently starts at the age of three or four years. Its appearance and progression may impose psychological effects on children and their families. We evaluated parental attitudes in the initial period of stuttering. PATIENTS AND METHODS: Twenty-two children or adolescents (16 males, 6 females; mean age 8.8+/-4.4 years; range 4 to 18 years) were assessed. A semi-structured clinical interview was administered to all the patients to determine whether stuttering was triggered by stressors and to examine the attitudes of parents and the course of their applying for treatment. RESULTS: After the onset of stuttering symptoms, the most frequent parental attitude was found as punishment and warning to their child (54.5%). Before stuttering appeared, the most frequent triggering event was of being excessively scared of anything (68.2%). The mean age of onset of stuttering was 3.4+/-1.1 years (range 2 to 7 years). CONCLUSION: The events that trigger stuttering also continue in the attitudes and thoughts of parents concerning stuttering. After the diagnosis, the parental attitude plays a significant role in the effectiveness of treatment. In this respect, parents should be informed during their first application for treatment.

Short-term efficacy and safety of risperidone in young children with autistic disorder (AD).

Recently, atypical antipsychotic treatments have been used in children with autistic disorder (AD). However, data on safety and efficacy of atypical antipsychotic agents in autistic children are limited. In this open, prospective trial, subjects were treated with risperidone for six weeks. Nineteen children (12 male, 7 female) aged 4 to 8 years were started on 0.5 mg daily with individual titration to a maximum of 1.5 mg daily. Behavioural assessments were completed by Conner's parent 10-item index, AD symptom checklist and CGI-Global improvement. Statistically significant improvement was observed in mean total scores of Conner's parent 10-item index from baseline to the end of study (p< 0.001). On the basis of the CGI-Global improvement item, 15 children were considered responders. Statistically significant improvement was also found in some aspects of social contact, impulsive-aggression and repetitive, ritualistic behaviour based on assessment with the AD-symptom checklist. Weight gain and increase in night-time sleep were the most frequent side effects.

Anxiety and extraction of third molars in Turkish patients.

Preoperative anxiety is widespread and adversely affects a patient's physical and psychological outcome. Extraction of third molars is common, and many patients complain of anxiety and emotional disturbance. We assessed the anxiety of patients in Turkey before extraction of third molars. A total of 120 patients were admitted for removal of one or more third molars under local anaesthesia. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and Spielberger's State Trait Anxiety Inventory (STAI) were used to evaluate anxiety. The results showed that women were significantly more anxious than men; women who had not had a previous operation were more anxious than other women; there was no difference in the anxiety scores of patients who had previously had a local anaesthetic and those who had not; there were no differences in anxiety as measured by trait scores; patients who wanted a lot of information were more anxious.

Venlafaxine in children and adolescents with attention deficit hyperactivity disorder.

The primary purpose of this study was to describe tolerability and efficacy of venlafaxine in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). A 6-week open trial of venlafaxine was conducted in 13 children and adolescents (mean age 9.9 +/- 2.5 years) with ADHD, and without comorbid depression. Venlafaxine was initiated at a dose of 18.75 mg/day and flexibly titrated to 56.25 mg/day. The Conners parent scale and Clinical Global Improvement (CGI) severity item were performed at baseline and at the end of the 6-week trial. All subjects completed the trial. Mean final dose of venlafaxine was 40.3 +/- 7.0. Venlafaxine was significantly effective in reducing the total score of the Conners parent scale from baseline to endpoint (P < 0.002, Z =-3.113) and the CGI severity item (P < 0.05). Transient side-effects such as somnolence (n = 2), stomachache (n = 2), and headache (n = 1) disappeared after second week of treatment. Also three subjects complained of sedation after raising the dose to 56.5 mg/day, therefore the dose was reduced to the previous level. These preliminary data suggest that venlafaxine may be an effective medication in the treatment of some children and adolescents with ADHD. Future double-blind controlled trials should be undertaken.

Quetiapine treatment of children and adolescents with Tourette's disorder.

OBJECTIVE: The purpose of this study was to investigate the short-term safety and effectiveness of quetiapine in the treatment of children and adolescents with Tourette's disorder. METHODS: This was an 8-week, open-label trial that included 12 subjects with a mean age of 11.4 +/- 2.4 years. The subjects were seen every week throughout the study. RESULTS: Clinical responses, as measured by the Turkish version of the Yale Global Tic Severity Scale, revealed a statistically significant reduction in tic scores ranging from 30-100%. Mean dose of quetiapine at the end of the study was 72.9 +/- 22.5 mg/day. Three subjects complained of sedation in the first week of treatment. CONCLUSIONS: The favorable results of this open-label study should be interpreted with caution due to the uncontrolled nature of the study. Spontaneous waxing and waning of symptoms should also be considered. Further controlled studies are required.

The psychological effects of forced emigration on Muslim Albanian children and adolescents.

OBJECTIVES: The object of this study was to investigate the psychological effects of forced emigration on Muslim Albanian children and adolescents who were forced to emigrate due to the war in Kosova. METHOD: The sample of the study consisted of 150 children between the ages 9-12 and 100 adolescents between the ages 15-19 living in the Gaziosmanpasa Refugee Shelter in Turkey, and as a control group, 66 children and 52 adolescents; making a total of 368 subjects were included in the study. We applied State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Children's Depression Inventory (CDI) as well as a semi-structured open-ended questionnaire investigating the socio-demographic characteristics and psychiatric symptoms of the study and control groups. RESULTS: Trait anxiety (TAI) levels of the children in the study group are higher than these in the control group. The analysis of the average Depressive Symptom scores of study group children (M = 15.70) and control group children (M = 7.37) was conducted with the application of t-test. The highly significant values of t = 7.73 p < 0.0001 indicate depressive symptoms among study group. Trait anxiety (TAI) scores of study group adolescents were higher than these in the control group (M = 43.56) and (M = 35.59), respectively and the values of t = 5.95, p < 0.0001 show that this is a highly significant difference. The comparison of the average depressive (BDI) symptom scores of study group and control group adolescents (M = 17.57 and M = 4.59 respectively) revealed the very significant values of t = 7.88, p < 0.0001. The evaluation of the semi-structured questionnaires also revealed that depressive symptoms, somatic symptoms and other psychiatric symptoms were also higher in the study group. CONCLUSION: Our findings support the common opinion that war and terror incidents severely hurt children.

Citalopram treatment of children and adolescents with obsessive-compulsive disorder: a preliminary report.

The purpose of the present study was to assess the efficacy and tolerability of citalopram in the acute treatment of children and adolescents with obsessive compulsive disorder (OCD) during an 8-week, open-label study. Fifteen patients (six female, nine male) with a mean age of 12.1 +/- 3.3 years (range: 6-17 years) were treated with citalopram (range of dose: 20-30 mg/day, mean dose: 24 +/- 5.5 mg/day). The children's version of the Yale-Brown Obsessive-Compulsive scale (CY-BOCS) was rated at the baseline, at the 4th week and at the 8th week of treatment. Fourteen patients had a decrease in total score of CY-BOCS from baseline to the 4th week of treatment (P < 0.01) and the 8th week of treatment (P < 0.01). Sedation (n = 1) and insomnia (n = 1) were reported in the first weeks of treatment. The primary data suggest the efficacy and tolerability of citalopram in young patients with OCD.