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Home » Geriatric Psychiatry

Psychiatric Times. Vol. 27 No. 9
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GERIATRIC PSYCHIATRY: PART 2 

Resilience, Stress, and the Neurobiology of Aging

By Helen Lavretsky, MD, MS | September 1, 2010

Dr Lavretsky is professor in the department of psychiatry and biobehavioral sciences and Semel Institute for Neuroscience and Human Behavior at UCLA’s David Geffen School of Medicine in Los Angeles. She reports that she has received research grants from Forest Research Institute, the National Institute of Mental Health, the National Institutes of Health, and the National Center for Complementary and Alternative Medicine.

Acknowledgment: This work was partially supported by NIH grants MH077650, MH086481, and AT003480.


Immunity, inflammation, and aging

The plasma concentrations of inflammatory mediators, such as cytokines and acute phase proteins, increase with aging, which results in low-grade inflammation. These changes lead to increased obesity and adiposity; a decrease in production of sex steroids; subclinical infections; and chronic aging-related disorders, such as cardiovascular disease and arthritis. Furthermore, aging is associated with a dysregulated cytokine response following stimulation.15

(MORE: Diabetes-Related Risk Factors and Cognitive Aging)

Several inflammatory mediators, such as tumor necrosis factor-α and interleukin-6 (IL-6), have the potential to induce and/or aggravate risk factors in age-associated pathology. Inflammatory mediators are also strong predictors of mortality independent of other known risk factors in elderly cohorts. For example, a proinflammatory factor IL-6 has been linked with Alzheimer disease, osteoporosis, rheumatoid arthritis, cardiovascular disease, and some forms of cancer, and it has been prospectively associated with general disability and mortality in large population-based studies.16-21

Neural circuitry and resilience

Brain imaging promotes understanding of brain regulation of positive emotions and resilience.22 The brain circuitry that is involved in emotional regulation includes several areas of the prefrontal cortex (PFC), amygdala, hippocampus, and anterior cingulate. The PFC plays a crucial role in the anticipation of future affective consequences of action as well as in the persistence of emotion.22

There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays a different role in emotional regulation. The amygdala appears to be crucial for learning new stimulus-threat contingencies and to be important in the expression of cue-specific fear.23 Tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Asymmetries within the PFC and activation of the amygdala are responsible for individual differences in affective style.22,23 Plasticity in this circuitry has implica-tions for cultivating positive affect and resilience.22,23

Resilience and aging

A coherent pattern of individual characteristics associated with resilience and successful adaptation has emerged. Salient characteristics include commitment, dynamism, humor in the face of adversity, patience, optimism, faith, and altruism.24 There are emotional and cognitive aspects of resilience that can be innate or learned. The innate affective or emotional styles that are likely to influence resilience refer to the individual styles of affect regulation, which are usually a part of personality structure (eg, optimism or pessimism), or social intelligence.

Temperament appears to be one of the determinants of resilience that is, at least, partially heritable. Protective temperamental factors include sociability, intelligence, social competence, internal locus of control, warmth and closeness of affectional ties, and active emotional support within the family network or within religious groups.25 As such, resilience may represent an important target for treatment and prevention of anxiety, depression, and abnormal stress reactions in aging persons (Figure).

Well-being and aging

A sense of well-being is an important characteristic of successful aging. Ryff and colleagues26 described 2 types of well-being: eudaimonic and hedonic. The aristotelian concept of eudaimonic well-being addresses ideas of self-development and self-acceptance, personal growth, positive relationships, and purposeful engagement. Hedonic well-being is concerned with positive feelings, such as happiness and contentment.

A sense of ill-being refers to all negative affect states, such as depression and anxiety. Different biological markers, including neuroendocrine (cortisol, epinephrine(Drug information on epinephrine), norepinephrine(Drug information on norepinephrine)), immune (IL-6, vaccine antibody response), cardiovascular (blood pressure, waist-hip ratio, cholesterol, glycosylated hemoglobin), sleep (duration/latency of rapid eye movement), and neural circuitry (cerebral asymmetry), are associated with the states of well-being or ill-being.26 The question remains whether resilience is responsible for the differences.

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by Josephine Later R.T.(Can).A.S.C.P.(U.S.A.) | January 14, 2011 7:02 PM EST

An excellent article re stress in the aging population.The emphasis placed on youth in our culture only exacerbates the problem.Can you imagine Zsa Zsa Gabor with only one leg??or even the youth who actually can't even imagine themselves as "old"?Resilience and an inner life is the key-thanks for the great article-JL.

by Robert Peers | December 11, 2010 9:19 PM EST

Unfortunately, one never sees in any discussions about stress, any mention of anxiety disorder, which affects, in varying degrees, 20-25% of Western people (it is unknown in traditional societies, like the Kaluli in Papua, or in Japanese fishing villages). This widespread misunderstanding may be due to the mistaken popular notion that anxiety and stress are the same thing, and are both caused by traffic jams and other purely external stressors. The proper description of the effect of external stress would be internal strain, which lasts for only minutes or hours, unlike true anxiety, which is lifelong. Anxiety disorder arises during foetal development, and is the result of a fatty maternal diet--that often causes gestational diabetes as well--the direct cause being a leakage of maternal cortisol across a mildly inflamed placenta. This hormone changes the foetal brain permanently, by epigenetically modifying the glucocorticoid receptor gene promoter, thereby reducing negative feedback from adrenal cortisol, which promotes increased CRF and HPA axis overactivity. Anxious folk lack resilience, and also comfort-eat fatty foods, which leads to obesity, diabetes, depression, vascular disease, arthritis, osteoporosis and muscle wasting. Fatty diet causes both insulin resistance and systemic oxidation, and the latter drives cytokine production and low-grade inflammation, and also drives telomere shortening. Low-fat diet turns depression back to anxiety in 2 weeks. To convert anxiety to resilience takes about 7 days: just give the subject 5 gm of Inositol supplement daily: this simple seed sugar allays anxiety by inhibiting serotonin 2A receptors, which blocks CRF action. Within 3 days there is unusual energy, and a shift of appetite from sweet fatty foods to salads and fruit. By the seventh day, there is newfound calmness and mental clarity, followed within weeks by fat loss, larger muscles, a liking for exercise, better libido, and better immunity. Hair and nails grow faster, and appear shinier and stronger. Inositol is ALSO anti-ageing--it is found abundantly in the legumes and whole grains (like oat porridge) eaten by most healthy centenarians (tip: citrus is a good source), and is known to activate 100s of anti-ageing genes (J Barger, 2008). Its IP5 metabolite inhibits the key nutrient-sensing enzyme PI3 Kinase, fooling the cell into thinking that the subject is on Caloric Restriction. Inositol is also directly involved in telomere maintenance (see "inositol and telomere" on PubMed). Remember, diet MUST be low fat, for best effect.

by William Taylor | September 03, 2010 12:55 PM EDT

Normal 0 0 1 250 1429 11 2 1754 11.1287 0 0 0

Wise advice! This post highlights the importance of stress management for children, teens and adults.

Families and school staff concerned about a student with such problems can turn to this link from the American Academy of Child and Adolescent Psychiatry listing free helpful pamphlets for most common emotional conditions affecting youth and families: http://www.aacap.org/cs/root/facts_for_families/facts_for_families

These pamphlets are available in English, Español, Malaysian, Polish, Icelandic, Arabic, Urdu and Hebrew. (Links are on the aacap site listed above.)

Another source of insight is the Stressed Family, Strong Family website,

at this link:  http://americanconfusion.com

where you will find many ideas from the e-book,

Stressed Family, Strong Family.

Many can learn to cope with stress more effectively, and support one another.

Also in this Special Report

Who Should Care About Geriatric Mental Health? Check the Mirror . . .

Drugs, Death, and Disconcerting Dilemmas

Palliative Care in Older Adults

Resilience, Stress, and the Neurobiology of Aging

Diabetes-Related Risk Factors and Cognitive Aging





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