Brain Health Across the Life Span Proceedings of a Workshop (2020) / Chapter Skim
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3 BrainBody Interactions
3 BrainBody Interactions
Pages 11-38
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From page 11... ...
Research should focus less on drawing distinct lines and more on describing the continuum of brain health. (Natalie Rasgon)
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From page 12... ...
The SCN also coordinates body temperature rhythms that synchronize the metabolic clocks throughout the other organs in the body, which can be set apart from the circadian clock in the brain by other factors, such as meal timing, for example. SOURCE: As presented by Colleen McClung at the workshop Brain Health Across the Life Span on September 24, 2019.
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From page 13... ...
At the beginning of the life span, a mother's circadian rhythms influence the development of fetal circadian rhythms, including tissue homeostasis and neurodevelopment as well as the development and consolidation of feeding, metabolic, and sleep–wake rhythms. Evidence is emerging that disruptions to a mother's circadian rhythms during pregnancy caused by shift work, for example, can have a long-term effect on the offspring (Logan and McClung, 2019)
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From page 14... ...
These lifestyle factors can have serious consequences for brain health and body health. Circadian Desynchrony Contributes to Different Diseases at Different Stages of Life Whether it is caused by genetic or environmental factors or both, circadian desynchrony contributes to a variety of conditions, including brain diseases that have circadian rhythms at their core, such as bipolar disorder, major depression, drug addiction, and schizophrenia (Kasper et al., 2018)
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SOURCES: As presented by Colleen McClung at the workshop Brain Health Across the Life Span on September 24, 2019 (courtesy of Dr. Brant Hasler)
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A poor diet leads to irregular circadian rhythmicity in mice, especially in the fat and in the liver, which also contributes to weight gain. This is a vicious cycle of disrupting circadian rhythms with unhealthy food intake, with those circadian rhythms also influencing metabolic rates (Kohsaka et al., 2007)
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From page 17... ...
Aβ = amyloid-beta; ER = endoplasmic reticulum; SCN = suprachiasmatic nucleus. SOURCES: As presented by Colleen McClung at the workshop Brain Health Across the Life Span on September 24, 2019; Chauhan et al., 2017.
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. Pharmacotherapies such as lithium and valproic acid -- two first-line treatments for bipolar disorder -- can enhance circadian rhythm amplitude (Johansson et al., 2011; Li et al., 2012)
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She asked if light therapy or some kind of sensory induction could promote a certain stabilization of the consciousness. McClung replied that there have not yet been many clinical tudies s to determine if changing circadian rhythms in these patients will improve their outcomes.
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Melatonin therapy also has the potential to help prevent or at least delay certain neurodegenerative diseases, she added. EARLY ENVIRONMENTAL RISK FACTORS FOR MENTAL HEALTH DISORDERS Elinor Sullivan explored how the early environment influences both brain health and the risk of mental health disorders later in life.
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However, female offspring of mothers who ate the WSD had increased latency to interact with all three novel objects. Thus, maternal WSD consumption leads to increased latency to explore novel objects in female offspring, suggesting that the offspring have increased anxiety compared to the other groups.
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From page 22... ...
Therefore, some effects are different primarily by the mother's diet, while other behavioral effects seem to be driven by the offspring's current diet. Possible Mechanisms for Behavioral Differences Sullivan said her group is exploring a set of mechanisms that may underlie the behavioral differences observed in the animal studies, including the following: • Increased inflammation • Maternal diet versus the maternal metabolic state • Changes in the development of neurotransmitter systems critical in behavioral regulation • Alterations in stress sensitivity as characterized by the hypotha lamic–pituitary–adrenal axis • Alterations in the early postnatal environment, such as maternal– infant behavior and attachment A primary mechanism is increased inflammation.
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Effect of Maternal Diet on Offspring Behavior Sullivan provided an overview of her 2010 study's conclusions about the effect of a maternal WSD on offspring behavior. In nonhuman primates, maternal WSD and obesity impair offspring brain development and behavior, with offspring from WSD mothers at increased risk for developing behavioral disorders.
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The primary behavioral outputs of anxiety, aggression, repetitive behaviors, and impaired social behavior are thought to be behavioral indicators of increased risk for mental health and neurodevelopmental disorders in humans, she added.
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The major study goals were to characterize the changes in the in utero environment associated with maternal obesity, poor nutrition, maternal stress, and maternal depression to determine which factors are the strongest predictors of alterations in infants' and toddlers' behaviors associated with ADHD and other neurodevelopmental disorders. Investigators are currently characterizing the infants and toddlers up to 3 years of age, and if their hypotheses are confirmed, they hope to develop new ideas for prevention and intervention to reduce neurodevelopmental disorders.
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Sullivan emphasized that this is an optimistic finding, suggesting that some healthy foods can ameliorate some of the behavioral changes programmed by maternal obesity. The investigators posit that inflammation is the common pathway to ADHD and other neurodevelopmental disorders.
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She described the purpose of using insulin as one of the linking agents -- both peripherally and centrally -- in body and brain connections and explored a conceptual framework for understanding brain health versus brain disease.
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ϵ4 is a particular allele of the gene that produces apolipoprotein E, and is the allele most associated with the development of dementia. SOURCES: As presented by Natalie Rasgon at the workshop Brain Health Across the Life Span on September 24, 2019; adapted from Rasgon and McEwen, 2016.
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. Taken together, these methods for assessing brain correlates of peripheral insulin resistance suggest that there is actually a CNS representation.
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A number of biomarkers of allostatic load and stress are predicted by childhood trauma and are related to peripheral insulin resistance. This allows for deeper endophenotyping of the metabolic type of depression: it is associated with childhood trauma, it is insulin resistant in the eriphery, and it is manifested by multiple distinct molecules as p
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From page 31... ...
Looking at central insulin resistance reveals that there could potentially be cross talk between the body and the brain in the molecular signature of those regulatory factors, but it could also be two completely distinct processes unrelated to each other. Data are emerging from studies of in vivo brain insulin resistance in patients with major depressive disorder and characterized by acetylcarnitine deficiency, suggesting that there is an in vivo nanotechnology method that can be used to assess actual central insulin resistance by measuring the same biomarkers of insulin function among others in exosomes, which are the peripherally circulating baggage from the central nervous system.
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NOTE: ACE = adverse childhood experience. SOURCES: As presented by Natalie Rasgon at the workshop Brain Health Across the Life Span on September 24, 2019; Watson et al., 2018.
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. Because these factors contribute to pathophysiology, interventions that target food intake, food composition, and caloric intake could have a positive effect related to the effect of insulin resistance on the metabolic endophenotype of depression and subsequent cognitive diseases.
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She noted that a question that commonly arises in discussions about the burden of brain disorders is whether the apparent increase in prevalence of disorders such as autism and Alzheimer's disease is attributable to people's brains becoming less healthy or to an increase in the willingness to talk about, diagnose, and report brain disorders. Similarly, brain disorders related to aging are often framed as an inevitable consequence of people living to older ages, without sufficient consideration as to how brain health is influenced by a person's body, their eating and sleeping habits, fulfillment of their basic needs, and how the person interacts with the external physical world.
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From page 35... ...
or bipolar disorder, for example, and asked if a person in that state of balance would not experience symptoms. Rasgon said that OCD and bipolar disorder are treatable, but not curable; other brain disorders such as Alzheimer's disease are not yet even treatable.
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Akil remarked that relatively simple public health interventions related to lifestyle factors (e.g., diet, sleep, exercise) that promote general health are the foundation of brain health (NRC and IOM, 2000)
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From page 37... ...
Simple early childhood measurements can also be used to predict the child's risk of developing ADHD later on in life. She asked participants to discuss the extent to which whether measuring physiological markers such as circadian rhythm, metabolic levels, and insulin resistance is truly relevant to brain health, or whether they are just low-hanging fruit.
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From page 38... ...
The field of brain health should seek to provide tools that match a range of styles and personalities, which will require another level of analysis. In addition to providing people with their own data, social supports will be needed to inform preventive measures and promote healthier lifestyles.
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