Peter R. Martin: Historical Vocabulary of Addiction, Vol. II
Anhedonia
According to the electronic version of the Oxford English Dictionary (OED), the noun anhedonia is a borrowing from Greek, combined with English elements, modelled on German and French lexical items. The ancient Greek word ἡδονή (meaning “pleasure,” as in the noun hedonism) follows the prefix an- (“forming nouns and adjectives, with the sense ‘without’; ‘not’; ‘-less’”) and precedes the suffix ‑ia (“a termination of Latin and Greek nouns, in Greek especially frequent as the ending of abstract nouns from adjectives”). The word is partly after the German Anhedonie (1878 or earlier) and partly after the French anhédonie (1896).
There is but one definition of anhedonia in OED: “Loss or diminution of the capacity to feel pleasure or to take interest in activities ordinarily considered pleasurable, occurring especially as a symptom of depressive disorders and certain other mental conditions.” The first use of anhedonia in the English language is exemplified by the translation of a quotation of the French psychologist Théodule-Armand Ribot (1839–1916) from his book The Psychology of the Emotions (1897): [Ribot referring to the French word anhédonie] — “(if I may coin a counter-designation to analgesia) has been very little studied… but there are cases of an insensibility relating to pleasure.”
The natural counterpoint of pleasure to pain was familiar to philosophers well before Ribot. Since experience of pleasure has always seemed important in the healthy emotional life of humans, its diminution or absence may well be experienced as painful. This is suggested by the famous quotation from Epicurus (341–270 BC), the ancient Greek philosopher and sage who founded a highly influential school of philosophy Epicureanism: “For it is then that we have need of pleasure, when we feel pain owing to the absence of pleasure.”
Though not termed as such, psychopathological symptomatology resembling anhedonia was already described in the early 19th century by John Haslam (1764–1844), an English apothecary, physician and medical writer, known for his work on mental illness. Haslam documented one of the earliest studies of insanity in Observations on Madness and Melancholy: Including practical remarks on those diseases, together with cases, and an account of the morbid appearances on dissection in which the following description is found (Haslam 1809):
“A degree of apparent thoughtfulness and inactivity precede, together with a diminution of the ordinary curiosity, concerning that which is passing before them; and they therefore neglect those objects and pursuits which formerly proved sources of delight and instruction. The sensibility appears to be considerably blunted; they do not bear the same affection towards their parents and relations; they become unfeeling to kindness, and careless of reproof. To their companions they shew a cold civility, but take no interest whatever in their concerns.”
The word anhedonia was first employed in psychiatry in association with what are now known as the negative symptoms of schizophrenia (Andreasen 1982). This use is indicated by the definition of the word in a popular American psychiatric lexicon of the mid-20th century Psychiatric Dictionary (Hinsie and Campbell 1960): “Anhedonia…is seen often in schizophrenic patients.” Subsequently, the concept of anhedonia came to be viewed as relevant to various forms of psychopathology other than schizophrenia. Especially, anhedonia was considered an essential symptom in specific, if not all forms of depressive disorders (Klein 1974; Pizzagalli, Iosifescu, Hallett et al. 2008) and even provided an early target for pharmacotherapy (Alexander and Berkeley 1959). Interestingly, anhedonia came close to disappearing for a time from our understanding of depressive disorders until its return near the turn of the present (21st) century (Snaith 1993), possibly because of a fascinating neurobiology that is increasingly amenable to detailed scientific investigation:
“In the last [18th] century psychopathologists attached importance to the concept of anhedonia, the loss of ability to experience pleasure. Its role in the diagnosis of melancholia was considered to be crucial. In the present [20th] century attention to anhedonia has faded, possibly because of the focus upon depressed mood as the pathognomonic feature of depressive disorders. Research on the symptomatology of endogenous depression did not include the concept; anhedonia was also lacking from the major instruments of psychiatric research, the depression rating scales.”
A significant interest in anhedonia has continued in psychopathologic studies. In fact, the genotypic underpinnings of this trait have been examined for its role in various psychiatric disorders and anhedonia is now recognized to have “a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions” (Kasyanov, Pinakhina, Rakitko et al. 2024). All the same, anhedonia has been considered difficult to accurately define because of the fact that its meaning is dependent upon that assigned to pleasure and it is “defined negatively, i.e. a reduction or abolition in a putative unitary function” (Berrios and Olivares 1995).
The term anhedonia is but one example of affective psychopathology initially identified in patients suffering from the most severe forms of psychopathology, “insanity” or “psychosis,” only to be recognized afterwards in diverse and less severe psychiatric disorders, including addiction, which is the focus of the present discussion. For example, the word alexithymia was coined to describe a specific example of affective dysfunction in schizophrenia. Subsequently, the term was demonstrated to play a role in other psychiatric disorders. Moreover, the association between alexithymia and addiction came to be considered as potentially causal in nature (Martin 2024).
Clinical investigation of the role of anhedonia in any psychopathologic diagnosis is greatly assisted by agreement on operationalized psychometric instruments for characterizing this trait (Chapman, Chapman and Raulin 1976; Snaith, Hamilton, Morley et al. 1995; Der-Avakian and Markou 2012). In early considerations of the association between anhedonia and addictive disorder, it was suggested that if anhedonia preceded the development of an addictive disorder, it may confer a specific vulnerability to addiction (Garfield, Lubman and Yücel 2014). On the other hand, if anhedonia were found to develop in an individual only after protracted engagement in addiction and these symptoms abated over the course of abstinence (Janiri, Martinotti, Dario et al. 2005), this characteristic may be viewed as a consequence or complication of the disorder.
While relatively few studies have directly addressed the sequential nature of this relationship between anhedonia and addictive disorders in humans, this issue has been intensively investigated in preclinical animal models of anhedonia; an attribute that has been termed reward responsiveness. This trait in animals can readily be dissected with psychophysiologic and psychopharmacologic methods into its stages or component parts — consummatory, anticipatory, motivational and learning (Der-Avakian and Markou 2012). Furthermore, these preclinical animal studies have served to elucidate the relevant neural circuitry that underpin the neurobiology of reward and anhedonia (Koob and Volkow 2010). These laboratory investigations together indicate that diminished reward responsiveness results from prolonged administration of drugs of abuse (Martin 2018, 2019a). In this model of anhedonia, reward responsiveness progressively normalizes over time in parallel with cessation of substance administration and diminution and termination of the withdrawal syndrome (Der-Avakian and Markou 2012).
Comprehensive reviews of the existing clinical literature on the relation between anhedonia and addiction have been less conclusive, though similar, than findings from the laboratory. The available evidence indicates that anhedonia is associated with addictive disorders in either of two ways: 1) anhedonia is a consequence of pathological alcohol/drug use, i.e., psychometric measures of the anhedonia trait are found to be similarly elevated in individuals who have been diagnosed with a range of substance use disorders, especially while the relevant drug of abuse is being actively self-administered, despite the fact that these drugs have distinct neuropsychopharmacologic actions; additionally, anhedonia severity diminishes over time for all of these substances as drug use is discontinued (Garfield, Lubman and Yücel 2014), even though the range of drugs may manifest disparate withdrawal phenomena (Uslaner, Kalechstein, Richter et al. 1999), or 2) anhedonia is typically associatedwith substance use disorders due to the very frequent occurrence of this symptom with depression and the highly prevalent co-occurrence of mood and substance use disorders (Regier, Farmer, Rae et al. 1990; Destoop, Morrens, Coppens et al. 2019).
Furthermore, anhedonia has also been demonstrated via childhood trauma (perhaps acting through depression/posttraumatic stress disorders) to be indirectly associated with alcohol use disorder and food addiction (Takgbajouah, Barnes, MacKillop et al. 2024). It is believed that people with anhedonia due to various causes may turn to substance use or addictive behaviors as a way to cope with their lack of pleasure or enjoyment in life. They might use drugs, alcohol or engage in addictive behaviors like gambling or overeating in an attempt to feel something positive or to escape from their feelings of emptiness and dissatisfaction. In this case, anhedonia may be viewed as a factor that contributes to the development or perpetuation of addictive disorders.
Epidemiologic studies have consistently demonstrated that populations with drug use disorders have high rates of various psychiatric disorders, especially mood disorders, in which anhedonia is often part of the clinical presentation (Regier, Farmer, Rae et al. 1990; Grant, Dawson, Stinson et al. 2004). Nevertheless, psychiatric comorbidity alone may only indirectly account for high rates of anhedonia in populations with addictive disorders, and consequent associations of anhedonia with craving, relapse and other phenomenology of addictive disorders may actually have a mechanistic basis (Garrison, Sinha, Potenza et al. 2023). For this reason, Garfield, Lubman and Yücel (2014) selected and examined publications in which subjects were diagnosed with drug use disorders, but without evidence of co-occurring non-substance-related psychiatric diagnoses. Among these studies, they found that:
“Elevated levels of anhedonia, correlational or predictive relationships between anhedonia and craving or changes in anhedonia levels over time, consistent with anhedonia having an important role in substance use disorders independent of its relationship with other psychiatric disorders.”
These findings concur with other studies (Hatzigiakoumis, Martinotti, Di Giannantonio et al. 2011; Kiluk, Yip, DeVito et al. 2019) suggesting that anhedonia is highly relevant to treatment of addictive disorders and based on this review of their uniquely selected patient population in the literature Garfield, Lubman and Yücel (2014) concluded:
“Overall, these findings suggest a number of commonalities across different addictive substances in the nature of the association between anhedonia and substance dependence. First, there is evidence for elevated levels of anhedonia among individuals dependent on alcohol, cannabis, methamphetamine and opioids. Second, studies of alcohol, cannabis, methamphetamine and nicotine-dependent samples highlight that anhedonia reduces over time with successful abstinence. Finally, anhedonia has been shown to correlate with other aspects of abstinence (such as duration of abstinence, craving and withdrawal symptoms) in studies of alcohol, nicotine and opioid-dependent populations. These findings emphasize the importance of addressing anhedonia in the treatment of substance dependence.”
The neurobiological foundation of anhedonia is considered to be a result of disturbances in the regulation of the brain reward system (Olds and Milner 1954; Pizzagalli, Iosifescu, Hallett et al. 2008; Treadway, Buckholtz, Schwartzman et al. 2009; Der-Avakian and Markou 2012; Volkow and Morales 2015). Accordingly, linking anhedonia with addictive disorders, which by definition are grounded in brain reward mechanisms has considerable face validity (Martin 2023). However, if discontinuation of chronic use of addictive substances with different mechanisms of action or engagement in addictive behaviors are all found to improve the associated anhedonia, as strongly suggested above, then the neural circuits that subserve withdrawal processes may also have some as yet poorly understood modulating influence.
Also as indicated above, anhedonia can be associated with psychiatric disorders that involve impairment of the experience of affect other than depression, including addiction, and may play a significant role in their pathogenesis. Anhedonia resembles several other modulating trait characteristics associated with addiction, namely it may be either primary or secondaryto the addictive disorder (Martin 2021), thus co-occurring.
Psychiatric disorders, especially depressive disorders in which anhedonia very commonly occurs, in turn, might be co-occurring with addictive disorders (Rich and Martin 2014) and thereby, further influence the pathogenesis of anhedonia. Accordingly, it is not surprising that the anhedoniaendophenotype has been determined to have a complex polygenic architecture and that the genetic underpinnings of this psychopathologic symptom are not exactly the same for each condition in which anhedonia is clinically significant. The presence of anhedonia in somatic diseases or in normal persons may actually be due to a genetic predisposition of the individual to mood or schizophrenia spectrum disorders (Kasyanov, Pinakhina, Rakitko et al. 2024).
A mechanistic explanation of the rather specific role of anhedonia in addictive disorders suggests that depression and drug use disorders have shared neurobiological foundations resulting in reduced ability to experience pleasure (Markou, Kosten and Koob 1998):
“It remains unclear whether drug abuse and depression are different symptomatic expressions of the same preexisting neurobiological abnormalities, or whether repeated drug abuse leads to the abnormalities mediating depression (i.e., drug-induced depressions). The hypothesis of self-medication of non-drug-and drug-induced depressions with drugs of abuse is also… a potentially important explanatory concept in understanding the observed clinical comorbidity of these two psychiatric disorders” (Martin 2019b).
Regardless of how one conceptualizes the pathogenesis of these disorders, understanding the neuroanatomic bases of human emotions has led to the recognition that the anhedonia trait does have specific brain structural underpinnings (Gorwood 2008). Therefore, individuals can be considered to have neuroanatomically based primary anhedonia and thus be at higher risk for development of a secondary psychiatric disorder.
In this discussion we have mainly focused on addictive disorders. However, other forms of psychopathology, especially depression, may clearly result from primary anhedonia, which, in turn, may also be considered a precursor of secondary addictive disorders.
Harvey, Pruessner, Czechowska et al. (2007) reported that in subjects who did not have clinical psychiatric disorders, trait anhedonia severity was negatively correlated with the volume of the anterior caudate and ventral striatum and was positively correlated with the activity of the ventromedial prefrontal cortex for the processing of information with positive valence (Martin 2020a,b). It is proposed that trait anhedonia may represent an endophenotype characterized by reliable structural and functional abnormalities (Davidson, Pizzagalli, Nitschke et al. 2002; Pizzagalli, Iosifescu, Hallett et al. 2008; Treadway, Buckholtz, Schwartzman et al. 2009). Namely, the fundamental diminution in the capacity to experience reward, or anhedonia, in individuals who do or do not meet criteria for a psychiatric diagnosis, may serve as either a precursor or consequence of drug use and other addictive disorders.
In support of neuroanatomic foundation of the anhedonia trait, similar psychopathologic findings can also result from brain damage sustained due to traumatic brain injury (Lewis, Krueger, Raymont et al. 2015) or various neurological disorders that demonstrate apathy and anhedonia (Husain and Roiser 2018). Importantly, it was proposed that the neural basis of anhedonia in traumatic brain injury involved disturbed reward processing, rather than the loss of sense of pleasure. Individuals with right ventrolateral injury reported greater severity of anhedonia compared to those with injury in the left ventrolateral region. These findings support an association between injury in the right ventrolateral prefrontal cortex and anhedonia.
However, brain injury is associated with addictive disorders via another route that can compound the predisposition to anhedonia. Namely, the chronic use of alcohol and other drugs and traumatic brain injury are inextricably and bidirectionally linked (Weinstein and Martin 1995). Thus, the risk of brain injury is greatly increased due to impaired performance and judgement associated with intoxication and chronic use of alcohol/drugs and may specifically or indirectly result in damage to brain reward pathways.
For example, chronic alcohol consumption and associated malnutrition may cause damage to the medial forebrain bundle as a consequence of thiamine deficiency (Martin, Adinoff, Weingartner et al. 1986). Analogously, diminished basal levels of synaptic dopamine within the nucleus accumbens has been reported in cocaine-withdrawn rats and may account for anhedonia, anergia and cocaine craving reported by withdrawn individuals with cocaine use disorder (Ackerman and White 1992) and other drug use disorders (Perlman, Wengler, Moeller et al. 2024). Therefore, chronic substance use can progressively cause changes in the reward system. Over time, the brain becomes desensitized to the substance both due to neuroadaptation from pharmacological effects of the drug and as a result of neurotoxic injury to the reward pathways, requiring more and more of it to achieve the same pleasurable effect, leading to anhedonia when the substance is not present.
In conclusion, anhedonia and addictive disorders can have a circular relationship where one can feed into the other, creating a vicious cycle that can be difficult to break. Additionally, both conditions can have other underlying causes, such as other psychiatric disorders (particularly depression) and trauma or chronic stress, and hence require an integrated pharmacopsychosocial approach to treatment (Martin, Weinberg and Bealer 2007).
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November 7, 2024