Browsing by Subject "Anxiety"
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Item A gut-derived metabolite alters brain activity and anxiety behaviour in mice(Springer Nature, 2022) Needham, Brittany D.; Funabashi, Masanori; Adame, Mark D.; Wang, Zhuo; Boktor, Joseph C.; Haney, Jillian; Wu, Wei-Li; Rabut, Claire; Ladinsky, Mark S.; Hwang, Son-Jong; Guo, Yumei; Zhu, Qiyun; Griffiths, Jessica A.; Knight, Rob; Bjorkman, Pamela J.; Shapiro, Mikhail G.; Geschwind, Daniel H.; Holschneider, Daniel P.; Fischbach, Michael A.; Mazmanian, Sarkis K.; Anatomy, Cell Biology and Physiology, School of MedicineIntegration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.Item A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder(Springer Nature, 2022) McDougle, Christopher J.; Thom, Robyn P.; Ravichandran, Caitlin T.; Palumbo, Michelle L.; Politte, Laura C.; Mullett, Jennifer E.; Keary, Christopher J.; Erickson, Craig A.; Stigler, Kimberly A.; Mathieu-Frasier, Lauren; Posey, David J.; Psychiatry, School of MedicineThis study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Item Acceptance and commitment therapy for breast cancer survivors with fear of cancer recurrence: A 3-arm pilot randomized controlled trial(Wiley, 2020) Johns, Shelley A.; Stutz, Patrick V.; Talib, Tasneem; Cohee, Andrea A.; Beck-Coon, Kathleen A.; Brown, Linda F.; Wilhelm, Laura R.; Monaham, Patrick O.; LaPradd, Michelle L.; Champion, Victoria L.; Miller, Kathy D.; Giesler, R. BrianBackground Fear of cancer recurrence (FCR) has a profound negative impact on quality of life (QOL) for many cancer survivors. Breast cancer survivors (BCS) are particularly vulnerable, with up to 70% reporting clinically significant FCR. To the authors' knowledge, evidence-based interventions for managing FCR are limited. Acceptance and commitment therapy (ACT) promotes psychological flexibility in managing life's stressors. The current study examined the feasibility and preliminary efficacy of group-based ACT for FCR in BCS. Methods Post-treatment BCS (91 patients with stage I-III disease) with clinical FCR randomly were assigned to ACT (6 weekly 2-hour group sessions), survivorship education (SE; 6 weekly 2-hour group sessions), or enhanced usual care (EUC; one 30-minute group coaching session with survivorship readings). FCR severity (primary outcome) and avoidant coping, anxiety, post-traumatic stress, depression, QOL, and other FCR-related variables (secondary outcomes) were assessed at baseline (T1), after the intervention (T2), 1 month after the intervention (T3), and 6 months after the intervention (T4) using intent-to-treat analysis. Results Satisfactory recruitment (43.8%) and retention (94.5%) rates demonstrated feasibility. Although each arm demonstrated within-group reductions in FCR severity over time, only ACT produced significant reductions at each time point compared with baseline, with between-group differences at T4 substantially favoring ACT over SE (Cohen d for effect sizes, 0.80; P < .001) and EUC (Cohen d, 0.61; P < .01). For 10 of 12 secondary outcomes, only ACT produced significant within-group reductions across all time points. By T4, significant moderate to large between-group comparisons favored ACT over SE and EUC with regard to avoidant coping, anxiety, depression, QOL, and FCR-related psychological distress. Conclusions Group-based ACT is a feasible and promising treatment for FCR and associated outcomes in BCS that warrants testing in larger, fully powered trials.Item Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice(Elsevier, 2017-12) Kasten, C.R.; Zhang, Y.; Boehm II, S.L.; Psychology, School of ScienceUse of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility.Item Acute Cannabinoids Produce Robust Anxiety-Like and Locomotor Effects in Mice, but Long-Term Consequences Are Age- and Sex-Dependent(Frontiers Media, 2019-02-20) Kasten, Chelsea R.; Zhang, Yanping; Boehm, Stephen L., II; Department of Psychology, School of ScienceThe rise in cannabinoid legalization and decriminalization in the US has been paired with an increase in adolescents that perceive marijuana as a "no risk" drug. However, a comprehensive review of human literature indicates that cannabinoid usage may have both beneficial and detrimental effects, with adolescent exposure being a critical window for harming cognitive development. Although the cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are often used together for recreational and medical purposes, no study has previously observed the acute and long-lasting effects of THC+CBD in a battery of behavioral assays analogous to subjective human reports. The current study observed the acute and long-term effects of THC, CBD, and THC+CBD on object recognition memory, anxiety-like behavior, and activity levels in adolescent and adult mice of both sexes. Acute THC alone and in combination with CBD resulted in robust effects on anxiety-like and locomotor behavior. A history of repeated cannabinoid treatment followed by a period without drug administration resulted in minimal effects in these behavioral assays. Most notably, the strongest effects of repeated cannabinoid treatment were seen in adult females administered THC+CBD, which significantly impaired their object recognition. No effects of repeated cannabinoid history were present on hippocampal protein expression. These studies represent a detailed examination of age- and sex-effects of acute and repeated cannabinoid administration. However, the acute and long-term effects of THC with and without CBD on additional behaviors in adolescents and adults will need to be examined for a more complete picture of these drug effects.Item Adolescent Worry about School Gun Violence: Data from a Nationally Representative Study of 14 – 17 Year Olds in the United States(2024-09) Kirkland, Danielle Renee; Hensel, Devon J.; Mintus, Kenzie L.; Shasanmi, Amy C.Using a nationally representative sample from the 2022 National Survey of Sexual Health and Behavior (N = 1,004), this research examined the prevalence of school gun violence worry (SGVW) among U.S. adolescents aged 14 – 17 in the United States and its impact on anxiety and depression. This research draws upon Minority Stress Theory, which states that stigmatized individuals face unique stressors contributing to health disparities. The impact of minority status including racial, sexual, and gender identity on SGVW and its relationship to mental health were also explored. Results revealed that almost three out of four adolescents (73.3%) experience some degree of SGVW. The youngest and oldest respondents reported being more worried compared to the remaining age groups. Higher levels of SGVW were associated with increased anxiety (OR = 1.396, 95% CI: 1.196 – 1.629, p<0.001), but not depression. In separate models, racial minorities (OR = 2.012, 95% CI: 1.455 – 2.784, p<0.001) and gender minorities (OR = 1.948, 95% CI: 0.989 – 3.838, p < 0.05) had higher odds of SGVW than White adolescents and cisgender females, while cisgender males had lower odds (OR = 0.698, 95% CI: 0.501 – 0.974, p<0.01) than cisgender females. The impact of SGVW on anxiety was significant for both heterosexual (OR = 1.350, 95% CI: 1.137 – 1.603, p<0.001) and sexual minority adolescents (OR = 1.763, 95% CI: 1.119 – 2.777, p<0.1). These findings suggest that SGVW is prevalent among adolescents in the U.S. and is associated with increased anxiety.Item Agreement between older adult patient and caregiver proxy symptom reports(Springer, 2022-05-14) Kroenke, Kurt; Stump, Timothy E.; Monahan, Patrick O.; Medicine, School of MedicineBackground: Proxy report is essential for patients unable to complete patient-reported outcome (PRO) measures themselves and potentially beneficial when the caregiver perspective can complement patient report. In this study, we examine agreement between self-report by older adults and proxy report by their caregivers when completing PROs for pain, anxiety, depression, and other symptoms/impairments. Methods: Four PROs were administered by telephone to older adults and their caregivers followed by re-administration within 24 h in a random subgroup. The PROs included the PHQ-9 depression, GAD-7 anxiety, PEG pain, and SymTrak multi-dimensional symptom and functional status scales. Results: The sample consisted of 576 older adult and caregiver participants (188 patient-caregiver dyads, 200 patients without identified caregiver). The four measures had good internal (Cronbach's alpha, 0.76 to 0.92) and test-retest (ICC, 0.63 to 0.92) reliability whether completed by patients or caregivers. Total score and item-level means were relatively similar for both patient and caregiver reports. Agreement for total score as measured by intraclass correlation coefficient (ICC) was better for SymTrak-23 (0.48) and pain (0.58) than for anxiety (0.28) and depression (0.25). Multinomial modeling showed higher (worse) patient-reported scale scores were associated with caregiver underreporting, whereas higher caregiver task difficulty was associated with overreporting. Conclusion: When averaged over individuals at the group level, proxy reports of PRO scores by caregivers tend to approximate patient reports. For individual patients, proxy report should be interpreted more cautiously for psychological symptoms as well as when patient-reported symptoms are more severe, or caregiver task difficulty is high.Item Angiotensin-II is a putative neurotransmitter in lactate-induced panic-like responses in rats with disruption of GABAergic inhibition in the dorsomedial hypothalamus(Society for Neuroscience, 2006-09-06) Shekhar, Anantha; Johnson, Philip L.; Sajdyk, Tammy J.; Fitz, Stephanie D.; Keim, Stanley R.; Kelley, Pamela E.; Gehlert, Donald R.; DiMicco, Joseph A.; Psychiatry, School of MedicineIntravenous sodium lactate infusions or the noradrenergic agent yohimbine reliably induce panic attacks in humans with panic disorder but not in healthy controls. However, the exact mechanism of lactate eliciting a panic attack is still unknown. In rats with chronic disruption of GABA-mediated inhibition in the dorsomedial hypothalamus (DMH), achieved by chronic microinfusion of the glutamic acid decarboxylase inhibitor L-allylglycine, sodium lactate infusions or yohimbine elicits panic-like responses (i.e., anxiety, tachycardia, hypertension, and tachypnea). In the present study, previous injections of the angiotensin-II (A-II) type 1 receptor antagonist losartan and the nonspecific A-II receptor antagonist saralasin into the DMH of "panic-prone" rats blocked the anxiety-like and physiological components of lactate-induced panic-like responses. In addition, direct injections of A-II into the DMH of these panic-prone rats also elicited panic-like responses that were blocked by pretreatment with saralasin. Microinjections of saralasin into the DMH did not block the panic-like responses elicited by intravenous infusions of the noradrenergic agent yohimbine or by direct injections of NMDA into the DMH. The presence of the A-II type 1 receptors in the region of the DMH was demonstrated using immunohistochemistry. Thus, these results implicate A-II pathways and the A-II receptors in the hypothalamus as putative substrates for sodium lactate-induced panic-like responses in vulnerable subjects.Item Anxiety in late life depression is associated with poorer performance across multiple cognitive domains(Cambridge University Press, 2024) Kryza-Lacombe, Maria; Kassel, Michelle T.; Insel, Philip S.; Rhodes, Emma; Bickford, David; Burns, Emily; Butters, Meryl A.; Tosun, Duygu; Aisen, Paul; Raman, Rema; Saykin, Andrew J.; Toga, Arthur W.; Jack, Clifford R., Jr.; Weiner, Michael W.; Nelson, Craig; Radiology and Imaging Sciences, School of MedicineObjective: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains. Method: Older adults with major depressive disorder (N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning. Results: Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity. Conclusions: Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.Item Anxiety sensitivity as a transdiagnostic risk factor for trajectories of adverse posttraumatic neuropsychiatric sequelae in the AURORA study(Elsevier, 2022-12) Short , Nicole A.; van Rooij , Sanne J. H.; Murty, Vishnu P.; Stevens, Jennifer S.; An , Xinming; Ji , Yinyao; McLean , Samuel A.; House , Stacey L.; Beaudoin, Francesca L.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch , Scott L.; Haran , John P.; Lewandowski, Christopher; Musey Jr., Paul I.; Hendry , Phyllis L.; Sheikh , Sophia; Jones , Christopher W.; Punches, Brittany E.; Swor , Robert A.; McGrath , Meghan E.; Hudak , Lauren A.; Pascual , Jose L.; Seamon , Mark J.; Datner , Elizabeth M.; Pearson , Claire; Peak , David A.; Merchant , Roland C.; Domeier , Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli , Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C .; Jovanovic , Tanja; Emergency Medicine, School of MedicineAnxiety sensitivity, or fear of anxious arousal, is cross-sectionally associated with a wide array of adverse posttraumatic neuropsychiatric sequelae, including symptoms of posttraumatic stress disorder, depression, anxiety, sleep disturbance, pain, and somatization. The current study utilizes a large-scale, multi-site, prospective study of trauma survivors presenting to emergency departments. Hypotheses tested whether elevated anxiety sensitivity in the immediate posttrauma period is associated with more severe and persistent trajectories of common adverse posttraumatic neuropsychiatric sequelae in the eight weeks posttrauma. Participants from the AURORA study (n = 2,269 recruited from 23 emergency departments) completed self-report assessments over eight weeks posttrauma. Associations between heightened anxiety sensitivity and more severe and/or persistent trajectories of trauma-related symptoms identified by growth mixture modeling were analyzed. Anxiety sensitivity assessed two weeks posttrauma was associated with severe and/or persistent posttraumatic stress, depression, anxiety, sleep disturbance, pain, and somatic symptoms in the eight weeks posttrauma. Effect sizes were in the small to medium range in multivariate models accounting for various demographic, trauma-related, pre-trauma mental health-related, and personality-related factors. Anxiety sensitivity may be a useful transdiagnostic risk factor in the immediate posttraumatic period identifying individuals at risk for the development of adverse posttraumatic neuropsychiatric sequelae. Further, considering anxiety sensitivity is malleable via brief intervention, it could be a useful secondary prevention target. Future research should continue to evaluate associations between anxiety sensitivity and trauma-related pathology.