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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 Adolescent alcohol and nicotine exposure alters the adult response to alcohol use(Frontiers Media, 2023-11-22) Hauser, Sheketha R.; Waeiss, Robert A.; Deehan, Gerald A., Jr.; Engleman, Eric A.; Bell, Richard L.; Rodd, Zachary A.; Psychiatry, School of MedicineAdolescence through young adulthood is a unique period of neuronal development and maturation. Numerous agents can alter this process, resulting in long-term neurological and biological consequences. In the clinical literature, it is frequently reported that adolescent alcohol consumption increases the propensity to develop addictions, including alcohol use disorder (AUD), during adulthood. A general limitation of both clinical and human pre-clinical adolescent alcohol research is the high rate of co-using/abusing more than one drug during adolescence, such as co-using/abusing alcohol with nicotine. A primary goal of basic research is elucidating neuroadaptations produced by adolescent alcohol exposure/consumption that promote alcohol and other drug self-administration in adulthood. The long-term goal is to develop pharmacotherapeutics for the prevention or amelioration of these neuroadaptations. This review will focus on studies that have examined the effects of adolescent alcohol and nicotine exposure on adult alcohol consumption, the hypersensitivity of the mesolimbic dopaminergic system, and enhanced responses not only to alcohol but also to nicotine during adulthood. Again, the long-term goal is to identify potential cholinergic agents to prevent or ameliorate the consequences of, peri-adolescent alcohol abuse.Item Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder(Frontiers Media, 2024) Getachew, Bruk; Hauser, Sheketha R.; Bennani, Samia; El Kouhen, Nacer; Sari, Youssef; Tizabi, Yousef; Psychiatry, School of MedicineReciprocal communication between the gut microbiota and the brain, commonly referred to as the “gut-brain-axis” is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed. This imbalance can lead to increased acquirement of reward-seeking and risk-taking behaviors during adolescence, and consequently eventuate in heightened risk for substance abuse. Thus, there is high initiation of alcohol drinking in early adolescence that significantly increases the risk of alcohol use disorder (AUD) in adulthood. The underlying causes for heightened AUD risk are not well understood. It is suggested that alcohol-associated gut microbiota impairment during adolescence plays a key role in AUD neurodevelopment in adulthood. Furthermore, alcohol-induced dysregulation of microglia, either directly or indirectly through interaction with gut microbiota, may be a critical neuroinflammatory pathway leading to neurodevelopmental impairments and AUD. In this review article, we highlight the influence of adolescent alcohol drinking on gut microbiota, gut-brain axis and microglia, and eventual manifestation of AUD. Furthermore, novel therapeutic interventions via gut microbiota manipulations are discussed briefly.Item Adolescent opioid abuse: Role of glial and neuroimmune mechanisms(Elsevier, 2022) Rahman, S.; Rahman, Z. I.; Ronan, P. J.; Lufty, K.; Bell, R. L.; Psychiatry, School of MedicineOpioids are widely prescribed for pain management, and prescription opioid misuse in adolescents has become a major epidemic in the United States and worldwide. Emerging data indicate that adolescence represents a critical period of brain development, and exposure to opioids during adolescence may increase the risk of addiction in adulthood. There is growing evidence that disruptions in brain glial function may be implicated in numerous chronic neuropathologies. Evidence suggests that glial mechanisms have an important role in the development and maintenance of opioid abuse and the risk for addiction. This review will describe glial and neuroimmune mechanisms involved in opioid use disorders during adolescence, which may increase substance use disorder liability later in life. Moreover, this review will identify some important neuro-glial targets, involved in opioid abuse and addiction, to develop future preventions and treatment strategies.Item An adolescent rat model of vincristine-induced peripheral neuropathy(Elsevier, 2021-11-11) Li, Ai-Ling; Crystal, Jonathon D.; Lai, Yvonne Y.; Sajdyk, Tammy J.; Renbarger, Jamie L.; Hohmann, Andrea G.; Pediatrics, School of MedicineChildhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood. We, consequently, developed an adolescent rodent model of VIPN which can be utilized to study possible long term consequences of vincristine treatment in the developing rat. We also evaluated the therapeutic efficacy of voluntary exercise and potential impact of obesity as a genetic risk factor in this model on the development and maintenance of VIPN. Out of all the dosing regimens we evaluated, the most potent VIPN was produced by fifteen consecutive daily intraperitoneal (i.p.) vincristine injections at 100 µg/kg/day, throughout the critical period of adolescence from postnatal day 35 to 49. With this treatment, vincristine-treated animals developed hypersensitivity to mechanical and cold stimulation of the plantar hind paw surface, which outlasted the period of vincristine treatment and resolved within two weeks following the cessation of vincristine injection. By contrast, impairment in grip strength gain was delayed by vincristine treatment, emerging shortly following the termination of vincristine dosing, and persisted into early adulthood without diminishing. Interestingly, voluntary wheel running exercise prevented the development of vincristine-induced hypersensitivities to mechanical and cold stimulation. However, Zucker fa/fa obese animals did not exhibit higher risk of developing VIPN compared to lean rats. Our studies identify sensory and motor impairments produced by vincristine in adolescent animals and support the therapeutic efficacy of voluntary exercise for suppressing VIPN in developing rats.Item Association Between Head Impact Exposure, Psychological Needs, and Indicators of Mental Health Among U.S. High School Tackle Football Players(Elsevier, 2023) Kercher, Kyle A.; Steinfeldt, Jesse A.; Rettke, Devin J.; Zuidema, Taylor R.; Walker, Miata J.; (Martinez) Kercher, Vanessa M.; Silveyra, Patricia; Seo, Dong-Chul; Macy, Jonathan T.; Hulvershorn, Leslie A.; Kawata, Keisuke; Psychiatry, School of MedicinePurpose: Age of first exposure to tackle football and head impact kinematics have been used to examine the effect of head impacts on mental health outcomes. These measures coupled with retrospective and cross-sectional designs have contributed to conflicting results. The purpose of this study was to identify the effect of one season of head impact exposure, age of first exposure to football, and psychological need satisfaction on acute mental health outcomes in adolescent football players. Methods: This prospective single-season cohort study used sensor-installed mouthguards to collect head impact exposure along with surveys to assess age of first exposure to football, psychological satisfaction, depressive symptoms, anxiety symptoms, and thriving from football players at four high schools (n = 91). Linear regression was used to test the association of head impact exposure, age of first exposure, and psychological satisfaction with acute mental health outcomes. Results: A total of 9,428 impacts were recorded with a mean of 102 ± 113 impacts/player. Cumulative head impact exposure and age of first exposure were not associated with acute mental health outcomes at postseason or change scores from preseason to postseason. Greater psychological satisfaction was associated with fewer depressive symptoms (β = -0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (β = -0.021, SE = 0.008, p = .010), and greater thriving scores (β = 0.278, SE = 0.040, p = < .001) at postseason. Discussion: This study does not support the premise that greater single-season head impact exposure or earlier age of first exposure to tackle football is associated with worse acute mental health indicators over the course of a single season in adolescent football players.Item Behavioral Profiles of Adolescent Alcohol-Preferring/Non-preferring (P/NP) and High/Low Alcohol-Drinking (HAD/LAD) Rats Are Dependent on Line but Not Sex(Frontiers Media, 2022) Lundberg, Stina; Roman, Erika; Bell, Richard L.; Psychiatry, School of MedicineInitial contact with alcohol generally occurs during adolescence, and high consumption during this period is associated with increased risk for later alcohol (AUDs) and/or substance use disorders (SUDs). Rodents selectively bred for high or low alcohol consumption are used to identify behavioral characteristics associated with a propensity for high or low voluntary alcohol intake. The multivariate concentric square field™ (MCSF) is a behavioral test developed to study rodents in a semi-naturalistic setting. Testing in the MCSF creates a comprehensive behavioral profile in a single trial. The current aim was to examine the behavioral profiles of adolescent, bidirectionally selectively bred male and female high alcohol-consuming (P and HAD1/2) and low alcohol-consuming (NP and LAD1/2) rat lines, and outbred Wistar rats. Alcohol-naïve rats were tested once in the MCSF at an age between postnatal days 30 and 35. No common behavioral profile was found for either high or low alcohol-consuming rat lines, and the effect of sex was small. The P/NP and HAD2/LAD2 lines showed within pair-dependent differences, while the HAD1/LAD1 lines were highly similar. The P rats displayed high activity and risk-associated behaviors, whereas HAD2 rats displayed low activity, high shelter-seeking behavior, and open area avoidance. The results from P rats parallel clinical findings that denser family history and risk-taking behavior are strong predictors of future AUDs, often with early onset. Contrarily, the HAD2 behavioral profile was similar to individuals experiencing negative emotionality, which also is associated with a vulnerability to develop, often with a later onset, AUDs and/or SUDs.Item Bullying, Weapons Carrying, and Mental Health Outcomes Among U.S. High School Students(2019-05) Kriech, Amber C.; Hensel, Devon J.; Mintus, Kenzie L.; Seybold, Peter J.Using data from the 2007-2017 cycles of the national Youth Risk Behavior Survey (YRBS), this researcher aimed to understand how weapons carrying mediates the association between bullying and mental health outcomes. I dichotomized four bullying outcomes to create one new carried a weapon after bullied (CWB) (no/yes; e.g. did not carry a weapon post-bullying vs. did carry a weapon post-bullying) for each bullying type. Mental health outcomes included (all dichotomized, past 2 weeks, no/yes): felt sad or hopeless, seriously considered suicide, had a plan for suicide and attempted suicide. I used descriptive statistics and binary logistic regression adjusted for YRBS sampling methods and weighting (Stata 15.0). Initial results showed that weapons carrying has a complex relationship with mental health after bullying. One notable finding is that individuals who had been in a physical fight were the most likely to carry a weapon (N = 268), followed by those who had been threatened at school (N = 233). Additionally, more students who had been bullied at school (N = 185) carried a weapon than those who were victims of cyberbullying (N = 166). Another interesting result found that across all bullying types, males were 2 to 3 times more likely to carrying a weapon as a result of being bullied. In terms of mental health, being threatened at school was the most significant bullying type in relation to suicidal ideation.Item Cannabis Use and the Developing Brain: Highs and Lows(Frontiers Media, 2023) Hurd, Yasmin L.; Ferland, Jacqueline-Marie N.; Nomura, Yoko; Hulvershorn, Leslie A.; Gray, Kevin M.; Thurstone, Christian; Psychiatry, School of MedicineAlthough cannabis is a naturally occurring plant with a long history of use by humans, the chemicals it contains, called cannabinoids, can act on the human body in many ways. Use of cannabis during important periods of development, such as during pregnancy and adolescence, can have a long-lasting impact on the way the brain forms and develops its systems to control emotions and other functions. This article gives an overview of some of the effects of cannabinoids on the developing brain, before birth and as teenagers, and provides information about how young people can prevent or minimize the negative effects of cannabis on their brains.Item Cognitive and Affective Empathy as Indirect Paths Between Heterogeneous Depression Symptoms on Default Mode and Salience Network Connectivity in Adolescents(Springer, 2023) Winters, Drew E.; Pruitt, Patrick J.; Gambin, Malgorzata; Fukui, Sadaaki; Cyders, Melissa A.; Pierce, Barbara J.; Lay, Kathy; Damoiseaux, Jessica S.; School of Social WorkDepression amongst adolescents is a prevalent disorder consisting of heterogeneous emotional and functional symptoms-often involving impairments in social domains such as empathy. Cognitive and affective components of empathy as well as their associated neural networks (default mode network for cognitive empathy and salience network for affective empathy) are affected by depression. Depression commonly onsets during adolescence, a critical period for brain development underlying empathy. However, the available research in this area conceptualizes depression as a homogenous construct, and thereby miss to represent the full spectrum of symptoms. The present study aims to extend previous literature by testing whether cognitive and affective empathy indirectly account for associations between brain network connectivity and heterogeneous depression symptoms in adolescents. Heterogeneous functional and emotional symptoms of depression were measured using the child depression inventory. Our results indicate that cognitive empathy mediates the association between default mode network functional connectivity and emotional symptoms of depression. More specifically, that adolescents with a stronger positive association between the default mode network and cognitive empathy show lower emotional depression symptoms. This finding highlights the importance of cognitive empathy in the relationship between brain function and depression symptoms, which may be an important consideration for existing models of depression in adolescents.