Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.

OBJECTIVES: Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. METHODS: Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. RESULTS: Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low-density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus > or = 1 obesity-related complication at follow-up. CONCLUSIONS: There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Plasma antioxidant capacity is reduced in Asperger syndrome.

Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.

Influence of resting energy expenditure on weight gain in adolescents taking second-generation antipsychotics.

BACKGROUND & AIMS: Weight gain is an undesirable side effect of second-generation antipsychotics (SGAs). We performed this study to examine the influence of SGAs on resting energy expenditure (REE) and the relationship of REE to weight gain in adolescent patients. METHODS: Antipsychotic-naïve or quasi-naïve (<72 h of exposure to antipsychotics) adolescent patients taking olanzapine, quetiapine, or risperidone in monotherapy were followed up for one year. We performed a prospective study (baseline, 1, 3, 6, and 12 months after treatment) based on anthropometric measurements, bioelectrical impedance analysis, and indirect calorimetry (Deltatrac™ II MBM-200) to measure REE. We also analyzed metabolic and hormonal data and adiponectin concentrations. RESULTS: Forty-six out of the 54 patients that started treatment attended at least 2 visits, and 16 completed 1 year of follow-up. Patients gained 10.8 ± 6.2 kg (60% in the form of fat mass) and increased their waist circumference by 11.1 ± 5.0 cm after 1 year of treatment. The REE/kg body mass ratio decreased (p = 0.027), and the REE/percentage fat-free mass (FFM) ratio increased (p = 0.007) following the fall in the percentage of FFM during treatment. Weight increase was significantly correlated with the REE/percentage FFM ratio at all the visits (1-3-6-12 months) (r = 0.69, p = 0.004 at 12 months). CONCLUSIONS: SGAs seem to induce a hypometabolic state (reflected as decreased REE/kg body mass and increased REE/percentage FFM). This could explain, at least in part, the changes in weight and body composition observed in these patients.

Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

AIM: The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. METHOD: NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). RESULTS: Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. CONCLUSIONS: NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses.

Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics.

OBJECTIVE: The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs). METHOD: 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a > or = 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) > or = 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) > or = 95th BMI percentile. RESULTS: After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011). CONCLUSION: Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.