Depression in Mexican Americans with Diagnosed and Undiagnosed Diabetes

Background: Depression and diabetes commonly co-occur; however, the strength of the physiological effects of diabetes as mediating factors towards depression is uncertain. Method: We analyzed extensive clinical, epidemiological and laboratory data from n = 2081 Mexican Americans aged 35-64 years, recruited from the community as part of the Cameron County Hispanic Cohort (CCHC) divided into three groups: Diagnosed (self-reported) diabetes (DD, n = 335), Undiagnosed diabetes (UD, n = 227) and No diabetes (ND, n = 1519). UD participants denied being diagnosed with diabetes, but on testing met the 2010 American Diabetes Association and World Health Organization definitions of diabetes. Depression was measured using the Center for Epidemiological Studies - Depression (CES-D) scale. Weighted data were analyzed using dimensional and categorical outcomes using univariate and multivariate models. Results: The DD group had significantly higher CES-D scores than both the ND and UD (p ⩽ 0.001) groups, whereas the ND and UD groups did not significantly differ from each other. The DD subjects were more likely to meet the CES-D cut-off score for depression compared to both the ND and UD groups (p = 0.001), respectively. The UD group was also less likely to meet the cut-off score for depression than the ND group (p = 0.003). Our main findings remained significant in models that controlled for socio-demographic and clinical confounders. Conclusions: Meeting clinical criteria for diabetes was not sufficient for increased depressive symptoms. Our findings suggest that the \u27knowing that one is ill\u27 is associated with depressive symptoms in diabetic subjects

Depression, Obesity, and Metabolic Syndrome: Prevalence and Risks of Comorbidity in a Population-Based Study of Mexican Americans

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

Association of Total and Differential White Blood Cell Counts to Development of Type 2 Diabetes in Mexican Americans in Cameron County Hispanic Cohort

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

Lifetime psychopathology among the offspring of Bipolar I parents

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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)NARSADKrus Endowed Chair in Psychiatry UTHSCSAFederal University of São Paulo Department of PsychiatryThe University of Texas Health Science Center Departments of Psychiatry and OrthodonticsUniversidade de São Paulo Faculdade de Medicina Department of PsychiatryUniversity of Texas Health Science CenterThe University of Texas Health Science Center Department of PsychiatryUNIFESP, Department of PsychiatryNARSAD: MH 69774NARSAD: RR 20571NARSAD: MH068280SciEL

Lifetime psychopathology among the offspring of Bipolar I parents

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

Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain

Objectives: The thickness of the brain’s cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. Methods: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 ± 13.2 years) recruited from 73 (9.7 ± 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. Results: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD ≥ 3.0) QTLs were localized within chromosome 15q22–23. More detailed localization reported no significant association (p \u3c 5·10−5) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤ 10−3) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer’s disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p \u3c 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p \u3c 0.05) but failed to show a significant correlation (p = 0.09) with FA. Discussion: This study identified a novel, significant QTL at 15q22–23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM–FA values

Discovering schizophrenia endophenotypes in randomly ascertained pedigrees

Background Although case-control approaches are beginning to disentangle schizophrenia’s complex polygenic burden, other methods will likely be necessary to fully identify and characterize risk genes. Endophenotypes, traits genetically correlated with an illness, can help characterize the impact of risk genes by providing genetically relevant traits that are more tractable than the behavioral symptoms that classify mental illness. Here we present an analytic approach for discovering and empirically validating endophenotypes in extended pedigrees with very few affected individuals. Our approach indexes each family member’s risk as a function of shared genetic kinship with an affected individual, often referred to as the coefficient of relatedness. To demonstrate the utility of this approach, we search for neurocognitive and neuroanatomic endophenotypes for schizophrenia in large unselected multigenerational pedigrees. Methods A fixed effect test within the variance component framework was performed on neurocognitive and cortical surface area traits in 1,606 Mexican-American individuals from large, randomly ascertained extended pedigrees who participate in the “Genetics of Brain Structure and Function” study. As affecteds are excluded from analyses, results are not influenced by disease state or medication usage. Results Despite having sampled just 6 individuals with schizophrenia, our sample provided 233 individuals at various levels of genetic risk for the disorder. We identified three neurocognitive measures (digit-symbol substitution, facial memory, and emotion recognition) and six medial temporal and prefrontal cortical surfaces associated with liability for schizophrenia. Conclusions With our novel analytic approach one can discover and rank endophenotypes for schizophrenia, or any heritable disease, in randomly ascertained pedigrees

Influence of age, sex and genetic factors on the human brain

We report effects of age, age(2), sex and additive genetic factors on variability in gray matter thickness, surface area and white matter integrity in 1,010 subjects from the Genetics of Brain Structure and Function Study. Age was more strongly associated with gray matter thickness and fractional anisotropy of water diffusion in white matter tracts, while sex was more strongly associated with gray matter surface area. Widespread heritability of neuroanatomic traits was observed, suggesting that brain structure is under strong genetic control. Furthermore, our findings indicate that neuroimaging-based measurements of cerebral variability are sensitive to genetic mediation. Fundamental studies of genetic influence on the brain will help inform gene discovery initiatives in both clinical and normative samples

Shared genetic variance between obesity and white matter integrity in Mexican Americans.

peer reviewedObesity 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 x 1.7 x 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 (rhoG = -0.25), body (rhoG = -0.30), and splenium (rhoG = -0.26) of the corpus callosum, internal capsule (rhoG = -0.29), and thalamic radiation (rhoG = -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 (rhoG = -0.39, p = 0.020; rhoG = -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