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1.
Neuropsychopharmacology ; 45(2): 266-275, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546248

RESUMO

The risky decision-making task (RDT) measures risk-taking in a rat model by assessing preference between a small, safe reward and a large reward with increasing risk of punishment (mild foot shock). It is well-established that dopaminergic drugs modulate risk-taking; however, little is known about how differences in baseline phasic dopamine signaling drive individual differences in risk preference. Here, we used in vivo fixed potential amperometry in male Long-Evans rats to test if phasic nucleus accumbens shell (NACs) dopamine dynamics are associated with risk-taking. We observed a positive correlation between medial forebrain bundle-evoked dopamine release in the NACs and risky decision-making, suggesting that risk-taking is associated with elevated dopamine sensitivity. Moreover, "risk-taking" subjects were found to demonstrate greater phasic dopamine release than "risk-averse" subjects. Risky decision-making also predicted enhanced sensitivity to the dopamine reuptake inhibitor nomifensine, and elevated autoreceptor function. Importantly, this hyperdopaminergic phenotype was selective for risky decision-making, as delay discounting performance was not predictive of phasic dopamine release or dopamine supply. These data identify phasic NACs dopamine release as a possible therapeutic target for alleviating the excessive risk-taking observed across multiple forms of psychopathology.

2.
eNeuro ; 6(4)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31387878

RESUMO

The majority of the research studying punishment has focused on an aversive stimulus delivered immediately after an action. However, in real-world decision-making, negative consequences often occur long after a decision has been made. This can engender myopic decisions that fail to appropriately respond to consequences. Whereas discounting of delayed rewards has been well studied in both human and animal models, systematic discounting of delayed consequences remains largely unexplored. To address this gap in the literature, we developed the delayed punishment decision-making task. Rats chose between a small, single-pellet reinforcer and a large, three-pellet reinforcer accompanied by a mild foot shock. The shock was preceded by a delay, which systematically increased throughout the session (0, 4, 8, 12, 16 s). On average, rats discounted the negative value of delayed punishment, as indicated by increased choice of the large, punished reward as the delay preceding the shock lengthened. Female rats discounted delayed punishment less than males, and this behavior was not influenced by estrous cycling. The addition of a cue light significantly decreased the undervaluation of delayed consequences for both sexes. Finally, there was no correlation between the discounting of delayed punishments and a traditional reward delay discounting task for either sex. These data indicate that the ability of punishment to regulate decision-making is attenuated when punishment occurs later in time. This task provides an avenue for exploration of the neural circuitry underlying the devaluation of delayed punishment and may assist in developing treatments for substance use disorders.

3.
Behav Brain Res ; 359: 579-588, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30296531

RESUMO

Excessive risk-taking is common in multiple psychiatric conditions, including substance use disorders. The risky decision-making task (RDT) models addiction-relevant risk-taking in rats by measuring preference for a small food reward vs. a large food reward associated with systematically increasing risk of shock. Here, we examined the relationship between risk-taking in the RDT and multiple addiction-relevant phenotypes. Risk-taking was associated with elevated impulsive action, but not impulsive choice or habit formation. Furthermore, risk-taking predicted locomotor sensitivity to first-time nicotine exposure and resilience to nicotine-evoked anxiety. These data demonstrate that risk preference in the RDT predicts other traits associated with substance use disorder, and may have utility for identification of neurobiological and genetic biomarkers that engender addiction vulnerability.


Assuntos
Tomada de Decisões , Comportamento Impulsivo , Atividade Motora/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Assunção de Riscos , Animais , Ansiedade/induzido quimicamente , Comportamento Aditivo/psicologia , Hábitos , Masculino , Ratos Long-Evans , Transtornos Relacionados ao Uso de Substâncias/psicologia
4.
J Child Adolesc Psychopharmacol ; 28(7): 474-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29920116

RESUMO

BACKGROUND: Antipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known. METHODS: The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8. RESULTS: Treatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation ±3.51) kg for molindone, 4.13 ± 3.79 kg for risperidone, and 7.29 ± 3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change. CONCLUSION: We identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703.


Assuntos
Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Ganho de Peso
5.
Neuropsychopharmacology ; 43(2): 325-333, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28849779

RESUMO

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.


Assuntos
Ansiolíticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Ansiolíticos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Fobia Social , Escalas de Graduação Psiquiátrica , Adulto Jovem
6.
Sensors (Basel) ; 17(11)2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29099790

RESUMO

In search and rescue activities, unmanned aerial vehicles (UAV) should exploit sound information to compensate for poor visual information. This paper describes the design and implementation of a UAV-embedded microphone array system for sound source localization in outdoor environments. Four critical development problems included water-resistance of the microphone array, efficiency in assembling, reliability of wireless communication, and sufficiency of visualization tools for operators. To solve these problems, we developed a spherical microphone array system (SMAS) consisting of a microphone array, a stable wireless network communication system, and intuitive visualization tools. The performance of SMAS was evaluated with simulated data and a demonstration in the field. Results confirmed that the SMAS provides highly accurate localization, water resistance, prompt assembly, stable wireless communication, and intuitive information for observers and operators.

7.
Psychiatry Res ; 255: 248-255, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28595147

RESUMO

The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) compared the efficacy of risperidone, olanzapine, and molindone over 8 weeks in 119 youths age 8-19 years with early-onset schizophrenia or schizoaffective disorder. From this large dataset, we examined predictors of treatment response and drop out using stepwise regression and receiver operating characteristics curve (ROC) analysis. Treatment response was defined as having both a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) score and a Clinical Global Impression-Improvement (CGI-I) score < 3. More severe baseline symptoms, having a history of being in an early education program, and previous prescription of a mood stabilizer increased the likelihood of responding to treatment. Anhedonia and poor community functioning predicted a reduction in symptom severity on the PANSS. Random assignment to different antipsychotic treatment was not predictive of outcome. Parental report of aggressive behaviors at baseline and being African American were associated with a greater likelihood of drop out. Our results suggest youth with more severe psychotic symptoms are most likely to benefit from treatment with antipsychotics and that aggressive youth may require additional support to improve treatment adherence. Further investigation is needed to understand potentially modifiable predictors of response like early education programs.


Assuntos
Pacientes Desistentes do Tratamento/psicologia , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Método Duplo-Cego , Diagnóstico Precoce , Feminino , Humanos , Olanzapina , Valor Preditivo dos Testes , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Risperidona/uso terapêutico , Resultado do Tratamento
8.
Am J Orthod Dentofacial Orthop ; 136(4): 478.e1-7; discussion 478-80, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19815136

RESUMO

INTRODUCTION: The cervical vertebrae maturation (CVM) method has been advocated as a predictor of peak mandibular growth. This method relies on the clinician's ability to determine the stage of maturation of the vertebrae. Careful examination of reports of this technique shows methodologic flaws that can lead to inflated levels of reproducibility. The purpose of this study was to evaluate the reproducibility of CVM stage determination by using a more stringent methodology. METHODS: Ten practicing orthodontists, trained in the CVM method, evaluated 30 individual and 30 pairs of cephalometric radiographs in 2 sessions to determine the CVM stage. Interobserver and intraobserver reliability was determined by using the Kendall coefficient of concordance and the weighted kappa statistic. RESULTS: All degrees of interobserver and intraobserver agreement were moderate (Kendall's W, 0.4-0.8). Interobserver agreement levels for CVM staging of the 10 orthodontists at both times were below 50%. Agreement improved marginally with the use of 2 longitudinal radiographs. Intraobserver agreement was only slightly better; on average, clinicians agreed with their own staging only 62% of the time. CONCLUSIONS: Based on these results, we cannot recommend the CVM method as a strict clinical guideline for the timing of orthodontic treatment.


Assuntos
Determinação da Idade pelo Esqueleto/estatística & dados numéricos , Vértebras Cervicais/crescimento & desenvolvimento , Mandíbula/crescimento & desenvolvimento , Determinação da Idade pelo Esqueleto/métodos , Antropometria , Pesos e Medidas Corporais , Cefalometria/métodos , Cefalometria/estatística & dados numéricos , Vértebras Cervicais/anatomia & histologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Estudos Longitudinais , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes
9.
Infectología ; 6(12): 543-5, 548-50, dic. 1986. ilus
Artigo em Espanhol | LILACS | ID: lil-52819

RESUMO

Para el hombre, desde la concepción hasta su muerte, la nutrición es quizá el factor más frecuente e importante que afecta su salud. Durante la gestación el estado nutricional de la madre determina la buena evolución pre y posnatal, además de la resistencia óptima del individuo ante las enfermedades a lo largo de su vida, en relación a la susceptibilidad o resistencia. Las enfermedades de tipo infeccioso y la desnutrición condicionan un estado ambiguo en la relación huésped-parásito, en donde las manifestaciones clínicas son atípicas y de escasa intensidad. Esto dificulta el diagnóstico del proceso patológico y no permite concluir cuál situación dio origen a la enfermedad. Hoy día los estudios epidemiológicos han establecido la relación entre los procesos infecciosos y el estado nutricional deficiente, deduciendo que la desnutrición afecta de manera importante la eficacia de los mecanismos inmunes. Por su parte, la infección limita la energía metabólica del hospedeiro. En general morbilidad y mortalidad se relacionan en forma intrínseca con los factores del agente infeccioso, ambientes y del huésped


Assuntos
Infecções/complicações , Desnutrição Proteico-Calórica/complicações , Cobre/deficiência
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