A systematic review and network meta-analysis on comparative efficacy, acceptability, and safety of treatments in acute bipolar mania in youths.

BACKGROUND: The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents. METHOD: We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455). RESULTS: Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ2 = 0.0072, I2 = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio. LIMITATIONS: Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered. CONCLUSIONS: Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.

Psychiatric comorbidity and familial factors in childhood epilepsy: Parental psychopathology, coping strategies, and family functioning.

OBJECTIVE: This study aimed to examine the psychiatric diagnoses, parenting attitudes, family functioning among children and adolescents with epilepsy, coping styles of their mothers, and psychiatric symptoms of their mothers and fathers. METHODS: Forty children and adolescents between the ages of 8 and 18 with epilepsy and 40 healthy controls were included in the study. The clinical interview and other measurements were used to assess psychiatric disorders and familial factors. RESULTS: At least one psychiatric disorder was diagnosed in 65% of children and adolescents with epilepsy. It was determined that the mothers and fathers in the epilepsy group had higher anxiety and depression scores than the control group, and the fathers' hostility scores were also higher. The Family Assessment Device (FAD) (problem-solving and affective responsiveness), Coping Strategies Scale (COPE) (mental disengagement and substance use), and Parent Attitude Scale (PAS) (strictness/supervision) subtest scores of the epilepsy group were higher than the control group. CONCLUSION: Psychiatric comorbidities, especially depression, anxiety disorders, and attention deficit hyperactivity disorder, are more common in children and adolescents with epilepsy. The mental health of parents, parent-child relationships, family functioning, and parental coping styles were adversely affected in families with children with epilepsy. It is essential to evaluate psychiatric comorbidity and family factors in children with epilepsy and to create a treatment plan for problem areas.

Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration.

AIM: Neurofilament light chain protein (NEFL), is defined as a structural protein which exists particularly in axones of neurons and is released to the cerum in consequence of neuroaxonal damage. The aim of this study is to investigate the peripheral cerumNEFLlevels of children and adolescents with early onset schizophrenia and bipolar disorder. METHOD: In this study, we evaluated serum levels of NEFL in children and adolescents (13-17 years) with schizophrenia, bipolar disorder and healthy control group. The study is conducted with 35 schizophrenia, 38 bipolar disorder manic episode patients and 40 healthy controls. RESULTS: The median age of the patient and control groups was 16 (IQR- Interquartile Range: 2). There was no statistical difference in median age (p = 0.52) and gender distribution(p = 0.53) between groups. NEFL levels of the patients with schizophrenia were significantly higher than the controls. NEFL levels of the patients with bipolar disorder were significantly higher than the controls. Serum levels of NEFL of the schizophrenia were higher than the bipolar disorder; however, the difference was not statistically significant. CONCLUSION: In conclusion, serum NEFL level, as a confidential marker of neural damage, is increased in the children and adolescents with bipolar disorder and schizophrenia. This result may indicatea degenerative period in neurons of children and adolescents with schizophrenia or bipolar disorder and may play a role in the pathophisiology of these disorders. This result shows that there is neuronal damage in both diseases, but neuronal damage may be more in schizophrenia.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Levels in Adolescent with Bipolar Disorder and Their Relationship with Metabolic Parameters.

Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the immune and metabolic regulatory agents. This study examined the serum PPARγ levels and metabolic syndrome (MetS) parameters in pediatric bipolar disorder (PBD) adolescents and compared them with healthy subjects. Serum PPARγ levels, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting insulin levels of 39 PBD-type I (age range: 14-18) and 36 age- and sex-matched healthy control subjects were compared. The anthropometric measurements were also analyzed, including body weight, height, body mass index (BMI), waist circumference (WC), and blood pressure measurements. The PPARγ levels were significantly lower, and the MetS prevalence was significantly higher in the PBD group than in the control group. The mean BMI, WC, serum TG, and FBG values of the PBD group were statistically higher than the healthy control group. There was no significant relationship between the PPARγ levels and metabolic parameters except fasting glucose. Lower PPARγ activity and higher MetS prevalence in PBD indicate dysregulation of immune and metabolic regulatory parameters. These results may shed light on developing new PBD medications.

Oropharyngeal Dysphagia as a Clinical Presentation of Lithium Intoxication: A Case Report.

Lithium is an effective treatment option for bipolar disorder in children and adolescents; however, the therapeutic window is narrow, and psychiatric, neurological, renal, gastrointestinal, dermatological, and endocrine side effects have been observed during lithium therapy.1 Iatrogenic dysphagia has been reported with psychotropic drugs, benzodiazepines, anti-inflammatory drugs, and some vasoactive drugs.2 However, oropharyngeal dysphagia due to lithium toxicity has not been reported in the literature.

Serum Ischemia-Modified Albumin Levels, Myeloperoxidase Activity and Peripheral Blood Mononuclear cells in Autism Spectrum Disorder (ASD).

Genetic, neurobiological, neurochemical, environmental factors and their interactions contribute to autism phenotypes. Blood from 48 (age range: 4-17) autism spectrum disorder diagnosed patients (ASD) and 38 age- and gender-matched healthy control subjects was analyzed for numbers of neutrophils, lymphocytes, monocytes, albumin, serum Ischemia-Modified Albumin (IMA) levels and myeloperoxidase activity. The serum IMA levels, myeloperoxidase activity and peripheral blood mononuclear cells count were significantly higher in ASD cases than in the control subjects. There were no significant differences in albumin levels between the patient and control groups. These results suggest that the immune system, oxidative stress and myeloperoxidase activity may be activated in ASD. There is a clinical benefit from the early detection of ASD using myeloperoxidase activity, IMA levels and monocyte counts.

Frequency and Correlates of Acute Dystonic Reactions After Antipsychotic Initiation in 441 Children and Adolescents.

Objective: To determine the incidence of acute dystonic reactions (ADRs) and risk factors for ADRs in children and adolescents treated with antipsychotics. Methods: This was a retrospective chart review-based cohort study of consecutive patients who attended a university hospital's child and adolescent psychiatry department between 2015 and 2017 and who were treated with antipsychotics and had at least two follow-up visits. Results: Thirty of 441 patients (6.8%) 4-19 years of age who were treated with antipsychotics for conduct disorders (21.5%), attention-deficit/hyperactivity disorder (13.2%) and, irritability and aggression that accompanied intellectual disability (12.9%) and followed for 99.5 ± 223.3 (median: 34) days developed ADRs. ADRs developed in 11/391 patients (2.8%) treated with one antipsychotic and 19/50 patients (38.0%) treated with two antipsychotics (p < 0.001). In patients treated with one antipsychotic that developed ADRs, the time to ADRs was 4.0 ± 4.0 days after antipsychotic initiation and 2.7 ± 2.4 days after an increase in the antipsychotic dose. The time to ADRs in those treated with two antipsychotics was 3.0 ± 2.3 days after the addition of the second antipsychotic and 1.6 ± 0.8 days after a dose increase in the second antipsychotic. The incidence of ADRs during antipsychotic monotherapy was 10.5% with first-generation antipsychotics (FGAs) and 2.2% with second-generation antipsychotics (SGAs; p = 0.037). The antipsychotic was changed due to ADRs in 12/30 (40.0%) of ADR cases. Independent factors associated with ADRs were antipsychotic polypharmacy (p < 0.0001), inpatient treatment (p = 0.013), FGA use (p = 0.015), and diagnoses of schizophrenia (p = 0.039) or bipolar disorder (p < 0.0001). Conclusion: SGAs and low-potency FGA monotherapy in children and adolescents were associated with a relatively low ADR risk, whereas high- and mid-potency FGAs were associated with a high risk. Independent predictors of ADRs were antipsychotic polypharmacy, inpatient treatment, FGAs, and schizophrenia or bipolar disorder diagnoses, which may be related to more aggressive antipsychotic dosing.

High prevalence of nonsuicidal self-injury, tattoos, and psychiatric comorbidity among male adolescent prisoners and their sociodemographic characteristics.

BACKGROUND: This study investigates the frequency of psychiatric disorders and the sociodemographic and clinical features in adolescent prisoners. METHOD: The psychiatric diagnoses and sociodemographic characteristics of treatment of 76 adolescent male prisoners and 76 age-matched patients were compared (age range: 15-17). RESULTS: Conduct disorder (85.5%), attention deficit hyperactivity disorder (61.8%), depression (50%), substance abuse (40.8%), post-traumatic stress disorder (19.7%), and psychotic disorder (3.9%) were more frequent among adolescent prisoners than the control group. The educational levels of parents of adolescent prisoners and their socioeconomic statuses were significantly lower, and the nonsuicidal self-injury (73.7%) and tattooing frequency (65.8%) were significantly higher among adolescent prisoners than the control group. Only 51.3% had both parents living together. CONCLUSION: Psychiatric disorders, low socioeconomic status, family disorganization, nonsuicidal self-injury, tattoos, and interruption of education were frequent in adolescent prisoners in this study. Our findings emphasize the importance of early psychiatric treatment and family-based interventions to help prevent adolescents from committing crimes. In addition, nonsuicidal self-injury and tattoos may be associated with criminal behavior in adolescents.

Psychiatric comorbidities of mild intellectual disability in children and adolescents in a clinical setting.

The aim of this study was to investigate the psychiatric disorders that accompany mild intellectual disability (ID) in school-aged children in a clinical setting. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview was conducted with the children with mild ID and their parents to diagnose any comorbid disorders. The mean age of the 111 children that fulfilled the study criteria was 12.09 ± 3.28 years, 59 of them (53.2%) were males, and 80.2% had at least one lifetime comorbid psychiatric diagnosis. Attention deficit hyperactivity disorder (64.9%), oppositional defiant disorder (21.6%), anxiety disorders (18.0%), were the most common comorbidities. The correlates of exhibiting comorbid psychiatric disorder were being male and irritability symptoms in the clinical history. Being aware of the comorbid psychiatric disorders and planning treatment strategies toward all of the diagnoses may help in the adaptation and rehabilitation of children with mild IDs.

Increased prolidase activity and high blood monocyte counts in pediatric bipolar disorder.

Various psychological, genetic, and biochemical factors are thought to be involved in the aetiology of pediatric bipolar disorder (PBD). However, few studies have evaluated the biochemical basis of PBD. The level of peripheral blood mononuclear cells and serum prolidase activity were determined in PBD and matched healthy comparison subjects. Blood from 38 (age range: 14-17) PBD-type I and 37 age- and gender-matched healthy comparison subjects was analyzed for numbers of neutrophils, lymphocytes, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and serum prolidase activity. The prolidase activity and monocyte count were significantly higher in PBD than the control group. There were no significant differences in numbers of neutrophils, lymphocytes, LMR and NLR between the patient and control groups. These results suggest that the immune system and prolidase activity may be activated in PBD. There is a clinical benefit from the early detection of PBD using serum prolidase activity levels and monocyte counts. Especially, prolidase activity may be a trait marker for diagnosing PBD. However, further studies are needed to verify these findings.

Effectiveness, Adverse Effects and Drug Compliance of Long-Acting Injectable Risperidone in Children and Adolescents.

BACKGROUND AND OBJECTIVES: Although the use of oral risperidone in children and adolescents has been well studied, there is little information on the intramuscular use of long-acting injectable risperidone (LAIR). The aims of this study were to investigate the effectiveness and adverse effects of LAIR in children and adolescents with conduct disorder, bipolar disorder, and schizophrenia. METHODS: In total, 42 patients (age range 12-17 years) who were non-adherent to oral antipsychotic drugs, received 25 mg of LAIR intramuscularly every 2 weeks. The drug was administered at least four times and up to 66 times (median drug use: 9.50 times). The effectiveness and adverse effects of the treatment were examined. RESULTS: There was an improvement in 13 (92.8%) of the 14 patients diagnosed with bipolar disorder, in 25 (78.1%) of 32 patients diagnosed with conduct disorder and in one (50%) of two patients diagnosed with schizophrenia. Six patients had comorbid conduct disorder and bipolar disorder. Totally, 81% of the patients improved with LAIR. Weight-gain, daytime somnolence, muscle stiffness and spasms, impaired concentration, and fatigue were the most common side effects through the whole sample. Menstrual problems were common in girls. In the study, 57.1% of the patients continued to receive their injections regularly until the end of the treatment, under physician control. A total of 16.7% discontinued the treatment due to non-adherence. The LAIR treatment was terminated in 26.2% of the patients, due to weight-gain, dystonia, and galactorrhea. CONCLUSIONS: In children and adolescents with conduct disorder, bipolar disorder and schizophrenia who show noncompliance with oral drugs, LAIR may improve treatment compliance. LAIR is a reliable treatment in terms of its effectiveness. Weight-gain, dystonia, and galactorrhea were the adverse effects that were responsible for LAIR treatment cessation.

High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders.

Objective: This study aims to investigate the level of peripheral blood mononuclear cells and their ratios which may point to the immunological mechanisms involved in the etiopathogenesis of ASD. Method: The complete blood count parameters of the 45 ASD cases were compared with those of healthy controls.Childhood Autism Rating Scale (CARS) was performed to measure the disease severity. Results: The monocytes of ASD group were significantly higher; and the lymphocyte-to-monocyte ratio (LMR) was lower than the controls'. LMR and neutrophil-to-lymphocyte ratio were found to be predictors of ASD. The decrease in LMR (B: -0.744; P=0.035; CI: -1.431 to -0.056) and the increase in age (B: 0.432; P=0.045; CI: 0.011-0.853) were related to high CARS scores in linear regression analyses. Conclusions: The results of this study support the role of altered immune cell counts and ratios in ASD. A high monocyte level and low LMR may have diagnostic values in autism.

Increased levels of serum neopterin in attention deficit/hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is the most frequently occurring neuropsychiatric disorder in childhood with an etiology that is not fully understood. A number of reviews that have addressed the neurobiology of ADHD have focused on imaging and genetics. Relatively little attention has been given to factors/mechanisms involved in the brain dysfunction. We suggest that changes in cellular immunity may be involved. Neopterin is a good indicator of cellular immunity, and we evaluated serum levels of neopterin in patients with ADHD. The study group consisted of 49 patients with ADHD. An age- and gender-matched control group was composed of 31 healthy subjects. Venous blood samples were collected, and the levels of neopterin were measured. The levels of neopterin were significantly higher in ADHD than in the comparison subjects. Cellular immunity may have a role in the etiopathogenesis of ADHD.

Lipid peroxidation markers in children with anxiety disorders and their diagnostic implications.

OBJECTIVE: Numerous factors, including genetic, neurobiological, neurochemical, and psychological factors, are thought to be involved in the development of anxiety disorders. The latest findings show that the pathophysiology of anxiety disorders might be associated with oxidative stress and lipid peroxidation; however, no studies have so far investigated lipid peroxidation markers in children with anxiety disorders. Serum levels of lipid hydroperoxide (LOOH) are a reliable marker of lipid peroxidation. Paraoxonase and arylesterase are two enzymes that protect against such peroxidation, and might also be diagnostic markers. In this study, we investigated whether there are associations between anxiety disorders and lipid peroxidation markers in children, and assessed the diagnostic performance of these markers. METHODS: The study group consisted of 37 patients (children and adolescents) with anxiety disorders. A control group, matched for age and gender, was composed of 36 healthy subjects. Venous blood samples were collected, and LOOH levels and paraoxonase and arylesterase activity were measured. RESULTS: LOOH levels were significantly higher in the anxiety disorders group than in the control group. There were no significant differences in paraoxonase or arylesterase activities between the patient and the control groups. DISCUSSION: Lipid peroxidation or oxidative damage might play a role in the aetiopathogenesis of anxiety disorders. LOOH may be a potential biological marker for anxiety disorders in children.

Serum nerve growth factor (NGF) levels in children with attention deficit/hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder of childhood. The etiopathogeny of ADHD has not been totally defined. Recent reports have suggested a pathophysiological role of neurotrophins in ADHD. In this study, we evaluated serum levels of nerve growth factor (NGF) in patients with ADHD. The sample population consisted of 44 child or adolescent patients diagnosed with ADHD according to DSM-IV criteria; 36 healthy subjects were included in the study as controls. Venous blood samples were collected, and NGF levels were measured. The mean serum NGF levels of the ADHD patients were significantly higher than those of the controls. Age and gender of the patients were not correlated with serum NGF levels. There were no significant differences in NGF levels among the combined and predominantly inattentive subtypes of ADHD. Our study suggests that there are higher levels of serum NGF in drug naive ADHD patients, and that increased levels of NGF might have an important role in the pathophysiology of ADHD.

Psychiatric comorbidity distribution and diversities in children and adolescents with attention deficit/hyperactivity disorder: a study from Turkey.

OBJECTIVE: We aimed to determine distribution and diversities of psychiatric comorbidities in children and adolescents with attention deficit/hyperactivity disorder (ADHD) in terms of age groups, sex, and ADHD subtype. MATERIALS AND METHODS: The sample included 6-18 year old children and adolescents from Turkey (N=108; 83 boys, 25 girls) diagnosed with ADHD. All comorbid diagnoses were determined based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version assessment. RESULTS: 96.3% of the cases were found to have at least one psychiatric comorbid diagnosis. The most frequent psychiatric comorbid disorder was oppositional defiant disorder (69.4%) followed by anxiety disorders (49%) and elimination disorders (27.8%). Disruptive behavior disorders were more common in ADHD-combined type. Depression and anxiety disorders were more common in girls. Separation anxiety disorder and elimination disorder were more common in children, whereas depression, bipolar disorder, obsessive-compulsive disorder, and social phobia were more common in the adolescents. CONCLUSION: According to our results, when a diagnostic tool was used to assess the presence of comorbid psychiatric disorders in children and adolescents diagnosed with ADHD, almost all cases had at least one comorbid diagnosis. Therefore, especially in the clinical sample, ADHD cases should not be solely interpreted with ADHD symptom domains, instead they should be investigated properly in terms of accompanying psychiatric disorders.

Changes in oxidative stress and cellular immunity serum markers in attention-deficit/hyperactivity disorder.

AIMS: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder with an etiopathogeny not fully understood. According to the prevailing view, the main factors contributing to the disorder are prefrontal dopamine deficiency and central dopaminergic dysfunction, but the factors/mechanisms involved in the brain dysfunction and its consequences are not well known. We suggest that changes in oxidative metabolism and cellular immunity may be involved. In this study, we aimed to investigate whether there are associations between ADHD and changes in serum levels of nitric oxide synthase (NOS), xanthine oxidase (XO), glutathione S-transferase (GST) and paraoxonase-1 (PON-1) activities, which are important markers of oxidative stress, and adenosine deaminase (ADA) activity, marker of cellular immunity. METHODS: The study sample consisted of 35 child or adolescent patients diagnosed with ADHD according to DSM-IV-TR criteria. Thirty-five healthy subjects were also included in the study as controls. Venous blood samples were collected, and NOS, XO, GST, PON-1 and ADA activities were measured. RESULTS: NOS, XO and ADA activities of the patients were significantly higher than those of the controls. GST and PON-1 activities of the patients were significantly lower than those of the controls. CONCLUSIONS: Changes in oxidative metabolism and cellular immunity may have a role in the etiopathogenesis of ADHD.