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Should pathological gambling be considered an addictive disorder?
Asian Journal of Psychiatry 5 (2012) 211–214
Contents lists available at SciVerse ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Review
Should pathological gambling be considered an addictive disorder? Om Prakash a,*, Ajit Avasthi b, Vivek Benegal c a
Institute of Human Behaviour & Allied Sciences (IHBAS), Delhi, India Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India c National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 June 2011 Received in revised form 18 December 2011 Accepted 19 January 2012
Although pathological gambling is a relatively common disorder, there are only limited data available about the validity of its diagnosis as an impulse control disorder. Interestingly, there is no single conceptual widely accepted model that adequately accounts for the multiple biological, psychological and ecological variables contributing to the development of pathological gambling. In this paper, the authors demonstrate aspects of addictive behavior of pathological gambling. It is suggested that despite conceptual difficulties associated with the variable of self-control, contemporary research into the addictive behavior of gambling has clearly demonstrated its closeness to addictions as compared to impulse control disorders. ß 2012 Elsevier B.V. All rights reserved.
Keywords: Pathological gambling Addictive disorders Nosology
Contents 1. 2. 3. 4. 5. 6. 7. 8.
Introduction . . . . . . . . . . . . . . . . . . . . . . Neurotransmitters . . . . . . . . . . . . . . . . . Genetics and neuro-imaging . . . . . . . . . Co-morbidity . . . . . . . . . . . . . . . . . . . . . Processes related to addictive behavior Epidemiology, course and prognosis . . . Management issues . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Neither gambling nor its problems are new to human history. However, it is only about two decades since pathological gambling gained acceptance as a mental disorder, (Potenza, 2008) and has rapidly emerged as a mental health concern with financial, employment, legal, psychological, familial, and physical health consequences. Approximately 5% of adults have been estimated to experience problems with gambling (American Psychiatric Association, 1980). At a behavioral level, gambling is an activity which involves a contract between two or more people, where property (i.e. the stake) is transferred between those taking parts, based on the outcome of uncertain events and involving voluntary participation.
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(Moran, 2000) Common forms of gambling involve Horse/dog race gambling, sports gambling, card playing, slot machine playing, scratch/lottery gambling (Petry, 2000). The contemporary use of the term ‘Addiction’ is almost exclusively applied to substance using behavior patterns that evidence adverse consequences, often including tolerance and withdrawal (Shaffer et al., 1999). Contemporary addiction workers have come to think of addictive behavior as having three primary components: (i) some element of craving and compulsion, (ii) loss of control; and (iii) persistence despite harm. This paper examines issues why pathological gambling should be considered within the same classification system as substance use disorders not as an impulse control disorders.
2. Neurotransmitters * Corresponding author. Tel.: +91 9868396843. E-mail addresses: [email protected] (O. Prakash), [email protected] (A. Avasthi), [email protected] (V. Benegal). 1876-2018/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ajp.2012.01.007
Neurotransmitter abnormalities that that are common to persons with substance use and pathological gambling disorders
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should be considered speculative relationships (Petry, 2006). Studies in gambling suggest that increased arousal and risk taking behavior may be linked to nor-adrenergic system dysfunction i.e. increased levels of nor-epinephrine metabolites (Roy et al., 1988, 1989). Dopaminergic and serotonergic functions have been found altered in pathological gamblers (Bergh et al., 1997; De-Caria et al., 1998). Low platelet mono-amine oxidase (MAO) activity reported in these patients indicates dysfunction in serotonergic systems (Carrasco et al., 1994; Blanco et al., 1996). The function of the dopaminergic system, possibly mediating positive and negative reward, and the noradrenergic system, possibly mediating selective attention, is similarly changed in persons with pathological gambling and those with addictive (drug) disorders. The severity of pathological gambling in humans is linked to increased levels of 5-HT (1B) Rs in the ventral striatum and anterior cingulate cortex regions of brain (Potenza et al., 2011). The efficacious use of serotonin selective reuptake inhibitors e.g. fluvoxamine in pathological gambling strengthens the view of dysfunction in serotonergic systems. Serotonin has been linked to behavioral initiation and dis-inhibition which are important in the onset of the gambling cycle and difficulty in decreasing the behavior (Hollander et al., 2000).
Center, 1999; Lesieur et al., 1986; McCormick, 1993; Castellani and Rugle, 1995). In studies of methadone maintenance patients, rates of pathological gambling range from 7% to 16% (Daghestani et al., 1996; Feigelman et al., 1995). Risky sexual behaviors are common among pathological gamblers (Spunt et al., 1995) and substance abusers. (Petry, 2000; Darke et al., 1990) Fourteen to forty percent of pathological gamblers meet diagnostic criteria for antisocial personality disorder. (Stimson et al., 1998; McCormick et al., 1987) Sixty percent of pathological gamblers engage in criminal activities such as forgery/fraud to maintain their addiction. (Blaszczynski and McConaghy, 1994) Such criminal behavior is fairly common among substance abusers. Like in drug abusers, stress related medical conditions such as hypertension, peptic ulcer disease, and migraine headaches, are also seen in pathological gamblers (Blaszczynski and Silove, 1996; Lorenz and Yaffee, 1986). High incidence of depression observed among pathological gamblers (Bergh et al., 1994; McCormick et al., 1984) is also common among drug abusers. Twenty percent of individuals seeking treatment for pathological gambling have a history of suicidal attempts. Interestingly, 1.7% of all suicides are gambling related. (Linden et al., 1986) Similarly, alcoholics attempt suicide frequently (Productivity Commission, 1999).
3. Genetics and neuro-imaging 5. Processes related to addictive behavior Biogenetic vulnerabilities have been identified among pathological gamblers (Comings, 1998; Slutske et al., 2000). There is evidence to suggest that among people without psychiatric disorders, there may be genetic markers for novelty-seeking behavior that can predispose people to take ‘‘chances’’ (Benjamin et al., 1996; Ebstein et al., 1996). In a twin sample study, inherited factors explained 54% liability for pathological behavior of gambling (Eisen et al., 1998). Possible associations have been suggested between a functional DNA polymorphism of the serotonin carrier gene and pathological gambling in affected men (Perez de Castro et al., 1997). One study conducted in Korean population suggested that the analyzed polymorphisms of the dopamine receptor genes might not be associated with pathological gambling (Lim et al., 2011 Aug 19). Several studies examined family co-aggregation of pathological gambling and alcohol dependence using family history method (Lesieur et al., 1991). Risk for alcohol dependence accounts for a significant but modest proportion of the genetic (12–20%) and environmental (3–8%) risk for sub-clinical and clinical pathological gambling. This further suggests common genetic vulnerability for pathological gambling and alcohol dependence in men (Slutske et al., 2000). Changes in ventromedial prefrontal cortex implicated for decision making impairments may also be seen in pathological gamblers (Dell et al., 1981). Interestingly, cocaine, opiate and alcohol abusers, too have shown abnormalities in ventro-medial prefrontal cortex during functional neuro-imaging studies (Cavedini et al., 2002; Hommer et al., 1997). 4. Co-morbidity The most well-established finding in literature consistent with the conceptualization of pathological gambling as an addictive disorder is high rates of alcohol dependence and other substance use disorders among individuals with pathological gambling (Volkow et al., 1991; Cunningham-William et al., 1998). Among chemically dependent treatment populations, rates of problem gambling are 5–10 times greater than among the population at large (Black and Moyer, 1998). In studies of in patient treated drug and alcohol-dependent patients, rates of probable pathological gambling range from 13% to 33% (National Opinion Research
One explanation for co-occurrence of substance use disorders and pathological gambling is that both may be manifestations of an underlying personality trait such as ‘impulsivity’. Heightened impulsivity is associated with the degree of severity of psychological and behavioral changes in both pathological gamblers and drug abusers. High scores of impulsivity have been reported on personal inventories in substance abusers (Schuckit et al., 1997; Rosenthal et al., 1990) and also in pathological gamblers (Allen et al., 1998; Carlton and Manowitz, 1994; Blaszczynski et al., 1997). Gambling problems and substance abuse had also an additive effect on impulsive choice behavior (Steel and Blaszczynski, 1998). Small quantities of alcohol have a significant effect on the psychological processes that underpin self-control over gambling. This further challenges the conceptual research paradigm of studying comorbidity or dual-addicted populations (Petry and Casarella, 1999). The central feature of all gambling is subjective excitement or arousal-often referred to as ‘gambler drug’. Individuals with pathological gambling experience a euphoric state similar to a drug-induced ‘‘high’’. (Kyngdon and Dickerson, 1999) Impaired control has long been central to formulations of heavy drinking, (Leiseur and Blume, 1991; Jellinek, 1960) and has been applicable to excessive gambling also (Edwards et al., 1977; Corless and Dickerson, 1989). 6. Epidemiology, course and prognosis Pathological gambling has been predominantly researched on male subjects and mostly male-dominated gambling sites have been investigated. Lottery gambling was negatively correlated with socio-economic status and income (O’Connor and Dickerson, 2003; Hendriks et al., 1997) like other addictive disorders. Groups at risk of pathological gambling are adolescents, or young adults, from lower socio-economic status (Shaffer et al., 1999). Like other addictive disorders, the natural history of pathological gambling is characterized by exacerbations and remissions, often related to life events. Similarly its prognosis is usually determined by the integrity of the underlying personality, depression or other neurotic disorder. Analogous to the progression from social drinking to alcohol dependence, gambling disorders are thought to develop by progression from social
O. Prakash et al. / Asian Journal of Psychiatry 5 (2012) 211–214
gambling through problem gambling to pathological gambling (Volberg et al., 2001; Moran, 1970). 7. Management issues Recovery from addictive problems without formal treatment is increasingly recognized as a common phenomenon in addictive disorders (Griffiths, 1996; McCartney, 1996) which has been also seen in gambling disorders (Sobell et al., 1996). Resolved gamblers were similar to alcohol and other drug treatment-seekers (Hodgins and El-Guebaly, 2000) in terms of the proportion endorsing each reason for resolution. The major reason for not seeking treatment by resolved gamblers was the desire to handle the problem without help, as has been consistently reported in studies of people with serious alcohol and other drug problems (Cunningham et al., 1995). Research on pathological gamblers in treatment has shown extensive overlap with substance use addictions. (Grant, 1997) Pathological gamblers have been known to substitute alcohol or other drug taking when they discontinue gambling. (Lesieur and Blume, 1993; Leisure et al., 1986) Similarly, gambling may replace alcohol or other drug use as an alternative means of arousal or avoidance of dysphoric mood. (Grant, 1997) Hence, a combined treatment plan for substance abuse and pathological gambling is an effective way of dealing with patients whose gambling problems are discovered when they enter treatment for another addiction, as well as for patients whose initial complaints include pathological gambling (Lesieur and Heineman, 1988). Gamblers Anonymous (GA; modeled on the 12-step program of Alcoholic Anonymous) participation combined with professionally delivered therapy may improve outcomes compared with GA participation alone (Blaszczynski et al., 1986). Management of pathological gamblers involves major changes in life style of the person concerned with the team approach of a psychiatrist, psychologist and social worker. Naltrexone, an important anti-craving agent for alcohol (Blackman et al., 1989) may also be effective in reducing symptoms of pathological gambling (Basu et al., 2005; Grant and Kim, 2002; Kim et al., 2001). Acamprosate and Baclofen were found ineffective in the treatment of pathological gambling (Dannon et al., 2011). 8. Conclusion Public awareness of pathological gambling is even considered as ‘addiction of the 1990s’. Both substance abuse and pathological gambling have been considered addictive disorders due to similarities (El-Guebaly et al., 2011) which include impaired control, preoccupation with behavior, seeking of a euphoric state or ‘high’, presence of craving, development of tolerance, withdrawal symptoms, increased activity during times of stress or depression, and continuation of the behavior despite adverse consequences in addition to common genetic component. The findings of this review may give new insights while new categorization of addictive disorders. Funding None. Conflict of interest None. References Allen, T., Moeller, F.G., Rhoades, H.M., Cherek, D.R., 1998. Impulsivity and history of drug dependence. Drug Alcohol Depend. 50, 137–145.
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Contents lists available at SciVerse ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Review
Should pathological gambling be considered an addictive disorder? Om Prakash a,*, Ajit Avasthi b, Vivek Benegal c a
Institute of Human Behaviour & Allied Sciences (IHBAS), Delhi, India Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India c National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 June 2011 Received in revised form 18 December 2011 Accepted 19 January 2012
Although pathological gambling is a relatively common disorder, there are only limited data available about the validity of its diagnosis as an impulse control disorder. Interestingly, there is no single conceptual widely accepted model that adequately accounts for the multiple biological, psychological and ecological variables contributing to the development of pathological gambling. In this paper, the authors demonstrate aspects of addictive behavior of pathological gambling. It is suggested that despite conceptual difficulties associated with the variable of self-control, contemporary research into the addictive behavior of gambling has clearly demonstrated its closeness to addictions as compared to impulse control disorders. ß 2012 Elsevier B.V. All rights reserved.
Keywords: Pathological gambling Addictive disorders Nosology
Contents 1. 2. 3. 4. 5. 6. 7. 8.
Introduction . . . . . . . . . . . . . . . . . . . . . . Neurotransmitters . . . . . . . . . . . . . . . . . Genetics and neuro-imaging . . . . . . . . . Co-morbidity . . . . . . . . . . . . . . . . . . . . . Processes related to addictive behavior Epidemiology, course and prognosis . . . Management issues . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Neither gambling nor its problems are new to human history. However, it is only about two decades since pathological gambling gained acceptance as a mental disorder, (Potenza, 2008) and has rapidly emerged as a mental health concern with financial, employment, legal, psychological, familial, and physical health consequences. Approximately 5% of adults have been estimated to experience problems with gambling (American Psychiatric Association, 1980). At a behavioral level, gambling is an activity which involves a contract between two or more people, where property (i.e. the stake) is transferred between those taking parts, based on the outcome of uncertain events and involving voluntary participation.
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(Moran, 2000) Common forms of gambling involve Horse/dog race gambling, sports gambling, card playing, slot machine playing, scratch/lottery gambling (Petry, 2000). The contemporary use of the term ‘Addiction’ is almost exclusively applied to substance using behavior patterns that evidence adverse consequences, often including tolerance and withdrawal (Shaffer et al., 1999). Contemporary addiction workers have come to think of addictive behavior as having three primary components: (i) some element of craving and compulsion, (ii) loss of control; and (iii) persistence despite harm. This paper examines issues why pathological gambling should be considered within the same classification system as substance use disorders not as an impulse control disorders.
2. Neurotransmitters * Corresponding author. Tel.: +91 9868396843. E-mail addresses: [email protected] (O. Prakash), [email protected] (A. Avasthi), [email protected] (V. Benegal). 1876-2018/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ajp.2012.01.007
Neurotransmitter abnormalities that that are common to persons with substance use and pathological gambling disorders
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should be considered speculative relationships (Petry, 2006). Studies in gambling suggest that increased arousal and risk taking behavior may be linked to nor-adrenergic system dysfunction i.e. increased levels of nor-epinephrine metabolites (Roy et al., 1988, 1989). Dopaminergic and serotonergic functions have been found altered in pathological gamblers (Bergh et al., 1997; De-Caria et al., 1998). Low platelet mono-amine oxidase (MAO) activity reported in these patients indicates dysfunction in serotonergic systems (Carrasco et al., 1994; Blanco et al., 1996). The function of the dopaminergic system, possibly mediating positive and negative reward, and the noradrenergic system, possibly mediating selective attention, is similarly changed in persons with pathological gambling and those with addictive (drug) disorders. The severity of pathological gambling in humans is linked to increased levels of 5-HT (1B) Rs in the ventral striatum and anterior cingulate cortex regions of brain (Potenza et al., 2011). The efficacious use of serotonin selective reuptake inhibitors e.g. fluvoxamine in pathological gambling strengthens the view of dysfunction in serotonergic systems. Serotonin has been linked to behavioral initiation and dis-inhibition which are important in the onset of the gambling cycle and difficulty in decreasing the behavior (Hollander et al., 2000).
Center, 1999; Lesieur et al., 1986; McCormick, 1993; Castellani and Rugle, 1995). In studies of methadone maintenance patients, rates of pathological gambling range from 7% to 16% (Daghestani et al., 1996; Feigelman et al., 1995). Risky sexual behaviors are common among pathological gamblers (Spunt et al., 1995) and substance abusers. (Petry, 2000; Darke et al., 1990) Fourteen to forty percent of pathological gamblers meet diagnostic criteria for antisocial personality disorder. (Stimson et al., 1998; McCormick et al., 1987) Sixty percent of pathological gamblers engage in criminal activities such as forgery/fraud to maintain their addiction. (Blaszczynski and McConaghy, 1994) Such criminal behavior is fairly common among substance abusers. Like in drug abusers, stress related medical conditions such as hypertension, peptic ulcer disease, and migraine headaches, are also seen in pathological gamblers (Blaszczynski and Silove, 1996; Lorenz and Yaffee, 1986). High incidence of depression observed among pathological gamblers (Bergh et al., 1994; McCormick et al., 1984) is also common among drug abusers. Twenty percent of individuals seeking treatment for pathological gambling have a history of suicidal attempts. Interestingly, 1.7% of all suicides are gambling related. (Linden et al., 1986) Similarly, alcoholics attempt suicide frequently (Productivity Commission, 1999).
3. Genetics and neuro-imaging 5. Processes related to addictive behavior Biogenetic vulnerabilities have been identified among pathological gamblers (Comings, 1998; Slutske et al., 2000). There is evidence to suggest that among people without psychiatric disorders, there may be genetic markers for novelty-seeking behavior that can predispose people to take ‘‘chances’’ (Benjamin et al., 1996; Ebstein et al., 1996). In a twin sample study, inherited factors explained 54% liability for pathological behavior of gambling (Eisen et al., 1998). Possible associations have been suggested between a functional DNA polymorphism of the serotonin carrier gene and pathological gambling in affected men (Perez de Castro et al., 1997). One study conducted in Korean population suggested that the analyzed polymorphisms of the dopamine receptor genes might not be associated with pathological gambling (Lim et al., 2011 Aug 19). Several studies examined family co-aggregation of pathological gambling and alcohol dependence using family history method (Lesieur et al., 1991). Risk for alcohol dependence accounts for a significant but modest proportion of the genetic (12–20%) and environmental (3–8%) risk for sub-clinical and clinical pathological gambling. This further suggests common genetic vulnerability for pathological gambling and alcohol dependence in men (Slutske et al., 2000). Changes in ventromedial prefrontal cortex implicated for decision making impairments may also be seen in pathological gamblers (Dell et al., 1981). Interestingly, cocaine, opiate and alcohol abusers, too have shown abnormalities in ventro-medial prefrontal cortex during functional neuro-imaging studies (Cavedini et al., 2002; Hommer et al., 1997). 4. Co-morbidity The most well-established finding in literature consistent with the conceptualization of pathological gambling as an addictive disorder is high rates of alcohol dependence and other substance use disorders among individuals with pathological gambling (Volkow et al., 1991; Cunningham-William et al., 1998). Among chemically dependent treatment populations, rates of problem gambling are 5–10 times greater than among the population at large (Black and Moyer, 1998). In studies of in patient treated drug and alcohol-dependent patients, rates of probable pathological gambling range from 13% to 33% (National Opinion Research
One explanation for co-occurrence of substance use disorders and pathological gambling is that both may be manifestations of an underlying personality trait such as ‘impulsivity’. Heightened impulsivity is associated with the degree of severity of psychological and behavioral changes in both pathological gamblers and drug abusers. High scores of impulsivity have been reported on personal inventories in substance abusers (Schuckit et al., 1997; Rosenthal et al., 1990) and also in pathological gamblers (Allen et al., 1998; Carlton and Manowitz, 1994; Blaszczynski et al., 1997). Gambling problems and substance abuse had also an additive effect on impulsive choice behavior (Steel and Blaszczynski, 1998). Small quantities of alcohol have a significant effect on the psychological processes that underpin self-control over gambling. This further challenges the conceptual research paradigm of studying comorbidity or dual-addicted populations (Petry and Casarella, 1999). The central feature of all gambling is subjective excitement or arousal-often referred to as ‘gambler drug’. Individuals with pathological gambling experience a euphoric state similar to a drug-induced ‘‘high’’. (Kyngdon and Dickerson, 1999) Impaired control has long been central to formulations of heavy drinking, (Leiseur and Blume, 1991; Jellinek, 1960) and has been applicable to excessive gambling also (Edwards et al., 1977; Corless and Dickerson, 1989). 6. Epidemiology, course and prognosis Pathological gambling has been predominantly researched on male subjects and mostly male-dominated gambling sites have been investigated. Lottery gambling was negatively correlated with socio-economic status and income (O’Connor and Dickerson, 2003; Hendriks et al., 1997) like other addictive disorders. Groups at risk of pathological gambling are adolescents, or young adults, from lower socio-economic status (Shaffer et al., 1999). Like other addictive disorders, the natural history of pathological gambling is characterized by exacerbations and remissions, often related to life events. Similarly its prognosis is usually determined by the integrity of the underlying personality, depression or other neurotic disorder. Analogous to the progression from social drinking to alcohol dependence, gambling disorders are thought to develop by progression from social
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gambling through problem gambling to pathological gambling (Volberg et al., 2001; Moran, 1970). 7. Management issues Recovery from addictive problems without formal treatment is increasingly recognized as a common phenomenon in addictive disorders (Griffiths, 1996; McCartney, 1996) which has been also seen in gambling disorders (Sobell et al., 1996). Resolved gamblers were similar to alcohol and other drug treatment-seekers (Hodgins and El-Guebaly, 2000) in terms of the proportion endorsing each reason for resolution. The major reason for not seeking treatment by resolved gamblers was the desire to handle the problem without help, as has been consistently reported in studies of people with serious alcohol and other drug problems (Cunningham et al., 1995). Research on pathological gamblers in treatment has shown extensive overlap with substance use addictions. (Grant, 1997) Pathological gamblers have been known to substitute alcohol or other drug taking when they discontinue gambling. (Lesieur and Blume, 1993; Leisure et al., 1986) Similarly, gambling may replace alcohol or other drug use as an alternative means of arousal or avoidance of dysphoric mood. (Grant, 1997) Hence, a combined treatment plan for substance abuse and pathological gambling is an effective way of dealing with patients whose gambling problems are discovered when they enter treatment for another addiction, as well as for patients whose initial complaints include pathological gambling (Lesieur and Heineman, 1988). Gamblers Anonymous (GA; modeled on the 12-step program of Alcoholic Anonymous) participation combined with professionally delivered therapy may improve outcomes compared with GA participation alone (Blaszczynski et al., 1986). Management of pathological gamblers involves major changes in life style of the person concerned with the team approach of a psychiatrist, psychologist and social worker. Naltrexone, an important anti-craving agent for alcohol (Blackman et al., 1989) may also be effective in reducing symptoms of pathological gambling (Basu et al., 2005; Grant and Kim, 2002; Kim et al., 2001). Acamprosate and Baclofen were found ineffective in the treatment of pathological gambling (Dannon et al., 2011). 8. Conclusion Public awareness of pathological gambling is even considered as ‘addiction of the 1990s’. Both substance abuse and pathological gambling have been considered addictive disorders due to similarities (El-Guebaly et al., 2011) which include impaired control, preoccupation with behavior, seeking of a euphoric state or ‘high’, presence of craving, development of tolerance, withdrawal symptoms, increased activity during times of stress or depression, and continuation of the behavior despite adverse consequences in addition to common genetic component. The findings of this review may give new insights while new categorization of addictive disorders. Funding None. Conflict of interest None. References Allen, T., Moeller, F.G., Rhoades, H.M., Cherek, D.R., 1998. Impulsivity and history of drug dependence. Drug Alcohol Depend. 50, 137–145.
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