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1.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30522995

RESUMO

BACKGROUND AND OBJECTIVES: Kidney biopsy is an essential tool for the diagnosis and treatment of patients with kidney disease; however, because of its invasive nature, bleeding complications may arise. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a meta-analysis of prospective or retrospective observational studies and randomized, controlled trials in pediatric patients undergoing native or transplant kidney biopsy in an inpatient or outpatient setting in MEDLINE-indexed studies from January 1998 to November 1, 2017 to determine the proportion of patients who develop hematoma, need blood transfusion, or need an additional intervention due to a complication after kidney biopsy. RESULTS: Twenty-three studies of 5504 biopsies met inclusion criteria. The proportion of patients developing hematoma after biopsy was between 11% (95% confidence interval, 7% to 17%) and 18% (95% confidence interval, 9% to 35%) using two analyses that included different time periods. The proportion needing blood transfusion was 0.9% (95% confidence interval, 0.5% to 1.4%). The proportion needing an additional intervention due to postbiopsy complication was 0.7% (95% confidence interval, 0.4% to 1.1%). Secondary analysis was not possible due to lack of data in the original manuscripts on laboratory values, needle gauges, number of needle passes, age of patient, or performer (attending versus trainee). Analysis with metaregression found that use of real-time ultrasound during biopsy did not modify the risk for hematoma, requirement of a blood products transfusion, or requirement of an additional procedure after biopsy. Analysis with metaregression comparing native biopsies with transplant biopsies did not reveal that biopsy type (native kidney biopsy versus transplant kidney biopsy) was associated with the need for a blood transfusion or requirement of an additional intervention after biopsy. CONCLUSIONS: The development of perinephric hematoma after kidney biopsy is not an infrequent finding. The proportion of patients requiring blood transfusion or needing an additional intervention as a result of kidney biopsy in pediatric patients is significantly smaller. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_12_06_CJASNPodcast_19_01_.mp3.

3.
J Matern Fetal Neonatal Med ; : 1-9, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30373419

RESUMO

BACKGROUND: Women that previously had preterm labor are at an increased risk for heart disease. Because spontaneous preterm birth is an adverse pregnancy outcome that affects millions of children worldwide, our objective was to review and analyze studies that have examined associations between maternal total cholesterol (TC), LDL-C, and HDL-C concentrations during pregnancy and the risk of preterm birth to potentially define biomarkers or targets for treatment. METHOD: A search was performed and 22 articles were found that examined the association of maternal plasma cholesterol concentrations and preterm birth. A meta-analysis was performed on 10 of the articles, those that used maternal lipid concentrations as the outcome and presented results as means plus variables, and a qualitative review was performed on all 22 articles. RESULTS: The meta-analysis showed no relationship between maternal TC, LDL-C, or HDL-C and increased risk of preterm birth, although, a near significant relationship between low maternal HDL-C concentration and preterm birth (p = .055). Importantly, associations increased when cholesterol concentrations were combined with inflammatory markers or metabolic syndrome factors. CONCLUSIONS: The relationship between maternal cholesterol levels and preterm birth is heterogeneous. Associations are strengthened when maternal cholesterol concentrations are combined with other factors that may be related to more recently defined lipoprotein functions.

4.
J Am Acad Child Adolesc Psychiatry ; 57(4): 235-244.e2, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29588049

RESUMO

OBJECTIVE: To determine the trajectory and magnitude of antidepressant response as well as the effect of antidepressant class and dose on symptomatic improvement in pediatric anxiety disorders. METHOD: Weekly symptom severity data were extracted from randomized, parallel group, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in pediatric anxiety disorders. Treatment response was modeled for the standardized change in continuous measures of anxiety using Bayesian updating. Posterior distributions for each study served as informative conjugate prior to distributions update subsequent study posteriors. Change in symptom severity was evaluated as a function of time, class and, for SSRIs, standardized dose. RESULTS: Data from 9 trials (SSRIs: n = 5; SNRIs, n = 4) evaluating 7 medications in 1,673 youth were included. In the logarithmic model of treatment response, statistically, but not clinically, significant treatment effects emerged within 2 weeks of beginning treatment (standardized medication-placebo difference = -0.054, credible interval [CI] = -0.076 to -0.032, p = .005, approximate Cohen's d ≤ 0.2) and by week 6, clinically significant differences emerged (standardized medication-placebo difference = -0.120, CI = -0.142 to -0.097, p = .001, approximate Cohen's d = 0.44). Compared to SNRIs, SSRIs resulted in significantly greater improvement by the second week of treatment (p = .0268), and this advantage remained statistically significant through week 12 (all p values <.03). Improvement occurred earlier with high-dose SSRI treatment (week 2, p = .002) compared to low-dose treatment (week 10, p = .025), but SSRI dose did not have an impact on overall response trajectory (p > .18 for weeks 1-12). CONCLUSIONS: In pediatric patients with generalized, separation, and/or social anxiety disorders, antidepressant-related improvement occurred early in the course of treatment, and SSRIs were associated with more rapid and greater improvement compared to SNRIs.

5.
J Affect Disord ; 234: 14-19, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29522938

RESUMO

BACKGROUND: The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. METHODS: Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. RESULTS: Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. LIMITATIONS: This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. CONCLUSIONS: Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Emoções/fisiologia , Adulto , Afeto , Mapeamento Encefálico , Análise Fatorial , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
6.
Bipolar Disord ; 20(7): 658-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29479787

RESUMO

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

7.
FASEB J ; 32(2): 717-727, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28982731

RESUMO

Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.-Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.


Assuntos
Apolipoproteína A-I/metabolismo , Colesterol/sangue , Desenvolvimento Fetal , Regulação da Expressão Gênica no Desenvolvimento , Lipoproteínas HDL/metabolismo , Placenta/metabolismo , Animais , Apolipoproteína A-I/genética , Feminino , Lipoproteínas HDL/genética , Camundongos , Camundongos Knockout , Gravidez
8.
J Clin Lab Med ; 2(1)2017.
Artigo em Inglês | MEDLINE | ID: mdl-29226278

RESUMO

World-wide, millions of women enter preterm labor or have small newborns. Effective biomarkers are needed to identify women at risk for these adverse outcomes. A time and cost effective way to examine any potentially new biomarkers in samples collected during prior studies or trials that had been assayed for other metabolites would be highly useful. Thus, the current study aimed to determine if samples that had been previously thawed and re-frozen could be re-assayed for novel biomarkers, those being lipoprotein composition (sizing, proteome, lipids) and combined cholesterol and cytokine concentrations. Fasting blood was collected from 51 young non-pregnant women and plasma was analyzed for lipoprotein composition and cytokine concentrations after multiple freeze/thaw cycles in the cold or at room temperature and after being stored for 18 months. Plasma LDL-C, HDL-C, total cholesterol, and triglyceride concentrations decreased <6-7% (cholesterols) or <20% (triglyceride) after 7 thaws in the cold, 3 thaws at room temperature, and after 18 months of storage. As these decreases were less than day-to-day reported variation of lipids, they do not appear to be physiologically significant. Cytokine (IL-6, TNF α, IL-8, IL-1ß) and hsCRP concentrations decreased by 22%, 8%, 8%, 22%, and 35%, respectively; only IL-6, IL-1ß and hsCRP concentrations showed significant decreases greater than day-to-day variations of 20%. For measured triglyceride and cytokine, but not cholesterol concentrations, decreases with freeze/thaw cycles were greater when concentrations were elevated. Multiple thaws also led to changes in lipoprotein sizing, specifically to a shift from medium- and large-sized HDL particles to small-sized HDL particles and from large LDL to IDL. No changes occurred for VLDL particle numbers. Though particle sizes changed, the HDL proteome did not change with multiple thaw cycles or after long term storage. Overall, the results demonstrate that it is possible to use previously obtained frozen samples for plasma cholesterol and triglyceride levels and the lipoprotein proteome, and lipoprotein sizing and cytokine concentrations if one knows the history of the sample as changes should be relative to one another.

9.
Bipolar Disord ; 19(4): 259-272, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28574156

RESUMO

OBJECTIVES: Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1 H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. METHODS: We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1 H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1 H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. RESULTS: LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. CONCLUSIONS: The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.


Assuntos
Sintomas Comportamentais , Transtorno Bipolar , Resistência a Medicamentos , Compostos de Lítio , Imagem por Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Antimaníacos/administração & dosagem , Antimaníacos/efeitos adversos , Inteligência Artificial , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/tratamento farmacológico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Monitoramento de Medicamentos/métodos , Feminino , Lógica Fuzzy , Humanos , Compostos de Lítio/administração & dosagem , Compostos de Lítio/efeitos adversos , Masculino , Imagem Multimodal/métodos , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico
10.
J Med Virol ; 89(11): 1904-1911, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28460153

RESUMO

A beneficial impact of the Human Pegivirus (HPgV)-formerly called GB virus C (GBV-C)-on HIV disease progression has been reported previously. One possible mechanism by which HPgV inhibits HIV replication is an alteration of the cytokine/chemokine milieu. Their expression has not been specifically evaluated in women despite their influence on disease progression and the possibility of gender-based differences in expression. Moreover, the impact of HPgV genotype on cytokine/chemokine expression is unknown. Sera levels of IL-2, IL-4, IL-7, IL-8, IL-10, IL-12p70, IL-13, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 were quantified in 150 HIV-positive women based on HPgV RNA status. Cytokines/chemokines with detection rates of at least 50% included IL-2, IL-4, IL-8, IL-10, IL-12p70, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 . Absolute values were significantly higher for HPgV positive compared to HPgV negative women for IL-7, IL-13, IL-12p70, and IFNγ. Absolute values were significantly lower for HPgV positive women for IL-4, IL-8, TGF-ß1 , and IP-10. IFNγ values were higher for HPgV genotype 2 than for genotype 1 (P = 0.036). Further study of cytokine/chemokine regulation by HPgV may ultimately lead to the development of novel therapeutic agents to treat HIV infection and/or the design of vaccine strategies that mimic the "protective" effects of HPgV replication.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/imunologia , Vírus GB C/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Adulto , Quimiocinas/genética , Quimiocinas/imunologia , Citocinas/genética , Citocinas/imunologia , Progressão da Doença , Feminino , Vírus GB C/isolamento & purificação , Genótipo , Humanos , Interleucina-12/sangue , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-2/sangue , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-4/sangue , Interleucina-4/genética , Interleucina-4/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/genética , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia , Estados Unidos
11.
J Affect Disord ; 209: 246-253, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27936454

RESUMO

BACKGROUND: Studying youth at high risk of developing bipolar disorder may clarify neurobiological factors associated with vulnerability to this illness. We present here a baseline characterization of brain structure in youth at-risk for bipolar disorder. METHODS: Magnetic resonance images were obtained from 115 child and adolescent offspring of bipolar disorder type I subjects and 57 healthy child and adolescent offspring of healthy parents (healthy control offspring). Offspring of parents with bipolar disorder were divided into healthy bipolar offspring (n=47) or symptomatic bipolar offspring (n=68), according to presence or absence of childhood-onset psychopathology. All bipolar offspring were free of major mood and psychotic disorders. Gray (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. RESULTS: No differences in GM volumes were found across groups. Healthy bipolar offspring presented with decreased WM volumes in areas of the right frontal, temporal and parietal lobes, and in the left temporal and parietal lobes compared to healthy control offspring. Symptomatic bipolar offspring did not present with any differences in WM volumes compared to either healthy bipolar offspring or healthy control offspring. LIMITATIONS: Cross-sectional design and heterogeneous sample of symptomatic bipolar offspring. CONCLUSIONS: WM volume decreases in areas of the frontal, occipital, and parietal lobes are present in bipolar offspring prior to the development of any psychiatric symptoms, and may be a correlate of familial risk to bipolar disorder. In this large cohort, we have not found evidence for regional GM volume abnormalities as an endophenotype for bipolar disorder.


Assuntos
Transtorno Bipolar , Encéfalo/diagnóstico por imagem , Filho de Pais Incapacitados , Pais , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Criança , Estudos Transversais , Endofenótipos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/fisiologia
12.
J Am Acad Child Adolesc Psychiatry ; 55(11): 980-989, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27806866

RESUMO

OBJECTIVE: To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. METHOD: Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. RESULTS: Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. CONCLUSION: During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Filho de Pais Incapacitados , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Risco , Adulto Jovem
13.
Respir Med ; 120: 1-9, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27817804

RESUMO

BACKGROUND: The predictive characteristics of different screening surveys for the recognition of individuals at risk for airflow obstruction (AFO) have not been evaluated simultaneously in the same population. PURPOSE: To compare five AFO/COPD screening questionnaires. METHODS: 383 individuals completed the Veterans Airflow Obstruction Screening Questionnaire, Personal Level Screener for COPD (VAFOSQ), the 11-Q COPD Screening Questionnaire (11-Q), the COPD Population Screener (COPD-PS) and the Lung Function Questionnaire (LFQ) and performed spirometry. AFO was defined as forced expiratory volume in one second divided by the forced vital capacity (FEV1/FVC) < 0.7, fixed ratio (FR) or FEV1/FVC < lower limit of normal (LLN). The predictive characteristics of the five questionnaires were calculated and non-parametric receiver operating characteristic (ROC) curves estimated by logistic regression. RESULTS: 376 participants completed at least two of the questionnaires and performed technically acceptable spirometry. AFO was present in 102 (27.1%) and 150 (39.9%) based on LLN and FR, respectively. The number of individuals positively selected by the VAFOSQ was 227, PLS 128, 11-Q 236, COPD-PS 217, and LFQ 328. The area under the ROC curves for the questionnaires was between 0.60 and 0.66 (LLN) and 0.58 and 0.66 (FR). CONCLUSIONS: Although these screening surveys have acceptable and similar predictive ability for the identification of AFO, their published thresholds lead to substantially different classification rates. The choice of an appropriate threshold for the identification of individuals with possible AFO/COPD should consider the underlying prevalence of AFO/COPD in the target population and the relative costs of misclassifying affected and unaffected cases. CLINICAL TRIAL REGISTRATION: None. PRIMARY SOURCE OF FUNDING: Veterans Health Administration.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória/métodos , Fatores de Risco , Espirometria/métodos , Veteranos , Saúde dos Veteranos , Capacidade Vital
14.
Hum Psychopharmacol ; 31(5): 382-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27650406

RESUMO

OBJECTIVE: To evaluate lisdexamfetamine dimesylate (LDX) in the treatment of binge eating disorder (BED). METHOD: Fifty participants with BED received LDX (20-70 mg/day) (n = 25) or placebo (n = 25) for up to 12 weeks in a single-center, randomized, double-blind, and flexible-dose trial. The primary outcome measure was binge eating (BE) days/week. RESULTS: In the primary longitudinal analysis, compared with placebo, LDX was not associated with a significantly greater rate of reduction in BE days/week, as well as BE episodes/week, and scores on the Clinical Global Impression-Severity or Yale-Brown Obsessive-Compulsive Scale modified for binge eating scales. It was, however, associated with significantly decreased weight, body mass index, and fasting triglyceride level. In the secondary last observation carried forward analyses, LDX was associated with statistically significant reductions in BE days/week, BE episodes/week, weight, and BMI, as well as a statistically significant greater level of categorical response and global improvement. The mean (standard deviation) LDX daily dose at endpoint evaluation was 59.6 (14.9) mg. One participant discontinued LDX for a serious adverse cardiovascular event, which resolved fully. CONCLUSION: Lisdexamfetamine dimesylate may have clinical utility for BED but further studies of its efficacy, tolerability, and safety in this population are needed. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Transtorno da Compulsão Alimentar/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Adulto , Índice de Massa Corporal , Peso Corporal , Estimulantes do Sistema Nervoso Central/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Dimesilato de Lisdexanfetamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Bipolar Disord ; 18(3): 300-6, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27087497

RESUMO

OBJECTIVES: Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. METHODS: A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. RESULTS: Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). CONCLUSIONS: Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder.


Assuntos
Transtorno Bipolar/sangue , Eritrócitos/metabolismo , Ácidos Graxos Insaturados/sangue , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/metabolismo , Membrana Eritrocítica/metabolismo , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Humanos , Ácido Linoleico/sangue , Valores de Referência
16.
Chronic Obstr Pulm Dis ; 3(4): 705-715, 2016 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28848897

RESUMO

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality within the Veterans Healthcare Administration (VHA) and is frequently under-diagnosed. We developed the Veterans Airflow Screening Questionnaire (VAFOSQ) to improve the identification of Veterans with airflow obstruction (AFO), the most commonly used criterion for the diagnosis of COPD.We created an initial survey with 78 variables that have been associated with AFO. A total of 825 patients in 3 primary care clinics performed spirometry after bronchodilator administration and completed the initial survey. Best sets regression was used to build a model that predicted AFO optimally. A total of 195 of 825 (23.3%) patients had AFO and 7 items positively predicted AFO. When the questionnaire score was greater than 25, the VAFOSQ accurately identified AFO with an area under the receiver operating curve of 0.72. In a prospective validation cohort of 376 participants, the positive predictive value was 32% and negative predictive value 81%. The VAFOSQ is a reliable and valid instrument for the identification of veterans at risk for AFO who would benefit from further evaluation with spirometry and assessment for COPD. The VAFOSQ is straightforward to use and can be easily self-administered and self-scored enabling widespread application within the VHA.

17.
Early Interv Psychiatry ; 10(3): 203-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26486098

RESUMO

AIM: Mood disorders are associated with low levels of the long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker. METHOD: Erythrocyte fatty acid composition was determined in healthy adolescents (n = 28, HC), asymptomatic adolescents with a biological parent with bipolar I disorder (n = 30; 'high risk', HR), adolescents with a biological parent with bipolar I disorder and major depressive disorder, or depressive disorder not otherwise specified (n = 36; 'ultra-high risk', UHR), and first-episode adolescent bipolar manic patients (n = 35, BP). RESULTS: Group differences were observed for DHA (P ≤ 0.0001) and EPA (P = 0.03). Compared with HC, erythrocyte EPA + DHA ('omega-3 index') was significantly lower in BP (-24%, P ≤ 0.0001) and UHR (-19%, P = 0.0006) groups, and there was a trend in the HR group (-11%, P = 0.06). Compared with HC (61%), a greater percentage of HR (77%, P = 0.02), UHR (80%, P = 0.005) and BP (97%, P = 0.001) subjects exhibited EPA + DHA levels of ≤4.0%. Among all subjects (n = 130), EPA + DHA was inversely correlated with manic (r = -0.29, P = 0.0008) and depressive (r = -0.28, P = 0.003) symptom severity. The AA/EPA + DHA ratio was significantly greater in BP (+22%, P = 0.0002) and UHR (+16%, P = 0.001) groups. CONCLUSIONS: Low EPA + DHA levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA + DHA deficits. Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.


Assuntos
Ácidos Docosa-Hexaenoicos/deficiência , Ácido Eicosapentaenoico/metabolismo , Eritrócitos/metabolismo , Sintomas Prodrômicos , Adolescente , Biomarcadores/metabolismo , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
18.
Nutr Neurosci ; 19(4): 145-55, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-24915543

RESUMO

OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of fish oil (FO) supplementation on cortical metabolite concentrations in adolescents with major depressive disorder (MDD). METHODS: Metabolite concentrations were determined by (1)H MRS in the anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with MDD before and following 10-week open-label supplementation with low (2.4 g/day, n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores and erythrocyte fatty acid levels were also determined. RESULTS: Baseline erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated, and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA) composition was inversely correlated with myo-inositol (mI) concentrations in the left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased, significantly following low-dose and high-dose FO supplementation. In the intent-to-treat sample, depressive symptom severity scores decreased significantly in the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose group (-20%, P = 0.06). There were no significant baseline-endpoint changes in metabolite levels in each voxel. In the low-dose group there were changes with large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18, d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8) and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group, there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d = 1.2). DISCUSSION: These preliminary data suggest that increasing the LCn-3 fatty acid status of adolescent MDD patients is associated with subtle changes in Glx, mI, and Cho concentrations in the DLPFC that warrant further evaluation in a larger controlled trial.


Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Deficiências Nutricionais/dietoterapia , Transtorno Depressivo Maior/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Essenciais/uso terapêutico , Óleos de Peixe/uso terapêutico , Adolescente , Adulto , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Deficiências Nutricionais/metabolismo , Deficiências Nutricionais/fisiopatologia , Deficiências Nutricionais/psicologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ácidos Graxos Essenciais/deficiência , Ácidos Graxos Essenciais/metabolismo , Feminino , Óleos de Peixe/administração & dosagem , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Humanos , Análise de Intenção de Tratamento , Perda de Seguimento , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Escalas de Graduação Psiquiátrica , Adulto Jovem
19.
Psychiatry Res ; 230(2): 447-53, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26477955

RESUMO

Deficits in long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with the pathophysiology of bipolar disorder. However, LCn-3 fatty acid status at the initial onset of mania and its association with treatment response are not known. Erythrocyte membrane fatty acid composition was determined in first-episode bipolar manic or mixed (n=40) and healthy (n=40) subjects. Mood symptom ratings were obtained with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Erythrocyte fatty acid composition and clinical ratings were also determined within a sub-group of bipolar subjects following 8-week (n=19) or 52-week (n=11) open-label treatment with lithium or quetiapine. At baseline bipolar subjects exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition compared with healthy subjects (-23%, p<0.0001). EPA (20:5n-3) and docosapentanoic acid (22:5n-3), and LCn-6 fatty acids including arachidonic acid were not different. Following 8- or 52-week treatment with lithium or quetiapine, YMRS and HDRS total scores decreased significantly whereas erythrocyte fatty acids including DHA did not change. These data indicate that selective erythrocyte DHA deficits coincide with the initial onset of manic symptoms, and reductions in mood symptoms following treatment are not mediated by changes in fatty acid status.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/sangue , Ácidos Docosa-Hexaenoicos/deficiência , Membrana Eritrocítica/química , Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adolescente , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Insaturados/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino , Testes Psicológicos , Adulto Jovem
20.
Psychosomatics ; 56(3): 242-53, 2015 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25660434

RESUMO

OBJECTIVE: To assess the efficacy and safety of duloxetine in patients with chronic fatigue syndrome. METHODS: A 12-week, randomized, double-blind study was designed to compare duloxetine 60-120 mg/d (n = 30) with placebo (n = 30) for efficacy and safety in the treatment of patients with chronic fatigue syndrome. The primary outcome measure was the Multidimensional Fatigue Inventory general fatigue subscale (range: 4-20, with higher scores indicating greater fatigue). Secondary measures were the remaining Multidimensional Fatigue Inventory subscales, Brief Pain Inventory, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression Scale, Centers for Disease Control and Prevention Symptom Inventory, Patient Global Impression of Improvement, and Clinical Global Impression of Severity. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the measure of effect. RESULTS: The improvement in the Multidimensional Fatigue Inventory general fatigue scores for the duloxetine group was not significantly greater than for the placebo group (P = 0.23; estimated difference between groups at week 12 = -1.0 [95% CI: -2.8, 0.7]). The duloxetine group was significantly superior to the placebo group on the Multidimensional Fatigue Inventory mental fatigue score, Brief Pain Inventory average pain severity and interference scores, Short Form-36 bodily pain domain, and Clinical Global Impression of Severity score. Duloxetine was generally well tolerated. CONCLUSION: The primary efficacy measure of general fatigue did not significantly improve with duloxetine when compared with placebo. Significant improvement in secondary measures of mental fatigue, pain, and global measure of severity suggests that duloxetine may be efficacious for some chronic fatigue syndrome symptom domains, but larger controlled trials are needed to confirm these results.


Assuntos
Cloridrato de Duloxetina/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Fadiga Mental , Pessoa de Meia-Idade , Dor , Resultado do Tratamento
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