Cytokine expression profiles in children and adolescents with tic disorders.

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.

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.

Relations of Childhood Trauma and Emotional Dysregulation with Suicide Ideation and Suicidal Behaviour Severity in a Clinical Sample of Depressive Female Adolescents.

Objective: This study aimed to explore the aspects of emotional dysregulation (ED) and childhood trauma (CT) which are associated with suicide ideation (SI) and suicidal behaviour (SB) severity in depressive female adolescents who previously attempted suicide. Method : In this cross-sectional study, we evaluated SI and SB severity. The Columbia-Suicide Severity Rating Scale (C-SSRS) was administered to 80 depressive female patients who had suicide attempts within the last month. Current suicide ideation (C-SI) and total score (C-TS), lifetime- suicide ideation (L-SI), and total score (L-TS) were obtained with the C-SSRS. Patients were recruited from five different provinces in Turkey. Additionally, the patients completed the Difficulties in Emotion Regulation Scale (DERS), Childhood Trauma Questionnaire (CTQ), and Beck Depression Inventory (BDI). The Pearson correlation test and a multiple linear regression analysis were used to determine variables predictive of suicide scores. Results: The results of multiple linear regression analysis indicated that the BDI and DERS - total scores explained 35% (adjusted R) of the variance in C-SI ((F (2;67) = 19.61, P < 0.001). C-TS was explained by 'BDI,' 'emotional neglect' and 'DERS impulse' (38% (adjusted R) (F (3;66) = 15.15, P < 0.001). L-SI was only associated with DERS strategies (explains 13% (adjusted R) of the variance in L-SI (F (1;68) = 10.411, P = 0.02). Concerning the C-SSRS L-TS, the DERS impulse and CTQ total accounted for 24% (adjusted R) of the variance (F (2;67) = 10.620, P < 0.001). Conclusion: The results of our study suggest that adolescents who have experienced emotional neglect and depressive symptoms are more at risk for suicidal ideation and behaviour. In addition, depressed adolescents who show impulsive behaviours and restricted emotional strategies are also at risk. Identifying neglected depressed adolescents and teaching impulse control and effective emotional strategies is important for the prevention of suicidal behaviours and thoughts.

Investigation of the forkhead box protein P2 gene by the next-generation sequence analysis method in children diagnosed with specific learning disorder.

OBJECTIVE: It was aimed to investigate the role of the forkhead box protein P2 (FOXP2) gene in the cause of specific learning disorder (SLD) with the next-generation sequencing method. MATERIAL AND METHODS: The study included 52 children diagnosed with SLD and 46 children as control between the ages of 6-12 years. Interview Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifelong Version in Turkish, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-Based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders, Specific Learning Disability Test Battery were applied to all participants. The FOXP2 gene was screened by the next-generation sequencing (NGS) method in all participants. RESULTS: A total of 17 variations were detected in the FOXP2 gene in participants. The number and diversity of variations were higher in the patient group. In the patient group, c.1914 + 8A>T heterozygous variation and three different types of heterozygous variation (13insT, 13delT and 4dup) in the c.1770 region were detected. It was found that the detected variations showed significant relationships with the reading phenotypes determined by the test battery. CONCLUSION: It was found that FOXP2 variations were seen more frequently in the patient group. Some of the detected variations might be related to the clinical phenotype of SLD and variations found in previous studies from different countries were not seen in Turkish population. Our study is the first to evaluate the role of FOXP2 gene variations in children with SLD in Turkish population, and novel variations in the related gene were detected.

Factors affecting disclosure time of sexual abuse in children and adolescents.

BACKGROUND: The aim of this study is to determine the factors affecting early and delayed disclosure time of child sexual abuse (CSA). Early disclosure of CSA is considered to be crucial for child protection. METHODS: A total of 125 sexually abused children and adolescents, who had been evaluated by child adolescent psychiatry and forensic medicine specialists, were enrolled in this study. Files of medical and criminal data were analyzed retrospectively and synchronously by child adolescent psychiatrist and forensic medicine specialist authors who had evaluated victims using the standard procedures of Düzce University Faculty of Medicine Child Abuse Assessment Council. Univariate and multivariate logistic regression analyses were conducted to evaluate predictors. RESULTS: Delayed disclosers were found to be younger than early disclosers. Among the delayed disclosers, there were also more victims of intrafamilial CSA, fewer victims of penetration, and fewer voluntary disclosures. Multivariate logistic regression revealed that "younger age" and "intrafamilial CSA" were independent predictors of delayed disclosure of CSA. CONCLUSIONS: The results of our study contribute to an understanding of the factors related to delayed disclosure and underline the need for age-appropriate education and prevention programs targeted to increase the awareness of sexual abuse, particularly intrafamilial abuse, and to promote voluntary disclosure in children and adolescents, especially for younger age groups. The education of potential recipients of CSA and further education of professionals is extremely important in order to support children and adolescents' voluntary disclosure of CSA.

Activation Syndrome in a Patient With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine: A Case Report.

ABSTRACT: "Activation syndrome" represents a cluster of symptoms of excessive emotional arousal or behavioral activation, which emerges after the first few weeks of antidepressant treatment or a dose increase and resolves with dose reduction or cessation of treatment. It was reported after treatment with selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor group of agents, but no case of activation syndrome has been reported with the norepinephrine reuptake inhibitor group. Atomoxetine is a norepinephrine reuptake inhibitor and nonstimulant and is used to manage symptoms of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine-related symptoms of mania and hypomania were reported in literature previously. Here, we report a case of activation syndrome arising after atomoxetine (ATX) dose titration in a prepubertal male child with ADHD. Differentiation of activation symptoms from mania/hypomania symptoms after treatment with ATX may be important for the clinicians to manage the adverse effects and understand the risk factors behind activation syndrome with use of ATX in children and adolescents diagnosed with ADHD.

Traumatic experiences of conditional refugee children and adolescents and predictors of post-traumatic stress disorder: data from Turkey.

AIM: We aimed to determine traumatic events, mental health problems and predictors of PTSD in a sample of conditional refugee children. METHODS: The sociodemographic features, chief complaints, traumatic experiences and psychiatric diagnoses according to DSM-5 were evaluated retrospectively. RESULTS: 20.7% (n = 70) of children experienced the armed conflict or exposed to firefights at their country of origin. Most common diagnoses were anxiety disorders (n = 82, 24.3%), major depressive disorder (n = 52, 15.4%) and PTSD (n = 43, 12.7%). Age, number of traumatic experiences, explosion and sexual violence are the most important predictors for PTSD. CONCLUSIONS: Our results suggest that the number of traumas exposed as well as their nature predicted PTSD diagnosis. Refugee children have increased risk for psychiatric problems after migration and resettlement underlining the importance of an adequate follow-up for mental health and ensuring social support networks.

High Depression Symptoms and Burnout Levels Among Parents of Children with Autism Spectrum Disorders: A Multi-Center, Cross-Sectional, Case-Control Study.

The diagnosis of autism spectrum disorder (ASD) in a child affects family processes, increases parenting stress and marital conflicts, and may lead to parental psychopathology. It may also affect the prognosis for their children. The aim of this study is to determine depression and burnout levels as well as their predictors among parents of children with ASD compared with those of healthy children. We also sought to evaluate rate of complementary and alternative medicine (CAM) interventions among parents and explore the associations of this phenomenon in an exploratory fashion. 145 children with ASD and 127 control children were enrolled along with their mothers and fathers. Beck Depression Inventory and Maslach Burnout Inventory were used to evaluate parents' depression symptoms and burnout levels. Symptoms of children with ASDs were evaluated according to the Childhood Autism Rating Scale by the clinicians. Family, child and CAM variables were screened by means of a sociodemographic data form. Descriptive, bivariate and correlation analyses were used in statistical evaluations. Predictors of burnout were evaluated with multiple regression analysis. Burnout and depression levels among parents of children with ASD were significantly elevated compared to controls. Burnout levels of mothers were significantly elevated compared to fathers while depression scores of fathers were significantly elevated compared to mothers. Maternal burnout was significantly predicted by presence of functional speech in child while paternal burnout was significantly predicted by paternal vocation. Maternal depression was associated with paternal depression, lack of speech in child and attendance of child to special education services. Paternal depression was associated with autistic symptom severity and maternal depression. More than half the parents sought CAM interventions. Education level did not affect search for CAM interventions while both maternal and paternal psychopathology and presence of epilepsy among children increased use of CAM methods. Psychological support should be provided to both mothers and fathers of a child receiving a diagnosis of ASD. Addressing parents' burnout and stress levels and facilitating their negotiation of knowledge on etiology and treatments for ASD may be beneficial for the family unit as a whole.

Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1ß, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-ß in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms.

Sleep habits of children diagnosed with attention/ deficit/ hyperactivity disorder and effects of treatment on sleep related parameters.

This study aimed to evaluate the baseline sleep habits of children with ADHD and the effects of treatment with methylphenidate (MPH) and atomoxetine (ATX) on sleep parameters. Treatment naive children with clinically normal intelligence diagnosed with ADHD were enrolled in the study. Children were treated naturalistically with MPH and ATX. Treatments were started at 0.5 mg/ kg/ day and titrated weekly to a maximum of 1.2 mg/ kg/ day. The daily equivalent dose was calculated according to clinician toolkits of Utah Academy of Child and Adolescent Psychiatry. DSM-IV Based Screening and Assessment Scale for Disruptive Behavior Disorders- Parent form (DBSASDBD) and Clinical Global Impression Scale were used to assess ADHD symptoms and Children's Sleep Habits Questionnaire (CSHQ)- Short Form was used to assess the sleep habits and problems before and after the treatment. Both MPH and ATX reduced symptom severity of ADHD in all domains and also reduced total CSHQ scores with similar effect sizes. (0.7 for MPH vs. 0.8 for ATX). The rate of clinically significant sleep problems at baseline was 93.5 %. At the end-point, 83.9 % of the sample still displayed clinically significant sleep problems while none of the children were judged to have moderate-severe sleep problems. Our results suggest that both ATX and MPH may selectively improve different sleep domains in children with ADHD. Studies using standardized dosing schemes for longer durations and evaluating sleep with objective measurements may clarify the differential effects of treatments on sleep among children with ADHD.

Novel inflammatory targets for immunotherapies in pediatric patients with trichotillomania.

Immune dysregulation may be important in the etiology of obsessive-compulsive and related disordersandbody-focusedrepetitivebehaviors, such as Trichotillomania (TTM). The role of inflammation and inflammatory markers in TTM has received relatively little attention. This study was aimed to determine the expression levels of inflammatory markers (i.e. IL-1ß, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-ß) in peripheral blood mononuclear cells of children with TTM and healthy controls and to evaluate their association with clinical variables. Seventy-seven patients with TTM and 107 healthy controls were enrolled in the study. Peripheral blood was collected in standardized conditions. The mean age of patients and controls did not differ significantly (10.8 ± 4.4 and 12.0 ± 3.2 years; respectively). The majority of patients with TTM and controls were females (n = 55, 71.4 % and n = 55, 51.4 %; respectively); with a greater preponderance of females among TTM. Patients with TTM had significantly elevated expression levels of TNF-α, IL-6 and IL-17 compared to controls. However, the expression level of IL-4 was significantly reduced in TTM patients compared to controls. Accordingly, we found a pro-inflammatory state in TTM and those findings may suggest novel treatment options for TTM and further, cross-disciplinary studies focusing on neuro- inflammation in TTM conducted on larger samples are needed.

Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls.

OBJECTIVE: We aimed to investigate the serum concentrations of vitamin B12, folate and homocysteine in children diagnosed with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and healthy controls. MATERIALS AND METHODS: Serum vitamin B12, folate and homocysteine concentrations were measured in 118 children (48 children diagnosed with ADHD, 35 children diagnosed with ASD and 35 healthy controls). Symptom severity in the ADHD and ASD groups was evaluated by the Childhood Autism Rating Scale and Turgay-DSM-IV-Based Screening and Assessment Scale for Disruptive Behavior Disorders. Multivariate analysis of covariance was used to evaluate the effects of diagnosis and gender on biochemical parameters. RESULTS: The ADHD and ASD groups and the healthy controls differed significantly regarding vitamin B12 and homocysteine concentrations, but not folate levels. Patients with ASD had the lowest vitamin B12 and the highest homocysteine levels. Vitamin B12 levels correlated negatively with hyperactivity and/orimpulsivity and oppositionality symptoms in children with ADHD. There were no relationships between psychometric evaluations and laboratory measurements in children with ASD. Gender did not affect vitamin concentrations. CONCLUSION: Previous studies found that vitamin B12 was reduced while homocysteine was elevated among patients with ADHD and ASDs. Our results also support those reported previously. Oppositionality and hyperactivity and/orimpulsivity may be related to vitamin B12 and homocysteine levels in children with ADHD. Further studies are required to define the role of these parameters and effects on the etiology and clinical manifestations of ASD and ADHD.

Prescribing Trends of Atypical Antipsychotic Drugs in an Outpatient Unit of a Child and Adolescent Clinic in Turkey.

OBJECTIVE: Use of antipsychotic agents in the management of various psychopathologies in Child and Adolescent Psychiatric practice is gradually increasing. This study aimed to evaluate the sociodemographic and clinical features of children and adolescents who applied to an outpatient clinic of child and adolescent psychiatry department in Turkey and were prescribed atypical antipsychotics. METHOD: Patients with prescription codes of ATC N05A (except N05AN lithium) were accepted to denote those with atypical antipsychotic treatment. Sociodemographic and clinical variables, pharmacological mechanisms and groups and use of multiple agents for 212 patients with atypical antipsychotic treatment were collected and recorded. RESULTS: Patients (6.6%) evaluated within a year were prescribed antipsychotic agents (APs). The majority of the sample consisted of adolescents and especially females. The most common diagnoses managed with atypical antipsychotic were attention-deficit/hyperactivity disorder, MDD, and mental retardation/intellectual disability in decreasing frequency. Males with attention-deficit/hyperactivity disorder, CD, and autism spectrum disorders and females with MDD and PTSD were more frequently prescribed APs. Most common indications were irritability, impulsivity, and self-harming behaviors. Most common agents were risperidone, aripiprazole, and quetiapine in decreasing order of frequency. Most common adverse effects were reported as sedation, increased appetite, and hyperprolactinemia. CONCLUSIONS: Our results support the prevalence of off-label use of AP agents in managing various childhood psychopathologies also in Turkey. Further studies from multiple centers and using reliable and valid measurements are needed to determine the extent and predictors of AP use in outpatient samples from different child and adolescent centers.

Increased Trichotillomania Symptoms in a Child With Fluoxetine Treatment.

Trichotillomania (TTM) is a mental disorder characterized by uncontrolled and impulsive hair pulling leading to hair loss, distress, and disordered functioning. Treatment choices include behavioral therapy (especially habit reversal training) and selective serotonin reuptake inhibitors. However, randomized controlled trials conducted with selective serotonin reuptake inhibitors have led to controversial results of effectiveness for TTM. Here, we report a female patient whose TTM symptoms increased after fluoxetine use.

Increased Frequency of Encopresis in a Child Diagnosed With Attention Deficit/Hyperactivity Disorder and Encopresis After Atomoxetine Use: A Case Report.

Attention deficit hyperactivity disorder (ADHD) is among the most frequently reported coexisting psychiatric conditions in children with encopresis. Some case reports state that atomoxetine-a selective presynaptic norepinephrine reuptake inhibitor-approved for treatment of ADHD is also effective in the treatment of coexisting encopresis. Contrasting those reports, here we present a case diagnosed with ADHD and secondary encopresis without constipation whose encopretic symptoms increased after atomoxetine treatment and discuss possible mechanisms.

Spontaneous Ejaculations in an Adolescent With Olanzapine Use: Case Report.

Olanzapine (OLZ) is a second-generation atypical antipsychotic (AAP) frequently used in acute and maintenance treatment of children and adolescents with psychotic disorders. Most commonly reported sexual problems caused by AAPs are decreases in libido or arousal, erectile dysfunctions, reduced/abnormal ejaculations, and problems in achieving or maintaining orgasm. Olanzapine is less commonly implicated for those adverse effects, which may reflect its more selective affinity to dopaminergic receptors or more transient effects on prolactin levels. Sexual dysfunction with AAPs, including OLZ, is reported predominantly in adult patients and adverse sexual effects in prepubertal/peripubertal patients with psychosis received scant attention. Studies and reports of sexual adverse effects of AAPs in this special population may benefit clinicians. Therefore, in this study, we report an adolescent male patient with psychosis who developed spontaneous ejaculations with OLZ and whose complaints remitted with change in treatment.