Wednesday, 25.11.2020

Peter R. Martin: Historical Vocabulary of Addiction

 

Resilience

 

        According to the current electronic version of Oxford English Dictionary (OED), the noun resilience is probably a borrowing from the post-classical Latin resilientia (“the action of rebounding”) and classical Latin resilient-, resiliēns, present participle of the verb, resilīre (“To draw back, withdraw, or distance oneself from an undertaking, declaration, course of action, opinion, etc.”) and the suffix,-ia

        The first use of the word resilience in the English language was in 1626 with a now obsolete meaning (“The action or an act of rebounding or springing back; rebound, recoil.”), as exemplified by a quotation of Francis Bacon (1561-1626), the English philosopher and statesman who is credited with developing the scientific method and has been called the father of empiricism (1658): “Whether there be any such Resilience in Eccho's.”  Subsequently, the meaning of resilience was used in physics to describe elasticity of matter (“the power of resuming an original shape or position after compression, bending, etc.”).  This meaning appeared in a lecture by Thomas Young (1773-1829), a British physician and natural philosopher, with notable and extensive contributions to the fields of vision, light, solid mechanics, energy, physiology, language, musical harmony and Egyptology (1807):  “The resilience is jointly proportional to its strength and its toughness and is measured by the product of the mass and the square of the velocity of a body capable of breaking it.” 

        The word was then applied to the study of mechanics (“The energy per unit volume absorbed by a material when it is subjected to strain; the value of this at the elastic limit.”).  This meaning is found in a quotation from William John Macquorn Rankine (1820-1872), a Scottish mechanical engineer who made significant contributions to civil engineering, physics, mathematics and the science of thermodynamics (1858): “The Resilience or Spring of a Beam is the work performed in bending it to the proof deflection.” 

        At about this same time, the word resilience spread to the biological sciences and found a particular meaning in the emerging field of psychology and in medicine (“The quality or fact of being able to recover quickly or easily from, or resist being affected by, a misfortune, shock, illness, etc.; robustness; adaptability.”). A quotation from John Cassell's Illustrated History of England provides an example: “In their struggles with the ponderous power of England [the Scotch] discovered an invincible vigour, not only of resistance, but of resilience” (Smith and Howitt 1856). This quotation does well to underline that fundamental attribute some possess, which only emerges with adversity, to which instead of succumbing as many do, a characteristic robustness or adaptability allows the individual to survive and even thrive. 

        The meaning of resilience used in the field of addiction is that from medicine and psychology.  The word has found an important role in conceptualization of individual predisposition to alcohol/drug use disorder – resilience diminishes, while risk increases, the likelihood of developing addiction by virtue of genetic and/or by environmental factors (Enoch 2006).  Additionally, resilience may contribute to success of addiction treatment and achieving recovery (Yi, Vitaliano, Smith et al. 2008; Martin 2020).  It is generally agreed that alcohol/drug use disorders tend to run in families but which of the many factors which tend to be passed from generation to generation are most relevant remains to be established.  

        A plethora of characteristics have been statistically linked with individual resilience/risk to addiction in family and other studies. Conceptually, susceptibility may operate through interactions among features of the individual, the drug of abuse and the environment: (1) the acute psychopharmacological effects of the drug; (2) the pharmacokinetics of the drug; (3) neuroadaptive brain changes with chronic use; (4) psychopathological characteristics of the user; and (5) vulnerability of the user to medical and psychiatric complications (Omenn and Motulsky 1972; Martin 1981; Enoch 2006). 

        The relative importance of environmental and hereditary factors in etiopathogenesis continued to be a subject of heated debate throughout most of the last century.  Essentially the same evidence has been marshalled to reach diametrically opposite conclusions in the nature-nurture controversy, as these disorders occur in roughly equal numbers among individuals with and without a positive family history (inherited vs. sporadic cases).  Only relatively recently, through advances in molecular and epidemiologic genetics, has the complexity of this pivotal debate become appreciated in its entirety (Cloninger 1987; Cadet 2016).  

        We now know that both arms of the machinery of heredity have important roles in transmission of biological information to the next generation through interaction of genes and the environment.  Lasker (1969) anticipated an enhanced role for adaptation of the human population via environmental pressure compared to what was understood in classical genetics: “This implies an evolutionary tendency to shift human adaptability from genetic selection to ontogenetic plasticity to reversible adaptability.”  In fact, the nature-nurture controversy has been reconciled to some degree through recognition of molecular alterations of gene expression by environmental events: "epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution" (Handel and Ramagopalan 2010).   (Darwinian and Lamarckian evolution is meant as evolutionary selection via genetic inheritance or acquired characteristics, respectively.) 

        The sometimes-vociferous debate about relative contributions of genes and the environment to development of addiction has been further complicated by inexact descriptions of the relevant phenotypes.   For example, consensus about the definition of addiction was relatively late in coming, most definitions served to identify with confidence only the most severe cases and there was tremendous biologic heterogeneity in these disorders, even in clinically similar patient populations (Martin 1981; Kwako, Schwandt, Ramchandani et al. 2019).  Also, many of the clinical characteristics of individuals, defined as having alcohol/drug use disorder, may actually represent complications of self-medication of co-occurring psychiatric disorders, rather than predisposing factors to harmful use of these psychoactive agents (Martin 2019).  Nevertheless, since abuse of alcohol/drugs is the sine qua non of the disorder, there exists a unique opportunity to study genetically high-risk individuals prior to exposure to the etiologic agent.  Additionally, it is possible to examine acute response to known amounts of the substance of abuse or the complications of prolonged use in individuals of variable risk (genetic and environmental).  From such studies, it is possible to identify factors that either increase or diminish the likelihood of development of addiction.

        The concept of resilience has acquired an increasingly important meaning in understanding the pathogenesis of addiction as an attribute of individuals who possess certain characteristics that seem to protect them from the disorder.  Much like apportioning elements of the risk for development of addiction, resilience can be classified as being within the realm(s) of the biological, psychological or social (Engel 1977).  Nevertheless, biologically-based resilience factors, predominantly the capacity to successfully cope with various form of stress (Selye 1937), are actually represented by brain functions which can incorporate and orchestrate all elements of the behavioral repertoire, so that psychosocial and biological elements are inexorably intertwined, as articulated by Sinha (2001): “This conceptualization permits separate consideration of (1) events that cause stress (stressors or stressful life events); (2) cognitive and affective processes evaluating the event and available coping resources (appraisal); (3) biological responses and adaptation needed to cope with the stressor; and (4) behavioral and cognitive response to the stressful event (coping).”  Hence, the tripartite elements comprising resilience modulate and can counteract to some degree determinants that enhance the likelihood of developing addiction; similarly, resilience can augment the prospect of recovery.  This hopeful perspective of resilience has widespread acceptance as expressed by Jerome Kagan (1929-), an American psychologist and one of the pioneers of developmental psychology (1976): “Young mammals seem to retain a capacity for recovery from early experiences that retard normal development if they are fortunate enough to be moved to a more benign context.”  Thus, the challenge is to understand the contributing factors of resilience through the life cycle so that they can be modified to help overcome experience of stress and either prevent or change the clinical course of addiction. 

        Various models of observed and experimentally induced psychosocial stress have been implemented to study risk versus resilience.  Attachment theory (1966) emerged from the observations of John Bowlby (1907-1990), a British psychiatrist and psychoanalyst, notable for his interest in child development.  Harry Harlow (1905-1981), an American psychologist known for his experiments on rhesus monkeys, elucidating the roles of maternal-separation, dependency needs and social isolation that demonstrated the fundamental role of caregiving and companionship to social and cognitive development, identified the implications of disturbed attachment in various forms of psychopathology (Seay, Hansen and Harlow 1962). The relevance of separation-related stress in pathogenesis of addiction was only inferred until it was formally demonstrated in a nonhuman primate model of alcohol abuse by the intellectual progeny of Harlow (Higley, Hasert, Suomi and Linnoila 1991).    

        Michael Rutter (1933-), a British child psychiatrist whose clinical research examined the implications of attachment for general child psychopathology, commented (1985): “although an appreciation that a variety of stressors may play a role in the genesis of psychiatric disorder has a long history, the systematic study of such effects is much more recent.” 

        Investigation of intrapsychic responses to adversity and stress, representing more or less effective coping mechanisms that might moderate the expression of psychopathology throughout development, have been incorporated into psychoanalytic thinking.  For example, Vaillant (1985) examined the “utility of the model of ego mechanisms of defense to explain psychological resilience in 307 middle aged men with socially disadvantaged childhoods” who were prospectively studied for 40 years.  He proposed that the “maturity of defenses” served as a means of coping with developmental stress.  Steinglass, Weiner and Mendelson (1971) suggested that rigidity of interactions within the family played a role in pathogenesis of alcoholism – clearly a means whereby genetic and environmental factors can interact at a psychological level.  

        Somewhat consonant with stress experienced from disturbed family interactions, is the experimental paradigm of “learned helplessness” wherein self-protective escape by rats from electric shock is prevented, resulting in lifelong neurobiological consequences (Garber, Fencil-Morse, Rosellini and Seligman 1979).   Impaired family coping of individuals can spread to communities via psychosocial phenomena related to “behavioral mimicry and contagion” (Chartrand and Lakin 2013).  The consequences of such and related psychobiological forms of stress and coping can be assessed using functional magnetic resonance imaging (fMRI) and adaptations of brain functions associated with recovery and resilience in addiction and its neurobiological correlates may be identified and studied (Burt, Whelan, Conrod et al. 2016; Charlet, Rosenthal, Lohoff et al. 2018).

        Elucidation of the biological mechanisms underpinning the effects of stress on the central nervous system offers a complementary perspective to clinical observations that stressful events often presage psychopathology and that the experience of stress itself, not only is associated with addiction, but is also exacerbated by alcohol/drug abuse (Meerloo 1954; McEwen 2007; Cadet 2016).  Covington, Maze, Sun et al. (2011) investigated how “substance abuse increases an individual's vulnerability to stress-related illnesses, which is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress.” They identified “repressive histone methylation in nucleus accumbens, an important brain reward region, as a key mechanism linking cocaine exposure to increased stress vulnerability.”  Moreover, the investigators demonstrated that specific epigenetic modification of gene expression protected mice from the consequences of subsequent increases in stress susceptibility associated with social stress and repeated cocaine exposure.  

        Of note, using a “food addiction mouse model,” Domingo-Rodriguez, Ruiz de Azua, Dominguez et al. (2020) demonstrated that “the development of food addiction-like behavior… is enhanced… associated with synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc)… In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking.” These findings are important because they support similar neurobiological underpinning of resilience and risk in behavioral addictions as those that have been identified for out-of-control self-administration of alcohol and drugs.  Enhancement of resilience with respect to drug-seeking behavior has also been demonstrated using cognitive training in mice (Boivin, Piscopo and Wilbrecht 2015) underlining that resilience is both pharmacologically and behaviorally modifiable as might be expected in a biopsychosocial disorder.

        Risk and resilience to the experience of stress is a characteristic that can be transmitted from one generation to the next based on epigenetic mechanisms, identified in animals in which maternal rearing practices were experimentally modified (Meaney 2001).  Translation of this idea to humans is found in the work of Yehuda, Schmeidler, Wainberg et al. (1998) who examined the progeny of mothers who survived the inordinate stress of the Holocaust prior to the birth of their children.  They found “an increased vulnerability to posttraumatic stress disorder and other psychiatric disorders among offspring of Holocaust survivors, thus identifying adult offspring as a possible high-risk group within which to explore the individual differences that constitute risk factors for PTSD.” Subsequently, the means of this intergenerational transmission of psychiatric vulnerability, resilience, and symptoms of PTSD in Holocaust survivors’ offspring, was found to be associated with epigenetic changes in expression of a protein regulator of glucocorticoid receptor responsivity (Bierer, Bader, Daskalakis et al. 2020). 

        A specific linkage of PTSD to alcohol/drug use disorders was demonstrated by Reed, Anthony and Breslau (2007), who prospectively followed incidence of drug use disorders in a sample of youngster who experienced traumatic events with and without developing PTSD.  They concluded that: “Posttraumatic stress disorder might be a causal determinant of drug use disorders, possibly representing complications such as attempts to self-medicate troubling trauma-associated memories, nightmares, or painful hyperarousal symptoms.”  Enoch (2006) placed these various determinants of intergenerational transmission of alcohol/drug use in perspective: “Severe childhood stressors have been associated with increased vulnerability to addiction, however, not all stress‐exposed children go on to develop alcoholism… Genetic vulnerability is likely to be conferred by multiple genes of small to modest effects, possibly only apparent in gene-environment interactions… It is likely that a complex mix of gene(s) – environment(s) interactions underlie addiction vulnerability and development. Risk-resilience factors can best be determined in longitudinal studies, preferably starting during pregnancy.”  This quotation suggests that, at this point in history, resilience is a characteristic which, in a practical sense, is only to be retrospectively inferred in humans.  Nevertheless, aspects of resilience can be recognized and possibly serve to allow those at risk to develop addiction to choose positive aspects of their environment.

        In conclusion, resilience is a more optimistic way to view the development of addictive disorders than is risk.  It allows focus on biopsychosocial factors that potentially can be modified to help either prevent or change the clinical course of addiction.  Most importantly, for those who are at risk for the disorder by virtue of their family and social circumstances, wherein addiction seems ubiquitous, this perspective provides pharmacopsychosocial options, which if chosen, increase the likelihood that s/he are not predestined to suffer from addiction and its complications (Martin, Weinberg and Bealer 2007).

 

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October 1, 2020