Jessica Merchán-Naranjo

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: Comprehensive review of prospective head-to-head and placebo-controlled comparisons

OBJECTIVEnTo review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders.nnnMETHODSnMedline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects.nnnRESULTSnIn total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n=788) were conducted in patients with schizophrenia, 6 (n=719) in subjects with bipolar disorder, and 19 (n=1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n=353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n=97), from 1.9 kg to 7.2 kg in those on risperidone (n=571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n=133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n=451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (-1.5 ng/mL to +13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences.nnnCONCLUSIONSnSGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances.

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

OBJECTIVESnDespite 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.nnnMETHODSnWeight 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.nnnRESULTSnBaseline 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.nnnCONCLUSIONSnThere are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Premorbid adjustment and clinical correlates of cognitive impairment in first-episode psychosis. The PEPsCog Study

BACKGROUNDnThe extent to which socio-demographic, clinical, and premorbid adjustment variables contribute to cognitive deficits in first-episode schizophrenia spectrum disorders remains to be ascertained.nnnAIMSnTo examine the pattern and magnitude of cognitive impairment in first-episode psychosis patients, the profile of impairment across psychosis subtypes and the associations with premorbid adjustment.nnnMETHODSn226 first-episode psychosis patients and 225 healthy controls were assessed in the PEPsCog study, as part of the PEPs study.nnnRESULTSnPatients showed slight to moderate cognitive impairment, verbal memory being the domain most impaired compared to controls. Broad affective spectrum patients had better premorbid IQ and outperformed the schizophrenia and other psychosis groups in executive function, and had better global cognitive function than the schizophrenia group. Adolescent premorbid adjustment together with age, gender, parental socio-economic status, and mean daily antipsychotic doses were the factors that best explained patients cognitive performance. General and adolescent premorbid adjustment, age and parental socio-economic status were the best predictors of cognitive performance in controls.nnnCONCLUSIONSnPoorer premorbid adjustment together with socio-demographic factors and higher daily antipsychotic doses were related to a generalized cognitive impairment and to a lower premorbid intellectual reserve, suggesting that neurodevelopmental impairment was present before illness onset.

Second-Generation Antipsychotic Use in Children and Adolescents: A Six-Month Prospective Cohort Study in Drug-Naïve Patients

OBJECTIVEnTo assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths.nnnMETHODnThis study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (meanxa0= 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group.nnnRESULTSnFrom baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (nxa0= 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (nxa0= 44; 11.5 kg and 1.08 BMI z score), and quetiapine (nxa0= 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be at risk of adverse health outcome increased during the 6 months from 8.9% to 29.2% for risperidone (pxa0< .0001), 6.8% to 38.1% for olanzapine (pxa0<xa0.0001), and 6.3%xa0to 4.0% for quetiapine (pxa0= .91).nnnCONCLUSIONnOlanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporalxa0side effect patterns.

A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis

BACKGROUNDnThe relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms.nnnMETHODSnA total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using a multivariate linear regression model after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up.nnnRESULTSnMean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p=0.007). Only shorter DUP (e.v. 8.7%, p=0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p=0.008) were significantly associated with greater improvement in EF.nnnCONCLUSIONSnIn early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.

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.

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

BACKGROUND & AIMSnWeight 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.nnnMETHODSnAntipsychotic-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.nnnRESULTSnForty-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).nnnCONCLUSIONSnSGAs 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.

QTc Changes after 6 Months of Second-Generation Antipsychotic Treatment in Children and Adolescents

PROLONGATION OF THE HEART-RATE corrected electrocardiographic QT interval (QTc) has been associated with an increased risk of severe cardiac arrhythmia (Moss 1993; de Bruyne et al. 1999; Hobbs et al. 2006; Straus et al. 2006). Antipsychotic medications are moderate risk factors associated with significant prolongation of the QTc interval (Warner et al. 1996; Reilly et al. 2000; Sadanaga et al. 2004; Mackin and Young 2005).

Reduced Gyrification Is Related to Reduced Interhemispheric Connectivity in Autism Spectrum Disorders.

OBJECTIVEnAutism spectrum disorders (ASD) have been associated with atypical cortical gray and subcortical white matter development. Neurodevelopmental theories postulate that a relation between cortical maturation and structural brain connectivity may exist. We therefore investigated the development of gyrification and white matter connectivity and their relationship in individuals with ASD and their typically developing peers.nnnMETHODnT1- and diffusion-weighted images were acquired from a representative sample of 30 children and adolescents with ASD (aged 8-18 years), and 29 typically developing children matched for age, sex, hand preference, and socioeconomic status. The FreeSurfer suite was used to calculate cortical volume, surface area, and gyrification index. Measures of structural connectivity were estimated using probabilistic tractography and tract-based spatial statistics (TBSS).nnnRESULTSnLeft prefrontal and parietal cortex showed a relative, age-dependent decrease in gyrification index in children and adolescents with ASD compared to typically developing controls. This result was replicated in an age-and IQ-matched sample provided by the Autism Brain Imaging Data Exchange (ABIDE) initiative. Furthermore, tractography and TBSS showed a complementary pattern in which left prefrontal gyrification was negatively related to radial diffusivity in the forceps minor in participants with ASD.nnnCONCLUSIONnThe present study builds on earlier findings of abnormal gyrification and structural connectivity in the prefrontal cortex in ASD. It provides a more comprehensive neurodevelopmental characterization of ASD, involving interdependent changes in microstructural white and cortical gray matter. The findings of related abnormal patterns of gyrification and white matter connectivity support the notion of the intertwined development of 2 major morphometric domains in ASD.