REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that usually do not result in acute symptoms and are therefore also referred to as “subconcussive” head impacts. RHI occur e.g., when heading the ball or during contact with another player. Evidence suggests that exposure to RHI may have cumulative effects on brain structure and function. However, little is known about brain alterations associated with RHI, or about the risk factors that may lead to clinical or behavioral sequelae. REPIMPACT is a prospective longitudinal study of competitive youth soccer players and non-contact sport controls aged 14 to 16 years. The study aims to characterize consequences of exposure to RHI with regard to behavior (i.e., cognition, and motor function), clinical sequelae (i.e., psychiatric and neurological symptoms), brain structure, function, diffusion and biochemistry, as well as blood- and saliva-derived measures of molecular processes associated with exposure to RHI (e.g., circulating microRNAs, neuroproteins and cytokines). Here we present the structure of the REPIMPACT Consortium which consists of six teams of clinicians and scientists in six countries. We further provide detailed information on the specific aims and the design of the REPIMPACT study. The manuscript also describes the progress made in the study thus far. Finally, we discuss important challenges and approaches taken to overcome these challenges.

Ventral tegmental area glutamate neurons mediate the nonassociative consequences of traumatic stress

Exposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data implicate ventral tegmental area (VTA) glutamate neuronal activity as functionally important for signaling aversive or threating stimuli. However, it is unknown whether VTA glutamate neurons regulate transsituational outcomes that result from stress and whether these neurons are sensitive to stressor controllability. This work established an operant mouse paradigm to examine the impact of stressor controllability on VTA glutamate neuron function and stressor outcome. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance in male mice. Cell-type-specific calcium recordings showed that both controllable and uncontrollable stressors increased VTA glutamate neuronal activity. Chemogenetic reduction of VTA glutamate neuron activity prevented the behavioral sequelae of uncontrollable stress. Our results provide causal evidence that mice can be used to model stressor controllability and that VTA glutamate neurons may contribute to transsituational stressor outcomes, such as social avoidance and exaggerated fear that are observed within trauma-related disorders.

The Behavioral Sequelae of Cannabis Use in Healthy People: A Systematic Review

Background: Cannabis is known to have a broad range of effects on behavior, including experiencing a “high” and tranquility/relaxation. However, there are several adverse behavioral sequalae that can arise from cannabis use, depending on frequency of use, potency (e.g., THC content), age of onset, and cumulative exposure. This systematic review examined evidence for cannabis-related adverse behavioral sequalae in otherwise healthy human subjects.Methods: Following PRISMA guidelines, we conducted a systematic review of cross-sectional and longitudinal studies from 1990 to 2020 that identified cannabis-related adverse behavioral outcomes in subjects without psychiatric and medical co-morbidities from PubMed and PsychInfo searches. Key search terms included “cannabis” OR “tetrahydrocannabinol” OR “cannabidiol” OR “marijuana” AND “anxiety” OR “depression” OR “psychosis” OR “schizophrenia” “OR “IQ” OR “memory” OR “attention” OR “impulsivity” OR “cognition” OR “education” OR “occupation”.Results: Our search detected a total of 2,870 studies, from which we extracted 124 relevant studies from the literature on cannabis effects in the non-clinical population. Effects of cannabis on several behavioral sequelae including cognition, motivation, impulsivity, mood, anxiety, psychosis intelligence, and psychosocial functioning were identified. The preponderance of the evidence suggests that frequency of cannabis use, THC (but not CBD) content, age of onset, and cumulative cannabis exposure can all contribute to these adverse outcomes in individuals without a pre-existing medical condition or psychiatric disorder. The strongest evidence for the negative effects of cannabis are for psychosis and psychosocial functioning.Conclusions: Although more research is needed to determine risk factors for development of adverse behavioral sequelae of cannabis use, these findings underline the importance of understanding vulnerability to the adverse effects of cannabis, which has implications for prevention and treatment of problematic cannabis use.

Early coagulopathy in children with isolated blunt head injury is associated with mortality and poor neurological outcomes

OBJECTIVETraumatic brain injury (TBI) is the leading cause of long-term disability and death in children and adolescents globally. Long-term adverse outcomes, including physical, cognitive, and behavioral sequelae, have been reported after TBI in a significant number of pediatric patients. In this study the authors sought to investigate the epidemiology of TBI-associated coagulopathy and its association with mortality and poor neurological outcome in a pediatric population with isolated moderate to severe blunt head injury treated at the authors’ institution.METHODSThis retrospective study was conducted in the children’s emergency department between January 2010 and December 2016. Children < 18 years old who presented with isolated moderate to severe blunt head injury were included in the study. The authors collected data on patient demographics, clinical presentation, and TBI management. Outcomes studied were death and poor neurological outcome defined by a score of < 7 (death, moderate to severe neurological disability) at 6 months postinjury on the pediatric version of the Glasgow Outcome Scale–Extended (GOS-E Peds).RESULTSIn 155 pediatric patients who presented with isolated moderate to severe blunt head injury, early coagulopathy was observed in 33 (21.3%) patients during the initial blood investigations done in the emergency department. The mean (SD) age of the study group was 7.03 (5.08) years and the predominant mechanism of injury was fall from height (65.2%). The median Abbreviated Injury Scale of the head (AIS head) score was 4 and the median GCS score was 13 (IQR 12–15). TBI-associated coagulopathy was independently associated with GOS-E Peds score < 7 (p = 0.02, adjusted OR 6.07, 95% CI 1.32–27.83). The overall mortality rate was 5.8%. After adjusting for confounders, only AIS head score and hypotension at triage remained significantly associated with TBI-associated coagulopathy.CONCLUSIONSTBI-associated coagulopathy was independently associated with GOS-E Peds score < 7 at 6 months postinjury. Larger prospective studies are needed to investigate the use of TBI-associated coagulopathy to prognosticate these critical clinical outcomes.

Behavioral and neurobiological alterations induced by chronic use of crack cocaine

Crack cocaine is the crystal form of cocaine and can be smoked, and rapidly absorbed, and, in part for this reason, is potently addictive. It is hypothesized that crack cocaine is able to induce important changes in different tissues and organs, and thus dramatically alter behavior. Nevertheless, which alterations in the central nervous system are related to its frequent use is still a matter of discussion. The present study is a literature review of articles published between the years 2008 and 2018 on the theme ‘crack cocaine and brain’ available in PUBMED, MEDLINE, EMBASE, and Google scholar databases. The results show that the use of crack cocaine induces important behavioral, neuroanatomical, and biochemical alterations. The main behavioral sequelae include cognitive and emotional changes, such as increased anxiety and depressive symptoms, attention and memory deficits, and hyperactivity. Among the neurobiological alterations are reductions in the activity of the prefrontal, anterior cingulate cortex, and nucleus accumbens. Molecular changes include decreases in neurotrophic factors and increases in oxidative stress and inflammatory cytokines, which may be responsible for the morphological alterations observed. It is also hypothesized that these neurobiological changes might explain the emotional and cognitive dysfunctions experienced by crack cocaine addicts.

Mechanisms of Black–White disparities in health among older adults: Examining discrimination and personality

We tested whether personality traits help explain the association between discrimination and racial health disparities in a sample of 1033 Black and White older adults. Participants completed measures of discrimination, personality, and self-reported physical and mental health. Elevated discrimination among Black participants was indirectly linked to worse physical and mental health outcomes through elevated neuroticism and lower agreeableness, controlling income, education, and gender. The specific facets of depression, impulsiveness, and trust were the most robust intervening personality factors. Interventions that target cognitive, emotional, and behavioral sequelae of discrimination may lessen its impact on health disparities.