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OBJECTIVE: While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D. METHODS: Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes. RESULTS: Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment--insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals. CONCLUSION: Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D.
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Moléculas de Adesão Celular/fisiologia , Diabetes Mellitus Tipo 2/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Resistência à Insulina , Estudos Longitudinais , Masculino , Menstruação , Americanos Mexicanos , TexasRESUMO
INTRODUCTION: We examined the prevalence of depression, obesity, and metabolic syndrome and associations between them in a population-based representative cohort of Mexican Americans living on the United States-Mexico border. METHOD: The sample in this cross-sectional analysis consisted of 1,768 Mexican American adults (≥ 18 years of age) assessed between the years 2004 and 2010, with whom we tested our central hypothesis of a significant relationship between obesity and depression. Depression was measured using the Center for Epidemiologic Studies-Depression scale (CES-D) with a cutoff score of ≥ 16 for depression and a cutoff score of ≥ 27 for severe depression. We categorized body mass index (BMI) values as obese (≥ 30kg/m(2)) and later subdivided the obese subjects into obese (30-39 kg/m(2)[inclusive]) and morbidly obese (≥ 40 kg/m(2)). Metabolic syndrome was defined using the American Heart Association definition requiring at least 3 of the following: increased waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and elevated fasting glucose. Weighted data were analyzed to establish prevalence of depression, obesity, and metabolic syndrome. Univariate and multivariable weighted regression models were used to test potential associations between these disorders. RESULTS: Using weighted prevalence, we observed high rates of depression (30%), obesity (52%), and metabolic syndrome (45%). Univariate models revealed female gender (P = .0004), low education (P = .003), low HDL level (P = .009), and increased waist circumference (P = .03) were associated with depression. Female gender (P = .01), low education (P = .003), and morbid obesity (P = .002) were risk factors for severe depression and remained significant in multivariable models. CONCLUSIONS: In this large cohort of Mexican Americans, obesity, female gender, and low education were identified risk factors for depression. These indicators may serve as targets for early detection, prevention, and intervention in this population.
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Depressão/epidemiologia , Síndrome Metabólica/epidemiologia , Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Adulto , Comorbidade , Estudos Transversais , Depressão/etnologia , Depressão/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/etnologia , Síndrome Metabólica/psicologia , Americanos Mexicanos/psicologia , Obesidade/etnologia , Obesidade/psicologia , Prevalência , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Sexuais , Texas/epidemiologiaRESUMO
Obesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 ± 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 × 1.7 × 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) = 0.49). FA shared significant portions of genetic variance with BMI in the genu (ρG = -0.25), body (ρG = -0.30), and splenium (ρG = -0.26) of the corpus callosum, internal capsule (ρG = -0.29), and thalamic radiation (ρG = -0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (ρG = -0.39, p = 0.020; ρG = -0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors.
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OBJECTIVE: To evaluate the relationship between total and differential White Blood Cell (WBC) counts with time to transition to type 2 diabetes in Mexican Americans using prospective data from the Cameron County Hispanic Cohort (CCHC). RESULTS: Multivariable Cox proportional hazards regression models revealed that obese Mexican-American cohort participants whose total WBC or granulocyte count increased over time had 1.39 and 1.35 times higher risk respectively of transition to type 2 diabetes when compared to overweight participants. The granulocyte or total WBC count in participants with BMI≥35 were significant risk factors for transition to type 2 diabetes. CONCLUSIONS: Increased total WBC and WBC differential counts, particularly lymphocytes and granulocytes, are associated with risk of transition to type 2 diabetes in obese Mexican Americans, after adjusting for other potential confounders. Screening and monitoring the WBC counts, including lymphocytes and granulocytes can help with monitoring potential transition to type 2 diabetes.
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OBJECTIVES: To evaluate temperament and character traits using the Junior Temperament and Character Inventory (JTCI) in children and adolescents with major depressive disorder (MDD) in comparison with healthy control subjects (HC), and to verify if comorbidity with disruptive behavioral disorders and being currently depressed influence JTCI scores. METHODS: A case-control study comprising 41 MDD children/adolescents matched to 40 HC by gender and age (8-17years). All participants were assessed diagnostically with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime (K-SADS-PL). Temperament and character traits were measured with the parent and child versions of JTCI, and depression was evaluated with the Children's Depression Rating Scale (CDRS). RESULTS: According to child and parent data, MDD subjects had significantly higher scores on harm avoidance and novelty seeking, and lower scores on reward dependence, persistence, self-directedness and cooperativeness compared with HC. According to parent data only, MDD subjects significantly differed from HC on self-transcendence (lower spirituality scores and higher fantasy scores). Comorbidity with disruptive behavioral disorders exerted influence on almost all dimensions, in general increasing the mean differences between MDD and HC subjects. Also, being currently depressed did not influence the results, except for reward dependence according to parent data. LIMITATIONS: The cross-sectional nature of the study and its limited sample size. CONCLUSIONS: MDD children/adolescents have a different temperament and character profile compared to HC subjects. This study supports previous findings of trait-like characteristics of harm avoidance and self-directedness.
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Caráter , Transtorno Depressivo Maior/psicologia , Temperamento , Adolescente , Análise de Variância , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Inventário de Personalidade , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Recent studies have demonstrated high rates of psychopathology in the offspring of parents with bipolar disorder. The aim of this study was to identify psychiatric diagnoses in a sample of children of bipolar parents. METHOD: This case series comprised 35 children and adolescents aged 6 to 17 years, with a mean age of 12.5 ± 2.9 years (20 males and 15 females), who had at least one parent with bipolar disorder type I. The subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime version (K-SADS-PL). Family psychiatric history and demographics were also evaluated. RESULTS: Of the offspring studied, 71.4% had a lifetime diagnosis of at least one psychiatric disorder (28.6% with a mood disorder, 40% with a disruptive behavior disorder and 20% with an anxiety disorder). Pure mood disorders (11.4%) occurred less frequently than mood disorders comorbid with attention deficit hyperactivity disorder (17.1%). Psychopathology was commonly reported in second-degree relatives of the offspring of parents with bipolar disorder (71.4%). CONCLUSIONS: Our results support previous findings of an increased risk for developing psychopathology, predominantly mood and disruptive disorders, in the offspring of bipolar individuals. Prospective studies with larger samples are needed to confirm and expand these results.
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Transtorno Bipolar/psicologia , Filho de Pais com Deficiência/psicologia , Transtornos Mentais/epidemiologia , Pais/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Prospectivos , Escalas de Graduação PsiquiátricaRESUMO
Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory. We also tested whether regional pattern in genetic pleiotropy is modulated by the phylogeny of WM development. BP and high-resolution (1.7 × 1.7 × 3 mm; 55 directions) diffusion tensor imaging data were analyzed for 332 (202 females; mean age 47.9 ± 13.3 years) members of the San Antonio Family Heart Study. Bivariate genetic correlation analysis was used to calculate the genetic overlap between several BP measurements (pulse pressure, systolic BP, and diastolic BP) and fractional anisotropy (whole-brain and regional values). Intersubject variance in pulse pressure and systolic BP exhibited a significant genetic overlap with variance in whole-brain fractional anisotropy values, sharing 36% and 22% of genetic variance, respectively. Regionally, shared genetic variance was significantly influenced by rates of WM development (r=-0.75; P=0.01). The pattern of genetic overlap between BP and WM integrity was generally in agreement with the pulse-wave encephalopathy theory. Our study provides evidence that a set of pleiotropically acting genetic factors jointly influence phenotypic variation in BP and WM integrity. The magnitude of this overlap appears to be influenced by phylogeny of WM development, suggesting a possible role for genotype-by-age interactions.
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Pressão Sanguínea/genética , Cérebro/anatomia & histologia , Pleiotropia Genética , Americanos Mexicanos/genética , Adulto , Idoso , Algoritmos , Anisotropia , Encéfalo/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Texas , Adulto JovemRESUMO
OBJECTIVE: The few studies applying single-voxel ¹H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low N-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol / phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study was to evaluate NAA, glycerophosphocholine plus phosphocholine (GPC+PC) and PCr+Cr in various frontal cortical areas in children and adolescents with BD. We hypothesized that NAA levels within the prefrontal cortex are lower in BD patients than in healthy controls, indicating neurodevelopmental alterations in the former. METHOD: We studied 43 pediatric patients with DSM-IV BD (19 female, mean age 13.2 ± 2.9 years) and 38 healthy controls (19 female, mean age 13.9 ± 2.7 years). We conducted multivoxel in vivo ¹H spectroscopy measurements at 1.5 Tesla using a long echo time of 272 ms to obtain bilateral metabolite levels from the medial prefrontal cortex (MPFC), DLPFC (white and gray matter), cingulate (anterior and posterior), and occipital lobes. We used the nonparametric Mann-Whitney U test to compare neurochemical levels between groups. RESULTS: In pediatric BD patients, NAA and GPC+PC levels in the bilateral MPFC, and PCr+Cr levels in the left MPFC were lower than those seen in the controls. In the left DLPFC white matter, levels of NAA and PCr+Cr were also lower in BD patients than in controls. CONCLUSIONS: Lower NAA and PCr+Cr levels in the PFC of children and adolescents with BD may be indicative of abnormal dendritic arborization and neuropil, suggesting neurodevelopmental abnormalities.
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Ácido Aspártico/análogos & derivados , Transtorno Bipolar/metabolismo , Química Encefálica , Córtex Pré-Frontal/crescimento & desenvolvimento , Prótons , Adolescente , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Glicerilfosforilcolina/química , Glicerilfosforilcolina/metabolismo , Humanos , Inositol/química , Inositol/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Fosfocreatina/química , Fosfocreatina/metabolismo , Fosforilcolina/química , Fosforilcolina/metabolismo , Córtex Pré-Frontal/químicaRESUMO
BACKGROUND: Recent studies have demonstrated high rates of psychopathology in the offspring of parents with bipolar disorder. The aim of this study was to identify psychiatric diagnoses in a sample of children of bipolar parents. METHOD: This case series comprised 35 children and adolescents aged 6 to 17 years, with a mean age of 12.5 + 2.9 years (20 males and 15 females), who had at least one parent with bipolar disorder type I. The subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime version (K-SADS-PL). Family psychiatric history and demographics were also evaluated. RESULTS: Of the offspring studied, 71.4 percent had a lifetime diagnosis of at least one psychiatric disorder (28.6 percent with a mood disorder, 40 percent with a disruptive behavior disorder and 20 percent with an anxiety disorder). Pure mood disorders (11.4 percent) occurred less frequently than mood disorders comorbid with attention deficit hyperactivity disorder (17.1 percent). Psychopathology was commonly reported in second-degree relatives of the offspring of parents with bipolar disorder (71.4 percent). CONCLUSIONS: Our results support previous findings of an increased risk for developing psychopathology, predominantly mood and disruptive disorders, in the offspring of bipolar individuals. Prospective studies with larger samples are needed to confirm and expand these results.
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Adolescente , Criança , Feminino , Humanos , Masculino , Transtorno Bipolar/psicologia , Filho de Pais com Deficiência/psicologia , Transtornos Mentais/epidemiologia , Pais/psicologia , Estudos Prospectivos , Escalas de Graduação PsiquiátricaRESUMO
OBJECTIVE: We compared temperament and character traits in children and adolescents with bipolar disorder (BP) and healthy control (HC) subjects. METHOD: Sixty nine subjects (38 BP and 31 HC), 8-17 years old, were assessed with the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime. Temperament and character traits were measured with parent and child versions of the Junior Temperament and Character Inventory. RESULTS: BP subjects scored higher on novelty seeking, harm avoidance, and fantasy subscales, and lower on reward dependence, persistence, self-directedness, and cooperativeness compared to HC (all p < 0.007), by child and parent reports. These findings were consistent in both children and adolescents. Higher parent-rated novelty seeking, lower self-directedness, and lower cooperativeness were associated with co-morbid attention-deficit/hyperactivity disorder (ADHD). Lower parent-rated reward dependence was associated with co-morbid conduct disorder, and higher child-rated persistence was associated with co-morbid anxiety. CONCLUSIONS: These findings support previous reports of differences in temperament in BP children and adolescents and may assist in a greater understating of BP children and adolescents beyond mood symptomatology.