Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cell ; 179(3): 589-603, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31607513

RESUMO

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

2.
Front Pharmacol ; 10: 83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837869

RESUMO

Background: Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic differences in patients seeking treatment for depression, which may further impact clinical antidepressant treatment recommendations. This study evaluated PK and PD genetic variation and the clinical use of such testing in treatment seeking patients with bipolar disorder (BP) and major depressive disorder (MDD) and history of multiple drug failures/treatment resistance. Methods: Consecutive depressed patients evaluated at the Mayo Clinic Depression Center over a 10-year study time frame (2003-2013) were included in this retrospective analysis. Diagnoses of BP or MDD were confirmed using a semi-structured diagnostic interview. Clinical rating scales included the Hamilton Rating Scale for Depression (HRSD24), Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Adverse Childhood Experiences (ACE) Questionnaire. Clinically selected patients underwent genotyping of cytochrome P450 CYP2D6/CYP2C19 and the serotonin transporter SLC6A4. PK and PD differences and whether clinicians incorporated test results in providing recommendations were compared between the two patient groups. Results: Of the 1795 patients, 167/523 (31.9%) with BP and 446/1272 (35.1%) with MDD were genotyped. Genotyped patients had significantly higher self-report measures of depression and anxiety compared to non-genotyped patients. There were significantly more CYP2C19 poor metabolizer (PM) phenotypes in BP (9.3%) vs. MDD patients (1.7%, p = 0.003); among participants with an S-allele, the rate of CYP2C19 PM phenotype was even higher in the BP (9.8%) vs. MDD (0.6%, p = 0.003). There was a significant difference in the distribution of SLC6A4 genotypes between BP (l/l = 28.1%, s/l = 59.3%, s/s = 12.6%) and MDD (l/l = 31.4%, s/l = 46.1%, s/s = 22.7%) patients (p < 0.01). Conclusion: There may be underlying pharmacogenomic differences in treatment seeking depressed patients that potentially have impact on serum levels of CYP2C19 metabolized antidepressants (i.e., citalopram / escitalopram) contributing to rates of efficacy vs. side effect burden with additional potential risk of antidepressant response vs. induced mania. The evidence for utilizing pharmacogenomics-guided therapy in MDD and BP is still developing with a much needed focus on drug safety, side effect burden, and treatment adherence.

3.
Transl Psychiatry ; 8(1): 188, 2018 09 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.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Predisposição Genética para Doença , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Adulto , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Fenótipo , Medição de Risco , Psicologia do Esquizofrênico
4.
J Affect Disord ; 201: 95-8, 2016 Sep 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
5.
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
6.
J Affect Disord ; 194: 120-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26820761

RESUMO

OBJECTIVES: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder. METHOD: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders. RESULTS: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46). LIMITATIONS: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses. CONCLUSION: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors.


Assuntos
Transtorno Bipolar/epidemiologia , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
7.
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
8.
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
9.
Int J Bipolar Disord ; 3(1): 30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26105627

RESUMO

BACKGROUND: We aimed to establish a bipolar disorder biobank to serve as a resource for clinical and biomarker studies of disease risk and treatment response. Here, we describe the aims, design, infrastructure, and research uses of the biobank, along with demographics and clinical features of the first participants enrolled. METHODS: Patients were recruited for the Mayo Clinic Bipolar Biobank beginning in July 2009. The Structured Clinical Interview for DSM-IV was used to confirm bipolar diagnosis. The Bipolar Biobank Clinical Questionnaire and Participant Questionnaire were designed to collect detailed demographic and clinical data, including clinical course of illness measures that would delineate differential phenotypes for subsequent analyses. Blood specimens were obtained from participants, and various aliquots were stored for future research. RESULTS: As of September 2014, 1363 participants have been enrolled in the bipolar biobank. Among these first participants, 69.0 % had a diagnosis of bipolar disorder type I. The group was 60.2 % women and predominantly white (90.6 %), with a mean (SD) age of 42.6 (14.9) years. Clinical phenotypes of the group included history of psychosis (42.3 %), suicide attempt (32.5 %), addiction to alcohol (39.1 %), addiction to nicotine (39.8 %), obesity (42.9 %), antidepressant-induced mania (31.7 %), tardive dyskinesia (3.2 %), and history of drug-related serious rash (5.7 %). CONCLUSIONS: Quantifying phenotypic patterns of illness beyond bipolar subtype can provide more detailed clinical disease characteristics for biomarker research, including genomic-risk studies. Future research can harness clinically useful biomarkers using state-of-the-art research technology to help stage disease burden and better individualize treatment selection for patients with bipolar disorder.

10.
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
11.
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
12.
J Affect Disord ; 172: 355-60, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25451437

RESUMO

BACKGROUND: There are no self-report scales that assess manic/hypomanic symptoms in patients with depression. The aim of this study was to explore the use of a modified screening instrument for bipolar disorder to assess current manic/hypomanic symptoms in patients with a depressive episode. METHODS: The study sample consisted of 188 patients with Structured Clinical Interview for DSM-IV-TR disorders (SCID) confirmed bipolar or major depressive disorder. We modified the Hypomania Checklist-32 (mHCL-32) to assess current instead of lifetime symptoms. An Exploratory Factor Analysis (EFA) was conducted to identify clusters of mHCL-32 items that were endorsed concurrently. A Latent Class Analysis (LCA) was carried out to identify groups of patients with similar mHCL-32 item endorsement patterns. RESULTS: The EFA identified 3 factors: factor #1 ("elation-disinhibition-increased goal directed activity"), factor #2 ("risk-taking-impulsivity-substance use") and factor #3 (distractibility-irritability). The LCA yielded 3 classes (2 showing manic/hypomanic features). While class #1 patients endorsed more items related to disinhibition and racing thoughts, class #2 patients recognized more items associated with irritability and substance use. LIMITATIONS: Lack of an adequate gold standard measure of mixed depression to compare to, the cross-sectional design and the lack of a validation sample. CONCLUSIONS: The mHCL-32 scale allowed a comprehensive and convergent delineation of hypomanic/manic symptoms in depression. Further validation of these findings is needed.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Ciclotímico/diagnóstico , Depressão/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Entrevista Psicológica/normas , Adulto , Lista de Checagem/normas , Estudos Transversais , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Agitação Psicomotora/diagnóstico , Fatores de Risco
13.
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
14.
J Affect Disord ; 169 Suppl 1: S17-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25533910

RESUMO

BACKGROUND: Depression is the predominant pole of illness disability in bipolar disorder and, compared with acute mania, has less systematic research guiding treatment development. The aim of this review is to present the therapeutic options currently available for managing bipolar depression and to highlight areas of unmet need and future research. METHODS: Literature search of PubMed, PsycINFO, and Cochrane databases and bibliographies from 2000 to August 2013 for treatments that have regulatory approval for bipolar depression or early controlled preliminary data on efficacy. RESULTS: Treatment options for bipolar depression have increased over the last decade, most notably with regulatory approval for olanzapine/fluoxetine combination, quetiapine, and lurasidone. Conventional mood stabilizers lamotrigine and divalproex have meta-analyses suggesting acute antidepressant response. Manual-based psychotherapies also appear to be effective in treating bipolar depression. The therapeutic utility of unimodal antidepressants, as a class, for the treatment of patients with bipolar depression, as a group, remains to be confirmed. There is a substantially unmet need to develop new interventions that are efficacious, effective, and have low side effect burden. LIMITATIONS: Additional compounds are currently being developed that may ultimately be applicable to the treatment of bipolar depression and early open-trial data encourage further studies, but both of these topics are beyond the scope of this review. CONCLUSION: Future registrational trials will need to establish initial efficacy, but increasing interest for personalized or individualized medicine will encourage further studies on individual predictors or biomarkers of response.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/terapia , Psicoterapia , Anticonvulsivantes/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/uso terapêutico , Combinação de Medicamentos , Fluoxetina/uso terapêutico , Previsões , Necessidades e Demandas de Serviços de Saúde , Humanos , Isoindóis/uso terapêutico , Lamotrigina , Cloridrato de Lurasidona , Fumarato de Quetiapina , Tiazóis/uso terapêutico , Triazinas/uso terapêutico
15.
Neuropharmacology ; 85: 482-92, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24929110

RESUMO

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders.


Assuntos
Fármacos do Sistema Nervoso Central/farmacologia , Atividade Motora/efeitos dos fármacos , Neurotensina/análogos & derivados , Núcleo Accumbens/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Neurotensina/agonistas , Animais , Benzazepinas/farmacologia , Bromocriptina/farmacologia , Agonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Meio Ambiente , Abrigo para Animais , Masculino , Camundongos Endogâmicos C57BL , Microinjeções , Atividade Motora/fisiologia , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Neurotensina/farmacologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia , Distribuição Aleatória , Receptores Dopaminérgicos/metabolismo , Receptores de Neurotensina/metabolismo , Teste de Desempenho do Rota-Rod
16.
J Affect Disord ; 152-154: 478-82, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24070907

RESUMO

BACKGROUND: Mixed depression is a common, dimensional phenomenon that is increasingly recognized in unipolar and bipolar disorders. We piloted a modified version of the Hypomania Checklist (mHCL-32) to assess the prevalence and clinical correlates of concurrent manic (hypo) symptoms in depressed patients. METHODS: The mHCL-32, Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAMD-24) were utilized in the assessment of unipolar (UP=61) and bipolar (BP=44) patients with an index major depressive episode confirmed by the Structured Clinical Interview for DSM-IV (SCID). Differential mHLC-32 item endorsement was compared between UP and BP. Correlation analyses assessed the association of symptom dimensions measured by mHCL-32, YMRS and HAMD-24. RESULTS: There was no significant difference between mood groups in the mean mHCL-32 and YMRS scores. Individual mHLC-32 items of increased libido, quarrels, and caffeine intake were endorsed more in BP vs. UP patients. The mHCL-32 active-elevated subscale score was positively correlated with the YMRS in BP patients and negatively correlated with HAMD-24 in UP patients. Conversely, the mHCL-32 irritable-risk taking subscale score was positively correlated with HAMD-24 in BP and with YMRS in UP patients. LIMITATIONS: Small sample size and cross-sectional design. CONCLUSION: Modifying the HCL to screen for (hypo) manic symptoms in major depression may have utility in identifying mixed symptoms in both bipolar vs. unipolar depression. Further research is encouraged to quantify mixed symptoms with standardized assessments.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Depressivo Maior/psicologia , Adulto , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Lista de Checagem/métodos , Lista de Checagem/normas , Estudos Transversais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Cooperação Internacional , Entrevista Psicológica , Masculino , Projetos Piloto , Prevalência , Escalas de Graduação Psiquiátrica
17.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA