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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.
Neuropsychopharmacology ; 43(11): 2256-2263, 2018 Oct.
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.

4.
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
5.
Nutr Neurosci ; 20(4): 246-254, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-26463682

RESUMO

OBJECTIVE: Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children. METHODS: Male children (aged 8-10 years, n = 36) were divided into 'low-DHA' (n = 18) and 'high-DHA' (n = 18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region. RESULTS: Erythrocyte DHA composition in the low-DHA group (2.6 ± 0.9%) was significantly lower than the high-DHA group (4.1 ± 1.1%, P ≤ 0.0001). Fish intake frequency was greater in the high-DHA group (P = 0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P < 0.05; corrected). The low-DHA group did not exhibit greater ACC functional connectivity with any region compared with the high-DHA group. On the CPT-IP task, the low-DHA group had slower reaction time (P = 0.03) which was inversely correlated with erythrocyte DHA among all subjects. DISCUSSION: These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.


Assuntos
Córtex Cerebral/fisiologia , Ácidos Docosa-Hexaenoicos/sangue , Giro do Cíngulo/fisiologia , Lobo Parietal/fisiologia , Atenção/fisiologia , Criança , Desenvolvimento Infantil , Estudos Transversais , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Tempo de Reação/fisiologia
6.
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
7.
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
8.
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
9.
J Child Adolesc Psychopharmacol ; 26(4): 372-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26783833

RESUMO

OBJECTIVE: We sought to evaluate the neurophysiology of mindfulness-based cognitive therapy for children (MBCT-C) in youth with generalized, social, and/or separation anxiety disorder who were at risk for developing bipolar disorder. METHODS: Nine youth (mean age: 13 ± 2 years) with a generalized, social, and/or separation anxiety disorder and a parent with bipolar disorder completed functional magnetic resonance imaging (fMRI) while performing a continuous processing task with emotional and neutral distractors (CPT-END) prior to and following 12 weeks of MBCT-C. RESULTS: MBCT-C was associated with increases in activation of the bilateral insula, lentiform nucleus, and thalamus, as well as the left anterior cingulate while viewing emotional stimuli during the CPT-END, and decreases in anxiety were correlated with change in activation in the bilateral insula and anterior cingulate during the viewing of emotional stimuli (p < 0.05, uncorrected; p < 0.005 corrected; cluster size, 37 voxels). CONCLUSIONS: MBCT-C treatment in anxious youth with a familial history of bipolar disorder is associated with increased activation of brain structures that subserve interoception and the processing of internal stimuli-functions that are ostensibly improved by this treatment.


Assuntos
Transtornos de Ansiedade/terapia , Transtorno Bipolar/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Atenção Plena/métodos , Adolescente , Transtornos de Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Criança , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Fatores de Risco , Resultado do Tratamento
10.
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
11.
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
12.
Bipolar Disord ; 17(4): 444-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25359589

RESUMO

OBJECTIVES: Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. METHODS: Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. RESULTS: At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003). CONCLUSIONS: These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Imagem por Ressonância Magnética , Córtex Pré-Frontal/efeitos dos fármacos , Fumarato de Quetiapina/uso terapêutico , Adolescente , Adulto , Afeto/efeitos dos fármacos , Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Adulto Jovem
13.
Psychiatry Res ; 223(3): 268-70, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25035298

RESUMO

This preliminary study investigated the neurofunctional effects of carbamazepine-extended release (XR) treatment in 11 manic youth with bipolar disorder during performance of a sustained attention task, the Continuous Performance Task - Identical Pairs version (CPT-IP), during functional magnetic resonance imaging (fMRI). All patients underwent baseline fMRI, and 10 patients were scanned again at endpoint. Nine demographically matched healthy youth, who were scanned once, served as controls. Carbamazepine-XR treatment was associated with normalization of activation in right Brodmann area 10 (BA). These results suggest that carbamazepine-XR treatment may correct prefrontal dysfunction in adolescent mania.


Assuntos
Antimaníacos/farmacologia , Atenção , Carbamazepina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Análise e Desempenho de Tarefas , Adolescente , Atenção/efeitos dos fármacos , Transtorno Bipolar , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino
14.
Addiction ; 109(11): 1901-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24962329

RESUMO

AIMS: To compare regional brain activation among adolescents with bipolar disorder and co-occurring cannabis use disorder. DESIGN: Cross-sectional study. SETTING: Cincinnati, OH, USA. PARTICIPANTS: Adolescents with bipolar disorder (BP, n = 14), adolescents with cannabis use disorder (MJ, n = 13), adolescents with co-occurring cannabis use and bipolar disorders (BPMJ, n = 25) and healthy adolescents (HC, n = 15). MEASUREMENTS: Cannabis craving, substance use, Blood Oxygenation Level Dependent (BOLD) signal assessed by the Marijuana Craving Questionnaire (MCQ), Teen-Addiction Severity Index (T-ASI) and a cannabis cue-reactivity task during a functional magnetic resonance imaging (fMRI) session, respectively. FINDINGS: The BP group exhibited significantly greater brain activation than the BPMJ group in the right amygdala (F = 4.14, P = 0.046), left nucleus accumbens (F = 3.8, P = 0.02), left thalamus (F = 3.8, P < 0.05) and the right thalamus (F = 6.2, P = 0.02). The BP group exhibited significantly greater activation than the HC group in the left nucleus accumbens (F = 11.5, P = 0.0001), right thalamus (F = 4.9, P = 0.03) and the left striatum (F = 3.6, P = 0.04). Left amygdala activation of the BPMJ group trended towards being significantly negatively correlated with the number of joints smoked (R = -0.4, P = 0.06). CONCLUSIONS: Bipolar adolescents with comorbid cannabis use do not exhibit the same over-activation of the regions involved in emotional processing as seen in adolescents with bipolar disorder alone. The absence of these findings in patients with comorbid bipolar and cannabis use disorders suggests that these individuals may have a unique endophenotype of bipolar disorder or that cannabis use may alter brain activation uniquely in bipolar disorder patients who use cannabis.


Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Abuso de Maconha/epidemiologia , Abuso de Maconha/fisiopatologia , Adolescente , Estudos de Casos e Controles , Criança , Comorbidade , Estudos Transversais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
15.
J Dual Diagn ; 10(1): 39-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24729763

RESUMO

OBJECTIVE: Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among adolescents with bipolar disorder (bipolar group; n = 14), adolescents with a cannabis use disorder (cannabis use group; n = 13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group; n = 25), and healthy adolescents (healthy controls; n = 15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups. METHODS: N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using proton magnetic resonance spectroscopy. RESULTS: Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p = .0002 and p = .0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations. CONCLUSIONS: Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder.


Assuntos
Ácido Aspártico/análogos & derivados , Transtorno Bipolar/complicações , Transtorno Bipolar/metabolismo , Abuso de Maconha/complicações , Abuso de Maconha/metabolismo , Córtex Pré-Frontal/metabolismo , Adolescente , Adulto , Ácido Aspártico/análise , Feminino , Humanos , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Adulto Jovem
16.
Psychiatry Res ; 213(3): 230-4, 2013 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-23810640

RESUMO

Although brain lactate levels are typically low and difficult to measure, a few previous investigators have reported that brain lactate levels are elevated in patients with bipolar disorder. The present study investigated the distribution of lactate in bipolar and healthy brains using 2D proton magnetic resonance spectroscopic imaging on a 4-Tesla magnetic resonance imaging system. Ratios of the concentration of lactate to N-acetylaspartate, and of lactate to total creatine, were significantly higher in bipolar than in healthy subjects. Lactate signals were primarily localized to the bipolar subjects' caudate and anterior cingulate cortices, components of the frontal-subcortical circuit, suggesting that affective dysregulation may be related to metabolic abnormalities in this network.


Assuntos
Transtorno Bipolar/patologia , Ácido Láctico/metabolismo , Adolescente , Adulto , Análise de Variância , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Transtorno Bipolar/tratamento farmacológico , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Escalas de Graduação Psiquiátrica , Adulto Jovem
17.
J Clin Psychopharmacol ; 33(4): 528-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23764689

RESUMO

Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.


Assuntos
Antipsicóticos/uso terapêutico , Ácido Aspártico/análogos & derivados , Transtorno Bipolar/tratamento farmacológico , Dibenzotiazepinas/uso terapêutico , Espectroscopia de Ressonância Magnética , Córtex Pré-Frontal/efeitos dos fármacos , Adolescente , Adulto , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/metabolismo , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Feminino , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo , Estudos Prospectivos , Fumarato de Quetiapina , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
J Affect Disord ; 150(3): 1109-13, 2013 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-23706839

RESUMO

BACKGROUND: Several lines of evidence suggest that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder, including prior studies indicating abnormalities in phosphometabolites. We examined abnormalities in biomarkers of cellular metabolism including adenosine triphosphate and adenosine diphosphate as well as the pH levels in the anterior cingulate (ACC) and left ventrolateral prefrontal cortices (VLPFC) of adolescents with bipolar disorder. METHOD: Nineteen unmedicated manic and 14 unmedicated euthymic bipolar adolescents as well as 20 healthy adolescents underwent (1)H and (31)P magnetic resonance spectroscopy scans. Intracellular pH levels and concentrations of phosphometabolites were compared among groups. RESULTS: A significant reduction in pHi was found in the ACC of manic adolescents compared to healthy subjects (p=0.03) but not in the left VLPFC. There was no difference in concentration of adenosine triphosphate in the ACC or the left VLPFC among groups. However, compared to healthy subjects, adenosine diphosphate was significantly lower in manic subjects in the ACC (p=0.01) and in euthymic subjects in the left VLPFC (p=0.02). LIMITATIONS: This was a cross-sectional study with a modest sample size. A longitudinal study of a larger number of bipolar adolescents who are treatment naïve would clarify the impact of mood state on metabolic function. CONCLUSION: These results are suggestive of abnormal cellular metabolism and mitochondrial dysfunction in the pathophysiology of bipolar disorder.


Assuntos
Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Transtorno Bipolar/metabolismo , Metabolismo Energético , Adolescente , Afeto , Criança , Estudos Transversais , Feminino , Giro do Cíngulo/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Mitocôndrias/metabolismo , Projetos Piloto , Córtex Pré-Frontal/metabolismo , Adulto Jovem
19.
Neuropsychobiology ; 67(4): 224-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23635944

RESUMO

BACKGROUND/AIMS: This study used proton magnetic resonance spectroscopy (¹H MRS) to evaluate the neurochemistry of the anterior cingulate cortex (ACC) in adolescents with generalized anxiety disorder (GAD). METHODS: Adolescents with GAD (n = 10) and healthy subjects (n = 10) underwent a ¹H MRS scan at 4 T. Glutamate (Glu), N-acetyl aspartate, creatine (Cr) and myo-inositol concentrations were measured in the ACC and were compared between untreated adolescents with GAD and age- and sex-matched healthy subjects. RESULTS: Glu/Cr ratios in the ACC correlated with the severity of both generalized anxiety symptoms on the Pediatric Anxiety Rating Scale and with total anxiety symptom severity as measured by the Hamilton Anxiety Rating Scale, but did not differ between adolescents with GAD and healthy subjects. In addition, no differences in N-acetyl aspartate, Cr, or myo-inositol were detected between groups. CONCLUSION: These findings suggest that Glu/Cr in untreated adolescents with GAD may relate to the severity of anxiety symptoms and raise the possibility that dysregulation of Glu within the ACC may be linked to the pathophysiology of pediatric GAD.


Assuntos
Transtornos de Ansiedade/metabolismo , Ácido Aspártico/análogos & derivados , Química Encefálica , Creatina/metabolismo , Ácido Glutâmico/metabolismo , Giro do Cíngulo/metabolismo , Inositol/metabolismo , Adolescente , Ácido Aspártico/análise , Ácido Aspártico/metabolismo , Estudos de Casos e Controles , Criança , Creatina/análise , Feminino , Ácido Glutâmico/análise , Giro do Cíngulo/química , Humanos , Inositol/análise , Espectroscopia de Ressonância Magnética , Masculino , Projetos Piloto
20.
Nutr Neurosci ; 16(4): 183-90, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23582513

RESUMO

Docosahexaenoic acid (DHA, 22:6n-3) is the principal omega-3 fatty acid in mammalian brain gray matter, and emerging preclinical evidence suggests that DHA has neurotrophic and neuroprotective properties. This study investigated relationships among DHA status, neurocognitive performance, and cortical metabolism measured with proton magnetic resonance spectroscopy (1H MRS) in healthy developing male children (aged 8-10 years, n = 38). Subjects were segregated into low-DHA (n = 19) and high-DHA (n = 19) status groups by a median split of erythrocyte DHA levels. Group differences in 1H MRS indices of cortical metabolism, including choline (Cho), creatine (Cr), glutamine + glutamate + γ-aminobutyric acid (Glx), myo-inositol (mI), and n-acetyl aspartate (NAA), were determined in the right and left dorsolateral prefrontal cortex (R/L-DLPFC, BA9) and bilateral anterior cingulate cortex (ACC, BA32/33). Group differences in neurocognitive performance were evaluated with the Kaufman Brief Intelligence Test and identical-pairs version of the continuous performance task (CPT-IP). Subjects in the low-DHA group consumed fish less frequently (P = 0.02), had slower reaction times on the CPT-IP (P = 0.007), and exhibited lower mI (P = 0.007), NAA (P = 0.007), Cho (P = 0.009), and Cr (P = 0.01) concentrations in the ACC compared with the high-DHA group. There were no group differences in ACC Glx or any metabolite in the L-DLPFC and R-DLPFC. These data indicate that low-DHA status is associated with reduced indices of metabolic function in the ACC and slower reaction time during sustained attention in developing male children.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Giro do Cíngulo/fisiopatologia , Espectroscopia de Ressonância Magnética/métodos , Estado Nutricional , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Atenção/efeitos dos fármacos , Criança , Colina/análise , Cromatografia Gasosa , Creatina/análise , Humanos , Inositol/análise , Testes de Inteligência , Masculino , Tempo de Reação/efeitos dos fármacos , Fatores Socioeconômicos , Inquéritos e Questionários , Ácido gama-Aminobutírico/análise
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