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BACKGROUND: Therapeutic drug monitoring of clozapine in children and adolescents has received insufficient attention. Calculation of concentration-to-dose (C/D) ratios from trough steady-state concentrations estimate drug clearance. METHODS: A systematic electronic literature search was conducted in 3 article databases from inception until January 10, 2023, and articles reporting clozapine concentrations in children and adolescents were retrieved. The pharmacokinetic quality of the studies was assessed, and clozapine C/D ratios were calculated using the sample mean clozapine dose and concentration. RESULTS: Of the 37 articles of potential interest, only 7 reported clozapine trough and steady-state concentrations. After excluding case reports and a study confounded by fluvoxamine, 4 studies on psychosis from Europe and the United States were included. The clozapine C/D ratios were similar to published adult values and ranged from 0.82 to 1.24 with a weighted mean of 1.08 ng/mL per mg/d. The weighted means were 334 mg/d for the dose and 380 ng/mL for the concentration. The stratified analysis of the weighted mean clozapine C/D ratios from 2 studies showed lower values in 52 male (1.05 ng/mL per mg/d) than in 46 female (1.46 ng/mL per mg/d) children and adolescents, with values similar to those reported for European adult nonsmokers. Two female adolescents had high clozapine C/D ratios (2.54 ng/mL per mg/d), an Asian American patient with borderline obesity and a patient with intellectual disability with low dosage (mean = 102 mg/d) and concentration (mean = 55 ng/mL). CONCLUSIONS: Reports on clozapine therapeutic drug monitoring in children and adolescents are limited in number and quality. Future studies should focus on basic pharmacokinetic issues, such as stratification by sex, smoking, and relevant comedications with inductive or inhibitory properties.
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Antipsicóticos , Clozapina , Transtornos Mentais , Transtornos Psicóticos , Adulto , Criança , Masculino , Humanos , Feminino , Adolescente , Clozapina/uso terapêutico , Clozapina/farmacocinética , Antipsicóticos/uso terapêutico , Antipsicóticos/farmacocinética , Monitoramento de Medicamentos , Transtornos Mentais/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológicoRESUMO
PURPOSE: Pregnancy is a risk period for the development of mental disorders. About 10% of pregnant women worldwide experience a mental disorder, mainly depression, and this percentage has been aggravated by the COVID-19 pandemic. This study aims to understand the impact of COVID-19 on the mental health of pregnant women. METHODS: Three hundred and one pregnant women in the week 21.85 ± 9.9 were recruited through social media and pregnant women forums from September 2020 to December 2020. A multiple-choice questionnaire was administered to evaluate the sociodemographic characteristics of the women, the care provided, and different aspects related to COVID-19. A Beck Depression Inventory was also delivered. RESULTS: Of the pregnant women 23.5% had seen or had considered seeing a mental health professional during pregnancy. Predictive models using multivariate logistic regression found that this fact was associated with an increased risk of depression (OR = 4.22; CI 95% 2.39-7.52; P < 0.001). Among women with moderate-severe depression, it was associated with an increased risk of having suicidal thoughts (OR = 4.99; CI 95% 1.11-27.9; P = 0.044) and age was found to be a protective variable (OR = 0.86; CI 95% 0.72-0.98; P = 0.053). CONCLUSIONS: The COVID-19 pandemic represents a major mental health challenge for pregnant women. Despite the decrease in face-to-face visits, there are opportunities for health professionals to identify the existence of psycho-pathological alterations and suicidal ideation by asking the patient if she is seeing or considering seeing a mental health professional. Therefore, it is necessary to develop tools for early identification to ensure correct detection and care.
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COVID-19 , Gestantes , Feminino , Humanos , Gravidez , Gestantes/psicologia , Depressão/diagnóstico , Pandemias , Ideação Suicida , COVID-19/epidemiologiaRESUMO
Several studies have shown an increased prevalence of anxiety, depression and suicidal ideation in the general population in relation to the COVID-19 pandemic.
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COVID-19 , Humanos , COVID-19/epidemiologia , Saúde Mental , Pandemias , Ansiedade/epidemiologia , Transtornos de AnsiedadeRESUMO
OBJECTIVE: To investigate oxidative stress markers and antioxidants in bipolar disorder (BD). METHODS: Electronic MEDLINE/PubMed/Cochrane-Library/Scopus/TripDatabase search until 06/30/2019 for studies comparing antioxidant or oxidative stress markers between BD and healthy controls (HCs). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for ≥3 studies. RESULTS: Forty-four studies (n = 3,767: BD = 1,979; HCs = 1,788) reported on oxidative stress markers malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), and total nitrites; antioxidants glutathione (GSH), uric acid, and zinc; or antioxidantenhancing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and GSH-transferase (GST). Compared with HCs, BD was associated with higher GST (P = .01), CAT (P = .02), nitrites (P < .0001), TBARS (P < .0001), MDA (P = .01), uric acid (P < .0001), and lower GSH (P = .006), without differences in SOD, GPX, and zinc. Compared to HCs, levels were higher in BD-mania for TBARS (P < .0001) and uric acid (P < .0001); in BD-depression for TBARS (P = .02); and BD-euthymia for uric acid (P = .03). Uric acid levels were higher in BD-mania vs BD-depression (P = .002), but not vs BD euthymia. TBARS did not differ between BD-mania and BD-depression. Medication-free BD-mania patients had higher SOD (P = .02) and lower GPX (P < .0001) than HCs. After treatment, BD did not differ from HCs regarding SOD and GPX. CONCLUSIONS: Beyond a single biomarker of oxidative stress, the combination of several parameters appears to be more informative for BD in general and taking into account illness polarity. BD is associated with an imbalance in oxidative stress with some phase-specificity for uric acid and TBARS and possible treatment benefits for SOD and GPX. Future studies should take into account confounding factors that can modify oxidative stress status and simultaneously measure oxidative stress markers and antioxidants including different blood sources.
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Antioxidantes , Transtorno Bipolar , Transtorno Bipolar/tratamento farmacológico , Glutationa Peroxidase/metabolismo , Humanos , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
The aim of this study was to investigate the factors associated with illness insight and medication adherence in bipolar disorder (BD). This is a cross-sectional study (with a retrospective evaluation of longitudinal variables) and a secondary analysis of a BD database. The insight of 108 outpatients (age, 48.2 ± 14.1 years, 69% women, 33% euthymic) was measured with three items of the Association of Methodology and Documentation in Psychiatry scale. Their adherence was assessed through patients' and caregivers' reports, plus serum levels. We performed multivariate logistic regression analyses. Full insight was independently and directly associated with adherence, a social support score, and depressive symptoms and inversely associated with intensity of manic symptoms, problems ever with alcohol, and age at onset of the first symptoms. Medication adherence was independently and directly associated with insight, being married, and having had a psychiatric hospitalization and inversely with having suffered a high number of depressive episodes, intensity of manic symptoms, and heavy tobacco smoking.
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Transtorno Bipolar/psicologia , Depressão/psicologia , Adesão à Medicação/psicologia , Apoio Social , Adulto , Idade de Início , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Pacientes Ambulatoriais , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Espanha , Fumar Tabaco/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: To study differences in oxidative stress markers and antioxidants among patients with bipolar depression (BPD) and unipolar depression (UPD). METHODS: Data sources. Electronic MEDLINE/PubMed/Cochrane Library/Scopus/TripDatabase database search until 30/06/2021. STUDY SELECTION: Included were articles comparing antioxidant or oxidative stress markers between adults with BPD or UPD and healthy controls (HCs). DATA EXTRACTION: Two authors extracted data independently. Random effects meta-analysis, calculating standardized mean differences for results from ≥3 studies. RESULTS: Oxidative stress markers reported in 40 studies -1 published repeatedly- (UPD, studies = 30 n = 3072; their HCs, n = 2856; BPD, studies = 11 n = 393; their HCs, n = 540; with 1 study reporting on both UPD and BPD) included thiobarbituric acid reactive substances (TBARS), antioxidant uric acid and antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPX). Compared with HCs, UPD and BPD were associated with significantly higher levels of TBARS, without differences between UPD and BPD (P = 0.11). Compared with HCs, UPD and BPD did not differ regarding the activity of the CAT (P = 0.28), SOD (P = 0.87) and GPX (P = 0.25) enzymes. However, uric acid levels were significantly higher vs HCs in BPD than in UPD among adult patients (P = 0.004). Results were heterogenous, which, for some parameters, decreased after stratification by the blood source (serum, plasma red blood cells, whole blood). LIMITATIONS: The main limitations are the small number of studies/participants in the BPD subgroup, and heterogeneity of the results. SUMMATIONS: Both BPD and UPD may be associated with an impaired oxidative stress balance, with significantly higher uric acid levels vs. HCs in UPD than in BPD.
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Antioxidantes , Transtorno Bipolar , Depressão , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Biomarcadores , Transtorno Bipolar/metabolismo , Catalase/metabolismo , Depressão/metabolismo , Glutationa Peroxidase , Humanos , Estresse Oxidativo/fisiologia , Superóxido Dismutase , Substâncias Reativas com Ácido Tiobarbitúrico , Ácido ÚricoRESUMO
The aim of this work is to investigate the effectiveness of Deep Brain Stimulation (DBS) in patients with severe Obsessive Compulsive Disorder (OCD) who are resistant to pharmacological treatments, focusing on obsessive compulsive, depressive and anxiety symptoms as well as global function. A systematic review and meta-analysis including 25 studies (without language restrictions) from between 2003 and 2020 was performed. A total of 303 patients were evaluated twice (before and after DBS). After DBS treatment OCD patients with resistance to pharmacological treatments showed a significant improvement of obsessive-compulsive symptoms (25 studies; SMD=2.39; 95% CI, 1.91 to 2.87; P<0.0001), depression (9 studies; SMD= 1.19; 95%CI, 0.84 to 1.54; P<0.0001), anxiety (5 studies; SMD=1.00; 95%CI, 0.32 to 1.69; P=0.004) and functionality (7 studies; SMD=-3.51; 95%CI, -5.00 to -2.02; P=0.005) measured by the standardized scales: Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Global Assessment of Function (GAF). Publication bias were discarded by using funnel plot. The main conclusions of this meta-analysis highlight the statistically significant effectiveness of DBS in patients with severe OCD who are resistant to conventional pharmacological treatments, underlying its role in global functioning apart from obsessive-compulsive symptoms.
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Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo , Humanos , Estimulação Encefálica Profunda/métodos , Transtorno Obsessivo-Compulsivo/diagnóstico , Ansiedade , Resultado do TratamentoRESUMO
In 2020, the Governments of many countries maintained different levels of confinement of the population due to the pandemic that produced the COVID-19. There are few studies published on the psychological impact in the child and adolescent population diagnosed with mental disorders, especially during the home confinement stage. Explanatory models based on socio-demographic and clinical variables provide an approximation to level changes in different dimensions of behavioural difficulties. A categorical-response logistic ordinal regression model, based on a cross-sectional study with 139 children and adolescents diagnosed with mental disorders is performed for each dimension under analysis. Most of the socio-demographic and clinical explanatory variables considered (24 of 26) were significant at population level for at least one of the four dimensions of behavioural difficulties (15 response variables) under analysis. Odds-ratios were interpreted to identify risk or protective factors increasing or decreasing severity in the response variable. This analysis provides useful information, making it possible to more readily anticipate critical situations due to extreme events, such as a confinement, in this population.
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Objective: The aim of this study is to determine the prevalence of three possible diagnostic specifiers, namely predominant polarity (PP) throughout illness, polarity of the first episode and early age at onset, in a sample of bipolar disorder (BD) patients and their association with important socio-demographic, clinical and course-of-illness variables. Methods: A retrospective and naturalistic study on 108 BD outpatients, who were classified according to the PP, polarity of the first episode and early age at onset (≤ 20 years) [vs. late (>20 years)] and were characterized by their demographics, clinical data, functionality and social support, among others features. After bivariate analyses, those variables showing certain association (P value < 0.25) with the three dependent variables were entered in logistic regression backward selection procedures to identify the variables independently associated with the PP, polarity of the first episode and early age at onset. Results: The sample consisted of 75 women ad 33 men, 74% with type I BD and 26% with type II. Around 70% had depressive PP, onset with a depressive episode and onset after age 20. Depressive PP was independently associated with depressive onset, higher score on the CGI severity scale and work disability. Onset with depressive episode was associated with type II BD, longer diagnostic delay and higher score on family disability. Early age at onset (≤ 20 years) was associate with younger age, longer diagnostic delay, presence of ever psychotic symptoms, current use of antipsychotic drugs and higher social support score. Conclusions: The results of this study show that BD patients with depressive PP, onset with depression and early age at onset may represent greater severity, because they are frequently associated with variables that worsen the prognosis. Our findings match up with the conclusions of two systematic reviews and we also include a disability factor (at family and work) that has not been previously reported. This work contributes to the use of polarity and age at onset in BD patients, as it can become a useful instrument in the prognostic and therapeutic applications.
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Introduction: Although attenuated psychotic symptoms often occur for the first time during adolescence, studies focusing on adolescents are scarce. Attenuated psychotic symptoms form the criteria to identify individuals at increased clinical risk of developing psychosis. The study of individuals with these symptoms has led to the release of the DSM-5 diagnosis of Attenuated Psychosis Syndrome (APS) as a condition for further research. We aimed to characterize and compare hospitalized adolescents with DSM-5-APS diagnosis vs. hospitalized adolescents without a DSM-5-APS diagnosis. Methods: Interviewing help-seeking, hospitalized adolescents (aged 12-18 years) and their caregivers independently with established research instruments, we (1) evaluated the presence of APS among non-psychotic adolescents, (2) characterized and compared APS and non-APS individuals regarding sociodemographic, illness and intervention characteristics, (3) correlated psychopathology with levels of functioning and severity of illness and (4) investigated the influence of individual clinical, functional and comorbidity variables on the likelihood of participants to be diagnosed with APS. Results: Among 248 consecutively recruited adolescents (age=15.4 ± 1.5 years, females = 69.6%) with non-psychotic psychiatric disorders, 65 (26.2%) fulfilled APS criteria and 183 (73.8%) did not fulfill them. Adolescents with APS had higher number of psychiatric disorders than non-APS adolescents (3.5 vs. 2.4, p < 0.001; Cohen's d = 0.77), particularly, disruptive behavior disorders (Cramer's V = 0.16), personality disorder traits (Cramer's V = 0.26), anxiety disorders (Cramer's V = 0.15), and eating disorders (Cramer's V = 0.16). Adolescents with APS scored higher on positive (Cohen's d = 1.5), negative (Cohen's d = 0.55), disorganized (Cohen's d = 0.51), and general symptoms (Cohen's d = 0.84), and were more severely ill (Cohen's d = 1.0) and functionally impaired (Cohen's d = 0.31). Negative symptoms were associated with lower functional levels (Pearson ρ = -0.17 to -0.20; p = 0.014 to 0.031). Global illness severity was associated with higher positive, negative, and general symptoms (Pearson ρ = 0.22 to 0.46; p = 0.04 to p < 0.001). APS status was independently associated with perceptual abnormalities (OR = 2.0; 95% CI = 1.6-2.5, p < 0.001), number of psychiatric diagnoses (OR = 1.5; 95% CI = 1.2-2.0, p = 0.002), and impaired stress tolerance (OR = 1.4; 95% CI = 1.1-1.7, p = 0.002) (r 2 = 0.315, p < 0.001). Conclusions: A considerable number of adolescents hospitalized with non-psychotic psychiatric disorders meet DSM-5-APS criteria. These help-seeking adolescents have more comorbid disorders and more severe symptoms, functional impairment, and severity of illness than non-APS adolescents. Thus, they warrant high intensity clinical care.
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Objectives: Bipolar disorder (BD) is a debilitating illness that often starts at an early age. Prevention of first and subsequent mood episodes, which are usually preceded by a period characterized by subthreshold symptoms is important. We compared demographic and clinical characteristics including severity and duration of subsyndromal symptoms across adolescents with three different bipolar-spectrum disorders. Methods: Syndromal and subsyndromal psychopathology were assessed in adolescent inpatients (age = 12-18 years) with a clinical mood disorder diagnosis. Assessments included the validated Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P). We compared phenomenology across patients with a research consensus conference-confirmed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnoses of BD-I, BD-not otherwise specified (NOS), or mood disorder (MD) NOS. Results: Seventy-six adolescents (age = 15.6 ± 1.4 years, females = 59.2%) were included (BD-I = 24; BD-NOS = 29; MD-NOS = 23) in this study. Median baseline global assessment of functioning scale score was 21 (interquartile range = 17-40; between-group p = 0.31). Comorbidity was frequent, and similar across groups, including disruptive behavior disorders (55.5%, p = 0.27), anxiety disorders (40.8%, p = 0.98), and personality disorder traits (25.0%, p = 0.21). Mania symptoms (most frequent: irritability = 93.4%, p = 0.82) and depressive symptoms (most frequent: depressed mood = 81.6%, p = 0.14) were common in all three BD-spectrum groups. Manic and depressive symptoms were more severe in both BD-I and BD-NOS versus MD-NOS (p < 0.0001). Median duration of subthreshold manic symptoms was shorter in MD-NOS versus BD-NOS (11.7 vs. 20.4 weeks, p = 0.002) and substantial in both groups. The most used psychotropics upon discharge were antipsychotics (65.8%; BD-I = 79.2%; BD-NOS = 62.1%; MD-NOS = 56.5%, p = 0.227), followed by mood stabilizers (43.4%; BD-I = 66.7%; BD-NOS = 31.0%; MD-NOS = 34.8%, p = 0.02) and antidepressants (19.7%; BD-I = 20.8%; BD-NOS = 10.3%; MD-NOS = 30.4%). Conclusions: Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing BD or other affective episodes requiring hospitalization.
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Transtorno Bipolar/fisiopatologia , Transtornos do Humor/epidemiologia , Psicotrópicos/administração & dosagem , Adolescente , Transtornos de Ansiedade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos da Personalidade/epidemiologia , Psicotrópicos/farmacologia , Índice de Gravidade de DoençaRESUMO
Studies on disordered eating behaviors (DEB) in multicultural populations with multiple religious/cultural affiliations are needed in order to clarify the relationship between cultural background and DEB. Therefore, we compared the presence of DEB among Christian and Muslim adolescents who share their school environment, controlling for the effect of body mass index, demographic variables and lifestyle habits. A sample of 493 girls and boys (339 Christian, 138 Muslim) whose mean (±SD) age was 14.8 (±1.7) years completed self-reporting questionnaires and underwent measurements of anthropometric data. Religious/cultural affiliation was defined by self-identification. The dependent variable, DEB was assessed by means of the Eating Disorders Inventory (EDI-2). Muslim girls and boys score higher than Christians on EDI-2 total scores, especially on the perfectionism subscale. Bivariate and multivariate analyses were used to determine the characteristics associated with DEB, which were detected in 24% of participants (19% of Christians and in 35% of Muslims). Among girls, DEB were directly associated with overweight or obesity, the presence of frequent quarrels with parents, academic failure and spending more than 3 h a day watching screen images. Among boys, DEB were directly associated with overweight or obesity and Muslim background; and inversely associated with age and socioeconomic status.
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Comportamento do Adolescente/etnologia , Cristianismo/psicologia , Cultura , Transtornos da Alimentação e da Ingestão de Alimentos/etnologia , Islamismo/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Fatores Etários , Antropometria , Índice de Massa Corporal , Comportamento Alimentar/etnologia , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Estilo de Vida , Masculino , Obesidade/etnologia , Obesidade/psicologia , Autorrelato , Fatores Sexuais , Classe Social , EspanhaRESUMO
OBJECTIVE: There is no standard method for assessing symptoms of the prodrome to bipolar disorder (BD), which has limited progress toward early identification and intervention. We aimed to validate the Bipolar Prodrome Symptom Scale-Abbreviated Screen for Patients (BPSS-AS-P), a brief self-report derived from the validated, clinician-rated Bipolar Prodrome Symptom Interview and Scale-Full Prospective (BPSS-FP), as a means to screen and identify people for whom further evaluation is indicated. METHOD: Altogether, 134 participants (aged 12-18 years) were drawn from a study of the pre-syndromal stage of mood and psychotic disorders. All participants had chart diagnoses of a mood- or psychosis-spectrum disorder. Participants were interviewed with the BPSS-FP and completed measures of mania and non-mood psychopathology. Prior to being interviewed, patients completed the BPSS-AS-P. Scores on the BPSS-AS-P were determined by summing the severity and frequency ratings for each item. RESULTS: BPSS-AS-P scores were highly reliable (Cronbach's alphaâ¯=â¯0.94) and correlated with the interview-based BPSS-FP Mania Symptom Index (râ¯=â¯0.55, p < .0001). BPSS-AS-P scores had good convergent validity, correlating with the General Behavior Inventory-10M (râ¯=â¯0.65, p < .0001) and Young Mania Rating Scale; râ¯=â¯0.48, p < .0001). The BPSS-AS-P had good discriminant validity, not being correlated with scales measuring positive and negative symptoms of psychotic disorders (p-valuesâ¯=â¯0.072-0.667). LIMITATIONS: Findings are limited by the cross-sectional nature of the study by the fact that the participants were all treatment-seeking. Future studies need to evaluate the predictive validity of the BPSS-AS-P for identifying those who develop BD in a community sample. CONCLUSION: BPSS-AS-P has promise as a screening tool for people at risk for BD. Adopting the BPSS-AS-P would support the goal of characterizing the prodrome systematically in order to facilitate research and clinical care.
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Transtorno Bipolar/diagnóstico , Programas de Rastreamento/normas , Sintomas Prodrômicos , Avaliação de Sintomas/normas , Adolescente , Transtorno Bipolar/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Psicometria , Transtornos Psicóticos/diagnóstico , AutorrelatoRESUMO
OBJECTIVE: To investigate the role of oxidative stress and antioxidants in depression. DATA SOURCES: We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant. STUDY SELECTION: Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. DATA EXTRACTION: Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated. DATA SYNTHESIS: Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. CONCLUSIONS: Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.
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Antidepressivos/farmacologia , Transtorno Depressivo Maior , Nitritos/sangue , Estresse Oxidativo , Peroxidases/sangue , Superóxido Dismutase/sangue , Ácido Úrico/sangue , Zinco/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/enzimologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
OBJECTIVES: DSM-5 conceptualized attenuated psychosis syndrome (APS) as self-contained rather than as a risk syndrome, including it under "Conditions for Further Study," but also as a codable/billable condition in the main section. Since many major mental disorders emerge during adolescence, we assessed the frequency and characteristics of APS in adolescent psychiatric inpatients. METHODS: Consecutively recruited adolescents hospitalized for nonpsychotic disorders (September 2009-May 2013) were divided into APS youth versus non-APS youth, based on the Structured Interview of Prodromal Syndromes (SIPS) and according to DSM-5 criteria, and compared across multiple characteristics. RESULTS: Of 89 adolescents (mean ± SD age = 15.1 ± 1.6 years), 21 (23.6%) had APS. Compared to non-APS, APS was associated with more comorbid disorders (2.7 ± 1.0 vs 2.2 ± 1.3), major depressive disorder (61.9% vs 27.9%), oppositional defiant disorder/conduct disorder (52.4% vs 25.0%), and personality disorder traits (57.1% vs 7.4%, the only diagnostic category surviving Bonferroni correction). APS youth were more severely ill, having higher SIPS total positive, negative, and general symptoms; Brief Psychiatric Rating Scale total and positive scores; depression and global illness ratings; and lower Global Assessment of Functioning (GAF). Conversely, Young Mania Rating Scale scores, suicidal behavior, prescribed psychotropic medications, and mental disorder awareness were similar between APS and non-APS groups. In multivariable analysis, lowest GAF score in the past year (odds ratio [OR] = 51.15; 95% confidence interval [CI], 2.46-2,439.0) and social isolation (OR = 27.52; 95% CI, 3.36-313.87) were independently associated with APS (r(2) = 0.302, P < .0001). Although psychotic disorders were excluded, 65.2% (APS = 57.1%, non-APS = 67.7%, P = .38) received antipsychotics. CONCLUSION: One in 4 nonpsychotic adolescent inpatients met DSM-5 criteria for APS. APS youth were more impaired, showing a complex entanglement with a broad range of psychiatric symptoms and disorders, including depression, impulse-control, and, especially, emerging personality disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01383915.
Assuntos
Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos Mentais/epidemiologia , Transtornos da Personalidade/epidemiologia , Transtornos Psicóticos/epidemiologia , Adolescente , Comorbidade , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , SíndromeRESUMO
INTRODUCTION: Despite drastic increases in antipsychotic prescribing in youth, data are still limited regarding their safety in this vulnerable population, necessitating additional tools for capturing long-term, real world data. METHODS: We present SENTIA (SafEty of NeurolepTics in Infancy and Adolescence; https://SENTIA.es), an online registry created in 2010 to track antipsychotic adverse effects in Spanish youth <18 years old currently taking or initiating with any antipsychotic treatment. SENTIA collects information on sociodemographic, diagnostic and treatment characteristics, past personal medical/psychiatric history, healthy lifestyle habits and treatment adherence. Additionally, efficacy and adverse effect data are recorded including the Children's Global Assessment Scale; Clinical Global Impressions scale for Severity and Improvement, the Safety Monitoring Uniform Report Form, Simpson-Angus Scale, Abnormal Involuntary Movement Scale, vital signs, blood pressure, and EKG. Finally, fasting blood is drawn for hematology, electrolytes, renal, liver and thyroid function, glucose, insulin, lipid, prolactin and sex hormone levels. Initially, a diagnostic interview and several psychopathology scales were also included. Patients are assessed regularly and followed even beyond stopping antipsychotics. RESULTS: Since 01/17/2011, 85 youth (11.5 ± 2.9 (range = 4-17) years old, 70.6% male) have been included at one inaugural center. After a mean duration of 17 ± 11 (range = 1-34) months, 78.8% are still actively followed. For feasibility reasons, the diagnostic interview and detailed psychopathology scales were dropped. The remaining data can be entered in <30 minutes. Several additional centers are currently being added to SENTIA. CONCLUSIONS: Implementation of a systematic online pharmacovigilance system for antipsychotic adverse effects in youth is feasible and promises to generate important information.
RESUMO
A six-year-old girl was referred to our child psychiatry outpatient clinic by the Pediatric Neurology Unit with a diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) and trichotillomania. She had neither eyebrows nor eyelashes. The clinical picture was of irritability, frequent tantrums, and aggressive behaviour. During the following year she presented several brief episodes of intense mood changes, which typically started with night-time onset trichotillomania and sleep disturbance. The episodes lasted no longer than five days and recurred within one or two months. A diagnosis of pediatric bipolar disorder (BD) was made after the first months of clinical follow-up. An MRI showed focal white matter hyperintensities (WMH) in T2.