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Neuropsychobiology ; 67(4): 224-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23635944


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.

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
Isr J Psychiatry Relat Sci ; 49(2): 112-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22801290


BACKGROUND: Prior research has found that manic adolescents with bipolar disorder exhibit neurofunctional changes in the amygdala and prefrontal cortex following treatment with some pharmacological agents. We examined the neurofunctional effects of ziprasidone in manic adolescents. METHOD: Manic adolescents with bipolar disorder (n=23) participated in a placebo-controlled study of ziprasidone and underwent a functional magnetic resonance imaging scanning session while performing a task of sustained attention at baseline, prior to treatment as well as on days 7 and 28 (or early termination) of treatment. A comparison group of healthy adolescents (n=10) participated in a single scanning session. Region of interest analyses were performed to assess activation changes associated with treatment in Brodmann Areas (BA) 10, 11 and 47 and in the amygdala. RESULTS: Compared with placebo, treatment with ziprasidone was associated with greater increases over time in right BA 11 and 47 activation. These effects were not associated with differences in symptom improvement between the treatment groups. Patients who subsequently responded to ziprasidone showed significantly greater deactivation in the right Brodmann area 47 at baseline than those who did not respond to ziprasidone. Similarly, among the bipolar adolescents who were treated with ziprasidone, baseline activation in right BA 47 was negatively correlated with improvement in Young Mania Rating Scale (YMRS) score. LIMITATIONS: The small sample size limits the ability to detect significant group differences in other regions of interest. Healthy comparison subjects were scanned only at a single timepoint, which limits the interpretation of the results. Ziprasidone is not currently approved by the United States Food and Drug Administration for the treatment of adolescents with mania, and, therefore, the clinical relevance of these results is limited. CONCLUSIONS: The increases in right BA 11 and 47 activation observed during sustained attention tasks following ziprasidone treatment and the association identified between lower baseline BA 47 activation and ziprasidone treatment response suggests that ziprasidone may correct prefrontal dysfunction in manic adolescents with bipolar disorder.

Tonsila do Cerebelo/efeitos dos fármacos , Antipsicóticos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Piperazinas/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Tiazóis/farmacologia , Adolescente , Antipsicóticos/administração & dosagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Piperazinas/administração & dosagem , Tiazóis/administração & dosagem
Depress Anxiety ; 29(11): 939-47, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22628125


BACKGROUND: Dysfunction of neural systems responsible for the processing of emotional stimuli is hypothesized to be involved in the pathophysiology of generalized anxiety disorder (GAD) in adolescents. We used standard fMRI and functional connectivity analyses to examine the functional neurocircuitry of GAD in adolescents. METHODS: Ten adolescents with GAD and 10 healthy comparison subjects underwent fMRI while performing a continuous performance task with emotional and neutral distractors. Standard event-related voxel-wise fMRI and steady-state functional connectivity analyses were performed. RESULTS: Increased activation was observed in the left medial prefrontal cortex and right ventrolateral prefrontal cortex (VLPFC) in response to emotional images compared to neutral imagines in youth with GAD. Connectivity analyses using the right VLPFC seed region suggested decreased connectivity between this region and the bilateral medial prefrontal cortex. Connectivity analyses using the right amygdala seed region revealed decreased correlation with the posterior cingulate cortex in adolescents with GAD. The left amygdala seed region demonstrated increased connectivity with the ipsilateral precuneus in youth with GAD compared to healthy subjects. CONCLUSIONS: In addition to increased activation of the medial prefrontal cortex and right VLPFC, we observed altered connectivity between the amygdala or VLPFC and regions, which subserve mentalization (e.g. posterior cingulate cortex, precuneus, and medial prefrontal cortex). This suggests that structures that regulate emotion and affect interact abnormally with key structures that are involved in mentalization, a process known to be disrupted in GAD.

Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Adolescente , Afeto , Tonsila do Cerebelo/fisiopatologia , Estudos de Casos e Controles , Criança , Emoções , Feminino , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Lobo Parietal/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/fisiopatologia
J Clin Psychiatry ; 68(5): 789-95, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17503991


OBJECTIVE: To investigate the effectiveness and tolerability of quetiapine for the treatment of adolescents at high risk for developing bipolar I disorder. METHOD: Twenty adolescents (aged 12-18 years) with mood symptoms that did not meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first-degree relative with bipolar I disorder were recruited from August 2003 to June 2005 to participate in a single-blind, 12-week prospective study of quetiapine. Subjects were diagnosed using the Washington University in St. Louis Kiddie Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined by a Young Mania Rating Scale (YMRS) score > or = 12 or a Childhood Depression Rating Scale-Revised Version (CDRS-R) score > or = 28 at baseline. The primary effectiveness measure was an endpoint Clinical Global Impressions-Improvement scale (CGI-I) score < or = 2 ("much" or "very much" improved). Secondary efficacy measures included change from baseline to endpoint in YMRS and CDRS-R scores. RESULTS: Mood disorder diagnoses in the adolescents consisted of bipolar disorder not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3), cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of patients (N = 12, 60%) were non-responders to previous trials of psychotropic agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent of patients were responders (CGI-I < or = 2) to quetiapine at week 12 (mean +/- SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at baseline to 8.7 +/- 7.9 at endpoint (p < .0001), and CDRS-R scores decreased from 38.2 +/- 9.8 to 27.7 +/- 9.3, (p = .0003). The most frequently reported adverse events were somnolence, headache, musculoskeletal pain, and dyspepsia. No subjects discontinued study participation due to adverse events. CONCLUSION: Although these findings are limited by the small sample size and open-label treatment, the results suggest that quetiapine may be an effective treatment for mood symptoms in adolescents with a familial risk for developing bipolar I disorder.

Antipsicóticos/uso terapêutico , Transtorno Bipolar/prevenção & controle , Dibenzotiazepinas/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Adolescente , Transtorno Bipolar/genética , Criança , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Fumarato de Quetiapina , Método Simples-Cego