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1.
Clin Neuropharmacol ; 42(6): 214-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31725476

RESUMO

OBJECTIVES: The purpose of this retrospective chart review was to evaluate lisdexamfetamine dimesylate (LDX) in the treatment of pediatric binge eating disorder (BED). METHODS: We examined the clinical records of 25 patients, 12 to 19 years of age, who were prescribed LDX and had a diagnosis of BED between 2014 and 2017. RESULTS: Binge eating disorder in adolescents was highly comorbid with attention deficit hyperactivity disorder, mood and anxiety disorders, and severe obesity. Fifteen participants reported some level of improvement of their BED symptoms with LDX treatment. Posttreatment body mass index (BMI) percentile was not significantly reduced, and all but 2 participants remained in their same BMI classification. Lisdexamfetamine dimesylate treatment duration was not associated with change in BMI percentile, and the medication was well tolerated. CONCLUSIONS: Lisdexamfetamine dimesylate may have clinical utility for BED in adolescents, but randomized, placebo-controlled studies of its efficacy, tolerability, and safety in this population are needed.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31264800

RESUMO

AIM: Previous studies suggest that Mindfulness-Based Cognitive Therapy for Children (MBCT-C) is feasible and may improve anxiety and emotion regulation in youth with anxiety disorders at-risk for bipolar disorder. However, controlled studies are warranted to replicate and extend these findings. METHODS: In the current study, 24 youth with anxiety disorders who have at least one parent with bipolar disorder participated in a MBCT-C treatment period (n = 24; Mage = 13.6, 75% girls, 79% White) with a subset also participating in a prior psychoeducation waitlist control period (n = 19 Mage = 13.8, 68% girls, 84% White). Participants in both the waitlist and MBCT-C periods completed independently-rated symptom scales at each time point. Participants in the waitlist period received educational materials 12 weeks prior to the beginning of MBCT-C. RESULTS: There were significantly greater improvements in overall clinical severity in the MBCT-C period compared to the waitlist period, but not in clinician- and child-rated anxiety, emotion regulation or mindfulness. However, increases in mindfulness were associated with improvements in anxiety and emotion regulation in the MBCT-C period, but not the waitlist period. CONCLUSIONS: Findings suggest that MBCT-C may be effective for improving overall clinical severity in youth with anxiety disorders who are at-risk for bipolar disorder. However, waitlist controlled designs may inflate effect sizes so interpret with caution. Larger studies utilizing prospective randomized controlled designs are warranted.

3.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

4.
Bipolar Disord ; 21(4): 330-341, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30864200

RESUMO

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.

5.
Eat Behav ; 33: 30-33, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852343

RESUMO

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

6.
Psychiatry Res Neuroimaging ; 286: 53-59, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903953

RESUMO

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

7.
J Affect Disord ; 242: 1-4, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30153563

RESUMO

BACKGROUND: Identifying correlates of capacity to provide informed consent among individuals with bipolar disorder is essential for patient protection. As part of a clinical trial involving approved, standard treatments, we investigated relationships between clinical characteristics and capacity to provide informed consent in adults with bipolar disorder using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). After administering the MacCAT-CR, continuing participants in the trial were capable of and provided informed consent. METHODS: Trained, board-certified psychiatrists administered the MacCAT-CR to potential study participants (N = 50) after they provided informed consent, but prior to initiation of study procedures. RESULTS: Higher Schedule for Assessment of Positive Symptoms (SAPS) scores were significantly correlated with worse MacCAT-CR Understanding and Appreciation (p < 0.04) subscale scores; lower Hamilton Depression Rating Scale (HDRS) scores and higher Clinical Global Impression-Severity (CGI-S) scores were significantly correlated with worse Reasoning and Understanding subscale scores (p < 0.03); and patients with comorbid substance use disorders (SUD) had better Appreciation and Reasoning subscale scores (p < 0.05). LIMITATIONS: The MacCAT-CR identifies areas where participants need explanation. However, there is not a predetermined score to indicate understanding of study procedures and therefore input from a trained clinician is needed to determine capacity to provide informed consent. CONCLUSIONS: Our findings suggest that certain measures of illness severity are associated with lower levels of capacity to provide informed consent among adults with bipolar disorder. This study provides important information for clinicians and researchers to consider when obtaining informed consent in this population.


Assuntos
Transtorno Bipolar/psicologia , Consentimento Livre e Esclarecido/psicologia , Competência Mental/psicologia , Adulto , Tomada de Decisões , Feminino , Humanos , Testes de Inteligência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resolução de Problemas
8.
Eur Eat Disord Rev ; 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30370658

RESUMO

OBJECTIVE: This study aims to explore predictors and clinical correlates of placebo response and cessation in binge eating disorder (BED). METHOD: Data from two identically designed, randomized, placebo-controlled, parallel-group, and multicenter pharmacotherapy studies for adults with moderate to severe BED were pooled. RESULTS: Of 360 placebo recipients, 134 (37%) were responders and 53 (15%) achieved 4-week binge eating cessation. Placebo response and cessation were each associated with higher baseline disability scores but not with measures of BED symptomatology severity. Compared with placebo noncessation, placebo cessation was further associated with increased blood pressure at baseline and greater improvement in pulse and triglyceride levels at endpoint. DISCUSSION: Future clinical trial design for BED pharmacotherapy trials might consider disability level among participants to enhance signal detection. Cessation of binge eating with placebo might be associated with improvement in cardiovascular and metabolic variables, at least over the short term.

9.
Innov Clin Neurosci ; 15(5-6): 17-21, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30013815

RESUMO

Objective: The goal of this study was to obtain preliminary data on the usefulness of the combination of phentermine and topiramate extended release (phentermine-topiramate) in binge-eating disorder (BED) associated with obesity or overweight. Design: Ten participants with BED and obesity or overweightness with at least one weight-related complication received phentermine-topiramate in an open-label, prospective, 12-week trial. The primary outcome measure was change in weight. The study was registered under the identifier NCT02659475 at ClinicalTrials.gov. Results: Seven participants completed the study. Phentermine-topiramate treatment was associated with significant reductions in weight, body mass index, binge-eating episode frequency, and measures of global clinical severity, eating disorder psychopathology, and obsessive-compulsive symptoms. Mean daily dose of phentermine-topiramate at endpoint was 6.8 to 41.4mg per day. The most common adverse event (AE) was dysgeusia. There were no serious AEs, and no participants displayed symptoms of medication misuse or withdrawal. Conclusion: Phentermine-topiramate could be helpful for weight loss and reduction of binge-eating symptoms in patients with obesity or overweight in addition to BED. Controlled studies are warranted.

10.
Psychoneuroendocrinology ; 94: 72-82, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29763783

RESUMO

Women and men differ in their risk for developing stress-related conditions such as alcohol use and anxiety disorders and there are gender differences in the typical sequence in which these disorders co-occur. However, the neural systems underlying these gender-biased psychopathologies and clinical course modifiers in humans are poorly understood and may involve both central and peripheral mechanisms regulating the limbic-hypothalamic-pituitary-adrenal axis. In the present randomized, double blind, placebo-controlled, triple-dummy crossover study, we juxtaposed a centrally-acting, citalopram (2 mg/unit BMI) neuroendocrine stimulation test with a peripherally-acting, dexamethasone (Dex) (1.5 mg)/corticotropin-releasing factor (CRF) (1 µg/kg) test in euthymic women (N = 38) and men (N = 44) with (54%) and without histories of alcohol dependence to determine whether sex, alcohol dependence or both influenced the adrenocorticotropic hormone (ACTH) and cortisol responses to the pharmacological challenges and to identify the loci of these effects. We found that central serotonergic mechanisms, along with differences in pituitary and adrenal sensitivity, mediated sexually-diergic ACTH and cortisol responses in a stressor-specific manner regardless of a personal history of alcohol dependence. Specifically, women exhibited a greater response to the Dex/CRF test than they did the citalopram test while men exhibited the opposite pattern of results. Women also had more robust ACTH, cortisol and body temperature responses to Dex/CRF than men, and exhibited a shift in their adrenal glands' sensitivity to ACTH as measured by the cortisol/log (ACTH) ratio during that session in contrast to the other test days. Our findings indicate that central serotonergic and peripheral mechanisms both play roles in mediating sexually dimorphic, stressor-specific endocrine responses in humans regardless of alcohol dependence history.

11.
Bipolar Disord ; 20(7): 658-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29479787

RESUMO

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

12.
Ann Clin Psychiatry ; 29(4): 258-265, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29069111

RESUMO

BACKGROUND: Despite the high prevalence of suicidality in psychiatrically hospitalized youth, its risk factors and impact on inpatient psychopharmacologic treatment are unknown. We identified characteristics associated with suicidality in psychiatrically hospitalized youth and determined the association of suicidality with subsequent psychopharmacologic interventions. METHODS: Medical records from consecutive psychiatric admissions to a large, acute care, urban, pediatric hospital were analyzed retrospectively (N = 1,309). Demographic, clinical, and treatment-related features of suicidal and nonsuicidal youth were characterized. Logistic regression identified predictors of suicidality, and multiple comparison analyses evaluated the association between suicidality and changes to antidepressant prescribing during inpatient course. RESULTS: Compared with nonsuicidal patients, inpatients who were suicidal were more likely to have a mood disorder or posttraumatic stress disorder, as well as Cannabis and alcohol use, were more commonly girls, and at least 13 years of age (all P ≤ .05). Hospitalization was shorter for suicidal patients, was more likely to be associated with antidepressant treatment (P ≤ .001), and among suicidal patients prescribed antidepressants at the time of admission, was associated with a greater likelihood of changing antidepressant treatment compared with nonsuicidal inpatients (P ≤ .05). CONCLUSIONS: These findings reveal differences between suicidal and nonsuicidal psychiatrically hospitalized youth and suggest that suicidality is associated with specific pharmacologic treatment approaches within this population.


Assuntos
Antidepressivos/uso terapêutico , Demografia/estatística & dados numéricos , Hospitais Psiquiátricos , Suicídio , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos do Humor , Estudos Retrospectivos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos
13.
Bipolar Disord ; 19(4): 259-272, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28574156

RESUMO

OBJECTIVES: Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1 H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. METHODS: We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1 H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1 H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. RESULTS: LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. CONCLUSIONS: The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.


Assuntos
Sintomas Comportamentais , Transtorno Bipolar , Resistência a Medicamentos , Compostos de Lítio , Imagem por Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Antimaníacos/administração & dosagem , Antimaníacos/efeitos adversos , Inteligência Artificial , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/tratamento farmacológico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Monitoramento de Medicamentos/métodos , Feminino , Lógica Fuzzy , Humanos , Compostos de Lítio/administração & dosagem , Compostos de Lítio/efeitos adversos , Masculino , Imagem Multimodal/métodos , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico
14.
J Affect Disord ; 209: 246-253, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27936454

RESUMO

BACKGROUND: Studying youth at high risk of developing bipolar disorder may clarify neurobiological factors associated with vulnerability to this illness. We present here a baseline characterization of brain structure in youth at-risk for bipolar disorder. METHODS: Magnetic resonance images were obtained from 115 child and adolescent offspring of bipolar disorder type I subjects and 57 healthy child and adolescent offspring of healthy parents (healthy control offspring). Offspring of parents with bipolar disorder were divided into healthy bipolar offspring (n=47) or symptomatic bipolar offspring (n=68), according to presence or absence of childhood-onset psychopathology. All bipolar offspring were free of major mood and psychotic disorders. Gray (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. RESULTS: No differences in GM volumes were found across groups. Healthy bipolar offspring presented with decreased WM volumes in areas of the right frontal, temporal and parietal lobes, and in the left temporal and parietal lobes compared to healthy control offspring. Symptomatic bipolar offspring did not present with any differences in WM volumes compared to either healthy bipolar offspring or healthy control offspring. LIMITATIONS: Cross-sectional design and heterogeneous sample of symptomatic bipolar offspring. CONCLUSIONS: WM volume decreases in areas of the frontal, occipital, and parietal lobes are present in bipolar offspring prior to the development of any psychiatric symptoms, and may be a correlate of familial risk to bipolar disorder. In this large cohort, we have not found evidence for regional GM volume abnormalities as an endophenotype for bipolar disorder.


Assuntos
Transtorno Bipolar , Encéfalo/diagnóstico por imagem , Filho de Pais Incapacitados , Pais , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Criança , Estudos Transversais , Endofenótipos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/fisiologia
15.
Hum Psychopharmacol ; 31(5): 382-91, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27650406

RESUMO

OBJECTIVE: To evaluate lisdexamfetamine dimesylate (LDX) in the treatment of binge eating disorder (BED). METHOD: Fifty participants with BED received LDX (20-70 mg/day) (n = 25) or placebo (n = 25) for up to 12 weeks in a single-center, randomized, double-blind, and flexible-dose trial. The primary outcome measure was binge eating (BE) days/week. RESULTS: In the primary longitudinal analysis, compared with placebo, LDX was not associated with a significantly greater rate of reduction in BE days/week, as well as BE episodes/week, and scores on the Clinical Global Impression-Severity or Yale-Brown Obsessive-Compulsive Scale modified for binge eating scales. It was, however, associated with significantly decreased weight, body mass index, and fasting triglyceride level. In the secondary last observation carried forward analyses, LDX was associated with statistically significant reductions in BE days/week, BE episodes/week, weight, and BMI, as well as a statistically significant greater level of categorical response and global improvement. The mean (standard deviation) LDX daily dose at endpoint evaluation was 59.6 (14.9) mg. One participant discontinued LDX for a serious adverse cardiovascular event, which resolved fully. CONCLUSION: Lisdexamfetamine dimesylate may have clinical utility for BED but further studies of its efficacy, tolerability, and safety in this population are needed. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Transtorno da Compulsão Alimentar/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Adulto , Índice de Massa Corporal , Peso Corporal , Estimulantes do Sistema Nervoso Central/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Dimesilato de Lisdexanfetamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Bipolar Disord ; 18(6): 490-501, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27647671

RESUMO

OBJECTIVES: We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers. METHODS: Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response. RESULTS: ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors. CONCLUSIONS: These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.


Assuntos
Tonsila do Cerebelo , Transtorno Bipolar , Lítio/uso terapêutico , Imagem por Ressonância Magnética/métodos , Fumarato de Quetiapina/uso terapêutico , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Antimaníacos/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtorno Bipolar/terapia , Emoções/fisiologia , Cuidado Periódico , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Análise e Desempenho de Tarefas , Resultado do Tratamento
17.
J Affect Disord ; 201: 95-8, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27195513

RESUMO

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


Assuntos
Transtorno da Compulsão Alimentar/diagnóstico , Transtorno Bipolar/diagnóstico , Adulto , Transtornos de Ansiedade/epidemiologia , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno da Compulsão Alimentar/psicologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Comorbidade , Efeitos Psicossociais da Doença , Comportamento Alimentar/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Prevalência , Inquéritos e Questionários
18.
Early Interv Psychiatry ; 10(3): 203-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26486098

RESUMO

AIM: Mood disorders are associated with low levels of the long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated LCn-3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker. METHOD: Erythrocyte fatty acid composition was determined in healthy adolescents (n = 28, HC), asymptomatic adolescents with a biological parent with bipolar I disorder (n = 30; 'high risk', HR), adolescents with a biological parent with bipolar I disorder and major depressive disorder, or depressive disorder not otherwise specified (n = 36; 'ultra-high risk', UHR), and first-episode adolescent bipolar manic patients (n = 35, BP). RESULTS: Group differences were observed for DHA (P ≤ 0.0001) and EPA (P = 0.03). Compared with HC, erythrocyte EPA + DHA ('omega-3 index') was significantly lower in BP (-24%, P ≤ 0.0001) and UHR (-19%, P = 0.0006) groups, and there was a trend in the HR group (-11%, P = 0.06). Compared with HC (61%), a greater percentage of HR (77%, P = 0.02), UHR (80%, P = 0.005) and BP (97%, P = 0.001) subjects exhibited EPA + DHA levels of ≤4.0%. Among all subjects (n = 130), EPA + DHA was inversely correlated with manic (r = -0.29, P = 0.0008) and depressive (r = -0.28, P = 0.003) symptom severity. The AA/EPA + DHA ratio was significantly greater in BP (+22%, P = 0.0002) and UHR (+16%, P = 0.001) groups. CONCLUSIONS: Low EPA + DHA levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA + DHA deficits. Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.


Assuntos
Ácidos Docosa-Hexaenoicos/deficiência , Ácido Eicosapentaenoico/metabolismo , Eritrócitos/metabolismo , Sintomas Prodrômicos , Adolescente , Biomarcadores/metabolismo , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
19.
Early Interv Psychiatry ; 10(5): 426-34, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-25582800

RESUMO

AIM: Children and adolescents with bipolar parents have an elevated risk for anxiety disorders. However, antidepressant medications commonly used to treat symptoms of anxiety may accelerate the onset of mania in these already at-risk youth. Therefore, studies evaluating innovative non-pharmacologic treatments for anxiety in this population are urgently needed. METHODS: Subjects participated in 12 weekly sessions of mindfulness-based cognitive therapy for children (MBCT-C), a manualized group psychotherapeutic intervention utilizing cognitive behavioural principles and mindfulness exercises to increase regulation of attention and non-judgmental acceptance of present moment thoughts, emotions and experiences. Independent raters administered symptoms rating scales prior to each treatment session. Spearman correlations and paired-samples signed rank tests were used to examine outcomes. After-intervention surveys and session transcripts were reviewed to assess feasibility and acceptability of the intervention. RESULTS: Participants included 10 youth (meanage = 13.2; 80% girls; 40% biracial) with generalized, social and/or separation anxiety disorders, and a parent with bipolar disorder. Clinician-rated anxiety was significantly reduced after intervention (meanbefore = 11.1; meanafter = 4.3; P < 0.01), as well as youth-rated trait anxiety (P = 0.03). Parent-rated emotion regulation significantly increased from before to after intervention (P = 0.05). Increases in mindfulness were associated with decreases in anxiety (P = 0.03). Finally, children and parents/guardians reported high levels of feasibility, acceptability and usefulness of the intervention. CONCLUSION: Findings support the feasibility, acceptability and preliminary efficacy of MBCT-C for treating anxiety in youth at risk for bipolar disorder. Future controlled and larger studies are needed to confirm these preliminary findings.


Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Atenção Plena , Adolescente , Transtorno Bipolar/psicologia , Criança , Feminino , Humanos , Masculino , Pais/psicologia , Projetos Piloto , Psicoterapia de Grupo
20.
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
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