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1.
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.

2.
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.

3.
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.

4.
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
5.
Psychiatr Serv ; 70(2): 130-134, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30526340

RESUMO

OBJECTIVE: The authors examined electronic medical record (EMR) outpatient data to determine whether African Americans with schizophrenia or schizoaffective disorder were more likely than non-Latino whites to screen positive for major depression. METHODS: EMR data for 1,657 patients at Rutgers University Behavioral Health Care certified community outpatient clinics were deidentified and accrued for 9 months starting July 1, 2017. A Fisher's exact test was used to compare differences in the proportion of patients with positive screens for major depression (cutoff score of ≥15 on the nine-item Patient Health Questionnaire) among African-American and non-Latino white patients diagnosed as having schizophrenia or schizoaffective disorder. RESULTS: Among patients diagnosed as having schizophrenia, African Americans were more likely than non-Latino whites (p<.003) to screen positive for major depression. The between-group difference in positive screens was not significant among patients diagnosed as having schizoaffective disorder. CONCLUSIONS: The results are consistent with findings from a large body of literature suggesting that racial differences in the diagnosis of schizophrenia in the United States result in part from clinicians underemphasizing the relevance of mood symptoms among African Americans compared with other racial-ethnic groups. If the results are replicated, a case could be made that routine screening for major depression in community mental health settings could reduce racial disparities in schizophrenia diagnoses.

7.
J Child Adolesc Psychopharmacol ; 28(6): 379-386, 2018 Jul/Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29847157

RESUMO

OBJECTIVES: Prior studies have shown that youth with bipolar disorder demonstrate neurofunctional changes in key prefrontal and subcortical brain regions implicated in emotional regulation following treatment with pharmacological agents. We recently reported a large response rate (>60%) to quetiapine (QUET) for treating depressive symptoms in adolescents with bipolar depression. This study investigates the neurofunctional effects of QUET using functional magnetic resonance imaging (fMRI). METHODS: Thirty-three unmedicated subjects, 10-17 years of age, with a current depressive episode (Children's Depression Rating Scale-Revised [CDRS-R] > 40) associated with bipolar I or II disorder were recruited in a two-site randomized, placebo (PBO)-controlled trial of QUET monotherapy for treatment of bipolar depression in adolescents. Twenty-three of these participants (nine male) underwent an MRI scan at baseline, then were randomized to QUET or PBO, followed for 8 weeks, and at the end of their study participation underwent another MRI scan. During the fMRI scan, subjects viewed negative and neutral pictures and rated the valence of each picture. RESULTS: Sixteen subjects had usable data at both time points: 10 subjects randomized to QUET, and 6 randomized to PBO. For QUET subjects, lower baseline activation in the left dorsolateral prefrontal cortex (p < 0.005) and higher baseline activation in the left ventrolateral prefrontal cortex (p = 0.0024) predicted greater improvement in CDRS-R scores from baseline to follow-up. When QUET and PBO groups were combined (n = 16), region-of-interest activation did not significantly predict change in CDRS-R. CONCLUSIONS: Baseline activation patterns in dorsal and ventral portions of the prefrontal cortex that are critical for the regulation of emotion-predicted response, but only within the QUET group. Thus, specific medications may be more effective in the context of specific prefrontal activation patterns in youth with bipolar depression. Larger studies of these youth would help to clarify the effects of QUET on brain activation.

9.
Bipolar Disord ; 20(6): 506-514, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29527766

RESUMO

OBJECTIVES: Health disparities between individuals of African and European ancestry are well documented. The disparities in bipolar disorder may be driven by racial bias superimposed on established factors contributing to misdiagnosis, including: evolving empirically based diagnostic criteria (International Classification of Diseases [ICD], Research Diagnostic Criteria [RDC] and Diagnostic and Statistical Manual [DSM]), multiple symptom domains (i.e. mania, depression and psychosis), and multimodal medical and additional psychiatric comorbidity. METHODS: For this paper, we reviewed the phenomenological differences between bipolar individuals of African and European ancestry in the context of diagnostic criteria and clinical factors that may contribute to a potential racial bias. RESULTS: Published data show that bipolar persons of African ancestry, compared with bipolar persons of non-African ancestry, are more often misdiagnosed with a disease other than bipolar disorder (i.e. schizophrenia). Additionally, studies show that there are disparities in recruiting patients of African ancestry to participate in important genomic studies. This gap in biological research in this underrepresented minority may represent a missed opportunity to address potential racial differences in the risk and course of bipolar illness. CONCLUSION: A concerted effort by the research community to increase inclusion of diverse persons in studies of bipolar disorder through community engagement may facilitate fully addressing these diagnostic and treatment disparities in bipolar individuals of African ancestry.

10.
J Affect Disord ; 234: 14-19, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29522938

RESUMO

BACKGROUND: The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. METHODS: Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. RESULTS: Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. LIMITATIONS: This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. CONCLUSIONS: Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Emoções/fisiologia , Adulto , Afeto , Mapeamento Encefálico , Análise Fatorial , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
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.
Clin J Sport Med ; 28(2): 100-105, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27755011

RESUMO

OBJECTIVE: To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. DESIGN: Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. SETTING: Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. PARTICIPANTS: Eleven former football players and 10 demographically similar track-and-field athletes. MAIN OUTCOME MEASURES: Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. RESULTS: Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. CONCLUSIONS: These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.


Assuntos
Concussão Encefálica/patologia , Futebol Americano/lesões , Córtex Pré-Frontal/patologia , Lobo Temporal/patologia , Substância Branca/patologia , Adulto , Atletas , Imagem de Tensor de Difusão , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto Jovem
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.
Ann Fam Med ; 15(2): 113-119, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28289109

RESUMO

PURPOSE: Care coordination has been identified as a key strategy in improving the effectiveness, safety, and efficiency of the US health care system. Our objective was to determine whether population or health care system issues are associated with primary care coordination gaps in the United States and other high-income countries. METHODS: We analyzed data from the 2013 Commonwealth Fund International Health Policy (IHP) survey with multivariate logistic regression analysis. Respondents were adult primary care patients from 11 countries: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, United Kingdom, and the United States. Poor primary care coordination was defined as participants reporting at least 3 gaps in the coordination of care out of a maximum of 5. RESULTS: Analyses were based on 13,958 respondents. The rate of poor primary care coordination was 5.2% (724/13,958 respondents) overall and highest in the United States, at 9.8% (137/1,395 respondents). Multivariate regression analysis among all respondents found that they were less likely to experience poor primary care coordination if their primary care physician often or always knew their medical history, spent sufficient time, involved them, and explained things well (odds ratio = 0.6 for each). Poor primary care coordination was more likely to occur among patients with chronic conditions (odds ratios = 1.4-2.1 depending on number) and patients younger than 65 years (odds ratios = 1.6-2.3 depending on age-group). Among US respondents, insurance status, health status, household income, and sex were not associated with poor primary care coordination. CONCLUSIONS: The United States had the highest rate of poor primary care coordination among the 11 high-income countries evaluated. An established relationship with a primary care physician was significantly associated with better care coordination, whereas being chronically ill or younger was associated with poorer care coordination.


Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Acesso aos Serviços de Saúde/estatística & dados numéricos , Assistência Centrada no Paciente/normas , Relações Médico-Paciente , Atenção Primária à Saúde/organização & administração , Adulto , Idoso , Idoso de 80 Anos ou mais , Australásia , Canadá , Países Desenvolvidos , Europa (Continente) , Feminino , Nível de Saúde , Humanos , Seguro Saúde/classificação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
15.
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
16.
J Am Acad Child Adolesc Psychiatry ; 55(11): 980-989, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27806866

RESUMO

OBJECTIVE: To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. METHOD: Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. RESULTS: Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. CONCLUSION: During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Filho de Pais Incapacitados , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Risco , Adulto Jovem
17.
Psychiatry Res ; 246: 803-807, 2016 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-27825781

RESUMO

Bipolar I disorder is associated with deficits in the long-chain omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3). The final biosynthesis of DHA is mediated by peroxisomes, and some heritable peroxisomal disorders are associated with DHA deficits and progressive psychopathology. The present cross-sectional study investigated whether medication-free asymptomatic and symptomatic youth with familial risk for bipolar I disorder exhibit impaired peroxisomal function using a comprehensive diagnostic blood panel. Measures of peroxisomal impairment included plasma concentrations of very long-chain fatty acids (VLCFA), branched-chain fatty acids, bile acid intermediates, and pipecolic acid, and erythrocyte plasmalogen and DHA levels. Compared with healthy subjects, significant erythrocyte DHA deficits were observed in ultra-high risk and first-episode bipolar groups, and there was a trend for lower DHA in the high-risk group. There were no significant group differences for any other measure of peroxisomal function, and erythrocyte DHA levels were not correlated with any measure of peroxisome function. These results indicate that familial risk for bipolar I disorder is not associated with impaired peroxisomal function, and that DHA deficits associated with familial bipolar disorder are not attributed to heritable defects in peroxisomal function.


Assuntos
Transtorno Bipolar/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/deficiência , Peroxissomos/metabolismo , Adolescente , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Criança , Estudos Transversais , Ácidos Docosa-Hexaenoicos/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/deficiência , Ácidos Graxos Ômega-3/genética , Feminino , Humanos , Masculino , Peroxissomos/genética , Plasmalogênios/sangue , Plasmalogênios/genética , Fatores de Risco , Adulto Jovem
18.
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
19.
J Clin Psychiatry ; 77(6): 781-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27232651

RESUMO

BACKGROUND: Early course in contemporary, clinically treated, nonaffective psychotic disorders other than schizophrenia remains incompletely defined. METHODS: We prospectively, repeatedly, and systematically assessed 114 patients hospitalized for a first episode of DSM-IV-TR nonaffective psychotic illness for ≥ 2 years (1989-1996) using structured (Structured Clinical Interview for DSM-III-R, Patient Edition; Clinical Global Impressions scale; Scale for the Assessment of Negative Symptoms; Scale for the Assessment of Positive Symptoms; and the expanded version of the Brief Psychiatric Rating Scale) and unstructured (best-estimate procedure, life charting) naturalistic follow-up procedures and survival analysis. RESULTS: Duration of untreated psychosis (22 ± 38 months) was longest with schizophrenia. Within 2 years, syndromal remission sustained for ≥ 8 weeks (recovery) was attained by 75 subjects (65.8%); median latency to syndromal recovery was 9.4 (95% CI, 5.7-13.3) weeks and was shorter with cycloid features, initial diagnosis of brief psychosis or schizophreniform disorder, and shorter initial hospitalization. Functional recovery within 2 years was achieved by 28 of 68 subjects (41.2%), more often without initial mood-psychomotor instability or homicidal ideation. New episodes occurred in 52 of 114 subjects (45.6%) and were more likely with less affective flattening, younger age, and white race. Median time to new episodes (43.7 [27.9-70.6] weeks) was earlier with initial first-rank auditory hallucinations, substance abuse, and functional nonrecovery. Diagnosis changed to other nonaffective, schizoaffective, or affective disorders within 2 years in 62 of 108 cases (57.4%). CONCLUSIONS: Three-quarters of patients presenting in first lifetime, nonaffective psychotic episodes achieved recovery within 2 years, but only 41% returned to baseline functioning, and nearly half experienced new episodes. Patients with schizophrenia had the longest duration of untreated psychosis. A majority changed diagnosis, indicating instability of some DSM psychotic-disorder diagnoses.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia Paranoide/diagnóstico , Esquizofrenia Paranoide/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Transtorno Bipolar/terapia , Transtorno Depressivo Maior/terapia , Feminino , Seguimentos , Homicídio/psicologia , Homicídio/estatística & dados numéricos , Hospitalização , Humanos , Masculino , Massachusetts , Transtornos Psicóticos/terapia , Recidiva , Esquizofrenia/terapia , Esquizofrenia Paranoide/terapia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Resultado do Tratamento
20.
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
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