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1.
Eur Neuropsychopharmacol ; 67: 53-65, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36495858

RESUMO

Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness.


Assuntos
Transtornos Cognitivos , Reserva Cognitiva , Esquizofrenia , Humanos , Esquizofrenia/complicações , Seguimentos , Transtornos Cognitivos/etiologia , Cognição , Testes Neuropsicológicos , Memória de Curto Prazo , Doença Crônica , Recidiva
2.
Schizophr Res ; 248: 331-340, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36155307

RESUMO

BACKGROUND: The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up. METHODS: Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, after >2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions. RESULTS: Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden. CONCLUSIONS: The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Antagonistas Colinérgicos/efeitos adversos , Testes Neuropsicológicos , Transtornos Psicóticos/psicologia , Cognição , Doença Crônica , Dopamina , Recidiva
3.
Schizophr Res ; 244: 46-54, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35594732

RESUMO

Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders. We examined the network structure of the cognitive scores of a sample of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis. Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected. Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research.


Assuntos
Transtornos Cognitivos , Transtornos Psicóticos , Cognição , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Humanos , Memória de Curto Prazo , Testes Neuropsicológicos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/psicologia
4.
Eur Neuropsychopharmacol ; 49: 54-68, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33857739

RESUMO

The aim of the present study was to evaluate the contribution of family environment styles and psychiatric family history on functioning of patients presenting first-episode psychosis (FEP). Patients with FEP and healthy controls (HC) were assessed at baseline and after 2 years. The Functional Assessment Short Test (FAST) was used to assess functional outcome and the Family Environment Scale (FES) to evaluate family environment. Linear regressions evaluated the effect that family environment exerts on functioning at baseline and at 2-year follow-up, when FEP patients were diagnosed according to non-affective (NA-PSYCH) or affective psychoses (A-PSYCH). The influence of a positive parents' psychiatric history on functioning was evaluated through one-way between-groups analysis of covariance (ANCOVA) models, after controlling for family environmental styles. At baseline, FEP patients presented moderate functioning impairment, significantly worse than HC (28.65±16.17 versus 3.25±7.92; p<0.001, g = 1.91). At 2-year follow-up, the functioning of NA-PSYCH patients was significantly worse than in A-PSYCH (19.92±14.83 versus 12.46±14.86; p = 0.020, g = 0.50). No specific family environment style was associated with functioning in FEP patients and HC. On the contrary, a positive psychiatric father's history influenced functioning of FEP patients. After 2 years, worse functioning in NA-PSYCH patients was associated with lower rates of active-recreational and achievement orientated family environment and with higher rates of moral-religious emphasis and control. In A-PSYCH, worse functioning was associated with higher rates of conflict in the family. Both family environment and psychiatric history influence psychosocial functioning, with important implications for early interventions, that should involve both patients and caregivers.


Assuntos
Funcionamento Psicossocial , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/psicologia
5.
Eur Neuropsychopharmacol ; 47: 98-111, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33658165

RESUMO

Functional impairment is a defining feature of psychotic disorders. The Functional Assessment Short Test (FAST) is one of the most widely used instruments to measure psychosocial functioning. However, cut-offs of impairment have been well-established for bipolar disorders, but not for other clinical populations. This study aims to analyse psychometric properties of the FAST and establish their corresponding cut-off values for the different severity gradations in a first-episode of non-affective psychosis (FEP) patients. Global Assessment Functioning (GAF) and FAST ratings from 212 non-affective FEP and 204 healthy controls were analyzed. The psychometric properties of FAST (internal consistency, concurrent validity, discriminant validity, factorial analyses and sensitivity to change) were analyzed. The severity gradations of the FAST were defined by the congruence between two grading methods: linear regression analysis (LRA) and percentiles. The FAST showed strong psychometric properties. LRA with the GAF scores yielded the following equation: GAFscore= 80.83 - 0.639*FASTscore. The FAST ranges in non-affective FEP patients derived from LRA and percentiles, were as follows: 0-9 (No impairment); 10-19 (Minimal impairment); 20-34 (Mild impairment); 35-45 (Moderate impairment); 46-72 (Severe impairment). Patients with no functional impairment had a higher socioeconomic status, fewer depressive and negative symptoms, lower severity of illness and higher cognitive reserve level than the others groups. In conclusion, the FAST shows optimal psychometric properties which corroborate its applicability in FEP populations. It is a well-demonstrated valid instrument and the present cut-off scores could be implemented in clinical and research practice to assess properly the psychosocial functional outcome of non-affective FEP populations.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Humanos , Modelos Lineares , Psicometria , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia
6.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33618030

RESUMO

BACKGROUND: There are few studies exploring the pathophysiological pathways that may condition differentially the emergence/course of neurodevelopmental disorders (ND) in very preterm and extremely preterm newborns (VPTN/EPTN). Furthermore, there are no established biological markers predictive of ND in this population. The aim of this study is four-fold: in two cohorts of VPTN/EPTN (i) to characterize the emergence/course of ND up to corrected-age 6 years, (ii) to identify those factors (from prenatal stages up to age 6 years) that explain the interindividual differences related to emergence/course of ND, (iii) to identify in the first hours/days of life a urinary metabolomic biomarker profile predictive of ND, and (iv) to determine longitudinally variations in DNA methylation patterns predictive of ND. METHODS: Observational, longitudinal, prospective, six-year follow-up, multicentre collaborative study. Two cohorts are being recruited: the PeriSTRESS-Valencia-cohort (n=26 VPTN, 18 EPTN, and 122 born-at-term controls), and the PremTEA-Madrid-cohort (n=49 EPTN and n=29 controls). RESULTS: We describe the rationale, objectives and design of the PeriSTRESS-PremTEA project and show a description at birth of the recruited samples. CONCLUSIONS: The PeriSTRESS-PremTEA project could help improve early identification of clinical, environmental and biological variables involved in the physiopathology of ND in VPTN/EPTN. It could also help to improve the early identification of non-invasive ND biomarkers in this population. This may allow early ND detection as well as early and personalised intervention for these children.

7.
J Child Adolesc Psychopharmacol ; 28(7): 463-473, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29975563

RESUMO

OBJECTIVE: To analyze liver function tests (LFT), weight, metabolic syndrome (MetS) and at risk of meeting MetS criteria (AR-MetS) in children and adolescents on antipsychotics (AP) during a year-long follow-up. METHODS: Two hundred sixteen patients, AP naïve or quasi-naïve (<30 days on AP), were included. Total bilirubin, the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), weight and other parameters of MetS were measured at baseline, and at 3, 6 and 12 months, while patients remained on the same AP. RESULTS: At baseline, patients (mean age: 14.1 ± 3.1 years; 60.2% male) were on risperidone (N = 143), olanzapine (N = 37), or quetiapine (N = 36), although the sample decreased over time to 67 patients at 12 months (risperidone N = 46, olanzapine N = 10, and quetiapine N = 11). Around 3% of patients had ALT/AST levels that were at least twice the upper limit of normal (ULN) at 3 and 6 months; whereas roughly 19% of patients had ALP levels that were at least twice the ULN in at least one assessment after baseline, but had no clinical symptoms. From baseline to 6 months, significant increases were observed in ALT levels in the whole sample (p = 0.005), whereas ALP increased only in patients on risperidone. Patients showed significant weight gain, and more individuals met criteria for MetS and AR-MetS over time (from baseline: 2.8% and 8.3%, to 1 year: 10.5% and 23.9%, respectively). There was a trend-level group effect in global ALT across time (p = 0.076). Patients with MetS showed higher ALT concentrations (28.9 [18.4-39.4] U/L) than AR-MetS (20.4 [8.5-32.2] U/L), and no-AR-MetS (19.2 [8.4-29.9] U/L). CONCLUSIONS: Less than 3% of children and adolescents on AP during 1-year follow-up showed an increase in ALT or AST levels in one or more of the assessments, and none of these increases was of clinical significance. Patients with MetS and AR-MetS increased during this period, and the possible role of ALT levels to monitor these patients deserves further study.


Assuntos
Antipsicóticos/efeitos adversos , Testes de Função Hepática/métodos , Síndrome Metabólica/diagnóstico , Antagonistas da Serotonina/efeitos adversos , Adolescente , Feminino , Humanos , Masculino , Estudos Prospectivos
9.
Eur Child Adolesc Psychiatry ; 26(11): 1361-1376, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28447268

RESUMO

Executive function (EF) performance is associated with measurements of white matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and without intellectual disability and twenty-one typical male participants (TP) matched for age, intelligence quotient, handedness, race and parental socioeconomic status were recruited. Five EF domains were assessed and several DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The ASD group had lower scores for attention (F = 8.37, p = 0.006) and response inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and WMS measurements were present in TP but attenuated in the ASD group. The strongest diagnosis-by-age effect was found for forceps minor, left anterior thalamic radiation and left cingulum angular bundle (all p's ≤ 0.002). In these tracts subjects with ASD tended to have equal or increased FA and/or reduced MD and/or RD at younger ages while controls had increased FA and/or reduced MD and/or RD thereafter. Only for TP individuals, increased FA in the left anterior thalamic radiation was associated with better response inhibition, while reduced RD in forceps minor and left cingulum angular bundle was related to better problem solving and working memory performance respectively. These findings provide novel insight into the age-dependency of EF performance and WMS in ASD, which can be instructive to cognitive training programs.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Encéfalo/patologia , Função Executiva/fisiologia , Substância Branca/fisiopatologia , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Masculino
10.
Eur Child Adolesc Psychiatry ; 26(1): 35-46, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27209421

RESUMO

To analyze weight gain, metabolic hormones, and homocysteine (Hcys) levels in children and adolescents on antipsychotics (AP) during a year-long follow-up. 117 patients, AP-naïve or quasi-naïve (less than 30 days on AP), were included. Weight, body mass index (BMI), BMI z-score (z-BMI), and levels of leptin, insulin, insulin resistance (HOMA-IR), adiponectin, ghrelin, thyroid stimulating hormone (TSH), free thyroxine (FT4), and Hcys were measured at baseline, and at 3, 6, and 12 months, while patients remained on the same AP. Patients (mean age: 14.4 ± 3 years; 64.1 % male) were on risperidone (N = 84), olanzapine (N = 20) or quetiapine (N = 13) from baseline up to 1-year follow-up and significantly increased weight (5.8 ± 4.3 kg at 3-month, 8.1 ± 6.1 kg at 6-month, and 11.6 ± 7.0 kg at 1 year), BMI, and z-BMI. Leptin levels significantly increased from baseline to 3 and 6 months, as did TSH levels from baseline to 3 months, while FT4 levels decreased from baseline to 3 and 6 months. Patients with BMI >85th percentile at baseline (N = 16) significantly increased weight, BMI, and z-BMI, more than patients with normal BMI over time. Higher baseline levels of insulin, HOMA-IR, and leptin were associated with increased weight/BMI during follow-up, while higher baseline levels of FT4, adiponectin, and ghrelin were associated with lower weight/BMI during follow-up. All AP were associated with increased weight and BMI/z-BMI in all of the assessments; however, at 1-year assessment, this increase was significantly higher for patients on quetiapine. Both higher baseline levels of insulin, HOMA-IR, and leptin, as well as being overweight/obese at baseline were associated with increased weight/BMI during 1-year follow-up in children and adolescents on AP. Awareness of weight-related parameters in this population may help inform decisions regarding AP prescriptions.


Assuntos
Antipsicóticos/efeitos adversos , Homocisteína/sangue , Obesidade/sangue , Obesidade/induzido quimicamente , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/fisiologia , Adolescente , Antipsicóticos/uso terapêutico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Grelina/sangue , Humanos , Insulina/sangue , Leptina/sangue , Masculino , Obesidade/diagnóstico , Olanzapina , Estudos Prospectivos , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
11.
Rev. psiquiatr. salud ment ; 9(1): 39-50, ene.-mar. 2016. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-149684

RESUMO

Introducción: Los estudios reflejan datos contradictorios sobre un posible deterioro en el funcionamiento ejecutivo en niños y adolescentes con trastorno del espectro autista sin discapacidad intelectual (TEA-SDI). El objetivo del estudio es evaluar el perfil cognitivo de funcionamiento ejecutivo en niños y adolescentes con TEA-SDI y compararlo con el de controles sanos pareados en sexo, edad, estatus socioeconómico, nivel educacional y cociente intelectual (CI). Métodos: Veinticuatro pacientes con TEA-SDI (edad media 12,8 ± 2,5 años; 23 varones; media de CI 99,20 ± 18,81) y 32 controles (edad media 12,9 ± 2,7 años; 30 varones; media de CI 106,81 ± 11,02) fueron seleccionados. Resultados: Se encontraron diferencias estadísticamente significativas en todos los dominios cognitivos evaluados a favor de un mejor rendimiento por parte del grupo control: atención (U = 185,0; p = 0,0005; D = 0,90), memoria de trabajo (T51,48 = 2,597; p = 0,006; D = 0,72), flexibilidad cognitiva (U = 236,0; p = 0,007; D = 0,67), control inhibitorio (U = 210,0; p = 0,002; D = 0,71) y solución de problemas (U = 261,0; p = 0,021; D = 0,62). Estas diferencias se mantuvieron cuando se realizaron los análisis controlando por CI. Conclusión: Los niños y adolescentes con TEA-SDI tienen dificultades para transformar y manipular mentalmente información verbal, presentan latencias de respuesta mayores, problemas atencionales (dificultades en el cambio del set), problemas en la inhibición de respuestas automáticas, así como en la solución de problemas, a pesar de tener un CI normal. Teniendo en cuenta las dificultades en funcionamiento ejecutivo de estos pacientes, se recomienda una intervención integral, que incluya el trabajo en este tipo de dificultades (AU)


Introduction: Studies of executive function in autism spectrum disorder without intellectual disability (ASD-WID) patients are contradictory. We assessed a wide range of executive functioning cognitive domains in a sample of children and adolescents with ASD-WID and compared them with age-, sex-, and intelligence quotient (IQ)-matched healthy controls. Methods: Twenty-four ASD-WID patients (mean age 12.8 ± 2.5 years; 23 males; mean IQ 99.20 ± 18.81) and 32 healthy controls (mean age 12.9 ± 2.7 years; 30 males; mean IQ 106.81 ± 11.02) were recruited. Results: Statistically significant differences were found in all cognitive domains assessed, with better performance by the healthy control group: attention (U = 185.0; P = .0005; D = 0.90), working memory (T51.48 = 2.597; P = .006; D = 0.72), mental flexibility (U = 236.0; P = .007; D = 0.67), inhibitory control (U = 210.0; P = .002; D = 0.71), and problem solving (U = 261.0; P = 0.021; D = 0.62). These statistically significant differences were also found after controlling for IQ. Conclusion: Children and adolescents with ASD-WID have difficulties transforming and mentally manipulating verbal information, longer response latency, attention problems (difficulty set shifting), trouble with automatic response inhibition and problem solving, despite having normal IQ. Considering the low executive functioning profile found in those patients, we recommend a comprehensive intervention including work on non-social problems related to executive cognitive difficulties (AU)


Assuntos
Humanos , Função Executiva/fisiologia , Transtorno Autístico/fisiopatologia , Inteligência/fisiologia , Síndrome de Asperger/fisiopatologia , Testes Neuropsicológicos/estatística & dados numéricos , Habilidades Sociais , 35249
12.
Rev Psiquiatr Salud Ment ; 9(1): 39-50, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26724269

RESUMO

INTRODUCTION: Studies of executive function in autism spectrum disorder without intellectual disability (ASD-WID) patients are contradictory. We assessed a wide range of executive functioning cognitive domains in a sample of children and adolescents with ASD-WID and compared them with age-, sex-, and intelligence quotient (IQ)-matched healthy controls. METHODS: Twenty-four ASD-WID patients (mean age 12.8±2.5 years; 23 males; mean IQ 99.20±18.81) and 32 healthy controls (mean age 12.9±2.7 years; 30 males; mean IQ 106.81±11.02) were recruited. RESULTS: Statistically significant differences were found in all cognitive domains assessed, with better performance by the healthy control group: attention (U=185.0; P=.0005; D=0.90), working memory (T51.48=2.597; P=.006; D=0.72), mental flexibility (U=236.0; P=.007; D=0.67), inhibitory control (U=210.0; P=.002; D=0.71), and problem solving (U=261.0; P=0.021; D=0.62). These statistically significant differences were also found after controlling for IQ. CONCLUSION: Children and adolescents with ASD-WID have difficulties transforming and mentally manipulating verbal information, longer response latency, attention problems (difficulty set shifting), trouble with automatic response inhibition and problem solving, despite having normal IQ. Considering the low executive functioning profile found in those patients, we recommend a comprehensive intervention including work on non-social problems related to executive cognitive difficulties.


Assuntos
Transtorno do Espectro Autista/psicologia , Função Executiva , Inteligência , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Testes de Inteligência , Masculino , Testes Neuropsicológicos
13.
J Child Adolesc Psychopharmacol ; 26(5): 449-57, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26779966

RESUMO

BACKGROUND: Prescriptions of antipsychotic drugs (AP) in children and adolescents have significantly increased in Europe as well as in the United States. However, there is limited evidence of the cardiac safety of second-generation antipsychotics (SGA) in the pediatric population. OBJECTIVE: The aim of the study is to evaluate the cardiac side effects of SGA in children and adolescents, and how they are influenced by clinical, demographic, and treatment factors. METHODS: This article presents a naturalistic, longitudinal, multicenter study conducted in 216 treatment-naïve or quasi-naïve children and adolescents receiving AP treatment. It analyzed the possible influence of AP treatment on variables such as corrected QT (QTc) intervals and heart rate for a period of 12 months (baseline, 3 months, 6 months, and 12 months). Differences among the three main prescribed drugs used in the sample (risperidone, quetiapine, and olanzapine) were assessed. RESULTS: A total of 211 received one of the three most prescribed AP (quetiapine, risperidone or olanzapine). There were no significant QTc variations in the sample during follow-up (p = 0.54). There were no differences in QTc rates between the different SGA (risperidone-olanzapine p = 0.43; risperidone-quetiapine p = 0.42; olanzapine-quetiapine p = 0.23). When demographic, clinical, or concomitant treatment variables were considered, only baseline overweight correlated with QTc prolongation (p = 0.003). The heart rate in the whole sample tended to decrease during follow-up (p = 0.054). However, patients on quetiapine showed increased heart rate compared with those on risperidone (p = 0.04). CONCLUSIONS: In this sample, SGA seem to have a safe heart side effect profile in the child and adolescent population. There was no observed mean increase in QTc or in heart rate.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/uso terapêutico , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Adolescente , Biomarcadores Farmacológicos , Criança , Pré-Escolar , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Síndrome do QT Longo/diagnóstico , Estudos Longitudinais , Masculino , Olanzapina , Estudos Prospectivos
14.
J Clin Psychopharmacol ; 35(6): 686-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26505569

RESUMO

OBJECTIVE: The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics. METHODS: This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression. RESULTS: Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up. CONCLUSIONS: Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and treatment factors predicted an increased risk of TD.


Assuntos
Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Discinesia Induzida por Medicamentos/etiologia , Doença de Parkinson Secundária/induzido quimicamente , Fumarato de Quetiapina/efeitos adversos , Risperidona/efeitos adversos , Adolescente , Criança , Pré-Escolar , Discinesia Induzida por Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Olanzapina , Doença de Parkinson Secundária/epidemiologia
15.
J Am Acad Child Adolesc Psychiatry ; 54(8): 668-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26210336

RESUMO

OBJECTIVE: Autism 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. METHOD: T1- 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). RESULTS: Left 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. CONCLUSION: The 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.


Assuntos
Transtorno do Espectro Autista/patologia , Córtex Cerebral/patologia , Adolescente , Transtorno do Espectro Autista/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Criança , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Neuroimagem , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia
16.
Eur Child Adolesc Psychiatry ; 24(12): 1447-59, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25726022

RESUMO

The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP.


Assuntos
Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Ajustamento Social , Fatores de Tempo
17.
Schizophr Res ; 164(1-3): 65-73, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25819935

RESUMO

BACKGROUND: The extent to which socio-demographic, clinical, and premorbid adjustment variables contribute to cognitive deficits in first-episode schizophrenia spectrum disorders remains to be ascertained. AIMS: To 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. METHODS: 226 first-episode psychosis patients and 225 healthy controls were assessed in the PEPsCog study, as part of the PEPs study. RESULTS: Patients 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. CONCLUSIONS: Poorer 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.


Assuntos
Transtornos Cognitivos/etiologia , Transtornos Psicóticos/complicações , Adolescente , Adulto , Análise de Variância , Criança , Transtornos Cognitivos/epidemiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/epidemiologia , Estatística como Assunto , Adulto Jovem
18.
J Am Acad Child Adolesc Psychiatry ; 53(11): 1179-90,1190.e1-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25440308

RESUMO

OBJECTIVE: To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths. METHOD: This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 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. RESULTS: From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 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 (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91). CONCLUSION: Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Adolescente , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/uso terapêutico , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Olanzapina , Prognóstico , Estudos Prospectivos , Fumarato de Quetiapina , Fatores de Risco , Risperidona/efeitos adversos , Risperidona/uso terapêutico
19.
J Clin Psychopharmacol ; 34(5): 613-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25154009

RESUMO

OBJECTIVE: The objective of this study was to analyze the initial treatment with antipsychotics (APs) and its changes during the first year of treatment in patients visited in specialized child and adolescent psychiatry departments. METHODS: Participants were 265 patients, aged 4 to 17 years, who attended consecutively at 4 different centers and were naive of AP or quasi-naive (less than 30 days since the beginning of AP treatment). Type of AP, dosage, and concomitant medication were registered at baseline, 1, 3, 6, and 12 months after beginning the treatment with AP. RESULTS: At baseline, the patients' mean age was 14.4 (2.9) years, and 145 (54.7%) patients were males. Antipsychotics were more prescribed in the following: schizophrenia spectrum disorders (30.2%), disruptive behavior disorders (DBDs) (18.9%), bipolar disorders (14.3%), depressive disorders (12.8%), and eating disorders (11.7%). A total of 93.2% of the patients were on an off-label indication of AP. Risperidone was the AP most prescribed in all the assessments, but differences were observed in the type of AP according to diagnosis. Thus, risperidone was significantly most prescribed in patients with DBD and olanzapine was most prescribed in patients with eating disorders. Olanzapine and quetiapine were the second-generation APs (SGAs) most prescribed after risperidone, and haloperidol was the most prescribed first-generation AP. Up to 8.3% of patients during the follow-up were on AP polypharmacy. Almost 16% patients had a change in its AP treatment during the follow-up, and the main switch was from one SGA to another. CONCLUSIONS: Second-generation APs were the APs most prescribed in our sample and approximately 93% of the patients used AP off-label. Risperidone was the most common AP used above all in patients with DBD, whereas olanzapine was most prescribed in patients with eating disorders. Antipsychotic polypharmacy and switch rates were low during the follow-up.


Assuntos
Antipsicóticos/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Polimedicação , Espanha
20.
Schizophr Res ; 158(1-3): 126-33, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25034759

RESUMO

BACKGROUND: The 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. METHODS: A 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. RESULTS: Mean 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. CONCLUSIONS: In early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.


Assuntos
Função Executiva , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Adolescente , Feminino , Seguimentos , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Análise Multivariada , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Fatores de Tempo
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