Wisdom alone is the science of other sciences.
—Plato (427–347 BC)1
Let no one be slow to seek wisdom when he is young nor weary in the search of it when he has grown old. For no age is too early or too late for the health of the soul.
—Epicurus (341–270 BC)2
Wisdom has been discussed since times immemorial in religious and philosophical literature. Empirical research in wisdom made its appearance in the 1970s, but its pace has accelerated during the last two decades. Still, to many people wisdom remains a fuzzy concept that is difficult to define, operationalize, and measure. In psychiatry, little attention has been paid to wisdom, with the exception of pioneers such as Vaillant.3–5 In this article, we begin with its historical background, followed by a review of empirical definitions and measurements of wisdom, potential neurobiology, relationship to aging, suggested evolutionary value, and finally a summary of emerging research on interventions seeking to enhance components of wisdom. We propose that wisdom is a complex human trait with several specific components: social decision making, emotional regulation, prosocial behaviors, self-reflection, acceptance of uncertainty, decisiveness, and spirituality. Growing research suggests that wisdom is a personally and societally useful construct; it has been linked to better overall physical and mental health,6–11 well-being,12 happiness,10,13–15 life satisfaction,10,11,16–18 and resilience.7 Wisdom likely increases with aging, indicating the possible evolutionary role of wise grandparents in promoting fitness of the species by helping enhance their children’s well-being, health, longevity, and fertility.19
It is worth noting that a number of seemingly fuzzy psychological constructs were previously thought to be non-scientific and non-biological because they could not be defined objectively—for example, consciousness, emotion, cognition, stress, resilience, and well-being. Yet, with advances in neurobiological and psychosocial sciences, all these constructs are accepted today as important scientific entities with major implications for biopsychosocial functioning of individuals. We believe that wisdom is in the early stages of moving from this once-dismissed to later-embraced list of constructs that are amenable to empirical research. This article is intended to be a call for additional research to explore, test, confirm, disprove, or revise specific hypotheses and thereby refine the conceptualization of wisdom presented below.
The concept of wisdom has long historical roots in religion and philosophy.20 Ancient civilizations amassed wisdom literature passed from one generation to the next, often expressed in the form of parables or songs to communicate proper social and moral conduct, and to provide life advice.21 Wisdom is frequently discussed in several ancient texts such as the Sebayt, Egyptian scrolls dating from 2000 to 1700 BC, and the Bhagavad Gita, a Hindu philosophical/religious scripture.20 The Old Testament books of Job, Psalms, and Proverbs also described paths to the attainment of wisdom. Influential ancient Eastern thinkers from Confucius to Buddha ruminated on wisdom. Ancient Greek philosophers, including Socrates, Plato, and Aristotle, described a wise person as one with extensive knowledge that he or she was able to teach others but who was also aware of the limitations of that knowledge.22
In modern psychology, Hall’s 1922 treatise Senescence: The Last Half of Life may have been the first broad discussion of wisdom.23 Hall theorized that the function of older adults was to glean wisdom, characterized by calmness, impartiality, and moral knowledge, from their previous experiences. Erikson conceptualized wisdom as the optimal outcome of a conflict between ego integrity and despair that typified the final phase of his postulated eight-stage course of human life.24,25 Per Erikson, a wise individual is content, with an “informed and detached concern with life itself in the face of death itself.”26
Beginning in the 1970s, early empirical research on wisdom was initiated by Baltes and Smith27 in Germany and by Clayton and Birren28 in the United States. Baltes and colleague23,29 believed that wisdom was rare and consisted of five criteria: rich factual knowledge of life’s conditions and changing situations; deep procedural knowledge for dealing with those conditions and situations; lifespan contextualism (understanding how different aspects of life interact); sense of relativism recognizing and respecting differences among individuals and cultures; and acceptance of uncertainties in life.
Clayton and Birren28 proposed that wisdom consisted of several discrete and measurable components: a reflective component involving introspection and intuition, an affective component involving empathy and peacefulness, and a cognitive component characterized by knowledge and experience.28
Subsequent investigators highlighted other aspects of wisdom. Sternberg’s balance theory of wisdom30–32 stated that common good was achieved through the application of tacit knowledge, mediated by a balance of intrapersonal, interpersonal, and extrapersonal interests to achieve a balance among adaptation to, and shaping of, existing environments and selection of new environments.30–32 Ardelt6,16 conceptualized wisdom as an integration of cognitive, reflective, and affective personality qualities that are predictive of subjective well-being.6,16 Staudinger23,29,33 proposed five criteria of wisdom: insight, personal growth, self-awareness of the current context, value relativism, and awareness and management of life’s uncertainties.23,29,33 Nusbaum and colleagues34 reported that more extensive experiences such as meditation and dance, rather than chronological age, were associated with increased cognitive, affective, and reflective wisdom.34
In the largest and longest investigation of its kind, Vaillant’s Harvard Study of Adult Development5,35 examined behaviors and factors that contributed to mental and physical well-being as well as longevity.5,35 Predictors of successful aging included unmodifiable factors (social class, temperament, physical health, and family history of longevity) and modifiable ones (marriage, coping strategies, physical activity, body weight, alcohol use, and smoking). Vaillant found that while wisdom and well-being at age 80 years were correlated, their predictors differed.36 Openness to new experiences as a young adult and lifelong psychosocial growth were predictive of wisdom in old age, while emotional stability and extraverted personality were predictive of well-being in old age. Cloninger studied how personality, the integration of temperament, and character traits contributed to well-being. He reported that personality traits of self-directedness, cooperativeness, and self-transcendence contributed to well-being.37 Blazer’s work on successful aging and the role of spirituality/religiosity in mental health38–40 highlighted the need to promote practical wisdom.38–40 Other groups have incorporated spirituality into definitions of wisdom. Achenbaum and Orwoll41 examined the book of Job to identify components of wisdom (faith in God, recognition of God’s existence and role, self-transcendence, with Job being considered the prototypical wise man.41 Perry42 defined spirituality as “feel[ing] love, fellowship or union with God or a higher being” and “living a spiritual life.”42 Jason43 highlighted the difficulty of increasing spirituality through challenging experiences, struggle, and resilience.43 Wink and Helson44 defined “transcendent wisdom” as transpersonal skills that included self-transcendence and other philosophical approaches.44 Spirituality has been defined broadly—from a general awareness of other powers/forces affecting the universe to a more religion-based exemplification of a spiritual life. Our perspective is that spirituality is often interconnected with, though independent from, religiosity; a person can be spiritual without being religious.
Modern pragmatic definitions of wisdom, such as described by Prensky,45 focus on “the ability to find practical, creative, contextually appropriate and emotionally satisfying solutions to complicated human problems.” Technology can be harnessed to make moral, ethical, and pragmatic decisions—through facilitating instantaneous feedback from trusted advisers or gathering input from, and disseminating data to, large numbers of people at once.45
While definitions of wisdom vary throughout the literature, the definitions are descriptive and conceptual. For example, the Oxford English Dictionary defines wisdom as “capacity of judging rightly in matters relating to life and conduct,”46 while other definitions focus on specific qualities like cognition (Baltes) or balance (Sternberg). The approach highlighted in this review uses empirical methods to operationalize and measure wisdom. There is value to both the holistic and empirical approaches. Ultimately, the basic concept of wisdom is similar: a high-level quality that is useful for optimal functioning in society.
Several methods have been used to derive a consensus definition of wisdom, including literature review, expert panel, examination of a scripture, and interviews of older adults. Remarkably, the components of wisdom identified in these different ways were similar.
The field of empirical wisdom research has grown considerably, as evidenced by a 28-fold increase in the number of articles on wisdom found in a PubMed database search from the 1970s through 2017 (Supplemental Figure 1, available at http://links.lww.com/HRP/A87).47 In a systematic review of the scientific literature on wisdom, Meeks and Jeste47 identified six common components: general knowledge of life and social decision making, emotional regulation, prosocial behaviors like compassion and empathy, insight or self-reflection, acceptance of different value systems, and decisiveness. A subsequent literature review added the components of spirituality, openness to new experiences, and sense of humor that had been proposed in some published studies.48 The relative weighting of these components may vary depending on the context or culture.
A panel of international experts on wisdom, who had published on this topic, completed anonymous surveys based on the Delphi or Rand Panel method.49 The study compared wisdom, intelligence, and spirituality on 53 items. The expert consensus was that while wisdom shared certain qualities with intelligence and spirituality, the three concepts were fundamentally distinct. The experts also agreed on the six core features of wisdom identified by the above-mentioned literature review.47 There was a consensus that wisdom is uniquely human, is driven by experience, is measurable and learned, and increases with age.
Wisdom in the Gita
The Bhagawad Gita, or Gita, is a 700-verse poem composed 500 years BC (summarizing much longer yogas that date back several thousand years BC). It remains the religious and philosophical guide to wisdom in everyday life for millions of people. A mixed-methods, qualitative-quantitative study of the Gita was undertaken (by the first author and others) to identify components of wisdom.20 Specific search terms related to wisdom were used to identify relevant verses and categorize them into specific domains of wisdom. Overall, the Gita seemed to highlight five of the six components of wisdom found in our literature review47 and expert consensus.47 The main differences were the Gita’s lower emphasis on acceptance of uncertainty and greater focus on religiosity/spirituality and lack of materialistic pursuits.
Perspectives of Older Adults Near the End of Their Lives
Another source of definition of wisdom is the perspective of older persons near the end of their lives—a time when most persons describe a clarity about the most meaningful aspects of life.50 Semistructured, qualitative interviews of 21 patients (aged 58–97 years) in hospice care sought to identify major components of wisdom and the effects of the terminal illness on perspectives of wisdom.48 The subjects described the tension between accepting the situation (acknowledging uncertainty, regulating emotion, self-reflection, using sense of humor) and growing/changing personally in response to the situation (increasing openness to new experiences, adopting prosocial attitudes and behaviors, social decision making, and exploring spirituality or religion). The terminal illness motivated the urge to find and accept a balance between these two sides.
Multidimensional Definition of Wisdom
Wisdom is a multidimensional trait comprising several specific components that are useful to the individual and to the society. The whole is greater than the sum of its parts, however, and the ultimate demonstration of wisdom is in behavior.
A requisite for good empirical studies of any construct is its optimal measurement. Subjective assessments form the core of evaluations of most psychological constructs that include well-being, (perceived) stress, optimism, and other personality traits. Our review of measures of wisdom published in peer-reviewed journals48 found that the most widely used measures were self-rated scales.
Baltes and colleagues27,51–53 used questionnaires, surveys, and interviews to develop the Berlin Wisdom Paradigm.27,51–53 It viewed wisdom as a set of measurable skills, rating the respondent’s problem-solving and reasoning skills in response to scenarios such as “A 15-year-old girl wants to get married right away. What should she consider and do?” Trained raters scored the respondents’ ruminations according to the Berlin paradigm’s five identified elements of wisdom (described above). A limitation of this paradigm is its dependence on the raters’ interpretations, which could be biased, and a lack of consideration for emotion and prosocial behaviors in defining wisdom.
Other methods for assessing wisdom have included rating or nomination of (wise) peers, or nomination and characterization of famous wise people—usually Mother Teresa, Mahatma Gandhi, and Nelson Mandela. These methods also have limitations, including a subject’s knowledge of the peer or celebrity as well as own biases.
Two of the self-rated scales with good psychometric properties are Three-Dimensional Wisdom Scale (3D-WS)6 and Self-Assessed Wisdom Scale (SAWS).54 The 3D-WS includes statements regarding the three dimensions of wisdom: cognitive, reflective, and affective. Respondents have to choose one of five options, from “strongly agree” to “strongly disagree” on statements such as “Ignorance is bliss” (cognitive), “I sometimes find it difficult to see things from another person’s point of view” (reflective), and “Sometimes I feel a real compassion for everyone” (affective). A limitation of the 3D-WS is its length (39 items). Recently, an abbreviated 12-item version, the 3D-WS-12,10 was developed and found to be efficient and reliable. The 40-item SAWS54 is based on five components: critical life experiences, reminiscence and life reflection, openness to experiences, emotional regulation, and humor. It uses a six-point Likert scale from “strongly disagree” to “strongly agree.”
Thomas and colleagues55 recently developed the San Diego Wisdom Scale (SD-WISE), the first scale to build upon a neurobiological model of wisdom, as described below. It assesses the six commonly identified wisdom components: social decision making, emotion regulation, prosocial behaviors, self-reflection, acceptance of uncertainty, and decisiveness. In the initial validation in 524 community-dwelling adults aged 25–104 years, the 24-item SD-WISE was found to be reliable, and demonstrated convergent and discriminant validity. The SD-WISE may be useful in both clinical practice and research settings.55 Cloninger’s suggestion for integrating psychometric and neurobiological data to understand personality56–58 is applicable to wisdom as well.56–58
Two articles examined a number of these wisdom-rating scales systematically.48,59 Gluck and colleagues59 compared four measures (SAWS, 3D-WS, Adult Self-Transcendence Inventory,60 and Berlin Wisdom Paradigm) within a group of 47 persons nominated as wise by their peers and 123 control participants. While no one scale was superior, Gluck and colleagues59 emphasized careful selection of the appropriate scale for the theoretical concept (personal vs. general vs. other wisdom) and developed the Brief Wisdom Screening Scale, based on items most highly correlated to the common factor. Meanwhile, Bangen and colleagues48 reviewed nine instruments and found that while each had specific strengths and limitations, several had merits related to their broad usage (Berlin Wisdom Paradigm), good psychometric properties (3D-WS), broad validity (Wisdom Development Scale,61,62 SAWS), and real-world applicability (reasoning about social conflicts63).
A common criticism of self-rated measures of positive characteristics is social-desirability bias—that is, participants may rate themselves more positively to present a favorable self-image. This bias has two potential sources: conscious manipulation of one’s image and subconscious belief in a positive self-image. Taylor and colleagues64 have reported that the problematic part of social-desirability bias arises from conscious image management rather than from self-deception. In the study of SD-WISE, an image-management measure did not correlate with self-reported wisdom measures.55
While objective measures seem to be desirable, self-reports have often been found to be valid—for example, for quality of life, which is subjective by definition. Similarly, self-rated general health is a significant predictor of morbidity and mortality.65 In a national-level study of 1.3 million Americans, the correlation between subjective well-being of residents (based on census report) and objective measures of community wellness (including cost of living, wages, employment rates, crime rates, education spending, and so on) was surprisingly large (r = 0.6; p < .001).66
Continuous observation of one’s behavior would seem desirable for assessing wisdom. However, aside from practical and ethical issues involved in recording people’s behavior, it is unclear who might be qualified to judge others’ behavior as wise or unwise.
In sum, all these methods have limitations. Eventually a multimodal assessment would be needed.
THE BRAIN REGIONS AND NEUROCIRCUITRY OF WISDOM
The observation that the basic concept of wisdom has not changed significantly from ancient periods (as exemplified in the Gita20) to the present times suggests that it probably has an underlying neurobiological basis.47 Early work on brain localization by Gall and Brodmann in the nineteenth and early twentieth centuries, respectively, attempted to map different abilities to specific neuroanatomical regions.67,68 Gall’s phrenology was ultimately deemed to be fraudulent, but Brodmann’s work was instrumental in numbering and assigning specific functions (e.g., motor, sensory) to specific parts of the cerebral cortex, now known as Brodmann areas. However, while motoric or sensory effects of stimulating or damaging certain brain regions can be discerned from animal studies, the areas responsible for wisdom or its components are far more difficult to pinpoint directly in animals or humans.
Meeks and Jeste47 reviewed the literature on neuroimaging, genetic, neurochemical, and neuropathological associations of each of the above mentioned six components of wisdom as well as conditions or behaviors reflecting a lack of these components (e.g., antisocial personality, impulsivity, dysregulated mood, and irrational acts). Specific “experiments of nature” were also sought—case reports in which focal lesions in the brain, due to trauma or disease, resulted in loss of behaviors that characterize wisdom. The most famous case is that of Phineas Gage, a construction foreman in Vermont in the late nineteenth century; he suffered a brain injury when an iron rod penetrated his skull and passed through the left frontal lobe, leaving the rest of his brain relatively unaffected.69,70 Gage did not lose consciousness, retained his speech and motor abilities, and lived for another 12 years. However, his personality distinctly changed, from a disciplined, shrewd, and well-liked person to a profane, impulsive, and intemperate one. Other cases of “modern-day Phineas Gages”71,72 have also reported localized brain damage in the prefrontal cortex (PFC) or limbic striatum, causing behavioral changes that indicate a loss of wisdom and a “precipitous decline in social and behavioral functioning.” Loss of wisdom has also been observed in frontotemporal dementia, a dementia that is initially characterized not by memory loss but by personality changes such as impulsivity, poor social awareness, disinhibition, antisocial behavior, and apathy.
Relevant Brain Regions
The lateral PFC is activated during analytical processes, such as decision making when choosing delayed rewards,73,74 impulse control,75 and understanding the perspectives of others.76,77 The lateral PFC inhibits activity in the amygdala and ventral striatum, structures having roles in emotional responses and in decision making regarding immediate rewards.74 Closely linked to the amygdala and ventrolateral PFC is the insular cortex, or insula, which is activated in connection with empathy, emotional awareness and processing, and moral decision making in the face of uncertainty.78,79 The lateral PFC has associated activity in the orbitofrontal cortex and anterior and posterior cingulate cortices. The orbitofrontal cortex is important for decision making in relation to delayed rewards, as lesions in this region are associated with impulsivity.80,81 Activity in the anterior and posterior cingulate cortices has been associated with moral decision making,82 recognizing moral dilemmas,83,84 social decision making,75 and inhibition of prejudicial responses.85,86 For more emotionally linked wisdom components, the medial PFC and reward circuitry have prominent roles. The medial PFC is involved in prosocial attitudes and behaviors (as discerned from studies of theory-of-mind tasks,87,88 social cooperation tasks,89–92 and empathy studies93–95) and also in recognizing moral dilemmas and moral reasoning,84,96 self-reflection,97 and self-transcendental experiences.98 Similarly, the medial PFC is involved in emotion reappraisal—attenuating the amygdala response to negative and positive emotional experiences.99–103 The reward circuitry is involved in social cooperation and altruism.89–92,104 The fronto-parieto-temporal network has been highlighted in the spirituality literature. Prefrontal regions are activated during prayer105 and meditation,106 whereas the superior parietal lobes and temporo-parietal junction have less activation.107 Greater cortical thickness in the parietal lobes is associated with greater importance of spirituality.108 Targeted stimulation studies have shown that inhibition of inferior parietal lobe activity results in increased spirituality.109 Disturbed temporal lobe activity is associated with religious visions.110,111 Mindfulness practices have been associated with the cortical midline structures (default mode network), insula, and amygdala.112
Neurocircuitry Subserving Wisdom and Its Components
Based on the totality of evidence, we have presented in Figure 1 a descriptive summary of neurocircuitry subserving wisdom and its components.47 This description posits that frontal areas including the lateral PFC (mainly, dorsolateral PFC), together with the dorsal anterior cingulate cortex, as well as the orbitofrontal cortex and medial PFC, inhibit or modulate brain regions involved in emotion processing and response (amygdala, ventral striatum, and insula). These inhibitory effects may facilitate wisdom components such as social decision making, emotion regulation, acceptance of diverse value systems, and dealing effectively with uncertainty. Prosocial behaviors may be subserved by the medial PFC, posterior cingulate cortex, insula, orbitofrontal cortex, and reward neurocircuitry. Interaction and balance between the ancient brain regions of the limbic cortex and the more recently evolved PFC appear to promote components of wisdom.47 It is worth noting that the PFC has been implicated in the neurobiology of character, and that the limbic striatum has been linked with temperament in studies of personality.58,113 Spirituality appears to involve multiple brain regions—the PFC, bilateral parietal lobes, and temporal lobes—though the interactions among these regions have not been elucidated. This proposed description assumes normal brain functioning and the absence of dementia and other major brain disorders.
Limitations of the Proposed Neurobiology of Wisdom
The neurobiological description of wisdom presented here is based on an exploratory analysis of the published literature. Wisdom is a holistic, complex, multidimensional trait that likely involves several different neurocircuits, neural contexts, and brain regions—beyond our current understanding of neuroanatomy and neurophysiology in regard to wisdom.114 Future advances in neuroscience will improve our knowledge of the neural networks that are related to such complex psychological traits. The literature that we reviewed has limitations of its own: varying definitions of wisdom components, discordance between experimental, laboratory-based tasks and real-world situations, different sample sizes, varied neuroanatomical definitions, and individual heterogeneity in brain structure and function. The research literature will continue to evolve with improved technological approaches and increased understanding of the biological processes underlying complex human traits.
HUMAN EVOLUTION, LONGEVITY, AND WISDOM
The average human lifespan in the United States has increased from 47 years in 1900 to 80 years today, and is expected to reach 90 by 2050, although there has not been a significant increase in the fertility span or health span.19,115 Thus, most people still have menopause or andropause at age 45–50, and physical strength also begins to decline around that age. Thus, most people now live for several decades after losing fertility. Another paradox of aging is that, despite increasing physical disability, self-reported well-being increases.7,116 As people age, they appear to become happier, suggesting that other psychological factors—for example, wisdom—must be contributing to greater wellness.
Several (but not all27) studies have suggested that wisdom (or its components) increase with age.33,63,117,118 For example, performance on the theory-of-mind tasks has been shown to be better in older than in younger adults.117 Grossman and colleagues63 examined a large community sample aged 25+ years and found that, relative to younger adults, older adults had improved reasoning in regard to social conflicts and that they used higher-order reasoning schemes that reflected tolerance of other perspectives, awareness of one’s limitations, and a willingness to compromise. In a study of two groups of adults (60–84 vs. 18–26 years old), Worthy118 reported that the older adults’ decision making took into account long-term consequences and utilized their past experiences, whereas the younger adults made decisions that were more immediately gratifying. Several studies have also reported that, compared to younger adults, older individuals have better emotion regulation,119,120 prosocial behaviors such as empathy and compassion,121 subjective emotional well-being,122,123 self-reflection or insight,120 and ability to maintain positive relationships.124,125 All these studies are cross-sectional, however, and point to a need for longitudinal studies to establish a link between wisdom and aging more directly.
Wisdom has been reported to be associated with better quality of life among older adults.11,16 Ardelt’s work16 suggests that in older adults, personality and developmental traits have greater impact on well-being than objective factors such as physical health and socioeconomic factors. Among older adults, wisdom was associated with better subjective well-being and life satisfaction, even when accounting for age, gender, race, marital status, physical health, socioeconomic status, financial situations, social involvement, and adversity.11,12,16 Greater wisdom seemed to ameliorate the negative effects of adversity on well-being.11,12 The correlation between wisdom and well-being was significantly stronger in older adults living in assisted care facilities or receiving hospice care compared to community-dwelling adults, and was mediated by a purpose in life and a sense of personal mastery.126
Wisdom is useful not only for the individual himself or herself but also for other people, including own offspring. In the mid 1950s, the biologist Williams127 first suggested a possible rationale for a long human life after menopause: the considerably higher “cost” of reproducing as women age may indicate that instead of expending energy on raising young children at that age, their efforts are better realized in aiding their adult offspring to reproduce. This “Grandma Hypothesis”115 posits that post-reproductive women may compensate for lost fertility by caring for their grandchildren, thus reducing the child-rearing burden on their own offspring. This allows their children to reproduce earlier, more frequently, and more successfully. Evidence for the Grandma Hypothesis comes from animal19 and human studies. Orca whales, who form multigenerational pods, have significantly increased mortality risk of offspring (up to 5-fold in daughters and 14-fold in sons) after the death of a post-reproductive female whale in the pod.128 Similarly, the presence of grandmothers in Asian elephant herds increases rates of reproduction and calf survival.129 Grandmothers aid directly in rearing offspring, as illustrated in Seychelles warblers, where post-reproductive females help the breeding pair feed chicks,130 and bottlenose dolphins, who nurse their grand-offspring.131
The anthropologist Hawkes reported a similar phenomenon in extant hunter-gatherer societies. Within the Hadza, a Tanzanian hunter-gathering society, involvement of grandmother helpers increase longevity of the grandchildren.132 Similarly, in modern societies, when grandparents are involved in the raising of grandchildren, the grandchildren have better outcomes: fewer emotional problems, fewer adjustment difficulties, and more prosocial behaviors.133 Similarly, findings from 127 multigenerational households (children, parents, grandparents) studied by Conger and colleagues in the Family Transitions Project134 showed that grandchildren with greater grandmother involvement had fewer behavioral problems. A multigenerational study of 2800 Canadian and Finnish women born before 1900 reported that the children of older mothers had better reproductive outcomes—having their own children earlier, more frequently, and more successfully.19
The ability of grandparents to care for grandchildren is negatively affected by age-related disease, including neurodegenerative disorders (e.g., Alzheimer’s disease) and cardiovascular disease. Thus, decreased vulnerability to such illnesses may confer evolutionary advantages, even on the gene-level. Varki and co-authors135 found that a variant of CD33 that suppresses the accumulation of amyloid beta peptide in the brain was four times more common in humans than in chimpanzees, one of our most genetically similar relatives. Similarly, while the APOE4 allele is a known risk factor for Alzheimer’s and cerebrovascular diseases, the APOE2 and APOE3 alleles appear to confer lower risk of dementia and are more prevalent in humans. These derived protective alleles, dubbed the “grandparent genes,” may have evolved to protect against neurodegeneration and cerebrovascular disease in order to maximize the contributions of post-reproductive, “wise” individuals to the raising of their kin.135
WISDOM-RELATED NEUROPLASTICITY OF AGING
The development of wisdom over the lifespan has been challenging to study. The current evidence is neither data based nor longitudinal. Though prospective longitudinal studies are lacking, the available evidence suggests that people have the potential to gain wisdom with age. Though life experiences appear to play a role, they are not sufficient to increase wisdom. Erikson’s theory defined wisdom as the final psychosocial conflict of the lifespan, as older adults reflect on their lives.24 Sternberg136 hypothesized several connections between aging and wisdom: increased wisdom after a spiritual awakening, increased wisdom during adolescence in tandem with increased fluid intelligence, increased wisdom throughout life in tandem with accumulated knowledge over the lifetime, initial increase and later plateau of wisdom in tandem with the changes in fluid and crystallized intelligence over the lifetime, and decreased wisdom with age due to loss of epistemic wisdom (self-centered overconfidence or self-defeating loss of wisdom). Trajectories of wisdom likely vary for each individual, with wisdom accumulating from personal experiences and relationships.29,137 Ardelt138 acknowledges that, while aging may not inherently increase wisdom, wise persons tend to be older because of the amount of time required to accumulate wisdom.
Though aging is generally associated with progressive cognitive dysfunction, the effect is not homogenous. With appropriate physical, cognitive, and psychosocial stimulation, brains continue to evolve even in later life, suggesting the neuroplasticity of aging. Gage and colleagues139 have reported that physical activity and psychosocial stimulation in old mice lead to increased synaptic connections, cerebrovascular growth, and neurogenesis in the dentate gyrus of the hippocampus and periventricular region. These findings have been replicated in other animal species.140,141 Such processes may serve to compensate for age-related brain degeneration in humans.142,143
Evidence suggest that compensatory phenomena have the effect of neutralizing or overcoming the deleterious effects of aging-associated neurodegenerative changes in people who are active. A review of 50 studies of structural brain imaging and cognitive aging144 showed an association of successful cognitive aging with larger structures and greater connectivity in the brain, notably in the PFC and medial temporal lobe. To compensate for aging processes in the brain that result in a loss of synapses and neurons, more neuronal networks may need to be involved in performing a mental activity in older than in younger adults.145 Active older adults’ brains are less likely to show atrophic changes than those of sedentary, lonely, inactive seniors.144,146–148 Hemispheric asymmetry reduction in older adults (HAROLD) refers to increased activity in the contralateral brain region and decreased lateralization in older adults.149 By engaging more of the brain, an active older adult may be able to do as well as a younger person in cognitive tasks, such as learning new things. In terms of specific enhancement of the activity of frontal and prefrontal cortex, studies suggest a posterior anterior shift with aging (PASA) that reflects decreased activity in the posterior regions and increased activity in the anterior brain regions in older adults.150,151
Aging is also associated with a change in emotional responsivity. Carstensen and colleagues123,152,153 showed that in older age, with a growing awareness of the limited time left, people worry less about the future and report greater personal satisfaction in past experiences. This “socioemotional selectivity” theory highlights the importance of emotional goals as the time horizon shrinks. Similarly, a study of brain scans and other tests of emotional activity demonstrated reduced “regret responsiveness” in older healthy participants than in younger adults.120 The older adults reported greater ability to dispel feelings of disappointment and remorse, and overall less concern about things that they could not change. Notable in this context is that the increased emotional positivity of older individuals is partially tied into changes in the brain itself: the aging amygdala becomes less responsive to stressful images and negative emotions on functional imaging studies;154,155 brain activation in response to negative emotional stimuli, regret, and fear is decreased;120 and dopaminergic activity in the reward circuitry is reduced,156 Notable, too, is the decreased functional connectivity between the amygdala and the hippocampus, and increased connectivity between the amygdala and dorsolateral prefrontal cortex—changes that may effectively reduce negative memories while enhancing positive ones.154,155
Can wisdom be increased? This important question deserves to be investigated empirically, and several reasons support the motion that wisdom is modifiable. Other traits such as resilience and optimism have been found to be moderately heritable (with estimates of 33% to 52%),157 suggesting that they can be influenced by environmental factors to a significant extent. While the heritability of wisdom is unstudied, it may be similar to that of other personality traits. Several recent studies have reported increases in resilience and optimism with behavioral interventions.158–162 While acknowledging limitations of these clinical trials, it seems that such traits can be improved through psychotherapeutic techniques. Importantly, if wisdom can be markedly impaired by specifically located brain trauma or diseases such as frontotemporal dementia, as discussed above, it should be theoretically possible to enhance it through interventions that enhance the functioning of those brain regions through biological or behavioral techniques. Moreover, deficits in wisdom may be global (e.g., frontotemporal dementia and impaired judgment, prosocial behaviors, and empathy) or targeted (e.g., autism and social cognition). Given that the components of wisdom overlap and are interrelated, improving one component of wisdom may improve others. Though interventions targeting one component may be easier to execute, multicomponent interventions may confer greater overall benefit, as when the combination of exercise and diet interventions results in greater weight loss.
We are conducting a systematic review of randomized, controlled trials (RCTs) (Jeste et al., unpublished). Our search identified interventions that mostly targeted compassion and empathy, emotion regulation, and spirituality—three of the major components of wisdom. A majority of studies were conducted in adult participants, including a few in adults over age 60. While some interventions were conducted in community participants (e.g., elementary or middle-school students, bullies in schools, couples in long-term relationships), several interventions involved subjects with mental illnesses (e.g., depression, anxiety disorders, and personality disorders, or physical illnesses (e.g., breast cancer and cardiovascular disease).
We only found two published interventions that improved wisdom as a whole—one RCT and one nonrandomized trial. The RCT was an illustrative cross-over study examining life-review therapy in older veterans with PTSD,163 which reported increased wisdom (as measured by SAWS) with the life-review therapy. The nonrandomized spirituality intervention164 involved group discussions of biblical passages and applications to contemporary situations, and reported increased self-rated wisdom (Wise Thinking and Acting Questionnaire).
A number of interventions focused on specific components of wisdom. An RCT in patients with binge eating disorder found that a three-week self-compassion training and food-planning intervention was significantly associated with improved eating disorder pathology and self-compassion compared to a food-planning/behavioral-strategies intervention and a wait-list control condition.165 An especially interesting RCT compared empathy and compassion training to a memory intervention control group in young adult women.166 It used an fMRI socio-affective video task to analyze the effects on activation of relevant brain regions. The training intervention significantly increased empathy and compassion on validated rating scales. Additionally, it enhanced brain activation in the anterior insula and anterior midcingulate cortex, regions associated with empathy regarding pain, as well as in the ventral striatum, anterior cingulate, and medial orbitofrontal cortex, regions identified in our proposed wisdom neurocircuit.
Several limitations of the intervention literature must be noted. The reports had variable information on study participants’ characteristics, theoretical basis underlying the intervention, trial methodology, outcomes evaluated, and statistics employed. Longer-term efficacy of the interventions is not known. Only one RCT and one nonrandomized pilot study used a scale for wisdom as an outcome measure;163 all others focused on individual components of wisdom. Notwithstanding these limitations, our review of wisdom-related interventions suggests that it is possible to improve certain components of wisdom in at least subgroups of subjects with or without mental or physical illnesses. Approximately half of the RCTs reported significant improvements in the primary outcome measures and in well-being, with medium to large effect sizes. Thus, well-chosen interventions have the potential to improve the well-being of persons with psychiatric disorders (especially for interventions involving prosocial behavior and emotion-regulation training) or physical illnesses (particularly for enhancing spirituality in illnesses such as cancer or as a component of palliative/hospice care) by enhancing wisdom components. Interventions that aim to improve overall wisdom should address multiple components and include outcomes related to mental and physical well-being. Clinically, such interventions have great relevance to brain disorders that lead to general loss of wisdom (e.g., frontotemporal dementia and brain injuries). Many clinical challenges associated with these illnesses are related to problems like impulsivity, lack of empathy, and difficulty with emotion regulation. Current medication-based therapies for mood lability and impulsivity are limited by undesirable side effects and inconsistent efficacy. Behavioral interventions to improve these problems would greatly benefit this clinical population. Furthermore, the general population of all ages would benefit from increased wisdom or components of wisdom as they navigate difficult situations in their everyday lives.
Carefully designed trials targeting wisdom as a contributor to overall health would be useful. We recommend larger, hypothesis-driven RCTs with appropriately selected control groups that use validated outcome measures of wisdom, well-being, and overall health. Technological tools such as biofeedback and virtual reality may be used to facilitate interventions. Finally family-, group-, and community-level interventions should be considered.
PROPOSED MODEL OF THE DEVELOPMENT OF WISDOM
Similar to the complex gene × environment interactions that have been postulated in the development of resilience,167 we propose a model of the development of wisdom that draws from genetic, epigenetic, and environmental influences (Figure 2). Specific genes (i.e., grandparent genes and others associated with positive psychological traits and wisdom components) may increase the propensity for wisdom. A pro-wisdom environment, either through a supportive family (e.g., the Grandma Hypothesis) or societal structure, influences an individual’s development of prosocial behaviors, emotion regulation, self-reflection, spirituality, and other wisdom components. The genetic and environmental influences are further modulated by changes associated with aging. Epigenetic changes are triggered by life events that range from different types of adversities to physical, cognitive, and social stimulation. Similarly, aging affects brain structures and connections within the wisdom neurobiology as well as their interconnections with outside structures such as the hippocampus. Aging of the brain in an active older person may be associated with the HAROLD and PASA mechanisms described above and also with reduced amygdala responsiveness to negative or stressful stimuli. All of these influences may contribute to stronger and more balanced functioning of the dorsolateral and ventromedial prefrontal cortex and limbic striatrum, leading to greater wisdom, with both individual- and societal-level benefits. Such benefits then feed back to sustain pro-wisdom genes and environments.
IMPLICATIONS AND RECOMMENDATIONS
Increased wisdom with aging provides at least a partial answer to two major paradoxes of aging: why humans survive for decades after their fertility period ends and why older people are happier than younger ones. Wisdom benefits both the individual and the society as a whole. Increased wisdom in older individuals enables them to flourish in later life, while the grandparents improve species survival (Grandma Hypothesis) and also impart wisdom to younger generations.
Future wisdom research has several potential applications and directions.
- –Wisdom has important associations with mental health and well-being. Future work should investigate the relationship of wisdom to physical health, including biomarkers of aging.
- –Wisdom has relevance to neuropsychiatric disorders that affect judgment and personality, such as frontotemporal dementia and frontal lobe injuries and tumors. Research on “personality rehabilitation” (comparable to physical or cognitive rehabilitation) to address this loss of wisdom would have public health significance.
- –Younger people report worse mental health than older individuals.116,124,125,154,168,169 Furthermore, research in the past 30 years has suggested that mental illnesses may be becoming more prevalent in youth but less common in older adults, attributed to declining incidence, better rates of recovery, and healthy survivor bias.170,171 Intergenerational activities such as the Baltimore Experience Corps, which recruited older community-dwelling adults to serve as volunteer mentors and tutors in elementary schools, have been shown to improve outcomes for both the children (whose grades rose along with mental health) and the older adults involved.172,173 Older participants not only had greater well-being, happiness, and purpose in life, but also increased cortical and hippocampal volumes at two-year follow-up compared to the control group.172 Research is warranted on biopsychosocial effects, including formal assessment of wisdom and its components, in both youth and older adults participating in different levels of intergenerational programs.
- –The educational system has traditionally valued intelligence and academic skills,174 but these do not necessarily translate to increasing wisdom (i.e., emotion regulation and prosocial behaviors) or ensure greater well-being. The need for teaching wisdom of life extends to graduate and professional education, including medical school. High rates of burnout, depression, and suicide among medical students and physicians have been attributed, in part, to intense work stress, and warrant a greater focus on well-being and happiness.175–178 The educational system would be an attractive venue to try to systematically increase wisdom, and thus well-being, to benefit both individuals and societies. Standardized assessments are critical to demonstrate effectiveness of such programs.
- –Further elucidating the biological mechanisms underlying wisdom could identify possible biomarkers of wisdom—for example, neuroimaging markers of greater or reduced activity of specific brain regions in response to selected tasks.
- –Development and testing of wisdom-enhancing interventions should be a key research area.
In conclusion, there is a need to expand empirical research on wisdom, given its immense but largely untapped potential for enhancing mental health of individuals and promoting well-being of the society at large.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
1. Plato; Jowett B, ed. & trans. The dialogues of Plato. 3rd ed. London: Oxford University Press, 1892.
2. Hicks RD. Stoic and Epicurean. New York: Charles Scribner’s Sons, 1910.
3. Vaillant GE. The wisdom
of the ego. Cambridge, MA: Harvard University Press, 1998.
4. Vaillant GE. Positive emotions, spirituality and the practice of psychiatry. Mens Sana Monogr 2008;6:48–62.
5. Vaillant GE. Aging well: surprising guideposts to a happier life from the Landmark Harvard Study of Adult Development. Boston: Little, Brown, 2002.
6. Ardelt M. Empirical assessment of a three-dimensional wisdom
scale. Res Aging 2003;25:275–324.
7. Jeste DV, Savla GN, Thompson WK, et al. Association between older age and more successful aging: critical role of resilience and depression. Am J Psychiatry 2013;170:188–96.
8. Roháriková R, Špajdel M, Cviková V, Jagla F. Tracing the relationship between wisdom
and health. Act Nerv Super Rediviva 2013;55:95–102.
9. Webster JD, Westerhof GJ, Bohlmeijer ET. Wisdom
and mental health across the lifespan. J Gerontol B Psychol Sci Soc Sci 2014;69:209–18.
10. Thomas ML, Bangen KJ, Ardelt M, Jeste DV. Development of a 12-item abbreviated Three-Dimensional Wisdom
Scale (3D-WS-12): item selection and psychometric properties. Assessment 2017;24:71–82.
11. Ardelt M. Antecedents and effects of wisdom
in old age—a longitudinal perspective on aging well. Res Aging 2000;22:360–94.
12. Ardelt M, Jeste DV. Wisdom
and hard times: the ameliorating effect of wisdom
on the negative association between adverse life events and well-being. J Gerontol B Psychol Sci Soc Sci 2018;73:1374–83.
13. Bergsma A, Ardelt M. Self-reported wisdom
and happiness: an empirical investigation. J Happiness Stud 2012;13:481–99.
14. Etezadi S, Pushkar D. Why are wise people happier? An explanatory model of wisdom
and emotional well-being in older adults. J Happiness Stud 2013;14:929–50.
15. Zacher H, McKenna B, Rooney D. Effects of self-reported wisdom
on happiness: not much more than emotional intelligence? J Happiness Stud 2013;14:1697–716.
16. Ardelt M. Wisdom
and life satisfaction in old age. J Gerontol B Psychol Sci Soc Sci 1997;52B:P15–27.
17. Ferrari M, Kahn A, Benayon M, Nero J. Phronesis, Sophia, and Hochma: developing wisdom
in Islam and Judaism. Res Hum Dev 2011;8:128–48.
18. Le TN. Life satisfaction, openness value, self-transcendence, and wisdom
. J Happiness Stud 2011;12:171–82.
19. Lahdenpera M, Lummaa V, Helle S, Tremblay M, Russell AF. Fitness benefits of prolonged post-reproductive lifespan in women. Nature 2004;428:178–81.
20. Jeste DV, Vahia IV. Comparison of the conceptualization of wisdom
in ancient Indian literature with modern views: focus on the Bhagavad Gita. Psychiatry 2008;71:197–209.
21. Sternberg RJ, Jordan J. A handbook of wisdom
: psychological perspectives. Cambridge, New York: University of Cambridge Press, 2005.
22. Takahashi M, Overton WF. Wisdom
: a culturally inclusive developmental perspective. Int J Behav Dev 2002;26:269–77.
23. Staudinger UM, Gluck J. Psychological wisdom
research: commonalities and differences in a growing field. Annu Rev Psychol 2011;62:215–41.
24. Erikson EH. Eight ages of man. Int J Psychiatry 1966;2:281–300.
25. Erikson EH. Identity and the life cycle. Psychol Issues 1959;1:173.
26. Erikson EH. Insight and responsibility: lectures on the ethical implications of psychoanalytic insight. New York: Norton, 1964.
27. Smith J, Baltes PB. Wisdom
related knowledge: age/cohort differences in response to life-planning problems. Dev Psychol 1990;26:494–505.
28. Clayton VP, Birren JE. The development of wisdom
across the life-span: a reexamination of an ancient topic. In: Baltes PB, Brim OG, eds. Life-span development and behavior. New York: Academic, 1980:103–35.
29. Baltes PB, Staudinger UM. Wisdom
: a metaheuristic (pragmatic) to orchestrate mind and virtue toward excellence. Am Psychol 2000;55:122–36.
30. Sternberg RJ. A balance theory of wisdom
. Rev Gen Psychol 1998;2:347–65.
31. Sternberg RJ. Wisdom
, intelligence, and creativity synthesized. Cambridge, New York: Cambridge University Press, 2003.
32. Sternberg RJ. Wisdom
and its relations to intelligence and creativity. In: Sternberg RJ, ed. Wisdom
: its nature, origins, and development. Cambridge: Cambridge University Press, 1990:142–59.
33. Mickler C, Staudinger UM. Personal wisdom
: validation and age-related differences of a performance measure. Psychol Aging 2008;23:787–99.
34. Williams PB, Mangelsdorf HH, Kontra C, Nusbaum HC, Hoeckner B. The relationship between mental and somatic practices and wisdom
. PLoS One 2016;11:e0149369.
35. Vaillant GE, Mukamal K. Successful aging. Am J Psychiatry 2001;158:839–47.
36. Ardelt M, Gerlach KR, Vaillant GE. Early and midlife predictors of wisdom
and subjective well-being in old age. J Gerontol B Psychol Sci Soc Sci 2018;73:1514–25.
37. Josefsson K, Cloninger CR, Hintsanen M, Jokela M, Pulkki-Raback L, Keltikangas-Jarvinen L. Associations of personality profiles with various aspects of well-being: a population-based study. J Affect Disord 2011;133:265–73.
38. Blazer DG. Successful aging. Am J Geriatr Psychiatry 2006;14:2–5.
39. Blazer D. Religion/spirituality and depression: what can we learn from empirical studies? Am J Psychiatry 2012;169:10–2.
40. George LK, Kinghorn WA, Koenig HG, Gammon P, Blazer DG. Why gerontologists should care about empirical research on religion and health: transdisciplinary perspectives. Gerontologist 2013;53:898–906.
41. Achenbaum WA, Orwoll L. Becoming wise: a psycho-gerontological interpretation of the Book of Job. Int J Aging Hum Dev 1991;32:21–39.
42. Perry CL, Komro KA, Jones RM, Munson K, Williams CL, Jason L. The measurement of wisdom
and its relationship to adolescent substance use and problem behaviors. J Child Adolesc Subst Abuse 2002;12:45–63.
43. Jason LA, Reichler A, King C, Madsen D, Camacho J, Marchese W. The measurement of wisdom
: a preliminary effort. J Community Psychol 2001;29:585–98.
44. Wink P, Helson R. Practical and transcendent wisdom
: their nature and some longitudinal findings. J Adult Dev 1997;4:1–15.
45. Prensky M. Brain gain: technology and the quest for digital wisdom
. New York: Palgrave Macmillan, 2012.
46. Mcarthur T, Lam-Mcarthur J, Fontaine E, eds. Oxford English dictionary, s.v. “wisdom
.” London, New York: Oxford University Press, 2018.
47. Meeks TW, Jeste DV. Neurobiology of wisdom
: a literature overview. Arch Gen Psychiatry 2009;66:355–65.
48. Bangen KJ, Meeks TW, Jeste DV. Defining and assessing wisdom
: a review of the literature. Am J Geriatr Psychiatry 2013;21:1254–66.
49. Jeste DV, Ardelt M, Blazer D, Kraemer HC, Vaillant G, Meeks TW. Expert consensus on characteristics of wisdom
: a Delphi method study. Gerontologist 2010;50:668–80.
50. Montross-Thomas LP, Joseph J, Edmonds EC, Palinkas LA, Jeste DV. Reflections on wisdom
at the end of life: qualitative study of hospice patients aged 58–97 years. Int Psychogeriatr 2018 Jan 24:1–8.
51. Baltes PB, Staudinger UM, Maercker A, Smith J. People nominated as wise: a comparative study of wisdom
-related knowledge. Psychol Aging 1995;10:155–66.
52. Staudinger UM, Baltes PB. Interactive minds: A facilitative setting for wisdom
-related performance? J Pers Soc Psychol 1996;71:746–62.
53. Gluck J, Baltes PB. Using the concept of wisdom
to enhance the expression of wisdom
knowledge: not the philosopher’s dream but differential effects of developmental preparedness. Psychol Aging 2006;21:679–90.
54. Webster JD. An exploratory analysis of a self-assessed wisdom
scale. J Adult Dev 2003;10:13–22.
55. Thomas ML, Bangen KJ, Palmer BW, et al. A new scale for assessing wisdom
based on common domains and a neurobiological model: the San Diego Wisdom
Scale (SD-WISE). J Psychiatr Res 2019;108:40–7.
56. Cloninger CR. The psychobiological theory of temperament and character: comment on Farmer and Goldberg (2008). Psychol Assess 2008;20:292–9; discussion 300–4.
57. Cloninger CR, Svrakic DM. Integrative psychobiological approach to psychiatric assessment and treatment. Psychiatry 1997;60:120–41.
58. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry 1993;50:975–90.
59. Gluck J, Konig S, Naschenweng K, et al. How to measure wisdom
: content, reliability, and validity of five measures. Front Psychol 2013;4:405.
60. Levenson MR, Jennings PA, Aldwin CM, Shiraishi RW. Self-transcendence: conceptualization and measurement. Int J Aging Hum Dev 2005;60:127–43.
61. Brown SC, Greene JA. The Wisdom
Development Scale: translating the conceptual to the concrete. J Coll Stud Dev 2006;47:1–19.
62. Greene JA, Brown SC. The Wisdom
Development Scale: further validity investigations. Int J Aging Hum Dev 2009;68:289–320.
63. Grossmann I, Na J, Varnum ME, Park DC, Kitayama S, Nisbett RE. Reasoning about social conflicts improves into old age. Proc Natl Acad Sci U S A 2010;107:7246–50.
64. Taylor M, Bates G, Webster JD. Comparing the psychometric properties of two measures of wisdom
: predicting forgiveness and psychological well-being with the Self-Assessed Wisdom
Scale (SAWS) and the Three-Dimensional Wisdom
Scale (3D-WS). Exp Aging Res 2011;37:129–41.
65. DeSalvo KB, Bloser N, Reynolds K, He J, Muntner P. Mortality prediction with a single general self-rated health question. A meta-analysis. J Gen Intern Med 2006;21:267–75.
66. Oswald AJ, Wu S. Objective confirmation of subjective measures of human well-being: evidence from the U.S.A. Science 2010;327:576–9.
67. Zola-Morgan S. Localization of brain function: the legacy of Franz Joseph Gall (1758–1828). Annu Rev Neurosci 1995;18:359–83.
68. Finger S. Origins of neuroscience: a history of explorations into brain function. New York: Oxford University Press, 1994.
69. Koenigs M, Young L, Adolphs R, et al. Damage to the prefrontal cortex increases utilitarian moral judgements. Nature 2007;446:908–11.
70. Haas LF. Phineas Gage and the science of brain localisation. J Neurol Neurosurg Psychiatry 2001;71:761.
71. Cato MA, Delis DC, Abildskov TJ, Bigler E. Assessing the elusive cognitive deficits associated with ventromedial prefrontal damage: a case of a modern-day Phineas Gage. J Int Neuropsychol Soc 2004;10:453–65.
72. Adolphs R, Tranel D, Damasio H, Damasio A. Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 1994;372:669–72.
73. Ernst M, Paulus MP. Neurobiology of decision making: a selective review from a neurocognitive and clinical perspective. Biol Psychiatry 2005;58:597–604.
74. McClure SM. Separate neural systems value immediate and delayed monetary rewards. Science 2004;306:503–7.
75. Congdon E, Canli T. The endophenotype of impulsivity: reaching consilience through behavioral, genetic, and neuroimaging approaches. Behav Cogn Neurosci Rev 2005;4:262–81.
76. Samson D, Apperly IA, Humphreys GW. Error analyses reveal contrasting deficits in “theory of mind”: neuropsychological evidence from a 3-option false belief task. Neuropsychologia 2007;45:2561–9.
77. Samson D, Apperly IA, Kathirgamanathan U, Humphreys GW. Seeing it my way: a case of a selective deficit in inhibiting self-perspective. Brain 2005;128:1102–11.
78. Mitchell DG. The nexus between decision making and emotion regulation: a review of convergent neurocognitive substrates. Behav Brain Res 2011;217:215–31.
79. Critchley HD. Neural mechanisms of autonomic, affective, and cognitive integration. J Comp Neurol 2005;493:154–66.
80. Berlin HA. Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions. Brain 2004;127:1108–26.
81. Eshel N, Nelson EE, Blair RJ, Pine DS, Ernst M. Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices. Neuropsychologia 2007;45:1270–9.
82. Thomas M, Martin AS, Eyler LT, et al. Individual differences in level of wisdom
are associated with brain activation during a moral decision-making task. Brain Behav 2019. doi: 10.1002/brb3.1302.
83. Greene JD, Nystrom LE, Engell AD, Darley JM, Cohen JD. The neural bases of cognitive conflict and control in moral judgment. Neuron 2004;44:389–400.
84. Robertson D, Snarey J, Ousley O, et al. The neural processing of moral sensitivity to issues of justice and care. Neuropsychologia 2007;45:755–66.
85. Amodio DM, Harmon-Jones E, Devine PG, Curtin JJ, Hartley SL, Covert AE. Neural signals for the detection of unintentional race bias. Psychol Sci 2004;15:88–93.
86. Cunningham WA, Johnson MK, Raye CL, Gatenby JC, Gore JC, Banaji MR. Separable neural components in the processing of black and white faces. Psychol Sci 2004;15:806–13.
87. Fletcher P. Other minds in the brain: a functional imaging study of “theory of mind” in story comprehension. Cognition 1995;57:109–28.
88. Brunet E, Sarfati Y, Hardy-Baylé M-C, Decety J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage 2000;11:157–66.
89. Rilling JK, Gutman DA, Zeh TR, Pagnoni G, Berns GS, Kilts CD. A neural basis for social cooperation. Neuron 2002;35:395–405.
90. Decety J, Jackson PL, Sommerville JA, Chaminade T, Meltzoff AN. The neural bases of cooperation and competition: an fMRI investigation. Neuroimage 2004;23:744–51.
91. Singer T, Kiebel SJ, Winston JS, Dolan RJ, Frith CD. Brain responses to the acquired moral status of faces. Neuron 2004;41:653–62.
92. de Quervain DJ, Fischbacher U, Treyer V, et al. The neural basis of altruistic punishment. Science 2004;305:1254–8.
93. Seitz RJ, Schäfer R, Scherfeld D, et al. Valuating other people’s emotional face expression: a combined functional magnetic resonance imaging and electroencephalography study. Neuroscience 2008;152:713–22.
94. Farrow TFD, Zheng Y, Wilkinson ID, et al. Investigating the functional anatomy of empathy and forgiveness. Neuroreport 2001;12:2433–8.
95. Seitz RJ, Nickel J, Azari NP. Functional modularity of the medial prefrontal cortex: involvement in human empathy. Neuropsychology 2006;20:743–51.
96. Greene JD. An fMRI investigation of emotional engagement in moral judgment. Science 2001;293:2105–8.
97. Fossati P, Hevenor SJ, Graham SJ, et al. In search of the emotional self: an fMRI study using positive and negative emotional words. Am J Psychiatry 2003;160:1938–45.
98. van Elk M, Aleman A. Brain mechanisms in religion and spirituality: an integrative predictive processing framework. Neurosci Biobehav Rev 2017;73:359–78.
99. Phan KL, Fitzgerald DA, Nathan PJ, Moore GJ, Uhde TW, Tancer ME. Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol Psychiatry 2005;57:210–9.
100. Goldin PR, McRae K, Ramel W, Gross JJ. The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biol Psychiatry 2008;63:577–86.
101. Ochsner KN, Bunge SA, Gross JJ, Gabrieli JDE. Rethinking feelings: an fMRI study of the cognitive regulation of emotion. J Cogn Neurosci 2002;14:1215–29.
102. Cooney RE, Joormann J, Atlas LY, Eugène F, Gotlib IH. Remembering the good times: neural correlates of affect regulation. Neuroreport 2007;18:1771–4.
103. Kim SH, Hamann S. Neural correlates of positive and negative emotion regulation. J Cogn Neurosci 2007;19:776–98.
104. Harbaugh WT, Mayr U, Burghart DR. Neural responses to taxation and voluntary giving reveal motives for charitable donations. Science 2007;316:1622–5.
105. Newberg A, Pourdehnad M, Alavi A, d’Aquili EG. Cerebral blood flow during meditative prayer: preliminary findings and methodological issues. Percept Mot Skills 2003;97:625–30.
106. Newberg AB. The neuroscientific study of spiritual practices. Front Psychol 2014;5:215.
107. Newberg A, Alavi A, Baime M, Pourdehnad M, Santanna J, d’Aquili E. The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study. Psychiatry Res 2001;106:113–22.
108. Miller L, Bansal R, Wickramaratne P, et al. Neuroanatomical correlates of religiosity and spirituality: a study in adults at high and low familial risk for depression. JAMA Psychiatry 2014;71:128–35.
109. Crescentini C, Aglioti SM, Fabbro F, Urgesi C. Virtual lesions of the inferior parietal cortex induce fast changes of implicit religiousness/spirituality. Cortex 2014;54:1–15.
110. Horga G, Schatz KC, Abi-Dargham A, Peterson BS. Deficits in predictive coding underlie hallucinations in schizophrenia. J Neurosci 2014;34:8072–82.
111. Chan D, Anderson V, Pijnenburg Y, et al. The clinical profile of right temporal lobe atrophy. Brain 2009;132:1287–98.
112. Marchand WR. Neural mechanisms of mindfulness and meditation: evidence from neuroimaging studies. World J Radiol 2014;6:471–9.
113. Cloninger CR. Temperament and personality. Curr Opin Neurobiol 1994;4:266–73.
114. Haber SN, Rauch SL. Neurocircuitry: a window into the networks underlying neuropsychiatric disease. Neuropsychopharmacology 2010;35:1–3.
115. Hamilton WD. The moulding of senescence by natural selection. J Theor Biol 1966;12:12–45.
116. Thomas ML, Kaufmann CN, Palmer BW, et al. Paradoxical trend for improvement in mental health with aging: a community-based study of 1,546 adults aged 21–100 years. J Clin Psychiatry 2016;77:e1019–25.
117. Happe FG, Winner E, Brownell H. The getting of wisdom
: theory of mind in old age. Dev Psychol 1998;34:358–62.
118. Worthy DA, Gorlick MA, Pacheco JL, Schnyer DM, Maddox WT. With age comes wisdom
: decision making in younger and older adults. Psychol Sci 2011;22:1375–80.
119. Mather M, Carstensen LL. Aging and motivated cognition: the positivity effect in attention and memory. Trends Cogn Sci 2005;9:496–502.
120. Brassen S, Gamer M, Peters J, Gluth S, Buchel C. Don’t look back in anger! Responsiveness to missed chances in successful and nonsuccessful aging. Science 2012;336:612–4.
121. Beadle JN, Sheehan AH, Dahlben B, Gutchess AH. Aging, empathy, and prosociality. J Gerontol B Psychol Sci Soc Sci 2015;70:215–24.
122. Helmuth L. Aging. The wisdom
of the wizened. Science 2003;299:1300–2.
123. Carstensen LL, Turan B, Scheibe S, et al. Emotional experience improves with age: evidence based on over 10 years of experience sampling. Psychol Aging 2011;26:21–33.
124. Birditt KS, Jackey LM, Antonucci TC. Longitudinal patterns of negative relationship quality across adulthood. J Gerontol B Psychol Sci Soc Sci 2009;64:55–64.
125. Birditt KS, Fingerman KL, Almeida DM. Age differences in exposure and reactions to interpersonal tensions: a daily diary study. Psychol Aging 2005;20:330–40.
126. Ardelt M, Edwards CA. Wisdom
at the end of life: an analysis of mediating and moderating relations between wisdom
and subjective well-being. J Gerontol B Psychol Sci Soc Sci 2016;71:502–13.
127. Williams GC. Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957;11:398–411.
128. Foster EA, Franks DW, Mazzi S, et al. Adaptive prolonged postreproductive life span in killer whales. Science 2012;337:1313.
129. Lahdenpera M, Mar KU, Lummaa V. Nearby grandmother enhances calf survival and reproduction in Asian elephants. Sci Rep 2016;6:27213.
130. Richardson DS, Burke T, Komdeur J. Grandparent helpers: the adaptive significance of older, postdominant helpers in the Seychelles Warbler. Evolution 2007;61:2790–800.
131. Carey JR, Gruenfelder C. Population biology of the elderly. In: Wachter K, Finch CE, eds. Between Zeus and the salmon. Washington, DC: National Academy, 1997:1–16.
132. Hawkes K, O’Connell JF, Blurton Jones NG. Hadza women’s time allocation, offspring provisioning, and the evolution of long postmenopausal life spans. Curr Anthropol 1997;38:551–77.
133. Attar-Schwartz S, Tan JP, Buchanan A, Flouri E, Griggs J. Grandparenting and adolescent adjustment in two-parent biological, lone-parent, and step-families. J Fam Psychol 2009;23:67–75.
134. Barnett MA, Scaramella LV, Neppl TK, Ontai LL, Conger RD. Grandmother involvement as a protective factor for early childhood social adjustment. J Fam Psychol 2010;24:635–45.
135. Schwarz F, Springer SA, Altheide TK, Varki NM, Gagneux P, Varki A. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline. Proc Natl Acad Sci U S A 2016;113:74–9.
136. Sternberg RJ. Older but not wiser? The relationship between age and wisdom
. Aging Int 2005;30:5–26.
137. Ardelt M, Jacobs S. Wisdom
, integrity and life satisfaction in very old age. In: Smith MC, ed. Handbook of research on adult learning and development. New York: Routledge, 2009:732–60.
138. Ardelt M. Wisdom
, age, and well-being. In: Schaie KW, Willis SL, eds. Handbook of the psychology of aging. 7th ed. London: Elsevier Science & Technology, 2011.
139. Muotri AR, Zhao C, Marchetto MC, Gage FH. Environmental influence on L1 retrotransposons in the adult hippocampus. Hippocampus 2009;19:1002–7.
140. Winocur G, Wojtowicz JM, Huang J, Tannock IF. Physical exercise prevents suppression of hippocampal neurogenesis and reduces cognitive impairment in chemotherapy-treated rats. Psychopharmacology (Berl) 2014;231:2311–20.
141. Gage FH. Neurogenesis in the adult brain. J Neurosci 2002;22:612–3.
142. Dennis NA, Hayes SM, Prince SE, Madden DJ, Huettel SA, Cabeza R. Effects of aging on the neural correlates of successful item and source memory encoding. J Exp Psychol Learn Mem Cogn 2008;34:791–808.
143. Dennis NA, Kim H, Cabeza R. Age-related differences in brain activity during true and false memory retrieval. J Cogn Neurosci 2008;20:1390–402.
144. Kaup AR, Mirzakhanian H, Jeste DV, Eyler LT. A review of the brain structure correlates of successful cognitive aging. J Neuropsychiatry 2011;23:6–15.
145. Bangen KJ, Kaup AR, Mirzakhanian H, Wierenga CE, Jeste DV, Eyler LT. Compensatory brain activity during encoding among older adults with better recognition memory for face-name pairs: an integrative functional, structural, and perfusion imaging study. J Int Neuropsychol Soc 2012;18:402–13.
146. Eyler LT, Sherzai A, Kaup AR, Jeste DV. A review of functional brain imaging correlates of successful cognitive aging. Biol Psychiatry 2011;70:115–22.
147. Brown BM, Peiffer JJ, Martins RN. Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer’s disease? Mol Psychiatry 2013;18:864–74.
148. Barnes JN. Exercise, cognitive function, and aging. Adv Physiol Educ 2015;39:55–62.
149. Cabeza R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging 2002;17:85–100.
150. Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R. Que PASA? The posterior-anterior shift in aging. Cereb Cortex 2008;18:1201–9.
151. Dennis NA, Cabeza R. Neuroimaging of healthy cognitive aging. In: Craik F, Salthouse TA, eds. The handbook of aging and cognition. 3rd ed. New York: Psychology, 2008:1–54.
152. Carstensen LL. The influence of a sense of time on human development. Science 2006;312:1913–5.
153. Reed AE, Carstensen LL. The theory behind the age-related positivity effect. Front Psychol 2012;3:339.
154. Mather M, Canli T, English T, et al. Amygdala responses to emotionally valenced stimuli in older and younger adults. Psychol Sci 2004;15:259–63.
155. St. Jacques PL, Bessette-Symons B, Cabeza R. Functional neuroimaging studies of aging and emotion: fronto-amygdalar differences during emotional perception and episodic memory. J Int Neuropsychol Soc 2009;15:819.
156. Dreher JC, Meyer-Lindenberg A, Kohn P, Berman KF. Age-related changes in midbrain dopaminergic regulation of the human reward system. Proc Natl Acad Sci U S A 2008;105:15106–11.
157. Boardman JD, Blalock CL, Button TM. Sex differences in the heritability of resilience. Twin Res Hum Genet 2008;11:12–27.
158. Adler AB, Williams J, McGurk D, Moss A, Bliese PD. Resilience training with soldiers during basic combat training: randomisation by platoon. Appl Psychol Health Well Being 2015;7:85–107.
159. Saltzman WR, Lester P, Beardslee WR, Layne CM, Woodward K, Nash WP. Mechanisms of risk and resilience in military families: theoretical and empirical basis of a family-focused resilience enhancement program. Clin Child Fam Psychol Rev 2011;14:213–30.
160. Loprinzi CE, Prasad K, Schroeder DR, Sood A. Stress Management and Resilience Training (SMART) program to decrease stress and enhance resilience among breast cancer survivors: a pilot randomized clinical trial. Clin Breast Cancer 2011;11:364–8.
161. Rose RD, Buckey JC Jr, Zbozinek TD, et al. A randomized controlled trial of a self-guided, multimedia, stress management and resilience training program. Behav Res Ther 2013;51:106–12.
162. Creswell JD, Irwin MR, Burklund LJ, et al. Mindfulness-based stress reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain Behav Immun 2012;26:1095–101.
163. Daniels LR, Boehnlein J, McCallion P. Aging, depression, and wisdom
: a pilot study of life-review intervention and PTSD treatment with two groups of Vietnam veterans. J Gerontol Soc Work 2015;58:420–36.
164. McLaughlin PT. The effects of a wisdom
intervention in a Christian congregation. PhD dissertation, George Fox University, 2017.
165. Kelly AC, Carter JC. Self-compassion training for binge eating disorder: a pilot randomized controlled trial. Psychol Psychother 2015;88:285–303.
166. Klimecki OM, Leiberg S, Lamm C, Singer T. Functional neural plasticity and associated changes in positive affect after compassion training. Cereb Cortex 2012;23:1552–61.
167. Russo SJ, Murrough JW, Han MH, Charney DS, Nestler EJ. Neurobiology of resilience. Nat Neurosci 2012;15:1475–84.
168. Birditt KS, Fingerman KL. Do we get better at picking our battles? Age group differences in descriptions of behavioral reactions to interpersonal tensions. J Gerontol B Psychol Sci Soc Sci 2005;60:P121–8.
169. Kennedy Q, Mather M, Carstensen LL. The role of motivation in the age-related positivity effect in autobiographical memory. Psychol Sci 2004;15:208–14.
170. Hudson CG. Declines in mental illness over the adult years: an enduring finding or methodological artifact? Aging Ment Health 2012;16:735–52.
171. Mackenzie CS, El-Gabalawy R, Chou KL, Sareen J. Prevalence and predictors of persistent versus remitting mood, anxiety, and substance disorders in a national sample of older adults. Am J Geriatr Psychiatry 2014;22:854–65.
172. Carlson MC, Kuo JH, Chuang YF, et al. Impact of the Baltimore Experience Corps Trial on cortical and hippocampal volumes. Alzheimers Dement 2015;11:1340–8.
173. Varma VR, Carlson MC, Parisi JM, et al. Experience Corps Baltimore: exploring the stressors and rewards of high-intensity civic engagement. Gerontologist 2015;55:1038–49.
174. McNally J, Honig B, Martin B. A preliminary exploration of the development of wisdom
in entrepreneurship education. Rev Empreendedorismo e Gestão de Pequenas Empresas 2018;7:1–34.
175. Dyrbye LN, West CP, Satele D, et al. Burnout among U.S. medical students, residents, and early career physicians relative to the general U.S. population. Acad Med 2014;89:443–51.
176. Rotenstein LS, Ramos MA, Torre M, et al. Prevalence of depression, depressive symptoms, and suicidal ideation among medical students: a systematic review and meta-analysis. JAMA 2016;316:2214–36.
177. Gold KJ, Sen A, Schwenk TL. Details on suicide among US physicians: data from the National Violent Death Reporting System. Gen Hosp Psychiatry 2013;35:45–9.
178. Cheng J, Kumar S, Nelson E, Harris T, Coverdale J. A national survey of medical student suicides. Acad Psychiatry 2014;38:542–6.