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1.
BMC Psychiatry ; 19(1): 420, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881956

RESUMO

BACKGROUND: Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. METHODS: This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. RESULTS: At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. CONCLUSIONS: The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Farmacogenética , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Duplo-Cego , Humanos , Resultado do Tratamento
2.
medRxiv ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410442

RESUMO

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

3.
Depress Anxiety ; 30(10): 940-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23893768

RESUMO

BACKGROUND: Genetics of Recurrent Early-Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early-onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD. METHODS: Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM-IV Axis I disorders were reported with best estimated age of onset. RESULTS: The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time-survival analyses to take into account timing in the PTSD-suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P< .0001). CONCLUSIONS: Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability.


Assuntos
Transtorno Depressivo Maior/complicações , Acontecimentos que Mudam a Vida , Transtornos de Estresse Pós-Traumáticos/complicações , Tentativa de Suicídio/psicologia , Violência/psicologia , Adulto , Idade de Início , Comorbidade , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Tentativa de Suicídio/estatística & dados numéricos
4.
Am J Med Genet B Neuropsychiatr Genet ; 159B(1): 112-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22170779

RESUMO

Epidemiological studies, such as family, twin, and adoption studies, demonstrate the presence of a heritable component to both attempted and completed suicide. Some of this heritability is accounted for by the presence of comorbid psychiatric disorders, but the evidence also indicates that a portion of this heritability is specific to suicidality. The serotonergic system has been studied extensively in this phenotype, but findings have been inconsistent, possibly due to the presence of multiple susceptibility variants and/or gene-gene interactions. In this study, we genotyped 174 tag and coding single nucleotide polymorphisms (SNPs) from 17 genes within the serotonin pathway on 516 subjects with a major mood disorder and a history of a suicide attempt (cases) and 515 healthy controls, with the goal of capturing the common genetic variation across each of these candidate genes. We tested the 174 markers in single-SNP, haplotype, gene-based, and epistasis analyses. While these association analyses identified multiple marginally significant SNPs, haplotypes, genes, and interactions, none of them survived correction for multiple testing. Additional studies, including assessment in larger sample sets and deep resequencing to identify rare causal variants, may be required to fully understand the role that the serotonin pathway plays in suicidal behavior.


Assuntos
Estudos de Associação Genética , Serotonina/genética , Transdução de Sinais/genética , Tentativa de Suicídio , Humanos , Polimorfismo de Nucleotídeo Único/genética , Tentativa de Suicídio/psicologia , Transmissão Sináptica/genética
5.
Arch Womens Ment Health ; 12(1): 27-34, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19137238

RESUMO

We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.


Assuntos
Transtornos do Humor/genética , Transtornos do Humor/fisiopatologia , Personalidade , Síndrome Pré-Menstrual/genética , Adulto , Transtorno Bipolar , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Entrevistas como Assunto , Razão de Chances , Linhagem , Síndrome Pré-Menstrual/psicologia , Estados Unidos
6.
Am J Med Genet B Neuropsychiatr Genet ; 150B(5): 693-702, 2009 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-19127563

RESUMO

The Neuregulin 1 gene (NRG1) has been associated with schizophrenia, and, to a lesser extent, with bipolar disorder (BP). We investigated the association of NRG1 with BP in a large family sample, and then performed analyses according to the presence of psychotic features or mood-incongruent psychotic features. We genotyped 116 tagSNPs and four Icelandic "core" SNPs in 1,199 subjects from 314 nuclear families. Of 515 BP offspring, 341 had psychotic features, and 103 had mood-incongruent psychotic features. In single-marker and sliding window haplotype analyses using FBAT, there was little association using the standard BP or mood-incongruent psychotic BP phenotypes, but stronger signals were seen in the psychotic BP phenotype. The most significant associations with psychotic BP were in haplotypes within the 5' "core" region. The strongest global P-value was across three SNPs: NRG241930-NRG243177-rs7819063 (P = 0.0016), with an undertransmitted haplotype showing an individual P = 0.0007. The most significant individual haplotype was an undertransmitted two-allele subset of the above (NRG243177-rs7819063, P = 0.0004). Additional associations with psychotic BP were found across six SNPs in a 270 kb central region of the gene. The most 3' of these, rs7005606 (P = 0.0029), is located approximately 4 kb from the type I NRG1 isoform promoter. In sum, our study suggests that NRG1 may be specifically associated with the psychotic subset of BP; however, our results should be interpreted cautiously since they do not meet correction for multiple testing and await independent replication.


Assuntos
Transtorno Bipolar/genética , Família , Proteínas do Tecido Nervoso/genética , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Neuregulina-1 , Fenótipo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Esquizofrenia/genética
7.
J Clin Psychiatry ; 80(6)2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31721487

RESUMO

OBJECTIVE: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. METHODS: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depre​ssion Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. RESULTS: Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission). CONCLUSIONS: By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02109939​.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Farmacogenética , Adulto , Transtorno Depressivo Maior/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Resultado do Tratamento
8.
J Psychiatr Res ; 111: 59-67, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30677646

RESUMO

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use as directed' or 'use with caution' test categories) or incongruent ('use with increased caution and with more frequent monitoring' test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Testes Farmacogenômicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Estudos de Coortes , Sistema Enzimático do Citocromo P-450/genética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 5-HT2A de Serotonina/genética , Indução de Remissão , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto Jovem
9.
J Affect Disord ; 227: 613-617, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29172054

RESUMO

BACKGROUND: Medication non-adherence is a critical challenge for many patients diagnosed with mood disorders (Goodwin and Jamison, 1990). There is a need for alternative strategies that improve adherence among patients with mood disorders that are cost-effective, able to reach large patient populations, easy to implement, and that allow for communication with patients outside of in-person visits. Technology-based approaches to promote medication adherence are increasingly being explored to address this need. The aim of this paper is to provide a systematic review of the use of mobile technologies to improve medication adherence in patients with mood disorders. METHODS: A total of nine articles were identified as describing mobile technology targeting medication adherence in mood disorder populations. RESULTS: Results showed overall satisfaction and feasibility of mobile technology, and reduction in mood symptoms; however, few examined effectiveness of mobile technology improving medication adherence through randomized control trials. LIMITATIONS: Given the limited number of studies, further research is needed to determine long term effectiveness. CONCLUSIONS: Mobile technologies has the potential to improve medication adherence and can be further utilized for symptom tracking, side effects tracking, direct links to prescription refills, and provide patients with greater ownership over their treatment progress.


Assuntos
Adesão à Medicação , Aplicativos Móveis , Transtornos do Humor/tratamento farmacológico , Telefone Celular , Análise Custo-Benefício , Humanos
10.
Biol Psychiatry ; 61(5): 725-7, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17046723

RESUMO

BACKGROUND: We are interested in identifying susceptibility genes that predispose subjects to attempted suicide. METHODS: We conducted a secondary analysis of genome-wide linkage data from 162 bipolar pedigrees that incorporated attempted suicide as a clinical covariate. RESULTS: The strongest covariate-based linkage signal was seen on 2p12 at marker D2S1777. The logarithm of odds (LOD) score at marker D2S1777 rose from 1.56 to 3.82 after inclusion of the suicide covariate, resulting in significant chromosome-wide empirically derived p-values for the overall linkage finding (p = .01) and for the change in LOD score after the inclusion of the covariate (p = .02). CONCLUSIONS: The finding on chromosome 2 replicates results from two previous studies of attempted suicide in pedigrees with alcohol dependence and in pedigrees with recurrent early-onset depression. Combined, these three studies provide compelling evidence for a locus influencing attempted suicide on 2p12.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Cromossomos Humanos Par 2 , Ligação Genética , Predisposição Genética para Doença , Tentativa de Suicídio , Mapeamento Cromossômico , Humanos , Escore Lod , Linhagem , Estatísticas não Paramétricas
11.
Am J Psychiatry ; 164(2): 236-47, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17267786

RESUMO

OBJECTIVE: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features. METHOD: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers. Subjects with mood-incongruent and mood-congruent psychotic features were compared on clinical variables. Familial aggregation was tested using a proband-predictive model and generalized estimating equations. A genome-wide linkage scan incorporating a mood-incongruence covariate was performed. RESULTS: Mood-incongruent psychotic features were associated with an increased rate of hospitalization and attempted suicide. A proband with mood-incongruence predicted mood-incongruence in relatives with bipolar I disorder when compared with all other subjects and when compared with subjects with mood-congruent psychosis. The presence of mood-incongruent psychotic features increased evidence for linkage on chromosomes 13q21-33 and 2p11-q14. These logarithm of the odds ratio (LOD) scores and their increase from baseline met empirical genome-wide suggestive criteria for significance. CONCLUSIONS: Mood-incongruent psychotic features showed evidence of a more severe course, familial aggregation, and suggestive linkage to two chromosomal regions previously implicated in major mental illness susceptibility. The 13q21-33 finding supports prior evidence of bipolar disorder/schizophrenia overlap in this region, while the 2p11-q14 finding is, to the authors' knowledge, the first to suggest that this schizophrenia linkage region might also harbor a bipolar disorder susceptibility gene.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 2/genética , Delusões/diagnóstico , Saúde da Família , Ligação Genética/genética , Alucinações/diagnóstico , Linhagem , Adulto , Transtorno Bipolar/psicologia , Mapeamento Cromossômico/estatística & dados numéricos , Estudos de Coortes , Delusões/genética , Delusões/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Feminino , Predisposição Genética para Doença/genética , Genótipo , Alucinações/genética , Alucinações/psicologia , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Fenótipo , Esquizofrenia/genética , Índice de Gravidade de Doença
12.
J Affect Disord ; 100(1-3): 171-7, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17126912

RESUMO

BACKGROUND: The study of chronicity in the course of major depression has been complicated by varying definitions of this illness feature. Because familial clustering is one component of diagnostic validity we compared family clustering of chronicity as defined in the DSM-IV to that of chronicity determined by an assessment of lifetime course of depressive illness. METHODS: In 1750 affected subjects from 652 families recruited for a genetic study of recurrent, early-onset depression, we applied several definitions of chronicity. Odds ratios were determined for the likelihood of chronicity in a proband predicting chronicity in an affected relative. RESULTS: There was greater family clustering of chronicity as determined by assessment of lifetime course (OR=2.54) than by DSM-IV defined chronic major depressive episode (MDE) (OR=1.93) or dysthymic disorder (OR=1.76). In families with probands who had preadolescent onset of MDD, familiality was increased by all definitions, with a much larger increase observed for chronicity by lifetime course (ORs were 6.14 for lifetime chronicity, 2.43 for chronic MDE, and 3.42 for comorbid dysthymic disorder). Agreement between these definitions of chronicity was only fair. LIMITATIONS: The data used to determine chronicity were collected retrospectively and not blindly to relatives' status, and assessment of lifetime course was based on global clinical impressions gathered during a semi-structured diagnostic interview. Also, it can be difficult to determine whether individuals with recurrent major depressive episodes who frequently experience long periods of low grade depressive symptoms meet the strict timing requirements of DSM-IV dysthymic disorder. CONCLUSIONS: An assessment of lifetime symptom course identifies a more familial, and thus possibly a more valid, type of chronic depression than the current DSM-IV categories which are defined in terms of particular cross-sectional features of illness.


Assuntos
Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Adolescente , Adulto , Idade de Início , Doença Crônica , Demografia , Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/psicologia , Linhagem , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Tentativa de Suicídio/estatística & dados numéricos
13.
J Affect Disord ; 99(1-3): 221-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17011632

RESUMO

BACKGROUND: We sought to determine the prevalence of, and association between, reproductive cycle-associated mood symptoms in women with affective disorders. We hypothesized that symptoms would correlate with each other across a woman's reproductive life span in both major depression (MDD) and bipolar I disorder (BP). METHODS: 2412 women with, MDD or BP were asked standardized questions about mood symptoms prior to menstruation, within a month of childbirth and during perimenopause. Lifetime rates for each of these symptom types were determined and an odds ratio was calculated correlating each of the types with the others. RESULTS: Of 2524 women with mood disorders, 67.7% reported premenstrual symptoms. Of those at risk, 20.9% reported postpartum symptoms and 26.4% reported perimenopausal symptoms. The rates did not differ between women with MDD and BP but were significantly different from women who were never ill. The symptoms were significantly correlated in women with MDD with odds ratios from 1.66 to 1.82, but were not in women with BP. LIMITATIONS: This is a secondary analysis of a sample that was collected for other purposes and is based upon retrospective reporting. CONCLUSIONS: Reproductive cycle-associated mood symptoms were commonly reported in women with mood disorders and did not differ based on diagnosis. In MDD, but not BP, the occurrence of these symptoms was trait-like as the presence of one predicted the occurrence of the others. Further prospective study is required to clarify the determinants of this trait.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Ciclo Menstrual/psicologia , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Climatério/fisiologia , Climatério/psicologia , Estudos Transversais , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/fisiopatologia , Depressão Pós-Parto/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Razão de Chances , Síndrome Pré-Menstrual/diagnóstico , Síndrome Pré-Menstrual/epidemiologia , Síndrome Pré-Menstrual/fisiopatologia , Síndrome Pré-Menstrual/psicologia , Estudos Prospectivos , Fatores de Risco , Estatística como Assunto
14.
Am J Psychiatry ; 163(9): 1554-60, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16946180

RESUMO

OBJECTIVE: The authors used a large sample collected for genetic studies to determine whether a chronic course of illness defines a familial clinical subtype in major depressive disorder. METHOD: A measure of lifetime chronicity of depressive symptoms (substantial mood symptoms most or all of the time) was tested for familial aggregation in 638 pedigrees from the Genetics of Recurrent Early-Onset Depression (GenRED) project. RESULTS: In subjects with chronic depression, the mean age at illness onset was lower and rates of attempted suicide, panic disorder, and substance abuse were higher than among those with nonchronic depression. Chronicity was assessed in 37.8% of affected first-degree relatives of probands with chronic depression and in 20.2% of relatives of probands with nonchronic depression. Analysis using the generalized estimating equation model yielded an odds ratio of 2.52 (SE=0.39, z=6.02, p<0.0001) for the likelihood of chronicity in a proband predicting chronicity in an affected relative. With stratification by proband age at illness onset, the odds ratio for chronicity in relatives by proband chronicity status was 6.17 (SE=2.09, z=5.35, p<0.0001) in families of probands whose illness onset was before age 13 and 1.92 (SE=0.34, z=3.72, p<0.0001) in families of probands whose illness started at age 13 or later. CONCLUSIONS: These findings suggest that chronicity of depressive symptoms is familial, especially in preadolescent-onset illness. Chronicity is also associated with other indicators of illness severity in recurrent, early-onset major depression. Further study using chronicity as a subtype in the genetic analysis of depressive illness is warranted. Refinement of the definition of chronicity in depressive illness may increase the power of such studies.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Família , Linhagem , Adolescente , Idade de Início , Criança , Doença Crônica , Comorbidade , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Masculino , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/epidemiologia , Projetos de Pesquisa , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Terminologia como Assunto
15.
J Clin Psychiatry ; 64 Suppl 5: 25-31, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12720481

RESUMO

With the release of new medications into the armamentarium for the treatment of bipolar disorder, clinicians are required to make prudent treatment decisions in light of insufficient research data for patients with a difficult-to-control illness. Increasingly, clinicians are turning toward a combination or adjunctive treatment out of necessity. Many studies suggest effectiveness of add-on agents in patients with mania who are unresponsive to one or more drugs, while only a limited number of controlled trials actually compare one particular combination regimen to another. Despite this lack of data, there has been no lack of advice for the clinician from clinical recommendations in the form of expert treatment guidelines to case reports describing suggestive findings from the off-label use of newer agents. With a particular emphasis on the treatment of mania, this article reviews the clinical data on the individual agents of foreseeable use in combination treatment for bipolar disorder. We suggest beginning with an agent of established effectiveness when combining medications for the treatment of bipolar disorder.


Assuntos
Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Lítio/uso terapêutico , Transtorno Bipolar/prevenção & controle , Quimioterapia Combinada , Humanos , Resultado do Tratamento
18.
J Subst Abuse Treat ; 37(2): 111-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19150200

RESUMO

Inpatient detoxification is frequently used to treat substance use disorders, despite consistent findings that drug use soon after detoxification is the norm. A number of lines of evidence suggest the most rational means of improving outcomes after detoxification is to improve postdetoxification treatment entry. This report presents outcomes from the Intensive Treatment Unit (ITU), a brief inpatient detoxification unit in Baltimore, MD, found to have good postdischarge treatment entry outcomes. The patients followed were predominantly male African Americans in early middle age who were sequentially admitted to the unit (N = 134) and demonstrated severe social disruption and psychiatric comorbidity. More than 80% of the patients discharged from the ITU were admitted to treatment postdetoxification, with most going to long-term residential settings or recovery houses. Success was associated with seeking residential treatment, and failure was concentrated among the minority discharged with no plan for aftercare and those seeking outpatient treatments. The report explores patient and process factors associated with these outcomes and discusses the possibility that the ITU may be a model system for improving outcomes postdetoxification.


Assuntos
Centros de Tratamento de Abuso de Substâncias , Síndrome de Abstinência a Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adulto , Assistência ao Convalescente/métodos , Baltimore , Diagnóstico Duplo (Psiquiatria) , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento Domiciliar , Comportamento Social , Resultado do Tratamento , Adulto Jovem
19.
Am J Psychiatry ; 166(11): 1229-37, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19755578

RESUMO

OBJECTIVE: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms. METHOD: Subjects were ascertained from two studies: the NIMH Genetics Initiative Bipolar Disorder project and the Genetics of Recurrent Early-Onset Depression. Subjects included women with a history of pregnancy, any mood disorder, and information about postpartum symptoms. In the linkage study, 1,210 women met criteria (23% with postpartum symptoms), and 417 microsatellite markers were analyzed in multipoint allele sharing analyses. For the association study, 759 women met criteria (25% with postpartum symptoms), and 16,916 SNPs in the regions of the best linkage peaks were assessed for association with postpartum symptoms. RESULTS: The maximum linkage peak for postpartum symptoms occurred on chromosome 1q21.3-q32.1, with a chromosome-wide significant likelihood ratio Z score (Z(LR)) of 2.93 (permutation p=0.02). This was a significant increase over the baseline Z(LR) of 0.32 observed at this locus among all women with a mood disorder (permutation p=0.004). Suggestive linkage was also found on 9p24.3-p22.3 (Z(LR)=2.91). In the fine-mapping study, the strongest implicated gene was HMCN1 (nominal p=0.00017), containing four estrogen receptor binding sites, although this was not region-wide significant. CONCLUSIONS: This is the first study to examine the genetic etiology of postpartum mood symptoms using genome-wide data. The results suggest that genetic variations on chromosomes 1q21.3-q32.1 and 9p24.3-p22.3 may increase susceptibility to postpartum mood symptoms.


Assuntos
Transtorno Bipolar/genética , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/genética , Transtorno Depressivo Maior/genética , Ligação Genética , Estudo de Associação Genômica Ampla , Adulto , Transtorno Bipolar/diagnóstico , Mapeamento Cromossômico , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 9/genética , Transtorno Depressivo Maior/diagnóstico , Feminino , Seguimentos , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Repetições de Microssatélites , Pessoa de Meia-Idade , Modelos Genéticos , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Gravidez
20.
Bipolar Disord ; 10(1): 38-44, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18199240

RESUMO

OBJECTIVES: We sought to determine if postpartum mood symptoms and depressive episodes exhibit familial aggregation in bipolar I pedigrees. METHODS: A total of 1,130 women were interviewed with the Diagnostic Interview for Genetic Studies as part of the National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative Study and were asked whether they had ever experienced mood symptoms within four weeks postpartum. Women were also asked whether either of two major depressive episodes described in detail occurred postpartum. We examined the odds of postpartum mood symptoms in female siblings, who had previously been pregnant and had a diagnosis of bipolar I, bipolar II, or schizoaffective (bipolar type) disorders (n = 303), given one or more relatives with postpartum mood symptoms. RESULTS: The odds ratio for familial aggregation of postpartum mood symptoms was 2.31 (p = 0.011) in an Any Mood Symptoms analysis (n = 304) and increased to 2.71 (p = 0.005) when manic symptoms were excluded, though this was not significantly different from the Any Mood Symptoms analysis. We also examined familial aggregation of postpartum major depressive episodes; however, the number of subjects was small. CONCLUSIONS: Limitations of the study include the retrospective interview, the fact that the data were collected for other purposes and the inability to control for such factors as medication use. Taken together with previous studies, these data provide support for the hypothesis that there may be a genetic basis for the trait of postpartum mood symptoms generally and postpartum depressive symptoms in particular in women with bipolar disorder. Genetic linkage and association studies incorporating this trait are warranted.


Assuntos
Transtorno Bipolar/genética , Depressão Pós-Parto , Transtorno Depressivo Maior/genética , Saúde da Família , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Escalas de Graduação Psiquiátrica Breve , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Entrevista Psicológica , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Estudos Retrospectivos , Fatores de Tempo
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