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Artigo em Inglês | MEDLINE | ID: mdl-31825249


Objective: To examine the potential effectiveness and tolerability of cariprazine in pediatric bipolar and psychotic disorders. Methods: We retrospectively reviewed the electronic health records of patients <21 years of age prescribed cariprazine to treat bipolar and psychotic disorders. Adverse effects, tolerability, therapeutic response (Clinical Global Impression-Improvement [CGI-I]), and severity of illness (Clinical Global Impression-Severity [CGI-S]) were determined through manual chart review. Results: We identified 16 patients aged 6-20 years who were treated with cariprazine (initial dose: 1.5 mg/day, interquartile range [IQR], 1.5-1.5; endpoint dose: 3 mg/day, IQR, 1.5-4.5). No serious adverse events were reported, but the most commonly reported side effect was weight gain (n = 3, 19%). Of the 14 patients for whom baseline and endpoint body mass index (BMI) data were available, neither changes in BMI (p = 0.391; 0.54 kg/m2, IQR, -0.33 to 1.38) nor BMI percentile (p = 0.71; 0.36%, IQR, -0.49 to 3.97) significantly differed between baseline and endpoint. However, patients receiving ≥4.5 mg/day had a significantly greater BMI increases during the course of treatment compared with those receiving ≤3 mg/day (p = 0.034; -1.14 kg/m2, IQR, -3.65 to 0.53 vs. 1.01 kg/m2, IQR, 0.17-4.88). CGI-S scores (p = 0.016; 4.5, IQR, 4-5 vs. 4, IQR, 3-4) significantly differed from baseline to endpoint. The response rate was 44% (n = 7/16), with responders being prescribed higher doses (p = 0.005; 6 mg/day, IQR, 4.875-6 vs. 3 mg/day, IQR, 3-4.125). Conclusions: Cariprazine may be well tolerated and effective for pediatric bipolar and psychotic disorders; however, compared with higher doses, total daily doses ≤3 mg/day appear to be more tolerable. Prospective controlled studies to further evaluate cariprazine in youth are needed.

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


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.

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
J Anxiety Disord ; 28(7): 717-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25155256


BACKGROUND: It is established that pediatric patients with generalized anxiety disorder (GAD) exhibit functional abnormalities and altered gray matter volumes in neural structures that subserve emotional processing, yet there are no data regarding the surface anatomy of the cerebral cortex in youth with GAD. METHODS: Using an automated surface-based approach (FreeSurfer), cortical thickness was assessed node-by-node over the entire cerebral cortex in adolescents with GAD and no co-occurring major depressive disorder (n=13) and healthy subjects (n=19). RESULTS: Compared with healthy adolescents, youth with GAD exhibited increased cortical thickness in the right inferolateral and ventromedial prefrontal cortex (i.e., inferior frontal gyrus), the left inferior and middle temporal cortex as well as the right lateral occipital cortex. No relationships were observed between cortical thickness and the severity of anxiety symptoms in the significant regions that were identified in the vertex-wise analysis. CONCLUSIONS: These findings suggest that, in adolescents with GAD, abnormalities in cortical thickness are present in an ensemble of regions responsible for fear learning, fear extinction, reflective functioning (e.g., mentalization), and regulation of the amygdala.

Transtornos de Ansiedade/patologia , Córtex Cerebral/patologia , Adolescente , Tonsila do Cerebelo/patologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Emoções/fisiologia , Medo/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/patologia
Curr Behav Neurosci Rep ; 1(3): 154-160, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25745592


While the fear-based anxiety disorders (i.e., generalized anxiety disorder, social phobia and separation anxiety disorder) are among the most common psychiatric conditions in children and adolescents, only recently has an integrated understanding of the neurobiology of these disorders developed. In this regard, both structural and functional neuroimaging studies have demonstrated neuroanatomic and functional abnormalities within the amygdala and prefrontal cortex in youth with fear-based anxiety disorders, and have also suggested altered functional connectivity among components of the anterior limbic network (ALN), as well as alterations in neurochemistry within the anterior cingulate cortex. Additionally, several prefrontal structures and regions (e.g., medial prefrontal cortex) appear to be dysregulated in youth who are at risk of developing anxiety disorders (e.g., youth with inhibited temperament, behavioral inhibition, etc.). Finally, emerging data raise the possibility that functional activity within these amygdala-prefrontal networks may be affected by successful psychopharmacologic and psychotherapeutic treatment and may predict outcome.

Bipolar Disord ; 15(3): 264-71, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23528067


OBJECTIVE: To examine conflict monitoring and conflict-driven adaptation in individuals at familial risk for developing bipolar disorder. METHODS: We recruited 24 adolescents who had a parent with bipolar disorder and 23 adolescents with healthy parents. Participants completed an arrow version of the Eriksen Flanker Task that included trials with three levels of conflict: neutral, congruent, and incongruent flanks. Differences in performance were explored based upon the level of conflict in the current and previous trials. RESULTS: Individuals at risk for developing bipolar disorder performed more slowly than youth with healthy parents in all trials. Analyses evaluating sequential effects revealed that at-risk subjects responded more slowly than youth of healthy parents for all trial types when preceded by an incongruent trial, for incongruent trials preceded by congruent trials, and for neutral and congruent trials when preceded by neutral trials. In contrast to the comparison group, at-risk adolescents failed to display a response time advantage for incongruent trials preceded by an incongruent trial. When removing subjects with attention-deficit hyperactivity disorder (ADHD), differences between groups in response time fell below significant level, but a difference in sequence modulation remained significant. Subjects at risk for bipolar disorder also displayed greater intra-subject response time variability for incongruent and congruent trials compared with the comparison adolescents. No differences in response accuracy were observed between groups. CONCLUSIONS: Adolescents at risk for developing bipolar disorder displayed specific deficits in cognitive flexibility, which might be useful as a potential marker related to the development of bipolar disorder.

Adaptação Psicológica , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Filho de Pais Incapacitados/psicologia , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
Br J Psychiatry ; 186: 442-3, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15863751


A cross-sectional study of 3426 referred children and adolescents showed that the presence of both migration history and family dysfunction was associated with a fourfold (95% CI 2-9) higher risk of psychotic symptoms compared with the absence of these factors. The relative risk was 2 (95% CI 1-4) for migration history only. Interaction between migration history and family dysfunction accounted for 58% (95% CI 5-91%) of those with psychotic symptoms. These results suggest a relationship between family dysfunction and migration in the development of psychosis.

Emigração e Imigração , Saúde da Família , Relações Familiares , Transtornos Psicóticos/etiologia , Adolescente , Criança , Estudos Transversais , Humanos , Fatores de Risco