Coynekokholm2335

Early life stress (ELS) is a risk factor for developing a host of psychiatric disorders. Adolescence is a particularly vulnerable period for the onset of these disorders and substance use disorders (SUDs). Here we discuss ELS and its effects in adolescence, especially SUDs, and their correlates with molecular changes to signaling systems in reward and stress neurocircuits. Using a maternal separation (MS) model of neonatal ELS, we studied a range of behaviors that comprise a "drug-seeking" phenotype. We then investigated potential mechanisms underlying the development of this phenotype. Corticotropin releasing factor (CRF) and serotonin (5-HT) are widely believed to be involved in "stress-induced" disorders, including addiction. Here, we show that ELS leads to the development of a drug-seeking phenotype indicative of increased susceptibility to addiction and concomitant sex-dependent upregulation of CRF and 5-HT system components throughout extended brain reward/stress neurocircuits.The number of older people is increasing in most if not all countries in the world. In addition, the amount of alcohol consumption in the aged population is increasing and the consumption pattern is often in a binge fashion. However, little is known if the effects of alcohol, either acute or chronic exposure, vary in the older population compared to younger populations. The current mini-review will provide an overview of the effects of acute and chronic ethanol exposure at three different periods of development adolescent, adult and aged on multiple different commonly studied behaviors. The overall conclusion is that biological age of the subject is a critical factor in understanding the effects of ethanol across the lifespan.Alcohol is the most commonly used drug of abuse in the world and binge drinking is especially harmful to the brain, though the mechanisms by which alcohol compromises overall brain health remain somewhat elusive. A number of brain diseases and pathological states are accompanied by perturbations in Blood-Brain Barrier (BBB) function, ultimately exacerbating disease progression. The BBB is critical for coordinating activity between the peripheral immune system and the brain. Importantly, BBB integrity is responsive to circulating cytokines and other immune-related signaling molecules, which are powerfully modulated by alcohol exposure. This review will highlight key cellular components of the BBB; discuss mechanisms by which permeability is achieved; offer insight into methodological approaches for assessing BBB integrity; and forecast how alcohol-induced changes in the peripheral and central immune systems might influence BBB function in individuals with a history of binge drinking and ultimately Alcohol Use Disorders (AUD).Adolescence is an evolutionarily conserved developmental period associated with behavioral change, including increased risk-taking and alcohol use. Experimentation with alcohol typically begins in adolescence and transitions to binge-like patterns of consumption. Alcohol exposure during adolescence can alter normative changes in brain structure and function. Understanding mechanisms by which ethanol impacts neurodevelopmental processes is important for preventing and ameliorating the deleterious consequences of adolescent alcohol abuse. This review focuses on the neuroimmune system as a key contributor to ethanol-induced changes in adolescent brain and behavior. After brief review of neuroimmune system development, acute and chronic effects of ethanol on adolescent neuroimmune functioning are addressed. Comparisons between stress/immunological challenges and ethanol on adolescent neuroimmunity are reviewed, as cross-sensitization is relevant during adolescence. The mechanisms by which ethanol alters neuroimmune functioning are then discussed, as they may portend development of neuropathological consequences and thus increase vulnerability to subsequent challenges and potentiate addictive behaviors.Opioids 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.Cannabis is the most used drug during adolescence, which is a period of enhanced cortical plasticity and synaptic remodeling that supports behavioral, cognitive, and emotional maturity. In this chapter, we review preclinical studies indicating that adolescent exposure to cannabinoids has lasting effects on the morphology and synaptic organization of the prefrontal cortex and associated circuitry, which may lead to cognitive dysfunction later in life. Additionally, we reviewed sex differences in the effects of adolescent cannabinoid exposure with a focus on brain systems that support cognitive functioning. The body of evidence indicates enduring sex-specific effects in behavior and organization of corticolimbic circuitry, which appears to be influenced by species, strain, drug, route of administration, and window/pattern of drug exposure. Caution should be exercised when extrapolating these results to humans. Adopting models that more closely resemble human cannabis use will provide more translationally relevant data concerning the long-term effects of cannabis use on the adolescent brain.Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs adult-initiated exposure is incomplete. We consider the existing animal research in this area for (meth)amphetamines. Established for a number of phenotypes, is lower sensitivity of peri-adolescents than adults to acute effects of (meth)amphetamines, including neurotoxic effects of binge-level exposure. More variable are data for long-term consequences of peri-adolescent exposure on motivational and cognitive traits. Moreover, investigations often exclude an adult-initiated exposure group critical for answering questions about outcomes unique to peri-adolescent initiation. Despite this, it is clear from the animal research that (meth)amphetamine exposure during the peri-adolescent period, whether self- or other-administered, impacts brain motivational circuitry and cognitive function, and alters adult sensitivity to other drugs and natural rewards. Such consequences occurring in humans have the potential to predispose toward unfortunate and potentially disastrous family, social and livelihood outcomes.Since the 2002 Institute of Medicine report, which many cite as a landmark in first defining and calling attention to the concept of health disparities in medicine, much work has been dedicated to characterizing health disparities in medical care with the aim of eliminating them. Epacadostat molecular weight Importantly, this report, "Unequal Treatment Confronting Racial and Ethnic Disparities in Health Care," laid bare the differences in quality of health care that are based on race, ethnicity, and socioeconomic status. Here, the authors elaborate on these issues and discuss the role of the neuro-oncologic workforce in potentially mitigating these disparities.Glioblastoma has emerged as an immunotherapy-refractory tumor based on negative phase III studies of anti-programmed cell death-1 therapy among newly diagnosed as well as recurrent patients. In addition, although much work on vaccine and cellular approaches is ongoing, therapeutic benefit with these approaches has been underwhelming. Much scientific insight into the multitiered layers of immunosuppression exploited by glioblastoma tumors is emerging that sheds light on the explanation for the disappointing results to date and highlights possible therapeutic avenues that may offer a better likelihood of therapeutic benefit for immune-based therapies.This article reviews the current epidemiology of central nervous system tumors. Population-level basic epidemiology, nationally and internationally, and current understanding of germline genetic risk are discussed, with a focus on known and well-studied risk factors related to the etiology of central nervous system tumors.Primary central nervous system lymphoma is a rare and aggressive extranodal non-Hodgkin lymphoma restricted to the brain, spinal cord, cerebrospinal fluid, and eyes. Optimization of treatment including high-dose methotrexate-based chemotherapy followed by consolidation therapy in the form of autologous stem cell transplant or whole-brain radiation leads to improved survival. However, several patients do not respond to upfront therapy and the relapse risk is high. Additionally, there is a risk of delayed neurotoxicity, particularly in older patients. Recent molecular insights underlying the pathophysiology of PCNSL have led to the development of clinical trials involving targeted therapies and immunotherapies for salvage.Meningiomas are largely indolent tumors with a benign clinical course, but a minority exhibit aggressive behavior characterized by rapid growth, neurologic deficits, and increased mortality. Identifying high-risk patients requiring intervention is challenging, but recent insights into meningioma biology provide a useful guide for decision making. Standard of care for recurrent or biologically aggressive tumors consists of surgery and radiation therapy. Systemic therapies targeting vascular endothelial growth factor signaling and somatostatin analogues are potential options for those with refractory disease but display only modest activity. New paradigms in meningioma clinical trial design provide hope for improved options in the future.In order to address etiologic, clinical, and treatment strategies applicable to Internet and video game addiction (IVGA), a working definition of addiction is presented and unique aspects of Internet and screen use disorders and addictive patterns are discussed. Addictions share common neurobiological mechanisms, cause, triggers, and behavioral sequelae-often presenting with similar symptomatology-although severity and impairment vary widely. This article reviews etiologic and neurobiological antecedents to Internet and video game addiction.Significant evidence suggests strong links between childhood trauma and psychosis, with childhood trauma considered a significant risk factor for psychosis, causing a more severe presentation of psychotic illness with a dose-response effect. The relationship between anxiety, mood, posttraumatic stress disorder, and childhood trauma and psychosis and the difficulties distinguishing between overlapping symptoms require careful attention of the treating clinician considering the presentation and treatment course. Finally, there also appears to be a link between childhood trauma and violent behavior in individuals with psychotic illness. More research is needed into the effectiveness and safety of trauma-focused psychotherapeutic interventions.