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1.
J Affect Disord ; 259: 164-172, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445343

RESUMO

INTRODUCTION: Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. METHODS: 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. RESULTS: Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. LIMITATIONS: Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. DISCUSSION: Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

2.
J Affect Disord ; 257: 17-22, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299400

RESUMO

BACKGROUND: Complex polypharmacy (CP) is common in bipolar disorder (BD). We assessed the associations between CP, adherence, and side effect burden, and patient traits associated with clinical improvement in relationship to CP. METHODS: We conducted a secondary analysis of 482 adult BD participants in the Bipolar CHOICE trial. We examined the associations between CP (use of ≥3 BD medications) and non-adherence (missing >30% of BD medication doses in the last 30 days) and side effect burden (Frequency, Intensity and Burden of Side Effects Rating scale) using multivariate models with patient random effects. We used logistic regression to assess the patient traits associated with remission among those with majority CP use (Clinical Global Impression-Severity for BD score ≤2 for 8+ weeks). RESULTS: 43% of patients had any CP and 25% had CP for the majority of the study. CP was associated with non-adherence (OR = 2.51, 95% CI [1.81, 3.50]), but not worse side effect burden. Among those with CP, 16% achieved remission; those with non-adherence, comorbid social or generalized anxiety disorder, or BD I vs. II were less likely to achieve remission among those with CP. LIMITATIONS: There could be unmeasured confounding between use of CP and side effect burden or adherence. Adherence was measured by self-report, which could be subject to reporting error. CONCLUSIONS: BD patients with CP were less likely to adhere to therapy, and those with worse adherence to CP were less likely to clinically respond. Clinicians should assess medication adherence prior to adding another agent to medication regimens.

3.
Psychiatry Res ; 274: 49-57, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30780062

RESUMO

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Predisposição Genética para Doença , Melatonina/metabolismo , Estimulação Luminosa/métodos , Saliva/metabolismo , Adolescente , Adulto , Biomarcadores/química , Biomarcadores/metabolismo , Transtorno Bipolar/genética , Criança , Ritmo Circadiano/fisiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Polissonografia/tendências , Reprodutibilidade dos Testes , Saliva/química , Sono/fisiologia , Transtornos do Sono do Ritmo Circadiano/diagnóstico , Transtornos do Sono do Ritmo Circadiano/genética , Transtornos do Sono do Ritmo Circadiano/metabolismo
4.
J Affect Disord ; 245: 812-818, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699864

RESUMO

BACKGROUND: Divalproex has become the most prevalent mood stabilizer for bipolar disorder. However, little is known its effects in the prevention of suicide in patients with bipolar disorder, and recent FDA announcement indicated an increased risk of suicidality when using anti-epileptic agents such as divalproex. The aim of this study is to investigate the effect of divalproex on suicide risk in patients with bipolar disorder. METHODS: A search strategy was used for the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov until June 13th, 2018. Peer-reviewed observationally clinical studies in humans, investigating the association of divalproex and suicidality in patients with bipolar disorder were included. A random-effects meta-analysis was implemented to calculate the relative risk (RR) and 95% confidence intervals (CIs) for suicidality among patients receiving divalproex and those without. RESULTS: Total 6 studies were included in the final meta-analysis. There was no significant difference in the incidence rates (reported as [RR]; 95% CI) of suicide attempts (0.921; 0.383-2.215) or completed suicides (0.607; 0.180-2.043) between participants receiving divalproex vs. no medication. There was no significant difference in the incidence rates of suicide attempts (0.815; 0.453-1.466) or completed suicides (1.009; 0.410-2.484) between participants receiving divalproex and carbamazepine. LIMITATIONS: The significantly heterogeneous sample sources and study design amount the included trials. CONCLUSIONS: Treatment with divalproex did not reduce or increase the incidence of suicide-related events in patients with bipolar disorder.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Internacionalidade , Estudos Observacionais como Assunto , Tentativa de Suicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Ácido Valproico/efeitos adversos , Antimaníacos/uso terapêutico , Humanos , Ácido Valproico/uso terapêutico
5.
Suicide Life Threat Behav ; 49(5): 1360-1378, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30450613

RESUMO

OBJECTIVE: To evaluate the effects of mood and anxiety symptoms in relation to personality dimensions and clinical features such as trauma and substance use on suicidal behaviors in a longitudinal sample of individuals with bipolar illness (BP) and healthy controls (HC). METHODS: Mood, personality, and clinical features were assessed in 151 individuals with BP I and 119 HC. Clinical data were collected at baseline and at 2-year follow-up. Personality traits were measured using the NEO PI-R. RESULTS: In bivariate analyses, personality measures were significantly different between BP and HC, and between BP based on suicide attempt history. However, in regression analyses, baseline measures of depression, mania, anxiety, trauma, education, and age of BP onset correlated with personality domains, while a history of suicide attempts did not. Logistic regressions showed that prospective depression or mania, and a pattern of mixed mood features and chronicity of illness, along with two Neuroticism facet scores (N4-Self-Consciousness and N6-Vulnerability) were predictive of suicide ideation (SI) in the 2-year follow-up period. CONCLUSIONS: While dimensions of personality, trauma, and substance use clearly correlated with suicidal behaviors in BP, in multivariate models emerging mood symptoms were the most robust predictors of suicidality. These results reinforce the importance and attributable role of mood and anxiety symptoms in evaluating suicidal risk.

6.
Neuropsychopharmacology ; 44(3): 620-628, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30487653

RESUMO

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.


Assuntos
Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Ritmo Circadiano , Fibroblastos , Compostos de Lítio/farmacologia , Adulto , Animais , Transtorno Bipolar/genética , Células Cultivadas , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Técnicas de Genotipagem , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Medições Luminescentes , Camundongos , Células NIH 3T3 , Proteínas Circadianas Period , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos
7.
Bipolar Disord ; 21(4): 350-360, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30383333

RESUMO

INTRODUCTION: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment. METHODS: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery-Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors. RESULTS: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial-responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non-responding class (9.7%) with sustained moderate-severe depressive symptoms. Bipolar type I predicted membership of the non-responding class and randomization to quetiapine predicted membership of either the responding or the non-responding class. CONCLUSION: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate-severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses.


Assuntos
Transtorno Bipolar , Depressão , Compostos de Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Prevalência , Prognóstico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
8.
J Affect Disord ; 246: 126-131, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30580198

RESUMO

BACKGROUND: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial. METHODS: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS. RESULTS: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics. LIMITATIONS: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders. CONCLUSIONS: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Escalas de Graduação Psiquiátrica , Adulto , Ansiolíticos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Comorbidade , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fumarato de Quetiapina/uso terapêutico , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
J Affect Disord ; 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30241956

RESUMO

BACKGROUND: Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior. METHODS: We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures. RESULTS: On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 = 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p = 0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only, F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating. LIMITATIONS: Bipolar CHOICE was not designed to study anthropometric outcomes. CONCLUSIONS: Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.

10.
J Clin Psychiatry ; 79(3)2018.
Artigo em Inglês | MEDLINE | ID: mdl-29873955

RESUMO

OBJECTIVE: Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. METHODS: Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. RESULTS: Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). CONCLUSIONS: These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Adulto , Transtornos Psicóticos Afetivos/induzido quimicamente , Fatores Etários , Transtorno Bipolar/induzido quimicamente , Doença Crônica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
11.
Psychopathology ; 51(4): 269-275, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29945124

RESUMO

Sleep disturbances are commonly reported in patients with bipolar I disorder (BPI) and are risk factors for mood episodes. In other populations, central nervous system (CNS) hyperarousal is associated with sleep initiation and maintenance problems, and CNS hypoarousal is associated with increased sleep drive. However, it is unclear whether CNS arousal levels are a useful index of sleep disruption in BPI. This study aimed to investigate daytime CNS arousal levels in relation to perceived sleep quality in BPI. Resting EEG, mood state, and self-reported sleep quality data were collected from 34 individuals with BPI. CNS hyperarousal was associated with pervasive poor subjective sleep quality including increased sleep disturbances, increased sleep latency, and reduced global sleep quality. CNS hypoarousal was associated with greater daytime sleepiness, indicating reduced arousal. These preliminary findings suggest that CNS arousal may be a useful index for identifying individuals at high risk for relapse into a mood episode. A limitation of this study is the use of self-report instruments for sleep quality assessment. Future research should investigate the temporal relationship of CNS arousal to sleep disturbances using objective measurements of sleep quality such as polysomnography. If these findings are replicated, measures of CNS arousals may allow for identification of high-risk patients with BPI.


Assuntos
Nível de Alerta/fisiologia , Transtorno Bipolar/complicações , Sistema Nervoso Central/fisiopatologia , Polissonografia/métodos , Fases do Sono/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Assessment ; : 1073191118754704, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29405754

RESUMO

Trait markers, or intermediate phenotypes linking different units of analysis (self-report, performance) from the Research Domain Criteria (RDoC) matrix across populations is a necessary step in identifying at-risk individuals. In the current study, 150 healthy controls (HC) and 456 individuals with bipolar disorder (BD) Type I or II, NOS (not otherwise specified) or Schizoaffective BD completed self-report neuropsychological tests of inhibitory control (IC) and executive functioning. Bifactor analyses were used to examine the factor structure of these measures and to evaluate for invariance across groups. Bifactor analyses found modest convergence of items from neuropsychological tests and self-report measures of IC among HC and BD. The factor scores showed evidence of a general IC construct (i.e., subdomain) across measures. Importantly, invariance testing indicated that the same construct was measured equally well across groups. Groups differed on the general factor for three of the four scales. Convergence on a general IC factor and invariance across diagnosis supports the use of combined dimensional measures to identify clinical risk and highlights how prospective RDoC studies might integrate units of analysis.

13.
Psychoneuroendocrinology ; 89: 194-202, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29414032

RESUMO

INTRODUCTION: Psychosocial stress contributes to onset/exacerbation of mood episodes and alcohol use, suggesting dysregulated diurnal cortisol rhythms underlie episodic exacerbations in Bipolar Disorder (BD). However, mechanisms underlying dysregulated HPA rhythms in BD and alcohol use disorders (AUD) are understudied. Knowledge of associated variance factors have great clinical translational potential by facilitating development of strategies to reduce stress-related relapse in BD and AUD. Evidence suggests structural changes to mitochondrial translocator protein (TSPO) (a regulator of steroid synthesis) due to the single nucleotide polymorphism rs6971, may explain much of this variance. However, whether rs6971 is associated with abnormal HPA rhythms and clinical exacerbation in humans is unknown. METHODS: To show this common TSPO polymorphism impacts HPA rhythms in BD, we tested whether rs6971 (dichotomized: presence/absence of polymorphism) predicted variance in diurnal cortisol rhythm (saliva: morning and evening for 3 days) in 107 BD (50 with and 57 without AUD) and 28 healthy volunteers of similar age and ethno-demographic distribution. RESULTS: Repeated measures ANOVA confirmed effects BD (F5,525 = 3.0, p = 0.010) and AUD (F5,525 = 2.9, p = 0.012), but not TSPO polymorphism (p > 0.05). Interactions were confirmed for TSPO × BD (F5,525 = 3.9, p = 0.002) and for TSPO × AUD (F5,525 = 2.8, p = 0.017). DISCUSSION: We identified differences in diurnal cortisol rhythm depending on presence/absence of common TSPO polymorphism in BD volunteers with or without AUD and healthy volunteers. These results have wide ranging implications but further validation is needed prior to optimal clinical translation.


Assuntos
Transtorno Bipolar/genética , Receptores de GABA/genética , Adulto , Alcoolismo/genética , Alcoolismo/metabolismo , Alelos , Ritmo Circadiano/fisiologia , Feminino , Frequência do Gene/genética , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Receptores de GABA/metabolismo , Saliva/química
14.
J Affect Disord ; 225: 563-568, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881294

RESUMO

BACKGROUND: Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium. METHODS: The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18-70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes. RESULTS: 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38-0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03). LIMITATIONS: Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure. CONCLUSIONS: Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.


Assuntos
Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Adolescente , Adulto , Afeto , Comportamento de Escolha , Feminino , Humanos , Humor Irritável , Compostos de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/complicações , Fumarato de Quetiapina/uso terapêutico , Resultado do Tratamento
15.
Bipolar Disord ; 20(1): 18-26, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28833984

RESUMO

OBJECTIVES: Although there is a common clinical assumption that bipolar disorder with psychotic features reflects greater severity than bipolar disorder without psychosis, the existing empirical literature is mixed. This study investigated the phenomenology of psychosis as well as demographic, clinical, functional, and neuropsychological features in a large, cross-sectional sample of participants with bipolar disorder divided by history of psychosis. METHODS: In a large single study, 168 affective-only bipolar disorder (BP-A) participants and 213 bipolar disorder with a history of psychosis (BP-P) participants completed a comprehensive clinical diagnostic interview and neuropsychological testing. t tests, chi-square tests, and Bayes factors were used to investigate group differences or lack thereof. RESULTS: The prevalence of psychosis in this sample (53%) was similar to published reports. Nearly half of BP-P participants experienced grandiose delusions, and relatively few endorsed "first-rank" hallucinations of running commentary or two or more voices conversing. There were no demographic or neuropsychological differences between groups. BP-A participants experienced greater chronicity of affective symptoms and a greater degree of rapid cycling than BP-P participants; there were no other clinical differences between groups. CONCLUSIONS: Overall, these results contradict the conventional notion that bipolar disorder with psychotic features represents a more severe illness than bipolar disorder without a history of psychosis. The presence of psychosis does not appear to be associated with poorer clinical/functional outcome or suggest a greater degree of neuropsychological impairment; conversely, the absence of psychosis was associated with affective chronicity and rapid cycling. Nosological and treatment implications are discussed.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Adulto , Sintomas Afetivos/diagnóstico , Teorema de Bayes , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Entrevista Psicológica/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Prognóstico , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia
17.
J Am Acad Child Adolesc Psychiatry ; 56(12): 1073-1080, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29173741

RESUMO

OBJECTIVE: Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). METHOD: Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. RESULTS: After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). CONCLUSION: BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Predisposição Genética para Doença , Trauma Psicológico/genética , Trauma Psicológico/psicologia , Comportamento Autodestrutivo/genética , Comportamento Autodestrutivo/psicologia , Adolescente , Transtorno Bipolar/diagnóstico , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Masculino , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Trauma Psicológico/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Comportamento Autodestrutivo/diagnóstico , Ideação Suicida , Tentativa de Suicídio/psicologia , Adulto Jovem
18.
Compr Psychiatry ; 78: 130-139, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28843850

RESUMO

BACKGROUND: Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. METHODS: We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006-2011. Youth offspring/relatives ("Relatives of BD probands;" n=267; mean age=16.8years; ±2.9S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands ("relatives of control probands;" n=149; mean age=17.4years; ±2.9S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. RESULTS: Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p=0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR=2.80-3.17; p<0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. CONCLUSION: Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population.


Assuntos
Transtorno Bipolar/psicologia , Família/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Austrália/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Adulto Jovem
19.
AAPS J ; 19(5): 1513-1522, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28685396

RESUMO

The purpose of this pharmacokinetics (PK) study was to investigate whether different release kinetics from bupropion hydrochloride (HCl) immediate release (IR), sustained release (SR), and extended release (ER) formulations alter its metabolism and to test the hypothesis that the unsuccessful bioequivalence (BE) study of the higher strength (300 mg) of bupropion HCl ER tablets based on the successful BE study of the lower strength (150 mg) was due to metabolic saturation in the gastrointestinal (GI) lumen. A randomized six-way crossover study was conducted in healthy volunteers. During each period, subjects took a single dose of IR (75/100 mg), SR (100/150 mg), or ER (150/300 mg) formulations of bupropion HCl; plasma samples for PK analysis were collected from 0-96 h for all formulations. In addition, each subject's whole blood was collected for the genotyping of various single-nucleotide polymorphisms (SNPs) of bupropion's major metabolic enzymes. The data indicates that the relative bioavailability of the ER formulations was 72.3-78.8% compared with IR 75 mg. No differences were observed for ratio of the area under the curve (AUC) of metabolite to AUC of parent for the three major metabolites. The pharmacogenomics analysis suggested no statistically significant correlation between polymorphisms and PK parameters of the various formulations. Altogether, these data suggested that the different release kinetics of the formulations did not change metabolites-to-parent ratio. Therefore, the differing BE result between the 150 and 300 mg bupropion HCl ER tablets was unlikely due to the metabolic saturation in the GI lumen caused by different release patterns.


Assuntos
Bupropiona/farmacocinética , Farmacogenética , Adulto , Bupropiona/química , Estudos Cross-Over , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos , Equivalência Terapêutica
20.
J Affect Disord ; 217: 29-33, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28365478

RESUMO

BACKGROUND: Psychotic bipolar depressive episodes remain remarkably understudied despite being common and having a significant impact on bipolar disorder. The aim of this study is to identify the characteristics of depressed bipolar patients with current psychosis compared to those without psychosis. METHODS: We used baseline data of a comparative effectiveness study of lithium and quetiapine for bipolar disorder (the Bipolar CHOICE study) to compare demographic, clinical, and functioning variables between those with and without psychotic symptoms. Of the 482 participants, 303 (62.9%) were eligible for the present study by meeting DSM-IV criteria for an acute bipolar depressive episode. Univariate analyses were conducted first, and then included in a model controlling for symptom severity. RESULTS: The sample was composed mostly of women (60.7%) and the mean age was 39.5±12.1 years. Psychosis was present in 10.6% (n=32) of the depressed patients. Psychotic patients had less education, lower income, and were more frequently single and unemployed. Psychosis was also associated with a more severe depressive episode, higher suicidality, more comorbid conditions and worse functioning. Most group differences disappeared when controlling for depression severity. LIMITATIONS: Only outpatients were included and the presence of psychosis in previous episodes was not assessed. CONCLUSION: Psychosis during bipolar depressive episodes is present even in an outpatient sample. Psychotic, depressed patients have worse illness outcomes, but future research is necessary to confirm if these outcomes are only associated with the severity of the disorder or if some of them are independent of it.


Assuntos
Transtorno Bipolar/diagnóstico , Transtornos Psicóticos/diagnóstico , Adulto , Transtorno Bipolar/complicações , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos Psicóticos/complicações , Adulto Jovem
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