QTc Interval Prolongation and Its Association With Electrolyte Abnormalities and Psychotropic Drug Use Among Patients With Eating Disorders.

Background: Eating disorders (EDs) often develop during adolescence with high mortality rates. Sudden cardiac death in these patients has been associated with corrected QT (QTc) interval prolongation. The significance of extrinsic factors on QTc prolongation in populations with EDs remains controversial. This study assessed the relationship between QTc prolongation in paediatric patients with EDs and extrinsic factors, such as QTc-prolonging medications and electrolyte abnormalities to investigate whether an ED alone is associated with an increased prevalence of QTc prolongation. Methods: Electrocardiograms, electrolytes, and psychopharmaceutical usage were retrospectively analysed from the charts of 264 paediatric patients with EDs. Descriptive statistics were used to assess QTc prolongation and its relationship with electrolyte abnormalities and psychopharmaceuticals. Results: Of 264 patients, 227 had normal QTc intervals (<440 ms), whereas 37 had borderline prolonged (440-460 ms) or prolonged (>460 ms) intervals. The prevalence of QTc intervals exceeding 440 ms in patients with normal electrolytes and not using QTc-prolonging psychotropics mirrored that of the general population (P = 0.59). Of the 23 patients taking psychotropics, 8 had abnormal QTc intervals. The average QTc was greater for patients using QTc-prolonging psychotropics (P = 0.05) with a correlation between interval length and psychotropic usage (P < 0.01). Average potassium (P = 0.08), calcium (P = 0.18), and magnesium (P = 0.08) levels did not significantly differ between those with normal and abnormal QTc intervals. Conclusions: This study suggests that EDs alone may not prolong QTc intervals in paediatric patients with EDs, but psychotropics appear to be a salient external factor in QTc prolongation.

Contexte: Les troubles des conduites alimentaires (TCA) surviennent surtout au cours de l'adolescence et entraînent un taux de mortalité élevé. Chez ces patients, la mort subite d'origine cardiaque a été associée à un allongement de l'intervalle QT corrigé (QTc). La portée des facteurs extrinsèques sur l'allongement de cet intervalle chez les patients atteints de TCA demeure un sujet controversé. La présente étude visait à évaluer la relation entre l'allongement de l'intervalle QTc chez les enfants atteints de TCA et des facteurs extrinsèques, comme la prise de médicaments causant l'allongement de l'intervalle QTc et les anomalies électrolytiques, pour déterminer si la présence d'un TCA est à elle seule associée à une prévalence élevée d'allongement de l'intervalle QTc. Méthodologie: Nous avons analysé rétrospectivement les électrocardiogrammes, les valeurs d'électrolytes et l'utilisation de médicaments psychotropes dans les dossiers de 264 enfants atteints de TCA. Des techniques de statistique descriptive ont été utilisées pour analyser l'allongement de l'intervalle QTc et les liens avec les anomalies électrolytiques et les médicaments psychotropes. Résultats: Parmi les 264 patients, 227 présentaient un intervalle QTc normal (< 440 ms) et 37 présentaient des résultats limites (440 à 460 ms) ou un allongement de l'intervalle (> 460 ms). La prévalence d'un intervalle QTc de 440 ms ou plus chez les patients présentant des taux d'électrolytes normaux et non traités par des médicaments psychotropes causant l'allongement de l'intervalle QTc était semblable à la prévalence dans la population générale (p = 0,59). Huit des 23 patients traités par des médicaments psychotropes présentaient un intervalle QTc anormal. La moyenne des intervalles QTc était supérieure dans le groupe des patients recevant des médicaments psychotropes causant un allongement de l'intervalle QTc (p = 0,05), et il existait une corrélation entre la durée de l'intervalle et de l'usage de médicaments psychotropes (p < 0,01). Les taux moyens de potassium (p = 0,08), de calcium (p = 0,18) et de magnésium (p = 0,08) ne différaient pas de façon significative entre les groupes présentant des intervalles QTc normaux et anormaux. Conclusions: Les résultats de notre étude donnent à penser que le TCA à lui seul ne provoque pas l'allongement de l'intervalle QTc chez les enfants qui en sont atteints, mais que l'utilisation de médicaments psychotropes constitue un facteur externe important dans l'allongement de l'intervalle QTc.

Modeling spinal locomotor circuits for movements in developing zebrafish.

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion.

The spinal cord is a column of nerve tissue that connects the brain to the rest of the body in vertebrate animals. Nerve cells in the spinal cord, called neurons, help to control and coordinate the body's movements. As the spinal cord develops, new neurons are born and new connections are made between neurons and muscles, resulting in more coordinated and skillful movements as time goes on. Zebrafish, for example, display body-bending maneuvers called coils within 24 hours of the egg being fertilized. Next, bursts of swimming movements emerge, which are driven by sporadic tail beats. These tail maneuvers become more consistent as the fish develops, and eventually result in smooth movements called beat-and-glide swimming. The groups of spinal cord neurons that appear at each stage of zebrafish development have been characterized, but it remains unclear how newly formed circuits (groups of neurons recently connected to each other) work together to produce swimming maneuvers. To answer this question, Roussel et al. simulated changes in the spinal cord that help zebrafish acquire new swimming movements as they grow. The computer models encoded neural circuits based on cell populations identified in experimental studies, and replicated swimming behaviors that emerge during the first few days of zebrafish development. Simulations tested how specific neural circuits generate the characteristic swimming movements that represent key developmental milestones in zebrafish. The results showed that adding new neurons and more cell-to-cell connections led to increasingly sophisticated swimming maneuvers. As the zebrafish spinal cord matured, the fish were better able to control the pace and duration of their swimming movements. Roussel et al. also identified specific patterns of neural activity linked to particular maneuvers. For example, tail beats switch direction when neurons on one side of the spinal cord excite neurons on the opposite side. This activity, which becomes more rhythmic, also needs to be exquisitely timed to produce and coordinate the right motion. Roussel et al.'s modelling of developmental milestones in growing zebrafish provides insights into how neural networks control movement. The computer models are among the first to accurately reproduce swimming behaviors in developing zebrafish. More experimental data could be added to the models to capture the full range of early zebrafish movements, and to further investigate how maturing spinal cord circuits control swimming. Since zebrafish and mammals have many spinal neurons in common, further research may aid our understanding of movement disorders in humans.