Increased Fear Response to Contextual Cues in Mice Lacking the 5-HT1A Receptor

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Repetitive concussive traumatic brain injury interacts with post-injury foot shock stress to worsen social and depression-like behavior in mice.

The debilitating effects of repetitive concussive traumatic brain injury (rcTBI) have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning) following brain injury (rcTBI). rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury

Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders

Although an influence of adult neurogenesis in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this form of plasticity may contribute to psychiatric disorders such as anxiety and depression. One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders. Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete, non-overlapping representations. Here we propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders, specifically post-traumatic stress disorder and panic disorder, and therefore represents an endophenotype for these disorders. The development of new, pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits

Social recognition test with previously cued fear conditioned mice.

<p>Time spent interacting with a stimulus mouse over 9 one-minute habituation sessions and a one-minute novel stimulus mouse session. Three-way ANOVA shows significant main effects of injury (p=0.004), shock (p=0.001), and time (p=0.000) during habituation. In the novel stimulus session, planned comparison t-tests show significant differences between rcTBI, shocked and rcTBI, not shocked (p=0.017, *); rcTBI, shocked and sham, shocked (p=0.000, ***); but not between sham, shocked and sham, not shocked (p=0.527, n.s.). Error bars represent SEM.</p

Cued fear conditioning and extinction.

<p>Error bars represent SEM. A) Freezing prior to (“p” tick mark) and during the 5 conditioned tones per day on testing days 1-4. Each point represents freezing during a 30 sec. period. B) Total freezing during tones on testing days 1-4 during a total of 20 tone presentations. 2-way ANOVA shows a main effect of shock (p<0.001), but no main effect of injury (p=0.349). Bonferroni post-hoc testing shows no significant difference between rcTBI, shocked and sham, shocked (p=0.340, n.s.), or rcTBI not shocked and uninjured sham, not shocked (p=1.000, n.s.).</p

Tail Suspension Test with previously cued fear conditioned mice.

<p>Time spent immobile during a 6 minute test. Two-way ANOVA shows a significant main effect of injury (p<0.001), shock (p=0.048), and a significant interaction between injury and shock (p=0.033). Bonferroni post hoc testing shows a significant difference between immobility time in rcTBI, shocked and rcTBI, not shocked (p=0.031), rcTBI, shocked and sham, shocked (p<0.001), and rcTBI, not shocked and sham, not shocked (p=0.012), but no difference between sham, shocked and sham, not shocked (p=1.000, n.s.). Error bars represent SEM.</p

Tail Suspension Test with previously context fear conditioned mice.

<p>Time spent immobile during a 6 minute test. Two-way ANOVA shows a significant main effect of injury (p<0.001), shock (p=0.041), and a significant interaction between injury and shock (p=0.042). Bonferroni post hoc testing shows a significant difference between immobility time in rcTBI, shocked and rcTBI, not shocked (p=0.044), rcTBI, shocked and sham, shocked (p<0.001), and rcTBI, not shocked and sham, not shocked (p=0.027), but no difference between sham, shocked and sham, not shocked (p=1.000, n.s.). Error bars represent SEM.</p

rcTBI Behavior Archive

This zip file includes the raw behavioral and histological data reported in the paper "Repetitive concussive traumatic brain injury interacts with post-injury foot shock stress to worsen social and depression-like behavior in mice". Behavioral tests include cued fear conditioning, contextual fear conditioning, social recognition, tail suspension, and sucrose preference. The histological data consists of counts of Iba1 positive cells in the corpus callosum. Abbreviations: rcTBI - repetitive concussive traumatic brain injur

Experimental timeline.

<p>rcTBI injury or sham-injury surgeries were carried out on two consecutive days, 24 ± 1 hours apart. After two days of recovery, animals were trained in cued or contextual fear conditioning. Animals were subsequently tested in the social recognition test (day 10), sucrose preference test (contextual fear conditioning group only; days 13-15), and the tail suspension test (day 18). On day 40 post-surgery, animals were sacrificed and perfused for histology.</p

Effect of Virtual Versus In Person Interpreting on Diabetes Outcomes in Non-English Language Preference Patients: A Pilot Study

Objective: The objective of this pilot study was to explore the impact of interpreter format (virtual vs in person) on clinical outcomes in patients with non-English language preference (NELP) and type 2 diabetes mellitus (T2DM) in a primary care setting. We hypothesized that NELP patients utilizing in person interpreters would have improved HbA1c values, better follow-up rate, and more complex care plans compared to patients utilizing virtual interpreters. Methods: We completed a retrospective chart review of 137 NELP patients with T2DM who required a medical interpreter (February to June 2021). We calculated univariate and bivariate statistics to characterize the sample and assess the extent to which measures of continuity (follow-up visit rate and time to follow-up visit), quality (change in HbA1c), and complexity (medication intervention complexity) were associated with interpreter type. Results: There was no statistically significant difference in follow-up rate or average days to follow-up visit for NELP patients with in person as opposed to virtual interpreters. Patients with virtual interpreters demonstrated a non-statistically significant decrease in HbA1c compared to those with in person interpreters. Finally, there was no statistically significant association between interpreter format and intervention complexity. Conclusions: Quality medical interpretation contributes to optimal health outcomes in NELP patients with diabetes. Our study suggests that both in person and virtual interpreters can be effective in providing care for NELP patients, especially for chronic disease management in the context of a primary care relationship. It also highlights the importance of pursuing additional qualitative and mixed method studies to better understand the benefits of various interpreter formats across different visit types