Kynurenine, Kynurenic Acid, Quinolinic Acid and Interleukin-6 Levels in the Serum of Patients with Autism Spectrum Disorder.

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.

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.

Accompanying migrainous features in pediatric migraine patients with restless legs syndrome.

The present study aimed to examine the frequency of restless legs syndrome (RLS) in pediatric patients with migraine and tension-type headache (TTH) and to investigate accompanying migrainous symptoms, sleep characteristics, as well as levels of serum ferritin between the pediatric migraine patients with RLS and those without RLS. We included 65 consecutive patients diagnosed with migraine, 20 patients with TTH, and 97 headache-free children in our study. Demographic, clinical, and laboratory data were noted. The presence of a primary headache was diagnosed using the ICHD-II criteria, and RLS was determined with face-to-face interviews conducted by an experienced neurologist based on the revised International RLS Study Group criteria for pediatrics. The frequency of RLS in pediatric migraine and TTH patients was significantly higher than in the controls (p = 0.0001 and p = 0.025, respectively). The frequencies of allodynia, vertigo/dizziness, and self-reported frequent arousals were significantly higher, and serum ferritin levels were significantly lower in migraine patients with RLS compared to those without RLS (p = 0.05, p = 0.028, p = 0.02, and p = 0.038, respectively). Our study suggests that the frequency of RLS is higher in pediatric migraine and TTH patients compared to controls. Therefore, pediatric headache patients should be questioned about the presence of RLS, as this co-occurrence may lead to more frequent accompanying migrainous symptoms and sleep disturbances.

Tibia stress fracture secondary to obsessive compulsive disorder.

Obsessive compulsive disorder (OCD) is a chronic psychiatric disorder characterized by obsessions and compulsions. Early-onset OCD is one of the most common mental illnesses of children and adolescents, with a prevalence of 1% to 3%. It is related to worse lifespan symptoms and prognosis. Therefore, the treatment of OCD in children and adolescent has gained importance. If it is not treated successfully, the compulsive behaviors may cause extreme stress for children and their parents. Although minor complications of OCD are commonly observed, major complications are considerably rare due to the nature of compulsive behaviors. Apparently, loss of vision, autocastration, rectal prolapse are examples of major complications secondary to OCD. As far as we know, it is the first case of tibia stress fracture secondary to OCD. In the present case report, we will discuss tibia stress fracture developing secondary to compulsive behavior due to OCD.

Atopic disorders are more common in childhood migraine and correlated headache phenotype.

BACKGROUND: The supportive clinical and pathophysiological data about the correlation between migraine and atopic disorders are far from a coincidence. In order to determine and investigate the correlates of atopic disorders in a specific dataset, we performed this retrospective cross-sectional clinical-based study. METHODS: The dataset was composed from three tertiary center web-based databases (http://www.childhoodheadache.org). Headache diagnosis and differential diagnosis were made according to the International Classification of Headache Disorders, 2nd version and the Diagnostic Statistical Manual of Mental Disorders, 5th edition. Migraine with aura, migraine without aura, chronic migraine and episodic and chronic tension type headache (TTH) patients were included. All other causes of headache disorders, including comorbid headache disorders like migraine plus TTH or "possible" causes of headache, were excluded. RESULTS: The study included 438 patients with migraine and 357 patients with TTH, whose age and sex distribution were identical. After descriptive statistics accordingly, 80 migraine (18.2%) and 23 TTH (6.4%) patients were found to have specific atopic disorders (P < 0.001). Atopic disorders are more commonly reported in patients with migraine with aura (21.6%) than those with migraine without aura and TTH (P < 0.001). The most common atopic disorders were seasonal rhinitis, conjunctivitis and asthma. There was also a close correlation between TTH with atopic disorders and psychiatric comorbid disorders of the patients. CONCLUSIONS: Although the International Classification of Headache Disorders, 2nd version, does not specify, atopic disorders should be suspected in all migraine patients and their relatives, not only for accurate diagnosis but also for planning prophylactic medications, such as ß-blockers.

Risperidone Related Raynaud's Phenomenon: An Adolescent Case.

Raynaud's phenomenon is a recurrent vasospastic condition with reducing in peripheral blood flow due to cold, or emotional stress. White, blue and red discolorations occur during the attacks. Serotonin reuptake inhibitors, psychostimulants, and aripiprazole are reported to be related with Raynaud's phenomenon. Risperidone is an atypical antipsychotic drug with dopaminergic and serotonergic effects. In children and adolescents, risperidone is used for bipolar disorder, tic disorders, conduct disorder, schizophrenia, symptoms of irritability and self-mutilation. Here we report a case of Raynaud's phenomenon associated with risperidone in a 12-year-old boy. Raynaud's phenomenon occurred two weeks after starting risperidone and disappeared after stopping risperidone.

The Effect of Methylphenidate on the Hearing of Children with Attention Deficit Hyperactivity Disorder.

Introduction There has been a sudden idiopathic hearing loss case presented after methylphenidate treatment in a child with attention deficit hyperactivity disorder (ADHD). Objective This study was performed to reveal the probable ototoxic side effects of methylphenidate use in patients with ADHD. Methods Thirty pediatric patients with ADHD were included in the study. Pure tone audiometry, speech discrimination scores, waves I, III, V absolute latencies and waves I-III, I-V, III-V interpeak latencies at the 80 dB nHL intensity after click stimulus auditory brainstem response (ABR) results were compared before and 3 months after methylphenidate treatment. Results There were no statistically significant difference between pretreatment and posttreatment pure tone and speech audiometry findings and ABR results (p > 0.05 for all parameters). Conclusion Methylphenidate can be regarded as a safe drug regarding ototoxic side effects. Additional studies with a larger sample size and longer follow-up may be needed.

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.

Neuroleptic Malignant Syndrome Associated with Valproate in an Adolescent.

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction that usually occurs after the administration of antipsychotic drugs. Antidepressants, benzodiazepines, and antiepileptic drugs are also suggested to be associated with NMS. It is believed to result from a dopaminergic blockade in the central nervous system. NMS is manifested by hyperthermia, muscle rigidity, autonomic dysfunction, altered mental status, leukocytosis, and elevated serum creatinine phosphokinase. Valproate is commonly used in the treatment of many psychiatric and neurologic disorders. Valproate can precipitate NMS, especially when used with antipsychotic drugs concurrently. A 17-year-old male patient, who presented with fever, muscular rigidity, confusion, sweating, and tachycardia was admitted to the emergency room. He had been taking only valproate for the last two months for bipolar disorder. His laboratory analyses revealed raised serum hepatic enzymes, creatinine phosphokinase, and myoglobin levels. Considering fever, rigidity, autonomic dysfunction, cognitive alteration, and high creatinine phosphokinase levels, the patient was diagnosed with NMS. In this paper, we aim to discuss the association between valproate and NMS.

Serum IL-4 and IL-10 Levels Correlate with the Symptoms of the Drug-Naive Adolescents with First Episode, Early Onset Schizophrenia.

OBJECTIVE: In 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. METHODS: The 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. RESULTS: There 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). CONCLUSION: IL4 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.

Persistent hiccups due to aripiprazole in an adolescent with obsessive compulsive disorder responding to dose reduction and rechallenge.

Our case involves persistent hiccup arising in an adolescent with obsessive compulsive disorder (OCD) who was using aripiprazole as an augmentation to fluoxetine and whose hiccups remitted with dose reduction and rechallenge. Treatment suggested that aripiprazole might lead to hiccups. Antipsychotics are also used for the treatment of hiccups, but recent case reports suggest that they cause hiccups as well. Within 12 h of taking 5 mg aripiprazole, the 13-year-old girl began having continuous hiccups, which lasted for 3-4 h. The hiccups resolved when the dose of aripiprazole was reduced to 2.5 mg. To achieve augmentation, aripiprazole was replaced with risperidone 0.5 mg/day for 1 month, but excess sedation was observed. As a result, aripiprazole was restarted at a dose of 2.5 mg/day, and 1 week later, it was increased to 5 mg/every other day. No hiccups were observed.

Serotonin Syndrome after Clomipramine Overdose in a Child.

Serotonin syndrome (SS) is a potentially life-threatening condition associated with increased serotonergic activity in central nervous system and may occur during the use of serotonergic drugs. Although increasing frequency of serotonergic drug use in children, pediatricians, emergency medicine and pediatric intensive care specialists have not enough knowledge and experience about SS that is a potentially life-threatening condition. A 12-year-old girl patient was admitted to our emergency room with the history of involuntary contractions on her extremities and alteration of consciousness. Her physical examination showed agitation, hyperthermia, dilated pupils, tremor, increased deep tendon reflexes, positive spontaneous clonus, agitation, flushed skin and diaphoresis, excessive perspiration, and continuous horizontal ocular movements. The patient diagnosed as SS by clinical history, physical and laboratory findings. In this paper, we will discuss SS occurred in a 12-year-old girl after concurrent clomipramine and risperidone use.

Risperidone Induced Pisa Syndrome in a Male Adolescent.

Pisa syndrome, a rare dystonic reaction resulting from prolonged exposure to antipsychotic medications, is characterized by persistent dystonia of trunk muscles and abnormal posture. It is called Pisa syndrome, because the abnormal posture resembles the Leaning Tower of Pisa. Different from other types of dystonic reactions, Pisa syndrome is more prevalent in females and in older patients with organic brain changes. A 15-year-old male patient with mental retardation was admitted to pediatric neurology clinic for the complaint of abnormal posturing. He had been taking only risperidone for the last four years. Over the last month, the patient gradually developed tonic flexion of trunk and head toward left and was diagnosed with Pisa syndrome. In this paper, we aimed to discuss the association between risperidone use and Pisa syndrome in light of the available literature.

Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder.

The purpose of this study was to determine the levels of leptin, ghrelin, and nesfatin-1 to elucidate the causes of poor appetite and growth retardation in patients receiving methylphenidate therapy for attention deficit hyperactivity disorder. The study was performed on 89 male subjects; 48 patients and 41 healthy controls, aged 7-14 years. Following treatment, patients' leptin levels increased and ghrelin levels decreased while no significant change was found in nesfatin-1 levels. Of the 48 patients, 34 developed lack of appetite. In patients who developed lack of appetite, body weight SDS, body mass index (BMI), and BMI SDS were statistically significantly reduced; moreover, height SDS was reduced, though not to a statistically significant extent. This study attempted to elucidate the mechanisms that mediate the association between methylphenidate and appetite and growth, for which no studies have yet to be published.

Dystonia in an adolescent on risperidone following the discontinuation of methylphenidate: a case report.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with common comorbidities that include oppositional defiant disorder, conduct disorder, anxiety disorder, and affective disorders. Because of these comorbidities, drug combination treatments and drug-drug interactions are becoming increasingly more frequent. The present case report describes an acute dystonic reaction following the abrupt discontinuation of methylphenidate from a drug regimen with risperidone. The patient experienced acute dystonic reactions on three separate occasions when he forgot to take his methylphenidate medication. The present report informs clinicians about the possible side effects, such as dystonia, when psychostimulant and antipsychotic drug combinations are altered and suggests that the abrupt cessation of stimulants may lead to the development of movement disorders. Therefore, appropriate care is necessary when changing the dose of a drug or abruptly discontinuing a drug from a combination of psychostimulants and antipsychotics.

The Effect of Methylphenidate on the Hearing of Children with Attention Deficit Hyperactivity Disorder

Abstract Introduction There has been a sudden idiopathic hearing loss case presented after methylphenidate treatment in a child with attention deficit hyperactivity disorder (ADHD). Objective This study was performed to reveal the probable ototoxic side effects of methylphenidate use in patients with ADHD. Methods Thirty pediatric patients with ADHD were included in the study. Pure tone audiometry, speech discrimination scores, waves I, III, V absolute latencies and waves IIII, I-V, III-V interpeak latencies at the 80 dB nHL intensity after click stimulus auditory brainstem response (ABR) results were compared before and 3 months after methylphenidate treatment. Results There were no statistically significant difference between pretreatment and posttreatment pure tone and speech audiometry findings and ABR results (p > 0.05 for all parameters). Conclusion Methylphenidate can be regarded as a safe drug regarding ototoxic side effects. Additional studies with a larger sample size and longer follow-up may be needed.