- Email: [email protected]
DEPRESSION PROBLEMS AMONG TURKISH TWINS
S972
Abstracts
M32. PER3 POLYMORPHISMS, MORNINGNESS-EVENINGNESS AND DEPRESSION: PRELIMINARY EVIDENCE IN A BRAZILIAN FAMILY-BASED COHORT, THE BAEPENDI HEART STUDY n
Francieli Ruiz ,1, Tâmara P. Taporoski5, Daniela Martinez5, Andrew Beale2, Felipe Beijamini3, José E. Krieger1, Kristen L. Knutson4, Alexandre Pereira1, Mario Pedrazzoli1, Homero Vallada5, Malcolm Von Schantz2 1
University of São Paulo University of Surrey 3 Federal University of Fronteira Sul 4 Northwestern University 5 Univesity of São Paulo Medical School 2
Background: There is a significant interest in the contribution of the circadian timing system to individual differences in a wider range of behaviour. This is in part because sleep complaints and disturbances of the circadian timing system are common in psychiatric disorders. Based on diurnal preference, people can be divided into chronotypes with demonstrated differences in sleep-wake patterns and a variety of circadian rhythms, behavioral rhythms, and diurnal variation in mood. Specifically, greater eveningness has been related to greater depression. The human PER3 gene contains a variable number tandem repeat (VNTR) which is associated with diurnal preference: the longer allele (five tandem repeats) has been reported to associate with greater morningness, and the shorter allele (four tandem repeats) with greater eveningness. We have investigated the PER3 polymorphism and its relationship to sleep, circadian and depression characteristics in a Brazilian family-based cohort. Methods: Baependi is a small rural town in Brazil that provides a window of opportunity to study the influence of sleep circadian patterns in a highly admixed rural population with a conservative lifestyle. Here, we studied 786 subjects (mean age7SD 46.5716.2, 42% female). Blood samples were collected from all participants. The Per3 length polymorphism was genotyped using PCR followed by gel electrophoresis. We tested for associations between the PER3 polymorphism and sleep characteristics, daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire, respectively. Depressive symptoms were assessed using the Beck Depression Inventory [BDI-II]). Results: Our genotyping data showed that 36% of the subjects were homozygous for the shorter allele (4/4), 51% of the participants were heterozygous (4/5) and 12% of the subjects were homozygous for the longer allele (5/5). Allele frequency was 0.62 for the 4-repeat and a 0.38 for the 5-repeat. The percentages of the chronotypes Morning type (M-type), Neither type (N-type) and Evening type (E-type) were 5%, 46% and 7%, respectively. We observed an increase of the depression symptoms in evening types [F(2, 1014)=4.8, p=0.007]. On the other hand, no such associations were observed the PER3 genotype. There were no significant differences in the MEQ score [F(2, 317)=0.46, p=0.63], daytime sleepiness [(F(2, 317)=0.23, p=0.79)], sleep efficiency [(F(2,
317)=2.59, p=0.07)] and sleep characteristics [(F(2, 317) =1.92, p=0.14)] between the PER3 genotypes. Discussion: We observed an association between eveningness and depression. Identifying factors contributing to individual differences in sleep and to describe how these factors are associated with physiological and psychological profiles may aid our understanding of the role of sleep and the circadian system in mental health. On the other hand, we were not able to replicate the association between the PER3 VNTR polymorphism and chronotype, which has been confirmed independently in multiple populations worldwide (including in Brazil). Neither did we observe any association with depression. CNPq – PVE 400791/2014-5.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.339
M33. DEPRESSION PROBLEMS AMONG TURKISH TWINS n
Fazil Aliev ,1, Sevgi Yurt Oncel2 1 2
Virginia Commonwealth University, Karabuk University Kirikkale University
Background: In this study, we investigate factors affecting depressive behavior among adult Turkish twins living in the Kırıkkale and Ankara regions of Turkey. Twins administered a health and lifestyle interview which included questions about smoking, alcohol and drug use, depression, demographics and factors possibly affecting behavior problems. Main focus was on binary variable pointing to depressive problems. Methods: We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to depression in this sample. Results: 256 participants (43.9%) were identified as having depressive problems, of which 45.3% were males and 54.7% were females. Mean for depression was significantly higher in males than in females (p = 0.0001). Our study showed that gender, presence of a twin with depression in the family, age, marital status, and daily sports activities all played a significant role in depressive behavior among twins. The twin analysis suggested that genetic factors play significant role on the liability to depressive problems. Discussion: Significant differences in the presence of depression in women versus men are observed for the Turkish population. We find that having a twin with depression plays a significant role in depression problems among Turkish twins. This study will enable us to better understand genetic and environmental influences on behavioral outcomes across diverse cultures.
Abstracts
S973
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.340
M34. A GENETIC RISK SCORE, DEPRESSION AND OBESITY: EVIDENCE FROM THE SPANISH POPULATION STUDY PISMA-EP n
Margarita Rivera ,1, Blanca Gutierrez2, Paula Rovira3, Esther Molina4, Maria Victoria Martín-Laguna2, Inmaculada Ibanez-Casas2, Kathryn McKenney2, Ana Ching-López2, Isabel Ruiz-Pérez5, Miguel Rodríguez-Barranco6, Jorge Cervilla2 1
King's College London University of Granada 3 Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Mental Health and Addictions, Hospital Universitari Vall d’Hebron 4 University of Seville 5 CIBER de Epidemiología y Salud Pública 6 Andalusian School of Public Health 2
amount of variance. We also hope that adding ‘traditional’ risk factors to GRS will significantly improve the predictive ability with the area under the curve (AUC) in the ROC analysis. We further expect that the GRS will discriminate depression better in obese individuals compare to normalweight subjects. Discussion: The association between depression and obesity has repeatedly been reported in many studies. Given the high prevalence of both disorders, we expect that incorporating genetic information, traditional risk factors and obesity status may largely improve the predicting ability for depression. Addressing obesity in people with depression or vice versa is highly important as both disorders are associated with substantial personal and societal economic costs worldwide.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.341
M35. GENOME-WIDE ASSOCIATION STUDY OF COMORBID DEPRESSION AND ANXIETY SYMPTOMS IN AN EXTENDED PEDIGREE COHORT
Background: Depression and obesity are highly prevalent diseases in the general population, responsible of disability burden worldwide. Both conditions are major risk factors for chronic physical diseases such as type 2 diabetes, cardiovascular disease and hypertension among others. The reason why obesity and depression cluster together is not totally understood and several mechanisms have been proposed. There are many factors driving this observation, such as individual lifestyle choices, socioeconomic factors, psychosocial stress, disparities in health care, medication, as well as biological and genetic factors. The aim of this study is to investigate whether a Genetic Risk Score (GRS) combining 85 candidate SNPs for depression and other major psychiatric disorders is associated with depression and predicts depression in individuals with obesity. Methods: The sample consists of 743 community-based individuals from the PISMA-ep study. The PISMA-ep is a cross-sectional epidemiological study of mental disorders based on a representative sample of the adult population of Andalusia, Spain. A DSM-IV diagnosis of major depression was ascertained using the MINI interview. Height and weight data reported from each individual was used to calculate Body Mass Index (BMI), as a measure of obesity, using the formula: weight(kg)/height(m)2. All individuals have been genotyped for the 85 candidate polymorphisms using TaqMans OpenArrayTM Genotyping System. These markers were selected according to genome location, function and previous evidence. Logistic regression models will be conducted to predict depression. We will calculate an unweighted GRS by summation of the number of risk alleles, and a weighted GRS as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver Operating Characteristic (ROC) analysis will be used to compare the discriminatory ability of predictors of depression. Results: We hope that both unweighted and weighted GRS will be associated with depression and explain a modest
n
Andre Brooking Negrao ,1, Tamara Taporoski1, Nubia Esteban2, Malcolm von Schantz3, Homero Vallada1, Alexandre Costa Pereira4 1
University of São Paulo Medical School National University of Colombia 3 University of Surrey 4 Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School 2
Background: Genetic markers of susceptibility for anxiety and depression have been elusive. Increased sample size, utilizing symptoms rather than disorders and, exploring genetic covariability between pairs of traits are known approaches to increase the power of GWAS and have been used isolatedly. We have previously demonstrated a strong genetic covariability between depression and anxiety symptoms in a family based cohort, The Baependi Heart Project. Combining two strategies, symptoms approach and genetic covariability in a GWAS can result in greater detection power of genetic markers associated with those traits. Methods: We investigated depression and anxiety symptoms, quantified using the Hospital and Depression Scale (HADS) in 1,375 individuals from 93 nuclear families recruited from an admixed population in Brazil. GWAS was performed for anxiety and depression scores both independently (univariate analysis), and using bivariate analysis taking into consideration the genotypic covariance between those traits (rhog = 0.81). The Baependi cohort was genotyped using different GWAS platforms (custom arrays to capture the tri-ancestry genetic structure of the Brazilian population; Affymetrix Axiom Incor array and Affymetrix SNP chip 6.0; Affymetrix, Santa Clara, CA). Results: The univariate approach revealed interesting genetic targets, but none with genome-wide significance.
Abstracts
M32. PER3 POLYMORPHISMS, MORNINGNESS-EVENINGNESS AND DEPRESSION: PRELIMINARY EVIDENCE IN A BRAZILIAN FAMILY-BASED COHORT, THE BAEPENDI HEART STUDY n
Francieli Ruiz ,1, Tâmara P. Taporoski5, Daniela Martinez5, Andrew Beale2, Felipe Beijamini3, José E. Krieger1, Kristen L. Knutson4, Alexandre Pereira1, Mario Pedrazzoli1, Homero Vallada5, Malcolm Von Schantz2 1
University of São Paulo University of Surrey 3 Federal University of Fronteira Sul 4 Northwestern University 5 Univesity of São Paulo Medical School 2
Background: There is a significant interest in the contribution of the circadian timing system to individual differences in a wider range of behaviour. This is in part because sleep complaints and disturbances of the circadian timing system are common in psychiatric disorders. Based on diurnal preference, people can be divided into chronotypes with demonstrated differences in sleep-wake patterns and a variety of circadian rhythms, behavioral rhythms, and diurnal variation in mood. Specifically, greater eveningness has been related to greater depression. The human PER3 gene contains a variable number tandem repeat (VNTR) which is associated with diurnal preference: the longer allele (five tandem repeats) has been reported to associate with greater morningness, and the shorter allele (four tandem repeats) with greater eveningness. We have investigated the PER3 polymorphism and its relationship to sleep, circadian and depression characteristics in a Brazilian family-based cohort. Methods: Baependi is a small rural town in Brazil that provides a window of opportunity to study the influence of sleep circadian patterns in a highly admixed rural population with a conservative lifestyle. Here, we studied 786 subjects (mean age7SD 46.5716.2, 42% female). Blood samples were collected from all participants. The Per3 length polymorphism was genotyped using PCR followed by gel electrophoresis. We tested for associations between the PER3 polymorphism and sleep characteristics, daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire, respectively. Depressive symptoms were assessed using the Beck Depression Inventory [BDI-II]). Results: Our genotyping data showed that 36% of the subjects were homozygous for the shorter allele (4/4), 51% of the participants were heterozygous (4/5) and 12% of the subjects were homozygous for the longer allele (5/5). Allele frequency was 0.62 for the 4-repeat and a 0.38 for the 5-repeat. The percentages of the chronotypes Morning type (M-type), Neither type (N-type) and Evening type (E-type) were 5%, 46% and 7%, respectively. We observed an increase of the depression symptoms in evening types [F(2, 1014)=4.8, p=0.007]. On the other hand, no such associations were observed the PER3 genotype. There were no significant differences in the MEQ score [F(2, 317)=0.46, p=0.63], daytime sleepiness [(F(2, 317)=0.23, p=0.79)], sleep efficiency [(F(2,
317)=2.59, p=0.07)] and sleep characteristics [(F(2, 317) =1.92, p=0.14)] between the PER3 genotypes. Discussion: We observed an association between eveningness and depression. Identifying factors contributing to individual differences in sleep and to describe how these factors are associated with physiological and psychological profiles may aid our understanding of the role of sleep and the circadian system in mental health. On the other hand, we were not able to replicate the association between the PER3 VNTR polymorphism and chronotype, which has been confirmed independently in multiple populations worldwide (including in Brazil). Neither did we observe any association with depression. CNPq – PVE 400791/2014-5.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.339
M33. DEPRESSION PROBLEMS AMONG TURKISH TWINS n
Fazil Aliev ,1, Sevgi Yurt Oncel2 1 2
Virginia Commonwealth University, Karabuk University Kirikkale University
Background: In this study, we investigate factors affecting depressive behavior among adult Turkish twins living in the Kırıkkale and Ankara regions of Turkey. Twins administered a health and lifestyle interview which included questions about smoking, alcohol and drug use, depression, demographics and factors possibly affecting behavior problems. Main focus was on binary variable pointing to depressive problems. Methods: We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to depression in this sample. Results: 256 participants (43.9%) were identified as having depressive problems, of which 45.3% were males and 54.7% were females. Mean for depression was significantly higher in males than in females (p = 0.0001). Our study showed that gender, presence of a twin with depression in the family, age, marital status, and daily sports activities all played a significant role in depressive behavior among twins. The twin analysis suggested that genetic factors play significant role on the liability to depressive problems. Discussion: Significant differences in the presence of depression in women versus men are observed for the Turkish population. We find that having a twin with depression plays a significant role in depression problems among Turkish twins. This study will enable us to better understand genetic and environmental influences on behavioral outcomes across diverse cultures.
Abstracts
S973
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.340
M34. A GENETIC RISK SCORE, DEPRESSION AND OBESITY: EVIDENCE FROM THE SPANISH POPULATION STUDY PISMA-EP n
Margarita Rivera ,1, Blanca Gutierrez2, Paula Rovira3, Esther Molina4, Maria Victoria Martín-Laguna2, Inmaculada Ibanez-Casas2, Kathryn McKenney2, Ana Ching-López2, Isabel Ruiz-Pérez5, Miguel Rodríguez-Barranco6, Jorge Cervilla2 1
King's College London University of Granada 3 Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Mental Health and Addictions, Hospital Universitari Vall d’Hebron 4 University of Seville 5 CIBER de Epidemiología y Salud Pública 6 Andalusian School of Public Health 2
amount of variance. We also hope that adding ‘traditional’ risk factors to GRS will significantly improve the predictive ability with the area under the curve (AUC) in the ROC analysis. We further expect that the GRS will discriminate depression better in obese individuals compare to normalweight subjects. Discussion: The association between depression and obesity has repeatedly been reported in many studies. Given the high prevalence of both disorders, we expect that incorporating genetic information, traditional risk factors and obesity status may largely improve the predicting ability for depression. Addressing obesity in people with depression or vice versa is highly important as both disorders are associated with substantial personal and societal economic costs worldwide.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.341
M35. GENOME-WIDE ASSOCIATION STUDY OF COMORBID DEPRESSION AND ANXIETY SYMPTOMS IN AN EXTENDED PEDIGREE COHORT
Background: Depression and obesity are highly prevalent diseases in the general population, responsible of disability burden worldwide. Both conditions are major risk factors for chronic physical diseases such as type 2 diabetes, cardiovascular disease and hypertension among others. The reason why obesity and depression cluster together is not totally understood and several mechanisms have been proposed. There are many factors driving this observation, such as individual lifestyle choices, socioeconomic factors, psychosocial stress, disparities in health care, medication, as well as biological and genetic factors. The aim of this study is to investigate whether a Genetic Risk Score (GRS) combining 85 candidate SNPs for depression and other major psychiatric disorders is associated with depression and predicts depression in individuals with obesity. Methods: The sample consists of 743 community-based individuals from the PISMA-ep study. The PISMA-ep is a cross-sectional epidemiological study of mental disorders based on a representative sample of the adult population of Andalusia, Spain. A DSM-IV diagnosis of major depression was ascertained using the MINI interview. Height and weight data reported from each individual was used to calculate Body Mass Index (BMI), as a measure of obesity, using the formula: weight(kg)/height(m)2. All individuals have been genotyped for the 85 candidate polymorphisms using TaqMans OpenArrayTM Genotyping System. These markers were selected according to genome location, function and previous evidence. Logistic regression models will be conducted to predict depression. We will calculate an unweighted GRS by summation of the number of risk alleles, and a weighted GRS as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver Operating Characteristic (ROC) analysis will be used to compare the discriminatory ability of predictors of depression. Results: We hope that both unweighted and weighted GRS will be associated with depression and explain a modest
n
Andre Brooking Negrao ,1, Tamara Taporoski1, Nubia Esteban2, Malcolm von Schantz3, Homero Vallada1, Alexandre Costa Pereira4 1
University of São Paulo Medical School National University of Colombia 3 University of Surrey 4 Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School 2
Background: Genetic markers of susceptibility for anxiety and depression have been elusive. Increased sample size, utilizing symptoms rather than disorders and, exploring genetic covariability between pairs of traits are known approaches to increase the power of GWAS and have been used isolatedly. We have previously demonstrated a strong genetic covariability between depression and anxiety symptoms in a family based cohort, The Baependi Heart Project. Combining two strategies, symptoms approach and genetic covariability in a GWAS can result in greater detection power of genetic markers associated with those traits. Methods: We investigated depression and anxiety symptoms, quantified using the Hospital and Depression Scale (HADS) in 1,375 individuals from 93 nuclear families recruited from an admixed population in Brazil. GWAS was performed for anxiety and depression scores both independently (univariate analysis), and using bivariate analysis taking into consideration the genotypic covariance between those traits (rhog = 0.81). The Baependi cohort was genotyped using different GWAS platforms (custom arrays to capture the tri-ancestry genetic structure of the Brazilian population; Affymetrix Axiom Incor array and Affymetrix SNP chip 6.0; Affymetrix, Santa Clara, CA). Results: The univariate approach revealed interesting genetic targets, but none with genome-wide significance.