Faculty Bibliography

Background: In ED patients who present with acute drug overdose, severe QTc prolongation (>500 ms) has been shown to be a predictor of adverse cardiovascular events (ACVE). However, it is unclear what clinical factors are associated with delayed severe QTc prolongation (dsQTp), and it is unknown whether dsQTp can predict ACVE. This study aims to: (1) Define clinical factors associated with dsQTp, and (2) test whether dsQTp is an independent predictor for ACVE.
Method(s): This was a prospective cohort study at 2 urban tertiary care EDs. Data was collected by trained research assistants, and included demographics, drug exposure, medication administration, initial and repeat ECG data, lab data, and outcome measures. dsQTp was defined as presence of initial QTc 499. The primary study outcome was the composite of ACVE defined as in-hospital occurrence of any of the following: MI, shock, ventricular dysrhythmia, and cardiac arrest. Univariate statistics and multivariable logistic regression calculations were made using SPSS version 24. With a fixed sample size of 1670, we calculated that we would have 99% power to show a 3-fold increase in risk with 0.05 alpha.
Result(s): Out of 2311 patients screened, 641 were excluded (age 500) leaving 1670 patients for analysis. The dsQTp group (N = 27) was found to be older than the control group (N = 1643)(40.1 vs 51.6, P
Conclusion(s): This cohort study reveals a subset of ED patients who are at greater risk of overdose-related ACVE but not immediately apparent by the initial ECG. Further study is needed to identify which patients are at risk for dsQTp, as they may require prolonged observation and repeated ECGs. Limitations include missing repeat QTc measurements, and inability to control for overdose severity as a surrogate for repeat ECGs. Future study is warranted to further characterize patients at risk for dsQTp to evaluate other exposure-related factors as yet undiscovered

Emotional lability and sensory sensitivity have been shown to contribute to the overall clinical picture in children with attention deficit hyperactivity disorder (ADHD; Dunn & Bennett, 2002; Sobanski et al., 2010). Further, both of these characteristics have been individually demonstrated to contribute to poorer quality of life, increased functional impairment, and poorer treatment response (Anastopoulos et al., 2010; Boterberg & Warreyn, 2016). However, to date, no study has evaluated the relationship among all three of these factors. The current study hypothesized that increased sensory sensitivity would moderate the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in youth. Results indicate that heightened sensory sensitivity strengthens the relationship between hyperactive/impulsive symptoms of ADHD and emotional lability in children with three or more clinically impairing ADHD symptoms. This dimensional approach was taken in accordance with growing evidence that even children with sub-threshold ADHD experience significant functional impairment and high rates of sensory sensitivity (Hong et al., 2014). These findings suggest that clinicians treating children with ADHD symptoms and emotional lability should consider assessing for sensory sensitivity as integration of multi-sensory techniques or referral to concurrent occupational therapy may significantly improve treatment outcomes and quality of life for these children and their families.

Clinical high-risk (CHR) individuals have been increasingly utilized to investigate the prodromal phases of psychosis and progression to illness. Research has identified medial and lateral temporal lobe abnormalities in CHR individuals. Dysfunction in the medial temporal lobe, particularly the hippocampus, is linked to dysregulation of glutamate and dopamine via a hippocampal-striatal-midbrain network that may lead to aberrant signaling of salience underpinning the formation of delusions. Similarly, lateral temporal dysfunction may be linked to the disorganized speech and language impairments observed in the CHR stage. Here, we summarize the significance of these neurobiological findings in terms of emergent psychotic symptoms and conversion to psychosis in CHR populations. We propose key questions for future work with the aim to identify the neural mechanisms that underlie the development of psychosis.

The dentate gyrus (DG) and its primary cell type, the granule cell (GC), are thought to be critical to many cognitive functions. A major neuronal subtype of the DG is the hilar mossy cell (MC). MCs have been considered to play an important role in cognition, but in vivo studies to understand the activity of MCs during cognitive tasks are challenging because the experiments usually involve trauma to the overlying hippocampus or DG, which kills hilar neurons. In addition, restraint typically occurs, and MC activity is reduced by brief restraint stress. Social isolation often occurs and is potentially confounding. Therefore, we used c-fos protein expression to understand when MCs are active in vivo in socially housed adult C57BL/6 mice in their home cage. We focused on c-fos protein expression after animals explored novel objects, based on previous work which showed that MCs express c-fos protein readily in response to a novel housing location. Also, MCs are required for the training component of the novel object location task and novelty-encoding during a food-related task. GluR2/3 was used as a marker of MCs. The results showed that MC c-fos protein is greatly increased after exposure to novel objects, especially in ventral DG. We also found that novel objects produced higher c-fos levels than familiar objects. Interestingly, a small subset of neurons that did not express GluR2/3 also increased c-fos protein after novel object exposure. In contrast, GCs appeared relatively insensitive. The results support a growing appreciation of the role of the DG in novelty detection and novel object recognition, where hilar neurons and especially MCs are very sensitive.