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1.
Expert Rev Neurother ; 19(9): 867-879, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269819

RESUMO

Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.

2.
Eat Behav ; 33: 30-33, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852343

RESUMO

PURPOSE: To examine the potential factor structure of the Eating Disorder Diagnostic Scale (EDDS) in a sample of individuals with bipolar disorder. METHOD: Exploratory common factor analyses were conducted in a sample of 1031 people with bipolar disorder as defined by the Structured Clinical Interview for DSM-IV-TR. RESULTS: Approximately 27% of participants had a comorbid eating disorder. Exploratory factor analysis yielded a 3 factor solution (i.e., shape/weight concerns; binge eating behaviors, compensatory behavior). CONCLUSIONS: The 3-factor solution of the EDDS in a bipolar disorder sample is consistent with major eating disorder symptom domains. Future research is necessary to replicate these findings in eating disorder samples with diverse comorbid psychopathology.

3.
Transl Psychiatry ; 8(1): 188, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201969

RESUMO

Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the clinical phenotype may increase the power to identify risk genes that contribute to particular BD subtypes. This study was designed to test the hypothesis that genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history of manic psychosis. Analyses were conducted using a Mayo Clinic Bipolar Biobank cohort of 957 bipolar cases (including 333 with history of psychosis during mania, 64 with history of psychosis only during depression, 547 with no history of psychosis, and 13 with unknown history of psychosis) and 778 controls. Polygenic risk score (PRS) analysis was performed by calculating a SZ-PRS for the BD cases and controls, and comparing the calculated SZ risk between different psychosis subgroups and bipolar types. The SZ-PRS was significantly higher for BD-I cases with manic psychosis than BD-I cases with depressive psychosis (Nagelkerke's R2 = 0.021; p = 0.045), BD-I cases without psychosis (R2 = 0.015; p = 0.007), BD-II cases without psychosis (R2 = 0.014; p = 0.017), and controls (R2 = 0.065; p = 2 × 10-13). No other significant differences were found. Our results show that BD-I with manic psychosis is genetically more similar to SZ than any other tested BD subgroup. Further investigations on genetics of distinct clinical phenotypes composing major psychoses may help refine the current diagnostic classification system.

4.
Transl Psychiatry ; 8(1): 40, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29391396

RESUMO

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.

6.
J Clin Psychiatry ; 78(9): 1337-1343, 2017 Nov/Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28199072

RESUMO

OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. RESULTS: GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. CONCLUSIONS: These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

7.
J Affect Disord ; 201: 95-8, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27195513

RESUMO

OBJECTIVE: To determine whether bipolar spectrum disorder with binge eating behavior (BE) is an important clinical sub-phenotype. METHODS: Prevalence rates and correlates of different levels of BE were assessed in 1114 bipolar spectrum patients participating in a genetic biobank. BE and eating disorders (EDs) were assessed with the Eating Disorder Diagnostic Scale (EDDS). Psychiatric illness burden was evaluated with measures of suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. Medical illness burden was evaluated with body mass index (BMI) and the Cumulative Index Rating Scale (CIRS). RESULTS: Thirty percent of patients had any BE and 27% had BE plus an ED diagnosis. Compared with bipolar spectrum patients without BE, bipolar spectrum patients with BE were younger and more likely to be female; had significantly higher levels of eating psychopathology, suicidality, mood instability, and anxiety disorder comorbidity; had a significantly higher mean BMI and a significantly higher rate of obesity; and had a significantly higher medical illness burden. Bipolar spectrum patients with BE but no ED diagnosis were more similar to bipolar spectrum patients without BE than to those with an ED. Nonetheless, the positive predictive value and specificity of BE predicting an ED was 0.90 and 0.96, respectively. LIMITATIONS: As only two patients had co-occurring anorexia nervosa, these results may not generalize to bipolar spectrum patients with restricting EDs. CONCLUSION: Bipolar spectrum disorder with broadly-defined BE may not be as clinically relevant a sub-phenotype as bipolar spectrum disorder with an ED but may be an adequate proxy for the latter when phenotyping large samples of individuals.


Assuntos
Transtorno da Compulsão Alimentar/diagnóstico , Transtorno Bipolar/diagnóstico , Adulto , Transtornos de Ansiedade/epidemiologia , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno da Compulsão Alimentar/psicologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Comorbidade , Efeitos Psicossociais da Doença , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Prevalência , Inquéritos e Questionários
8.
Bipolar Disord ; 18(2): 124-35, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26934194

RESUMO

OBJECTIVES: Bipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome-wide association study, we found that BMI modified the association of rs12772424 - a common variant in the gene encoding transcription factor 7-like 2 (TCF7L2) - with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions. Here, using an independent sample, we evaluated 26 TCF7L2 single nucleotide polymorphisms (SNPs) to explore further the association of BD with the TCF7L2-BMI interaction. METHODS: Using a sample of 662 BD cases and 616 controls, we conducted SNP-level and gene-level tests to assess the evidence for an association between BD and the interaction of BMI and genetic variation in TCF7L2. We also explored the potential mechanism behind the detected associations using human brain expression quantitative trait loci (eQTL) analysis. RESULTS: The analysis provided independent evidence of an rs12772424-BMI interaction (p = 0.011). Furthermore, while overall there was no evidence for SNP marginal effects on BD, the TCF7L2-BMI interaction was significant at the gene level (p = 0.042), with seven of the 26 SNPs showing SNP-BMI interaction effects with p < 0.05. The strongest evidence of interaction was observed for rs7895307 (p = 0.006). TCF7L2 expression showed a significant enrichment of association with the expression of other genes in the Wnt canonical pathway. CONCLUSIONS: The current study provides further evidence suggesting that TCF7L2 involvement in BD risk may be regulated by BMI. Detailed, prospective assessment of BMI, comorbidity, and other possible contributing factors is necessary to explain fully the mechanisms underlying this association.


Assuntos
Transtorno Bipolar , Índice de Massa Corporal , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
9.
J Affect Disord ; 191: 216-21, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26682490

RESUMO

OBJECTIVE: To determine prevalence rates and clinical correlates of current DSM-5 eating disorders in patients with bipolar disorder (BP). METHODS: Prevalence rates of current DSM-5- and DSM-IV-defined binge eating disorder (BED), bulimia nervosa (BN), and anorexia nervosa (AN) were assessed with the Eating Disorder Diagnostic Scale (EDDS) in 1092 patients with BP. Psychiatric illness burden was evaluated with five proxy measures of BP illness severity. Medical illness burden was evaluated with the Cumulative Index Rating Scale (CIRS). RESULTS: Twenty-seven percent of patients had a current DSM-5 eating disorder: 12% had BED, 15% had BN, and 0.2% had AN. Rates of DSM-5-defined BED and BN were higher than clinical diagnosis rates and rates of DSM-IV-defined BED and BN. Compared with BP patients without an eating disorder, BP patients with a DSM-5 eating disorder were younger and more likely to be women; had an earlier age of onset of BP; had higher EDDS composite scores and higher degrees of suicidality, mood instability, and anxiety disorder comorbidity; and had a higher mean BMI, higher rate of obesity, and higher CIRS total scores. In a logistic regression model controlling for previously identified correlates of an eating disorder, younger age, female gender, and higher BMI remained significantly associated with an eating disorder. LIMITATIONS: The EDDS has not been validated in BP patients. CONCLUSION: DSM-5-defined BED and BN are common in BP patients, possibly more common than DSM-IV-defined BED and BN, and associated with greater psychiatric and general medical illness burden. Further studies assessing DSM-5 eating disorders in people with BP are greatly needed.


Assuntos
Anorexia Nervosa/epidemiologia , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno Bipolar/psicologia , Bulimia Nervosa/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia Nervosa/psicologia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno da Compulsão Alimentar/psicologia , Índice de Massa Corporal , Bulimia Nervosa/psicologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/psicologia , Prevalência , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Suicídio/psicologia , Suicídio/estatística & dados numéricos
10.
Bipolar Disord ; 17(6): 645-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26528762

RESUMO

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. METHODS: DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. RESULTS: Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). CONCLUSIONS: These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder.


Assuntos
Transtorno Bipolar , Fator Neurotrófico Derivado do Encéfalo/genética , Adulto , Idade de Início , Alelos , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Estados Unidos
11.
Bipolar Disord ; 17(6): 670-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26529373

RESUMO

OBJECTIVES: To examine the independent effects of sex on the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I disorder (BP-I) or bipolar II disorder (BP-II). METHODS: We analyzed data from the first 1,225 patients enrolled in the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. Demographic and clinical variables were ascertained using standardized questionnaires; height and weight were assessed to determine body mass index (BMI). Rates of rapid cycling, cycle acceleration, and increased severity of mood episodes over time were compared between women and men overall and within subgroups defined by bipolar disorder subtype (BP-I or BP-II). Multiple logistic regression analysis was used to assess the independent effect of sex on the risk of these indicators of adverse illness course. RESULTS: Women had significantly higher rates of rapid cycling than men. Overall rates of rapid cycling were higher in patients with BP-II than BP-I; and sex differences in the rate of rapid cycling were more pronounced in patients with BP-II than BP-I, although the power to detect statistically significant differences was reduced due to the lower sample size of subjects with BP-II. Female sex was a significant predictor of rapid cycling, cycle acceleration, and increased severity of mood episodes over time after adjusting for age, bipolar disorder subtype, BMI, having any comorbid psychiatric disorder, and current antidepressant use. CONCLUSIONS: Female sex was associated with significantly higher risk of rapid cycling, cycle acceleration, and increased severity of mood episodes over time in a sample of 1,225 patients with bipolar disorders.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar , Adulto , Afeto/fisiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Escalas de Graduação Psiquiátrica , Medição de Risco , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários
12.
Bipolar Disord ; 17(5): 518-27, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26062406

RESUMO

OBJECTIVES: To determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder. METHODS: This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM-IV-TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS). This 13-item organ-based scale includes cardiac disease severity quantification. Confirmed by medical record review, patients who scored 1 (current mild or past significant problem) or higher in the cardiac item were compared by logistic regression to patients who scored 0 (no impairment), adjusting for CVD risk factors that were selected using a backwards stepwise approach or were obtained from the literature. RESULTS: In a multivariate model, age [odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.66-5.54, p < 0.0001], hypertension (OR = 2.43, 95% CI: 1.69-3.55, p < 0.0001), and history of psychosis (OR = 1.48, 95% CI: 1.03-2.13, p = 0.03) were associated with CVD. When CVD risk factors from the literature were added to the analysis, age (OR = 3.19, 95% CI: 1.67-6.10, p = 0.0005) and hypertension (OR = 2.46, 95% CI: 1.61-3.76, p < 0.01) remained significant, with psychosis being at the trend level (OR = 1.43, 95% CI: 0.96-2.13, p = 0.08). CONCLUSIONS: The phenotype of psychotic bipolar disorder may reflect higher illness severity with associated cardiac comorbidity. Further studies are encouraged to clarify the effect of the disease burden (i.e., depression), lifestyle, and treatment interventions (i.e., atypical antipsychotics) on this risk association.


Assuntos
Transtorno Bipolar/epidemiologia , Doenças Cardiovasculares/epidemiologia , Transtornos Psicóticos/epidemiologia , Adulto , Fatores Etários , Idoso , Transtorno Bipolar/classificação , Transtorno Bipolar/psicologia , Comorbidade , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transtornos Psicóticos/psicologia , Índice de Gravidade de Doença
13.
J Clin Psychiatry ; 76(2): 174-80, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25611077

RESUMO

INTRODUCTION: Identifying clinical and genetic risk factors associated with antidepressant-induced mania (AIM) may improve individualized treatment strategies for bipolar depression. METHOD: From 2009 to 2012, bipolar depressed patients, confirmed by DSM-IV-TR-structured interview, were screened for AIM. An AIM+ case was defined as a manic/hypomanic episode within 60 days of starting or changing dose of antidepressant, while an AIM- control was defined as an adequate (≥ 60 days) exposure to an antidepressant with no associated manic/hypomanic episode. 591 subjects (205 AIM+ and 386 AIM-) exposed to an antidepressant and a subset of 545 subjects (191 AIM+ and 354 AIM-) treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) were used to evaluate the association of AIM with phenotypic clinical risk factors previously published. 295 white subjects (113 AIM+ cases, 182 AIM-controls) were genotyped for 3 SLC6A4 variants: the 5-HTTLPR, single nucleotide polymorphism (SNP) rs25531, and the intron 2 variable number of tandem repeats (VNTR). Tests of association with AIM were performed for each polymorphism and the haplotype. RESULTS: The only clinical risk factors associated with AIM in the overall and the SSRI + SNRI analysis was bipolar I subtype. The S allele of 5-HTTLPR was not significantly associated with AIM; however, a meta-analysis combining this sample with 5 prior studies provided marginal evidence of association (P = .059). The L-A-10 haplotype was associated with a reduced risk of AIM (P = .012). DISCUSSION: Narrowly defined, AIM appears to be at greatest risk for bipolar I patients. Our haplotype analysis of SLC6A4 suggests that future pharmacogenetic studies should not only focus on the SLC6A4 promotor variation but also investigate the role of other variants in the gene.


Assuntos
Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/genética , Variação Genética/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inibidores de Captação de Serotonina/efeitos adversos , Adulto , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Fatores de Risco , Inibidores de Captação de Serotonina/uso terapêutico
14.
J Psychosom Res ; 78(3): 199-204, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25258356

RESUMO

OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1±0.4 vs. 25.0±1years old, p=0.002). On average, RYGB patients reported resuming alcohol consumption 1.4±0.2years post-surgery, meeting criteria for AUD at 3.1±0.5years and seeking treatment at 5.4±0.3years postoperatively. Pre-surgical drinks per day were significantly fewer compared to post-surgical consumption [2.5±0.4 vs. 8.1±1.3, p=0.009]. Prior to admission, RYGB patients reported fewer drinking days per week vs. controls (4.7±0.3 vs. 5.5±1.8days, p=0.02). Neither RYGB, gender, age nor BMI was associated with differential drinking patterns. CONCLUSION: The results of this study suggest that some patients develop progressive AUD several years following RYGB. This observation has important clinical implications, calling for AUD-preventive measures following RYGB. Further large-scale longitudinal studies are needed to clarify the association between RYGB and AUD onset.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/complicações , Derivação Gástrica , Obesidade/psicologia , Obesidade/cirurgia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/diagnóstico , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Período Pós-Operatório , Estudos Retrospectivos
15.
J Affect Disord ; 165: 151-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24882193

RESUMO

BACKGROUND: Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. METHODS: Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. RESULTS: Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. LIMITATIONS: Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. CONCLUSIONS: This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.


Assuntos
Apolipoproteínas B/genética , Transtorno Bipolar/complicações , Bulimia/complicações , Estudo de Associação Genômica Ampla , Transtorno Bipolar/genética , Bulimia/genética , Humanos , Polimorfismo de Nucleotídeo Único
16.
J Affect Disord ; 150(3): 981-6, 2013 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-23742827

RESUMO

BACKGROUND: To explore the relationship between binge eating disorder (BED) and obesity in patients with bipolar disorder (BP). METHODS: 717 patients participating in the Mayo Clinic Bipolar Biobank completed structured diagnostic interviews and questionnaires for demographic and illness-related variables. They also had weight and height measured to determine body mass index (BMI). The effects of BED and obesity (BMI≥30 kg/m(2)), as well as their interaction, were assessed on one measure of general medical burden and six proxies of psychiatric illness burden. RESULTS: 9.5% of patients received a clinical diagnosis of BED and 42.8% were obese. BED was associated with a significantly elevated BMI. Both BED and obesity were associated with greater psychiatric and general illness burden, but illness burden profiles differed. After controlling for obesity, BED was associated with suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. After controlling for BED status, obesity was associated with greater general medical comorbidity, but lower substance abuse comorbidity. There were no significant interaction effects between obesity and BED, or BMI and BED, on any illness burden outcome. LIMITATIONS: There may have been insufficient power to detect interactions between BED and obesity. CONCLUSIONS: Among patients with BP, BED and obesity are highly prevalent and correlated, but associated with different profiles of enhanced illness burden. As the association of BED with greater psychiatric illness burden remained significant even after accounting for the effect of obesity, BP with BED may represent a clinically important sub-phenotype.


Assuntos
Transtorno da Compulsão Alimentar/diagnóstico , Transtorno Bipolar/diagnóstico , Obesidade/diagnóstico , Adulto , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno Bipolar/epidemiologia , Índice de Massa Corporal , Peso Corporal , Comorbidade , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fenótipo , Prevalência , Suicídio
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