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1.
Pediatr Blood Cancer ; 70(12): e30667, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37726889

RESUMO

BACKGROUND: Sickle cell disease (SCD) pain is associated with functional impairment, and treatment is often limited to pharmacological approaches with unwanted side effects. Although behavioral interventions exist for non-SCD pain populations, interventions designed to address pain-related impairment in SCD are lacking. METHODS: Twenty youth (9-17 years) with SCD completed a four-week telemedicine pain intervention (NCT04388241). Participants and caregivers completed baseline and post-intervention PROMIS pain measures and the Treatment Evaluation Inventory-Short Form (TEI-SF). Descriptive analyses assessed feasibility and acceptability. Reliable Change Index analyses assessed for significant post-intervention changes in pain functioning. Paired t test analyses compared baseline and post-intervention opioid prescription fills. RESULTS: All participants completed at least one treatment session. Eighteen (90%) youth completed all sessions. Youth (100%) and caregivers (94%) rated the intervention as moderately or highly acceptable on the TEI-SF. Forty-seven percent of caregivers and 44% of youth reported reliably significant improvements in pain interference after the intervention (median T-score differences: 24.8 and 23.5, respectively). Sixty-five percent of caregivers (T-score improvement difference: 19.3) and 31% of youth (T-score improvement difference: 32) reported improvements in pain behaviors. There was no significant difference in opioid prescription fills pre- and post-intervention (P > 0.05). CONCLUSIONS: The Balance Program is feasible, highly acceptable, and can be delivered remotely to reduce barriers to care. Approximately half of youth and caregivers reported significant declines in pain interference following the intervention, with substantial improvements in functioning for treatment responders. Behavioral pain interventions are important adjunctive treatments to uniquely address functional impairment associated with acute and chronic pain in SCD.

2.
Pediatr Blood Cancer ; 70(3): e30125, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36518026

RESUMO

INTRODUCTION: Patients with sickle cell disease (SCD) need frequent health maintenance visits and may face barriers accessing care. Telemedicine, during COVID pandemic, has provided a unique model of care to improve access; however, potential barriers and satisfaction with its use in SCD have not been fully evaluated. OBJECTIVE: To determine caregiver, patient, and healthcare provider (HCP) perspectives and satisfaction with telemedicine in healthcare delivery. METHODS: We surveyed patients with SCD, caregivers, and HCP, who participated in at least one telemedicine visit from March 2020 to June 2021, using the Telemedicine Usability Questionnaire (TUQ). We also accessed and compared the Press Ganey surveys completed by families who completed a telemedicine or in-person visit. Data were summarized using descriptive statistics. The internal reliability of TUQ was assessed using Cronbach's coefficient alpha. Press Ganey data comparing satisfaction with telemedicine versus in-person visits were analyzed by Mann-Whiney U test. RESULTS: Fifty-two patients/caregivers and 10 HCP completed the survey. Patients/caregivers rated satisfaction "excellent" in the five areas (Usefulness, Ease of use, Effectiveness, Reliability and Satisfaction). HCP rated Usefulness, Ease of use, Effectiveness, Satisfaction as "good," and Reliability as "excellent." Press Ganey scores for satisfaction with care for telemedicine and in-person visits were not statistically different (p > .05). DISCUSSION: We found high satisfaction for caregivers and patients as well as HCP in the delivery of clinical services via telemedicine for SCD. We suggest that telemedicine is a viable option for this population and may help overcome the barriers SCD families often face accessing care.


Assuntos
Anemia Falciforme , COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , Reprodutibilidade dos Testes , Satisfação do Paciente , Anemia Falciforme/terapia , Pais
3.
J Pediatr Hematol Oncol ; 43(5): e666-e676, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625087

RESUMO

Children with sickle cell disease (SCD) face academic challenges because of direct and indirect disease-related events. This study examined the proportion of youth with SCD with educational plans and whether cognitive functioning is associated with educational support. Ninety-one youth (7 to 16 y) with SCD completed the WISC-V; caregivers reported educational support (504 Plan/Individualized Education Program) and completed the Behavior Rating Inventory of Executive Function. χ2 square and t test analyses explored whether overall intelligence (full-scale intelligence quotient [FSIQ]), relative weaknesses in processing speed and working memory (> 1SD below FSIQ), and parent-reported executive functioning were associated with educational plans. Participants with a FSIQ<90 were more likely to have support (74%) compared with youth with a FSIQ≥90 (47%; P=0.012). Those with FSIQ≥90 and FSIQ=80 to 89 were less likely to have support (47%, 58%, respectively) compared with those with FSIQ≤79 (89%; P=0.004). Relative weaknesses in processing speed were associated with educational support (83% vs. 52%, P=0.018) as well as behavioral aspects of executive functioning (Ps<0.05). Despite universal eligibility for a 504 Plan, 42% of youth with SCD in our sample did not have educational support. Significant deficits in intellectual functioning, processing speed, and parent-observed executive functioning are associated with having a plan, but children with subtle deficits seem less likely to be identified for educational support.


Assuntos
Desempenho Acadêmico , Anemia Falciforme/fisiopatologia , Cognição , Adolescente , Anemia Falciforme/complicações , Criança , Função Executiva , Feminino , Humanos , Inteligência , Testes de Inteligência , Masculino , Memória de Curto Prazo
4.
Complement Ther Med ; 60: 102680, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33601015

RESUMO

CONTEXT: Painful vaso-occlusive crises (VOCs) associated with sickle cell disease (SCD) are the most common cause of morbidity, hospitalizations, and poor quality of life. Additional symptoms such as sleep disturbances, fatigue, and stress are also common. Non-traditional approaches are often used by families, but concerns remain that patients may forgo standard of care effective therapies in favor of dangerous unproven alternatives. OBJECTIVES: To describe a single center experience related to a multidisciplinary integrative medicine clinic within the division of hematology dedicated to children and young adults with SCD. METHODS: The Sickle Cell Integrative Clinic at Children's National Hospital services patients with SCD. The main goal of this clinic is to provide access to non-pharmacologic interventions, and to manage patients' symptoms in a holistic manner along with standard of care management of SCD. This IRB approved study evaluated experiences of both patients and parents who attended this clinic. RESULTS: Thirty-seven unique patients attended this clinic over 2 years and 31 participated in the study. After attending the SCD integrative clinic, the majority of patients reported integrative therapies to be an acceptable way of treating pain and believed these to be effective. Overall, the vast majority (88 %) of patients reported having a positive experience with the therapies offered in the clinic. None of the patients experienced any adverse events related to integrative therapies provided in the clinic. CONCLUSION: Our experience suggests that encouraging conversations and offering safe and potentially effective integrative therapies alongside conventional SCD therapies under medical guidance allows patients to have an open discussion about their beliefs and treatment goals, improves patient satisfaction and can improve outcomes.


Assuntos
Anemia Falciforme , Medicina Integrativa , Adolescente , Anemia Falciforme/terapia , Criança , Humanos , Dor/etiologia , Manejo da Dor , Qualidade de Vida , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-33483833

RESUMO

Calcium-activated potassium (KCa) channels contribute to multiple neuronal properties including spike frequency and afterhyperpolarizing potentials (AHPs). KCa channels are classified as KCa1.1, KCa2, or KCa3.1 based on single-channel conductance and pharmacology. Ca2+-dependent AHPs in vertebrates are categorized as fast, medium, or slow. Fast and medium AHPs are generated by KCa1.1 and KCa2 channels, respectively. The KCa subtype responsible for slow AHPs is unclear. Prolonged, Ca2+-dependent AHPs have been described in several leech neurons. Unfortunately, apamin and other KCa blockers often prove ineffective in the leech. An alternative approach is to utilize KCa modulators, which alter channel sensitivity to Ca2+. Vertebrate KCa2 channels are targeted selectively by the positive modulator CyPPA and the negative modulator NS8593. Here we show that AHPs in identified motor and mechanosensory leech neurons are enhanced by CyPPA and suppressed by NS8593. Our results indicate that KCa2 channels underlie prolonged AHPs in these neurons and suggest that KCa2 modulators may serve as effective tools to explore the role of KCa channels in leech physiology.


Assuntos
Hirudo medicinalis/efeitos dos fármacos , Hirudo medicinalis/fisiologia , 1-Naftilamina/análogos & derivados , 1-Naftilamina/farmacologia , Animais , Cálcio/metabolismo , Potenciais da Membrana , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Canais de Potássio Cálcio-Ativados/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia
6.
Pediatr Blood Cancer ; 66(9): e27823, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31131984

RESUMO

BACKGROUND: Pain is a major complication of sickle cell disease (SCD), spanning vaso-occlusive crises and persistent pain. Although it is known that persistent pain is associated with considerable impairment in youth without SCD, little is known about the functional effects of persistent pain in SCD. The current study aimed to (a) characterize persistent pain in youth with SCD and (b) determine the extent to which youth with SCD and persistent pain differ in disease morbidity, functional impairment, and neurocognitive and psychological functioning. PROCEDURE: Eighty-nine participants (ages 7-16) and caregivers completed questionnaires (BRIEF [Behavior Rating Inventory of Executive Function], Conners-3 [Conners-third edition], and PedsQL™-SCD Module, where PedsQL is Pediatric Quality of Life Inventory). Participants completed neurocognitive tests WISC-V [Wechsler Intelligence Scale for Children-fifth edition], WJ-III [Woodcock Johnson Tests of Achievement-third edition], and WIAT-III [Wechsler Individual Achievement Test-third edition]). Youth were classified as having persistent pain if they reported daily pain for 7 days. Chi-square and independent sample t-test analyses were used to assess group differences (those with vs without persistent pain). RESULTS: Patients with persistent pain (n = 18) reported lower health-related quality of life (P = .000). Caregivers were more likely to rate youth with persistent pain as having lower planning/organization abilities (P = .011) and clinically elevated symptoms of defiance/aggression and oppositional defiance (Ps = .00; .01). Patients with persistent pain demonstrated poorer working memory (P = .023) and processing speed (P = .027), and fewer demonstrating reading fluency abilities in the average or above range (P = .026). CONCLUSIONS: Youth with SCD and persistent pain are at risk for psychosocial and neurocognitive impairments, suggesting that persistent pain may be an important indicator of disease burden. Furthermore, disease management may be enhanced by assessing cognitive and psychosocial functioning and incorporating interdisciplinary treatments addressing impairment associated with persistent pain.


Assuntos
Anemia Falciforme , Disfunção Cognitiva , Transtornos da Memória , Dor , Qualidade de Vida , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/fisiopatologia , Anemia Falciforme/psicologia , Cuidadores , Criança , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Testes de Estado Mental e Demência , Dor/epidemiologia , Dor/etiologia , Dor/fisiopatologia , Dor/psicologia , Inquéritos e Questionários
7.
Nutrients ; 11(3)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30870970

RESUMO

Although some studies have demonstrated the beneficial effects of watermelon supplementation on metabolic diseases, no study has explored the potential mechanism by which watermelon consumption improves body weight management. The objective of this study was to evaluate the effects of fresh watermelon consumption on satiety, postprandial glucose and insulin response, and adiposity and body weight change after 4 weeks of intervention in overweight and obese adults. In a crossover design, 33 overweight or obese subjects consumed watermelon (2 cups) or isocaloric low-fat cookies daily for 4 weeks. Relative to cookies, watermelon elicited more (p < 0.05) robust satiety responses (lower hunger, prospective food consumption and desire to eat and greater fullness). Watermelon consumption significantly decreased body weight, body mass index (BMI), systolic blood pressure and waist-to-hip ratio (p ≤ 0.05). Cookie consumption significantly increased blood pressure and body fat (p < 0.05). Oxidative stress was lower at four week of watermelon intervention compared to cookie intervention (p = 0.034). Total antioxidant capacity increased with watermelon consumption (p = 0.003) in blood. This study shows that reductions in body weight, body mass index (BMI), and blood pressure can be achieved through daily consumption of watermelon, which also improves some factors associated with overweight and obesity (clinicaltrials.gov, NCT03380221).


Assuntos
Citrullus , Sobrepeso/dietoterapia , Resposta de Saciedade , Adolescente , Adulto , Apetite , Glicemia , Pressão Sanguínea , Peso Corporal , Estudos Cross-Over , Exercício Físico , Feminino , Humanos , Hiperglicemia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
8.
FEBS Lett ; 593(7): 732-742, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30821397

RESUMO

Dysfunction of the dopaminergic pathway is linked to numerous diseases of the nervous system. The D1-D2 receptor heteromer is known to play a role in certain neuropsychiatric disorders, such as depression. Here, we synthesized an eight amino acid residue peptide, EAARRAQE, derived from the third intracellular loop of the D2 receptor and show that the peptide binds to the D1 receptor with comparable efficiency as that of the full-length D2 receptor protein. Moreover, immunoprecipitation studies show the existence of a heteromeric complex formed both in vitro and in total protein derived from temporal and frontal lobe tissue from normal and depressed subjects. The efficiency of the peptide to block the D1-D2 heteromeric complex was comparable in all the samples tested.


Assuntos
Antagonistas dos Receptores de Dopamina D2/farmacologia , Neurônios/metabolismo , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Animais , Mapeamento Encefálico , Depressão/genética , Depressão/patologia , Dopamina/genética , Dopamina/metabolismo , Antagonistas dos Receptores de Dopamina D2/síntese química , Lobo Frontal/metabolismo , Humanos , Imunoprecipitação , Neurônios/efeitos dos fármacos , Neurônios/patologia , Peptídeos/síntese química , Peptídeos/farmacologia , Ligação Proteica/genética , Ratos , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D2/química , Lobo Temporal/metabolismo
9.
J Nurs Manag ; 26(7): 881-887, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29675870

RESUMO

AIM: To examine clinical leadership of registered nurses in an emergency department, based on evidence that it is important for nurses to feel psychologically and structurally empowered in order to act as clinical leaders. BACKGROUND: Every registered nurse has the ability to act as a clinical leader. Clinical leadership is the registered nurse's behaviours that provide direction and support to patients and the team in the delivery of patient care. This study explores the connection between the need for structural and psychological empowerment and clinical leadership behaviours. METHODS: A mixed method, non-experimental survey design was used to examine the psychological empowerment, structural empowerment and clinical leadership of registered nurses working in an emergency department. RESULTS: Emergency department nurses believe they show clinical leadership behaviours most of the time, even though their sense of being psychologically empowered is only moderate. CONCLUSION: While registered nurses believe they perform clinical leadership behaviours, it is also clear that improvements in structural and psychological empowerment would improve their ability to act as clinical leaders. IMPLICATIONS FOR NURSING MANAGEMENT: The results show that for nurses to be able to provide clinical leadership to their patients and colleagues, management must create empowering environments.


Assuntos
Liderança , Enfermeiros Administradores/normas , Enfermeiras e Enfermeiros/psicologia , Poder Psicológico , Autonomia Profissional , Adulto , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Enfermeiros Administradores/psicologia , Inquéritos e Questionários
10.
Psychiatry Res ; 234(3): 336-45, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26490568

RESUMO

We aimed to characterize the extent to which there were differences in neural activation between female participants who were diagnosed with or without depression while viewing negative and neutral imagery. The study enrolled 105 medication-free, right-handed female participants between 17 and 63 years who met criteria for current Major Depressive Disorder (n=47) or no prior psychiatric diagnoses (n=58). All participants completed a clinical assessment and underwent a functional Magnetic Resonance Imaging (fMRI) scan while responding to an implicit affect task that required them to identify the location of ideographs embedded in one of four corners of each valenced image. When unpleasant (termed negative) stimuli were presented, depressed relative to healthy participants showed significantly decreased activation of the left amygdala and right Inferior Parietal Lobe (IPL). When activation was assessed during the negative versus neutral condition, depressed relative to healthy participants showed significantly increased activation in the Anterior Cingulate Cortex (ACC) and the left IPL. Notably, within-group analyses of healthy participants under the negative condition showed that depressive severity was positively correlated with activation in the left amygdala and left IPL. Our findings suggest that depression influences bottom-up and top-down processing of unpleasant information.


Assuntos
Afeto , Tonsila do Cerebelo/patologia , Transtorno Depressivo Maior/psicologia , Imageamento por Ressonância Magnética/métodos , Lobo Parietal/fisiopatologia , Adulto , Estudos de Casos e Controles , Depressão/psicologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos
11.
J Psychiatr Res ; 68: 384-91, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26070246

RESUMO

The extent to which affective reactivity and associated neural underpinnings are altered by depression remains equivocal. This study assessed striatal activation in fifty-one unmedicated female participants meeting DSM-IV criteria for Major Depressive Disorder (MDD) and 61 age-matched healthy females (HC) aged 17-63 years. Participants completed an affective reactivity functional magnetic resonance imaging task. Data were preprocessed using SPM8, and region-of-interest analyses were completed using MarsBaR to extract caudate, putamen, and nucleus accumbens (NAcc) activation. General linear repeated measure ANOVAs were used to assess group differences and correlational analyses were used to measure the association between activation, depression severity, and anhedonia. Main effects of hemisphere, valence, and group status were observed, with MDD participants demonstrating decreased striatal activation compared with HC. Across groups and valence types, the left hemisphere demonstrated greater activation than the right hemisphere in the putamen and nucleus accumbens, whereas the right hemisphere demonstrated greater activation than the left in the caudate. Additionally, unpleasant stimuli elicited greater activation than pleasant and neutral stimuli in the caudate and putamen, and unpleasant stimuli elicited greater activation than neutral stimuli in the NAcc. There were no significant associations between activation, depression severity, and anhedonia. Overall, depression was characterized by reduced affective reactivity in the striatum, regardless of stimuli valence, supporting the emotion context insensitivity model of depression.


Assuntos
Anedonia/fisiologia , Corpo Estriado/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Lateralidade Funcional/fisiologia , Imageamento por Ressonância Magnética/métodos , Índice de Gravidade de Doença , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
12.
Biol Psychol ; 109: 184-91, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26073417

RESUMO

BACKGROUND: The functional localization of negativity bias, an influential index of emotion information processing, has yet to be identified. METHOD: Depressed (n=47) and healthy participants (n=58) completed a clinical interview for DSM-IV Axis I disorders, symptom checklists, a behavioral task to measure negativity bias, and then viewed positive and negative images of social and nonsocial scenes during an event-related fMRI task. Two subsamples of participants with high (i.e., 75%; n=26) and low (i.e., 25%; n=26) negativity bias scores were as included in subsequent analyses to examine neural differences. RESULTS: Depressed participants with a higher, relative to lower, negative bias showed significantly greater neural activation in the left inferior frontal gyrus. CONCLUSION: High negativity bias evokes a distinctive pattern of brain activation in the frontal cortex of depressed participants. Increased activation occurred in the left inferior frontal gyrus, related to Brodmann area 44, which is associated with language and semantic processing, response inhibition, and cognitive reappraisal. This finding may reflect an abnormality in integrative emotional processing rather than processing of individual emotional dimensions in depressed participants with negativity bias.


Assuntos
Afeto/fisiologia , Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologia , Adulto Jovem
13.
Depress Anxiety ; 31(7): 559-65, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23798350

RESUMO

BACKGROUND: We used a dot-probe paradigm to examine attention bias toward threat (i.e., angry) and happy face stimuli in severe mood dysregulation (SMD) versus healthy comparison (HC) youth. The tendency to allocate attention to threat is well established in anxiety and other disorders of negative affect. SMD is characterized by the negative affect of irritability, and longitudinal studies suggest childhood irritability predicts adult anxiety and depression. Therefore, it is important to study pathophysiologic connections between irritability and anxiety disorders. METHODS: SMD patients (N = 74) and HC youth (N = 42) completed a visual probe paradigm to assess attention bias to emotional faces. Diagnostic interviews were conducted and measures of irritability and anxiety were obtained in patients. RESULTS: SMD youth differed from HC youth in having a bias toward threatening faces (P < .01). Threat bias was positively correlated with the severity of the SMD syndrome and depressive symptoms; degree of threat bias did not differ between SMD youth with and without co-occurring anxiety disorders or depression. SMD and HC youth did not differ in bias toward or away from happy faces. CONCLUSIONS: SMD youth demonstrate an attention bias toward threat, with greater threat bias associated with higher levels of SMD symptom severity. Our findings suggest that irritability may share a pathophysiological link with anxiety and depressive disorders. This finding suggests the value of exploring further whether attention bias modification treatments that are effective for anxiety are also helpful in the treatment of irritability.


Assuntos
Ira/fisiologia , Transtornos de Ansiedade/fisiopatologia , Atenção/fisiologia , Expressão Facial , Humor Irritável/fisiologia , Transtornos do Humor/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
14.
Am J Psychiatry ; 170(10): 1186-94, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23732841

RESUMO

OBJECTIVE: Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation. METHOD: The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions. RESULTS: Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group's responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups. CONCLUSIONS: In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.


Assuntos
Encéfalo/fisiopatologia , Frustração , Interpretação de Imagem Assistida por Computador , Humor Irritável/fisiologia , Imageamento por Ressonância Magnética , Transtornos do Humor/fisiopatologia , Adolescente , Tonsila do Cerebelo/fisiopatologia , Atenção/fisiologia , Mapeamento Encefálico , Criança , Doença Crônica , Manual Diagnóstico e Estatístico de Transtornos Mentais , Dominância Cerebral/fisiologia , Retroalimentação Psicológica , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Neostriado/fisiopatologia , Orientação/fisiologia , Lobo Parietal/fisiopatologia , Valores de Referência
15.
Am J Psychiatry ; 169(6): 633-41, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22581312

RESUMO

OBJECTIVE: Despite increased interest in the developmental trajectory of the pathophysiology mediating bipolar disorder, few studies have compared adults and youths with bipolar disorder. Deficits in motor inhibition are thought to play an important role in the pathophysiology of the illness across the age spectrum. The authors compared the neural circuitry mediating this process in bipolar youths relative to bipolar adults and in healthy volunteers. METHOD: Participants were pediatric (N=16) and adult (N=23) patients with bipolar disorder and healthy child (N=21) and adult (N=29) volunteers. Functional MRI (fMRI) data were acquired while participants performed the stop-signal task. RESULTS: During failed inhibition, an age group-by-diagnosis interaction manifested in the anterior cingulate cortex, with bipolar youths exhibiting hypoactivation relative to both healthy youths and bipolar adults, and bipolar adults exhibiting hyperactivation relative to healthy adults. During successful inhibition, a main effect of diagnosis emerged in the right nucleus accumbens and the left ventral prefrontal cortex, with bipolar patients in both age groups showing less activation than healthy subjects. CONCLUSIONS: Anterior cingulate cortex dysfunction during failed motor inhibition was observed in both bipolar youths and adults, although the nature of this dysfunction differed between the two groups. Adults and youths with bipolar disorder exhibited similar deficits in activation of the nucleus accumbens and the ventral prefrontal cortex during successful inhibition. Therefore, while subcortical and ventral prefrontal cortex hypoactivation was present in bipolar patients across the lifespan, anterior cingulate cortex dysfunction varied developmentally, with reduced activation in youths and increased activation in adults during failed inhibition. Longitudinal fMRI studies of the developmental trajectory of the neural circuitry mediating motor inhibition in bipolar disorder are warranted.


Assuntos
Transtorno Bipolar/fisiopatologia , Inibição Neural/fisiologia , Adolescente , Adulto , Fatores Etários , Corpo Estriado/fisiopatologia , Feminino , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Desempenho Psicomotor
16.
Prog Neuropsychopharmacol Biol Psychiatry ; 38(2): 127-33, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22414616

RESUMO

BACKGROUND: A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD. METHODS: 19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3 T scanner. RESULTS: Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups. CONCLUSIONS: Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task.


Assuntos
Transtorno Bipolar/fisiopatologia , Corpo Estriado/fisiopatologia , Inibição Psicológica , Desempenho Psicomotor/fisiologia , Adolescente , Atenção/fisiologia , Mapeamento Encefálico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tempo de Reação/fisiologia , Risco
17.
Biol Psychol ; 89(1): 148-55, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22008364

RESUMO

Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations.


Assuntos
Transtorno Bipolar/patologia , Transtorno Bipolar/psicologia , Giro do Cíngulo/fisiopatologia , Inibição Psicológica , Humor Irritável/fisiologia , Atividade Motora/fisiologia , Adolescente , Análise de Variância , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Mapeamento Encefálico , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Transtornos do Humor , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Detecção de Sinal Psicológico/fisiologia
18.
J Psychiatr Res ; 46(1): 22-30, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22024484

RESUMO

BACKGROUND: Youth with bipolar disorder (BD) show behavioral and neural deficits in cognitive flexibility; however, whether such deficits exist among youths at risk for BD has not been explored. METHODS: The current fMRI study examined the neural basis of cognitive flexibility in BD youth (n = 28), unaffected youth at risk for BD (AR; n = 13), and healthy volunteer youth (HV; n = 21) by comparing brain activation patterns while participants performed the change task. On change trials, subjects must inhibit a prepotent response and execute an alternate one. RESULTS: During successful change trials, both BD and AR youth had increased right ventrolateral prefrontal and inferior parietal activity, compared to HV youth. During failed change trials, both BD and AR youth exhibited increased caudate activation relative to HV youth, but BD youth showed increased activation in the subgenual anterior cingulate cortex (ACC) relative to the other two groups. CONCLUSIONS: Abnormal activity in ventrolateral prefrontal cortex, inferior parietal cortex, and striatum during a cognitive flexibility task may represent a potential BD endophenotype, but subgenual ACC dysfunction may represent a marker of BD illness itself.


Assuntos
Transtorno Bipolar/complicações , Mapeamento Encefálico , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Adolescente , Análise de Variância , Atenção , Transtorno Bipolar/genética , Encéfalo/irrigação sanguínea , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Escalas de Graduação Psiquiátrica , Tempo de Reação
19.
Neurosci Lett ; 484(1): 30-4, 2010 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-20705119

RESUMO

Sibutramine hydrochloride monohydrate is the only centrally active weight-modifying agent currently approved by the FDA for long-term use in the treatment of obesity. Systemic sibutramine treatment has been shown to reduce food intake in humans and rodent models in a manner that is consistent with the enhancement of satiety mechanisms. Although it is generally assumed that the hypophagic effects of the drug are mediated by actions within the brain, the locus or loci of these effects remains unclear. These experiments compared the effects of systemic and intracranial injections of sibutramine on the intake of a palatable diet in non-deprived animals. Consistent with prior reports, systemic injections of sibutramine hydrochloride (at 0, 0.5, 1.0, or 3.0mg/kg sibutramine i.p.) dose-dependently reduced feeding on a high fat/high sucrose diet across a 2-h feeding session, but did not alter water intake or locomotor activity. In contrast, bilateral injections of sibutramine (at 0.0, 2.0, 4.0 and 10.0µg/0.5µl/side) into either the paraventricular nucleus of the hypothalamus (PVN) or the medial nucleus accumbens shell (ACb) significantly and dose-dependently increased food intake of the sweetened fat diet. ACb treatment also modestly inhibited locomotor behavior; intracranial injections had no effect on water consumption. These experiments are the first to suggest that sibutramine treatment may have distinct actions upon separate neural circuits that modulate food intake behavior in the rat.


Assuntos
Ciclobutanos/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Análise de Variância , Animais , Depressores do Apetite/administração & dosagem , Dieta , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
20.
Behav Neurosci ; 123(5): 1046-57, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19824770

RESUMO

Substantial evidence suggests that pharmacological manipulations of neural serotonin pathways influence ingestive behaviors. Despite the known role of the nucleus accumbens in directing appetitive and consummatory behavior, there has been little examination of the influences that serotonin receptors may play in modulating feeding within nucleus accumbens circuitry. In these experiments, the authors examined the effects of bilateral nucleus accumbens infusions of the 5-HT1/7 receptor agonist 5-CT (at 0.0, 0.5, 1.0, or 4.0 microg/0.5 microl/side), the 5-HT receptor agonist EMD 386088 (at 0.0, 1.0, and 4.0 microg/0.5 microl/side), or the 5-HT2C preferential agonist RO 60-0175 (at 0.0, 2.0, or 5.0 microg/0.5 microl/side) on food intake and locomotor activity in the rat. Intra-accumbens infusions of 5-CT caused a dose-dependent reduction of food intake and rearing behavior, both in food-restricted animals given 2-hr free access to Purina Protab RMH 3000 Chow, as well as in nondeprived rats offered 2-hr access to a highly palatable fat/sucrose diet. In contrast, stimulation of 5-HT receptors with EMD 386088 caused a dose-dependent increase of intake under both feeding conditions, without affecting measures of locomotion. Infusions of the moderately selective 5-HT2C receptor agonist RO 60-0175 had no effects on feeding or locomotor measures in food-restricted animals, but did reduce intake of the fat/sucrose in nonrestricted animals at the 2.0 microg, but not the 5.0 microg dose. Intra-accumbens infusions of selective antagonists for the 5-HT (SB 269970), 5-HT (SB 252585), and 5-HT2C (RS 102221) receptors did not affect locomotion, and demonstrated no lasting changes in feeding for any of the groups tested. These data are the first to suggest that the activation of different serotonin receptor subtypes within the feeding circuitry of the medial nucleus accumbens differentially influence consummatory behavior.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Análise de Variância , Animais , Dieta , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Ingestão de Alimentos/fisiologia , Privação de Alimentos , Masculino , Atividade Motora/fisiologia , Núcleo Accumbens/fisiologia , Ratos , Ratos Sprague-Dawley
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