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1.
Bipolar Disord ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089593

RESUMO

OBJECTIVES: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, was previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after 8 weeks of treatment compared to those who did not. METHODS: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received 8 weeks of treatment. Twenty-one remitted following treatment. Participants completed fMRI scans, at baseline and following 8 weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n = 41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups. RESULTS: At baseline, non-remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate 8 weeks following treatment. CONCLUSIONS: Results provide evidence of alterations in anterior cingulate amygdala and caudate functional connectivity in bipolar disorder non-remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First-episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowskirank=1.

2.
J Neurotrauma ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33115345

RESUMO

This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury. The GFT system was trained using one-week total PCSS scores, 48 volumetric magnetic resonance imaging inputs, and 192 DTI inputs per participant over 225 training runs. Each training run contained a randomly selected 80% of the total sample followed by a 20% validation run. Over a different randomly selected sample distribution, GFT was also compared with six common classification methods. The cascading GFT structure controlled an effectively infinite solution space that classified participants as recovered or not recovered significantly better than chance. It demonstrated 100% and 62% classification accuracy in training and validation, respectively, better than any of the six comparison methods. Recovery sensitivity and specificity were 59% and 65% in the GFT validation set, respectively. These results provide initial evidence for the effectiveness of a GFT system to make clinical predictions of trauma symptom recovery using objective brain measures. Although clinical and research applications will necessitate additional optimization of the system, these results highlight the future promise of AI in acute care.

3.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(5): 481-488, Sept.-Oct. 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1132115

RESUMO

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

4.
Braz J Psychiatry ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32876131

RESUMO

OBJECTIVE: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). METHODS: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. RESULTS: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). CONCLUSIONS: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

5.
Braz J Psychiatry ; 42(5): 481-488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401870

RESUMO

OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pais , Estudos Prospectivos , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-32008167

RESUMO

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

7.
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.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atenção/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia
8.
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.


Assuntos
Transtorno da Compulsão Alimentar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adulto , Transtorno da Compulsão Alimentar/diagnóstico por imagem , Transtorno da Compulsão Alimentar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Feminino , Humanos , Dimesilato de Lisdexanfetamina/farmacologia , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Resultado do Tratamento
9.
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.


Assuntos
Sintomas Afetivos , Transtorno Bipolar , Filho de Pais Incapacitados/psicologia , Creatina/análise , Giro do Cíngulo/metabolismo , Fosfocreatina/análise , Córtex Pré-Frontal/metabolismo , Medição de Risco , Adolescente , Adulto , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/metabolismo , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Criança , Creatina/metabolismo , Feminino , Humanos , Estudos Longitudinais , Masculino , Espectroscopia de Prótons por Ressonância Magnética/métodos , Medição de Risco/métodos
10.
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
11.
Neuropsychopharmacology ; 43(11): 2256-2263, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29946107

RESUMO

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Córtex Cerebral/diagnóstico por imagem , Carbonato de Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adolescente , Antidepressivos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Criança , Feminino , Humanos , Carbonato de Lítio/farmacologia , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Valor Preditivo dos Testes , Fumarato de Quetiapina/farmacologia , Resultado do Tratamento
12.
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
13.
Bipolar Disord ; 20(7): 658-665, 2018 11.
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.


Assuntos
Transtorno Bipolar , Ácidos Graxos Ômega-3 , Síndrome Metabólica , Psicotrópicos/uso terapêutico , Triglicerídeos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Índice de Massa Corporal , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricos , Triglicerídeos/sangue , Triglicerídeos/metabolismo
14.
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
15.
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
16.
J Affect Disord ; 209: 246-253, 2017 Feb.
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
17.
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
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.
Nutr Neurosci ; 19(4): 145-55, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-24915543

RESUMO

OBJECTIVE: To use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of fish oil (FO) supplementation on cortical metabolite concentrations in adolescents with major depressive disorder (MDD). METHODS: Metabolite concentrations were determined by (1)H MRS in the anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with MDD before and following 10-week open-label supplementation with low (2.4 g/day, n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores and erythrocyte fatty acid levels were also determined. RESULTS: Baseline erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated, and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA) composition was inversely correlated with myo-inositol (mI) concentrations in the left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased, significantly following low-dose and high-dose FO supplementation. In the intent-to-treat sample, depressive symptom severity scores decreased significantly in the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose group (-20%, P = 0.06). There were no significant baseline-endpoint changes in metabolite levels in each voxel. In the low-dose group there were changes with large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18, d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8) and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group, there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d = 1.2). DISCUSSION: These preliminary data suggest that increasing the LCn-3 fatty acid status of adolescent MDD patients is associated with subtle changes in Glx, mI, and Cho concentrations in the DLPFC that warrant further evaluation in a larger controlled trial.


Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Deficiências Nutricionais/dietoterapia , Transtorno Depressivo Maior/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Essenciais/uso terapêutico , Óleos de Peixe/uso terapêutico , Adolescente , Adulto , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Deficiências Nutricionais/metabolismo , Deficiências Nutricionais/fisiopatologia , Deficiências Nutricionais/psicologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/metabolismo , Manual Diagnóstico e Estatístico de Transtornos Mentais , Ácidos Graxos Essenciais/deficiência , Ácidos Graxos Essenciais/metabolismo , Feminino , Óleos de Peixe/administração & dosagem , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Humanos , Análise de Intenção de Tratamento , Perda de Seguimento , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Escalas de Graduação Psiquiátrica , Adulto Jovem
20.
J Affect Disord ; 191: 248-55, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26688494

RESUMO

OBJECTIVES: To investigate tissue-dependent cerebral energy metabolism by measuring high energy phosphate levels in unmedicated adolescents diagnosed with bipolar I disorder. METHODS: Phosphorus-31 magnetic resonance spectroscopic imaging data were acquired over the entire brain of 24 adolescents with bipolar I disorder and 19 demographically matched healthy comparison adolescents. Estimates of phosphocreatine (PCr) and adenosine triphosphate (ATP, determined from the γ-resonance) in homogeneous gray and white matter in the right and left hemispheres of the cerebrum of each subject were obtained by extrapolation of linear regression analyses of metabolite concentrations vs. voxel gray matter fractions. RESULTS: Multivariate analyses of variance showed a significant effect of group on high energy phosphate concentrations in the right cerebrum (p=0.0002) but not in the left (p=0.17). Post-hoc testing in the right cerebrum revealed significantly reduced concentrations of PCr in gray matter and ATP in white matter in both manic (p=0.002 and 0.0001, respectively) and euthymic (p=0.004 and 0.002, respectively) bipolar I disorder subjects relative to healthy comparisons. LIMITATIONS: The small sample sizes yield relatively low statistical power between manic and euthymic groups; cross-sectional observations limit the ability to determine if these findings are truly independent of mood state. CONCLUSIONS: Our results suggest bioenergetic impairment - consistent with downregulation of creatine kinase - is an early pathophysiological feature of bipolar I disorder.


Assuntos
Trifosfato de Adenosina/metabolismo , Transtorno Bipolar/metabolismo , Cérebro/metabolismo , Metabolismo Energético , Fosfocreatina/metabolismo , Adolescente , Afeto , Biomarcadores/metabolismo , Encéfalo/metabolismo , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Substância Cinzenta/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Isótopos de Fósforo , Substância Branca/metabolismo , Adulto Jovem
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