There has been concern about the potential sequelae of mild traumatic brain injury (mTBI) in children. This study used data from the Adolescent Brain Cognitive DevelopmentSM (ABCD) study to ...investigate associations between mTBI and behavior and sleep in school-aged children. Generalized additive mixed models were run to examine the association between TBI and parent-reported Child Behavior Checklist and Sleep Disturbance Scale for Children scores. mTBI with or without loss of consciousness (LOC) in 9- and 10-year old children was associated with 1) higher internalizing, externalizing and total problems and 2) greater sleep disturbance scores on the CBCL. The study also demonstrated a higher incidence of mTBI with and without LOC in boys compared to girls. This study shows a statistically significant but modest association between mTBI and behavioral and sleep changes, suggesting that in a non-clinical, sociodemographically diverse community sample of school-aged children mTBI does not result in clinically significant behavioral or psychological sequelae.
Caloric restriction (CR) without micronutrient deficiency has been shown to increase both lifespan and healthspan. In animals, CR has been demonstrated to increase glutathione (GSH), a ...neuroprotective antioxidant, in the brain and preserve brain mitochondrial function by altering neuroenergetics. In humans it has been associated with improvements in mood states and cognitive function. However, most CR studies have employed a 30–60% reduction in calories which is likely too stringent for most people to adhere to long-term. Thus, there is an unmet need for nutritional supplements which can mimic the biological effects of CR, without the need for calorie limitations.
The purpose of the present randomized, placebo-controlled clinical trial was to use Proton (1H) Magnetic Resonance Spectroscopic (MRS) measurements to determine non-invasively whether a blend of micronutrients, a putative CR mimetic, positively modulates metabolites related to neuroprotection and neuroenergetics in the brain.
Healthy middle-aged men and women (N = 63 33 women; age: 40–60 years) were randomized in a double-blind manner to 6 weeks supplementation with either the putative CR mimetic or placebo. At baseline and 6 weeks, subjects underwent MRS at 3 T to investigate changes in brain chemistry, including the neurometabolites: GSH, Glutamate (Glu), Glutamine (Gln) and N-Acetylaspartate (NAA).
GSH, a marker of antioxidant and cellular redox status, increased in the brain of participants in the supplement group. The supplement group also showed an increase in the Glu/Gln ratio, a marker of excitatory neurotransmission and bioenergetics. A trend for an increase in NAA/H2O, a marker of neuronal integrity, was observed in females in the supplement group.
The present study reveals that 6-weeks daily supplementation with a micronutrient blend elicits positive changes in brain neurochemistry. This is the first study to demonstrate that a putative CR mimetic increases brain GSH concentrations and improves neuroprotection and neuroenergetics in the brain of healthy humans. This study was registered at www.clinicaltrials.gov as NCT02439983.
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•Caloric restriction (CR) mimetic supplementation increases glutathione.•CR mimetic supplementation increases the Glutamate (Glu)/Glutamine (Gln) ratio.•CR mimetic supplementation increases N-acetylaspartate (NAA)/H2O ratio in females.
The authors recently observed a correlation between state altitude and suicide rate in the United States, which could be explained by higher rates of gun ownership and lower population density in the ...intermountain West. The present study evaluated the relationship between mean county and state altitude in the United States and total age-adjusted suicide rates, firearm-related suicide rates, and non-firearm-related suicide rates. The authors hypothesized that altitude would be significantly associated with suicide rate.
Elevation data were calculated with an approximate spatial resolution of 0.5 km, using zonal statistics on data sets compiled from the National Geospatial-Intelligence Agency and the National Aeronautics and Space Administration. Suicide and population density data were obtained through the Centers for Disease Control and Prevention (CDC) WONDER database. Gun ownership data were obtained through the CDC's Behavioral Risk Factor Surveillance System.
A significant positive correlation was observed between age-adjusted suicide rate and county elevation (r=0.51). Firearm (r=0.41) and non-firearm suicide rates (r=0.32) were also positively correlated with mean county elevation.
When altitude, gun ownership, and population density are considered as predictor variables for suicide rates on a state basis, altitude appears to be a significant independent risk factor. This association may be related to the effects of metabolic stress associated with mild hypoxia in individuals with mood disorders.
The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal ...dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.
Insula function has been associated with emotional regulation, adjusting to changing outcomes under risk, reward and loss anticipation, discounting of future rewards, and self-rated impulsivity. The ...role of the insula in these processes may be fundamentally related to prospective thinking, a trait that increases with age. There is evidence that insular cortical thickness shows age related decreases that parallel age related increases in future orientation and planning. We tested the hypothesis that nonplanning decreases with age and that insula thickness is related to both age and nonplanning impulsivity. Fifty-nine male and female participants, ranging in age from 10 to 22 years old, underwent structural magnetic resonance imaging (MRI) procedures and were assessed using the Barratt Impulsiveness Scale (BIS). We observed that anterior insula thickness and nonplanning impulsivity show an inverse relationship with age and that there is a significant positive linear relationship between anterior insula thickness and nonplanning.
Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the ...neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP), a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.
The overall length of the CSP and the prevalence of abnormal enlargement of the CSP were assessed and compared in 65 opiate-dependent subjects (41 adolescent-onset opiate users and 24 adult-onset opiate users) and 67 healthy subjects.
Opiate-dependent subjects showed a greater prevalence of abnormal CSP enlargement relative to healthy subjects (odds ratio OR=3.64, p=0.034). The overall CSP length of adolescent-onset opiate-dependent subjects was greater, as compared not only with healthy subjects (F₁,₁₀₄=11.03, p=0.001) but also with those who began opiate use during adulthood (F₁,₆₁=4.43, p=0.039).
The current findings provide the first evidence that abnormal CSP enlargement, which reflects limbic system dysgenesis of neurodevelopmental origin, may be linked to later development of opiate dependence. In addition, a greater CSP length, which indicates more severe limbic abnormalities, appears to confer higher risk for earlier onset of opiate use.
Although cognitive deficits in bipolar disorder (BD) have been repeatedly observed, our understanding of these impairments at a mechanistic level remains limited. Few studies that investigated ...cognitive impairments in bipolar illness have examined the association with brain biochemistry. This pilot study utilized proton magnetic resonance spectroscopy (1H-MRS) to evaluate the relationship between neurocognitive performance and brain metabolites in youth with BD.
Thirty participants, twenty depressed BD participants and ten healthy comparison participants, ages 13–21, completed mood and executive function measures. 1H-MRS data were also acquired from the anterior cingulate cortex (ACC) using two-dimensional (2D) J-resolved 1H-MRS sequence. Proton metabolites including N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) were quantified for both groups.
Participants with BD performed significantly lower on executive functioning measures than comparison participants. There were significant positive correlations between Wisconsin Card Sorting Test (WCST) performance and NAA (p < .001) and GABA (p < .01) in the ACC in bipolar youth, such that as WCST performance increased, both NAA and GABA levels increased.
Small sample size and lack of control for medications.
These findings build on previous observations of biochemical alterations associated with BD and indicate that executive functioning deficits in bipolar youth are correlated with NAA and GABA. These results suggest that cognitive deficits occur early in the course of illness and may reflect risk factors associated with altered neurochemistry. Further investigation of the relationship between brain metabolites and cognition in BD may lead to important information for developing novel, targeted interventions.
•Bipolar participants exhibited executive functioning deficits compared to controls.•Executive functioning was correlated with NAA and GABA in bipolar youth.•Cognitive and metabolite changes may reflect prodromal features of the disorder.
Understanding factors that influence behavioral performance in high-pressure contexts is relevant to critical occupations such as first responders, military personnel, and frontline medical workers. ...A recent study by Yancey et al. (2019) demonstrated an association between boldness, a biobehavioral trait reflecting social dominance and fearlessness, and enhanced task-switching performance during threat of shock relative to a no-shock (safe) condition. This study used a sustained threat manipulation in which cues signaling possible shock were present throughout blocks of multiple task trials. Here, we extended this work by evaluating the relationship between boldness and task-switching performance under acute threat of shock conditions, in which cues signaling possible shock occurred during individual task trials, intermingled with safe trials. Participants (N = 79) completed a task-switching procedure involving acute threat of shock in which unwarned noise probes were presented to elicit blink-startle responses. Boldness was associated with better switching performance under threat versus safe conditions, with high-bold participants who exhibited low startle potentiation during threat showing the best performance. These findings provide additional evidence that dispositional boldness is a meaningful individual difference characteristic related to effective performance in high-pressure situations and have implications for personnel selection and assignment.
Public Significance Statement
The current study investigated factors related to cognitive performance in the context of an external stressor consisting of imminent threat of electric shock. We found that individuals scoring high on the trait of boldness were least susceptible to the effects of acute threat on performance. These findings have implications for identifying individuals likely to function effectively in high-pressure situations (e.g., first responders, military personnel).
The two halves of the brain are believed to play different roles in emotional processing, but the specific contribution of each hemisphere continues to be debated. The right-hemisphere hypothesis ...suggests that the right cerebrum is dominant for processing all emotions regardless of affective valence, whereas the valence specific hypothesis posits that the left hemisphere is specialized for processing positive affect while the right hemisphere is specialized for negative affect. Here, healthy participants viewed two split visual-field facial affect perception tasks during functional magnetic resonance imaging, one presenting chimeric happy faces (i.e. half happy/half neutral) and the other presenting identical sad chimera (i.e. half sad/half neutral), each masked immediately by a neutral face. Results suggest that the posterior right hemisphere is generically activated during non-conscious emotional face perception regardless of affective valence, although greater activation is produced by negative facial cues. The posterior left hemisphere was generally less activated by emotional faces, but also appeared to recruit bilateral anterior brain regions in a valence-specific manner. Findings suggest simultaneous operation of aspects of both hypotheses, suggesting that these two rival theories may not actually be in opposition, but may instead reflect different facets of a complex distributed emotion processing system.
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