UNIVERSITÀ DI PISA
Dipartimento di Medicina Clinica e Sperimentale
Scuola di Specializzazione in Psichiatria
Direttore: Prof. Liliana Dell’Osso
Tesi di Specializzazione
Verso una psicopatologia specifica dei Disturbi Correlati a Sostanze e Disturbi da
Addiction: Confronto fra Disturbo da Uso di Eroina e Disturbo da Gioco d’Azzardo
Towards a specific psychopathology of Substance-Related and Addictive Disorders.
Comparison between Heroin Use Disorder and Gambling Disorder patients
Candidato
Relatore
Dott.ssa Denise Gazzarrini
Prof. Icro Maremmani
1 Abstract
This doctoral dissertation aims, in its first part, to define Gambling Disorder on the basis of the terminology history, aetiology, clinical aspects, medical and psychiatric comorbidity and treatment options. In the second part comparison between psychopathology of Heroin Use Disorder and GD patients has been made.
Gambling, defined as placing something of value at risk in the hope of gaining something
of greater value, has been observed across cultures for millennia.
Gambling is a harmless form of entertainment for most consumers, but it has the capacity to become dysfunctional in a minority. The negative consequences could be severe, and include financial debt, bankruptcy, family dissolution, and criminal behaviour. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), Pathological Gambling become Gambling Disorder (GD) and it moved from “Impulse Control Disorder” to the chapter of “Substance-Related and Addictive Disorders”. DSM-5 in this way is the first diagnostic system to recognize a behavioural addiction. As in addiction to substances, there are similar elements in term of clinical expression (e.g., craving, tolerance, withdrawal symptoms) and diagnostic criteria, comorbidity, neurobiological profile, heritability, natural history, treatment, and treatment outcome. Actually, 0.12-5.8% of the world’s population meets criteria for GD and in Italy, the prevalence estimated is between 0,5 and 2,2%. Neurobiological studies underline involvement of Serotoninergic, Dopaminergic, GABAergic, Glutamatergic and Noradrenergic systems both in GD and in Substance Use Disorder and GD’s heritability is similar to heritability rates of other Addictions. Indeed, several neuropsychological differences have been found between subjects with GD and control subjects and that have been linked to brain regions such as ventral striatum, ventromedial prefrontal cortex, orbitofrontal cortex, dopaminergic midbrain and insula, fundamental structures in the reward system and decision processes. GD is more frequent in males than females, in
younger than in older people; 96% of individuals with lifetime GD also meet criteria for at least one other lifetime psychiatric disorder. High rates of co-occurrence between SUDs and GD are present in both directions. Similarities between GD and SUD are: (1) Euphoric state/ excitement or arousal-state; euphoric state such as ‘‘high’’. (2) Loss of control/ impaired control. (3) Craving/failure to resist an impulse, drive, or temptation to perform an act. (4) Recidivism/exacerbations and remissions. (5) Alteration in global functioning/impaired control. Currently, three main pharmacological approaches exist for GD derived from the psychopathological and phenomenological perspectives of the disorder itself: considering GD as a behavioural addiction, as belonging to the obsessive- compulsive disorder spectrum, or as the result of an emotional dysregulation related to mood disorders. Opioid antagonist, SSRIs antidepressant and Mood Stabilizers are
generally used. Cognitive Behavioural Therapy has been used to
reduce gambling behaviour.
In the experimental study, the aim was to investigate psychopathology and to test if the specific psychopathology already found in HUD patients could be likewise detected in GD patients. The five psychopathological dimensions found, by our research group, in Substance-Related Disorders were applied to a Non-Substance-Related Disorder, comparing a sample of Heroin Use Disorder (HUD) with Gambling Disorder (GD) patients at univariate and multivariate level. At univariate level the number of psychopathological symptoms were more severe in HUD patients and all the five psychopathological dimensions were significantly more severe in HUD patients. Psychopathological subtypes were not the most important discriminant factor to differentiate HUD from GD patients. Psychopathological subtypes characterized by ‘Somatic Symptoms’ and ‘Violence-Suicide’ symptomatology were more frequent in HUD patients, whereas ‘Panic Anxiety’ symptomatology were more frequent in GD individuals. At multivariate level, prominent
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characteristic of PG individuals was only the absence of ‘Somatic Symptoms’ psychopathological subtype membership. The SCL-90-defined structure of opioid addiction seems to represent a trait-dependent, rather than a state-dependent psychopathology also in non-substance-related disorders of addictive disorders, further supporting the existence of a specific psychopathology of addiction.
Key words: Gambling Disorder; Heroin Use Disorder; Addictive behaviour; Specific Psychopathology of Addiction
Part A: Gambling Disorder. History, Aetiology, Clinical Aspect, Comorbidity and Treatment Options 1 Introduction ... 1 1.1 History ... 1 1.2 From Problem-Gambling to Gambling-Disorder through Pathological-Gambling ...4 2 Epidemiology ... 5 3 Aetiology ... 7 3.1 Biological factors ... 7 3.1.1 Neuroimaging ... 12 3.2 Genetic factors ... 15 3.3 Psychosocial factors ... 16 3.3.1 Gender ... 16 3.3.2 Cognition ... 17 4 Clinical aspects ... 20 4.1 Clinical picture ... 20 4.2 Longitudinal aspects ... 23 4.3 Diagnosis ... 25 4.4 Substance Use Disorder Comorbidity with special reference to Heroin Use Disorder ... 26 4.5 Comorbidity ... 28 4.5.1 Psychiatric Comorbidity ... 28 4.6 Medical Comorbidity ... 29 5 Treatment of GD ... 29 5.1 Pharmacological treatment ... 29
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5.2 Psychosocial treatment ... 30
Part B Specific Psychopathology of Addiction Comparison between Heroin Use Disorder and Gambling Disorder patients 6 Introduction ... 31 7 Methods ... 32 7.1 Design of the study ... 32 7.2 Sample ... 33 7.3 Instruments ... 33 7.3.1 Self-Report Symptom Inventory (SCL-90) ... 33 7.3.2 Psychiatric Diagnostic Evaluation. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Clinician Version. ... 36 7.4 Data analysis ... 36 8 Results ... 37 8.1 Demographic differences at treatment entry ... 37 8.2 Differences in severity of psychopathological symptoms ... 37 8.3 Differences in psychopathological typology ... 38 9 Discussion ... 38 10 Conclusions ... 41 REFERENCES ... 42 Tables ... 53 Appendix 1. ... 56 Appendix 2 ... 58 Figure 1. ... 60
Part A
Gambling Disorder
History, Aetiology, Clinical Aspect, Comorbidity and Treatment Options
1 Introduction
1.1 History
In the past, “gambling” referred to playing unfairly or cheating at play. A gambler was defined as a fraudulent gamester, sharper, or rook who habitually plays for money, especially extravagantly high stakes (Oxford English Dictionary, second edition, 1989). Nowadays, gambling means placing something of value at risk in the hope of gaining something of greater value. Humans have always gambled and there has been apprehension about excessive risk-taking and intemperate gambling. Through the centuries histories of gamblers who lose control recur: some famous Roman emperors were avid gamblers, like Claudius and Nero (Wildman, 1997) and from early times their behaviour was named as addiction. In early Roman law, the original addict was a debtor (Rosenthal, 1987 ) who, because he could not pay what he owed, was enslaved. In the crusades, King Richard the Lion- Hearted restricted the dice playing because of the fear of loss of control by his soldiers (Fleming, 1978). Dostoyevsky in The Gambler (Dostoyevsky, 1866) based of his own experiences, describes well the cognitive distortions, loss of control and self-esteem, and hopelessness currently associated with clinical definitions of severe gambling problems.
In The Western County Magazine, in 1791, gambling was called “addiction” for the first time, mentioning many cases of individuals who lost everything and committed suicide for this problem (Steinmetz, 1869). Admonitions against gambling were also prominent during the 1820s and 1830s, as part of the temperance movement. In 1834, and in 1838
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addictive vice that would render men mad (Caldwell, 1834) and described most of the criteria and associated features of gambling problems: the shame, the guilt, and the secrecy of the gambler; the cognitive polarization and preoccupation with gambling; neglect of wife and home; neglect of employment; extravagant spending; turning to theft and other illegal activities to support gambling and other expenses; and, finally, suicide (Taylor, 1838 ).
In the 20th century, Freud thought gambling was an addiction and he placed it in a triad with alcoholism and drug dependence (Freud, 1928 ).
Availability of legalized gambling took place in the 1930s in the United States and in December 1957, in Los Angeles, took place the first meeting of Gamblers Anonymous. Its famous 20-items questionnaire became the standard used to establish whether or not
gambling behaviours were problematic (see Appendix 1) and became the basis for modern
classification systems that determine the chronicity and seriousness of gambling problems in part by the consequences of gambling behaviour.
In 1980, the American Psychiatric Association adopted the term “pathological gambling” as the official nomenclature in the DSM-III to describe excessive gambling as an impulse disorder. Sometimes the terms “pathological” and “compulsive” are used interchangeably; however, “compulsive” is the historical term and the one used by Gamblers Anonymous (Gamblers Anonymous, 1997 ) but for most scholars and many clinicians, the knowledge of compulsive gambling as a description of pathological gamblers is a technical mistake (Lesieur & Rosenthal, 1991). In the psychiatric lexicon, a compulsive behaviour is involuntary and “ego-dystonic”- external or foreign to the self is an attempt to rid oneself of discomfort and pain- pathological gamblers, in contrast, typically experience gambling as ego-syntonic and pleasurable until late in the disorder. In 1994 the DSM-IV, and in 2000 his text revision, provides a widely accepted definition and diagnostic criteria for pathological gambling as an impulse disorder not otherwise specified while in the fifth
edition of the DSM “Pathological Gambling” (PG) become “Gambling Disorder” (GD) and it moved from “Impulse Control Disorder” to the chapter of “Substance-Related and Addictive Disorders” (Rash & Petry, 2016) due to similarity with those disorders. In this way, DSM-5 is the first diagnostic system to recognize a behavioural addiction. As in addiction to substances, there are similar elements in term of clinical expression (e.g., craving, tolerance, withdrawal symptoms), comorbidity, neurobiological profile, heritability, longitudinal course, treatment, treatment outcome, and the content of existing treatment protocols (Weinstock & Rash, 2014) although scepticism remains (Schuckit, 2013; Yau & Potenza, 2015).
The concept of a continuum of gambling severity implies that people can be located at a point on this continuum. They can move from that point, developing more or less serious difficulties. Some authors conceptualize gambling behaviours on a developmental continuum and observe that a gambler can move across a linearity in problem severity, with respect to frequency and intensity, but there is no evidence that actual progression of the illness is linear (Shaffer, 1997). Moreover, most of clinicians and the self-help treatment community believe that pathological gamblers cannot successfully return to a level of social or recreational gambling. Conceptualizing the behaviour on a continuum ranging from no gambling to pathological gambling may provide a useful model for developing public health system of treatment, or to introduce preventative measures but it is insufficiently detailed to provide a scientific explanation of the new emergence of GD. Custer (Custer, 1984) has proposed 6 different types of players: (1) professionals (they live on gambling that represents for them a true work; they are not dependent, as they can control the amount of money wagered and time spent playing); (2) antisocial players (they obtain money illegally through gambling, e.g., playing with marked cards or being involved in rigged races); (3) socially appropriate players (they play for fun and socializing, and gambling does not interfere too much with their lives); (4) socially serious
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players (they invest time in gambling, which is their main kind of relaxation and fun but they are able to maintain control over gambling activities and do not neglect work and/or family); (5) escape and relief players, without addiction (they use gambling to cope with feelings of anxiety, depression, loneliness, and boredom; therefore, gambling represents for them a powerful way to forget other things); and (6) compulsive gamblers, with addiction (they no longer have control over gambling; it has become the most important thing in their lives, so that they cannot stop).
1.2 From Problem-Gambling to Gambling-Disorder through Pathological-Gambling The language used to designate different levels of gambling involvement and their consequences is heterogeneous. Authors use “problem gambling,” “at-risk gambling,” “potential pathological gambling”, “probable pathological gambling”, “disordered gambling,” and “pathological gambling” (PG). Problem gambling is somewhat more difficult to conceptualize and define but it is most commonly characterized as describing those individuals who meet some criteria but less than five DSM-IV criteria for the diagnosis of PG (Lesieur & Rosenthal, 1991). Epidemiologists and clinical researchers often do not use the same terminology. Nevertheless, the frequency and intensity of problems associated with gambling can range from none to a lot. Thus, in the absence of rigorously achieved and convincing validity data, any classification label is inherently arbitrary to some degree and may be too simple to describe such a complex and multidimensional concept as gambling severity (Walker & Dickerson, 1996). In the fifth edition of the DSM the name of the disorder was changed from Pathological Gambling to
GD for nomenclature consistency within the new category and to reduce stigma associated
with the diagnostic label (i.e., removing “pathological”).
Gambling is a harmless form of entertainment for most consumers, but it has the capacity to become dysfunctional in a minority. The negative consequences could be severe, and
include financial debt, bankruptcy, family dissolution, and criminal behaviour (Murch & Clark, 2016).
2 Epidemiology
Today, 0.12-5.8% of the world’s population meets criteria for GD: 0.1–5.8% of individuals during the last year, 0.7–6.5% during their lifetime. In North America the past-year problem gambling prevalence rates ranged from 2% to 5%, in Asia 0.5% to 5.8%, in Oceania 0.4% to 0.7%, and in Europe 0.1% to 3.4% (Calado & Griffiths, 2016).
European studies show heterogeneous data: GD prevalence range between 0.6% in the UK and 6.5% in Estonia (Griffiths et al., 2009). In Italy, the dimension of the phenomenon is hardly to estimate because of the lack of validate studies. Indeed, according to the
EURISPES report, in 2009, about 70-80% of adult population gamble once in a year
(about 30 million people), mainly man between 20 and 60 years old (Dipartimento Politiche Antidroga, 2009). According to Health Ministry data, in 2012, problematic gamblers vary from 1.3% to 3.8% of the general population while disordered gamblers seem to be in a range between 0.5 and 2.2% (Ministero della Salute, 2012). The Italian CNR (National Council of Research) estimate problematic gambler at 2.3% of young population (15-24 years) and 2.2% of adult population (25-64 years) (IPSAD, 2013). Considering also soft problems, 1 Italian out 10 has problem on gambling. An analysis of the growing spread of gambling shows that in Italy, there has been an exponential growth of the phenomenon over the past decade, placing the country among the first in the world for volumes of gambling and money spent per capita.
More gamblers don’t mean more disordered gamblers: in Southern Italy there is the most prevalence of gamblers (in Molise 13.8% are gamblers), but in Friuli Venezia Giulia problematic gamblers are near 8.1%. Northern Italy is less interested by GD: Valle d’Aosta, Piedmont, Lombardy and Trentino Alto Adige are the territory in which the
6 disorder is less prevalent (IPSAD, 2013)
While some authors (Welte et al., 2002; Desai et al., 2004) found that prevalence of GD among older adults is lower than that among younger it seems a significant problem, as identified by studies that report prevalence figures upwards of 10% among older adults (Ladd et al., 2003; Erickson et al., 2005; Zaranek & Lichtenberg, 2008). Older adults may gamble more in an effort to ameliorate negative emotional states (Clarke, 2008); they may have more limits (limited access to other exciting activities or they may be unable to participate in activities that they were previously able to do) and they might attempt to fill this gap with gambling. Zaranek and Lichtenberg suggest that gambling fills a void in the life of older adults and offers a substitute for social support (Zaranek & Lichtenberg, 2008).
Pathological Gambling among heroin addicts in maintenance treatment seems to be a frequent diagnoses with percentage variable between 7 and 29% among the different studies (Spunt, 2002; Toneatto & Brennan, 2002; Weinstock et al., 2006; Peles et al., 2009; Peles et al., 2010; Castren et al., 2015; Bonnaire et al., 2016). Percentage of Pathological gambling lifetime was also higher as Weinstock and colleagues show us: in their sample of 167 patients receiving methadone maintenance treatment (MMT) 52.7% of patient has PG and the majority of them have gambled during the past 2 years (Weinstock et al., 2006). Even if it is an interesting field, there are few studies that investigate the course of this comorbidity: Peles compared two groups of PG in MMT in Tel Aviv and in Las Vegas and found similar percentage of that reported earlier and different timing: 58% of Tel Aviv patients gambled before opiate while in Las Vegas 66% after (Peles et al., 2010). The balanced average was 55% that started gambling before.
In Italy, in 2010, the collection of games amounted to 61.4 billion euro, then increased to 88.2 billion in 2015. According to data released by the Customs Agency in 2016, the collection amounts to 96 billion. Revenue went from 8.7 billion in 2010 to over 10 billion in 2016. The Italian Customs and Monopoly Agency with a press release of 13 February 2017 stated that Italian spending on gambling in 2016 was approximately 19 billion (just under 1% of GNP): spending was gets by deducting from the amount of annual profit (96 billion) the total winnings of the corresponding period (approximately 77 billion). Expense, in other words, corresponds to how much the gaming community loses in the reference period. Such an enormous amount of winnings, most of which is not high, tends to spread among a multitude of winners (Italian Customs and Monopoly Agency, 2017).
3 Aetiology
3.1 Biological factors
Gambling addiction is an illness that has neural and biological basis and that hit a vulnerable person, meaning a person who has individual risky factors, and has modifications in cerebral areas as prefrontal cortex (responsible of voluntary behaviour), nucleus accumbens (reward system), circuits of endogenous opioids (reward system, anxiety and attachment) and amygdala (aggressive behaviours and fear sensations). The behaviour of affected people is the result of the interaction of neural- physiological and pathological factors and environmental factors. The start of the behaviour could be exogenous, as visual, olfactory, auditory stimulus, or endogenous, such as memory and remembrance of past gambling behaviour.
Numerous brain structures and neurotransmitters are implicated in GD. In development and maintenance of addictive behaviour the central role of prefrontal cortex and mesolimbic reward system is highlighted by all the existing addiction theories: reward
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deficiency hypotheses (Comings & Blum, 2000), incentive-sensitization theory (Robinson
& Berridge, 1993) and impaired response inhibition and salience attribution (Volkow et al., 2003). Neuroimaging research on substance use disorder has demonstrated changes in frontal-striatal circuits at the brain’s structural and functional levels (Goldstein & Volkow, 2011; Hommer et al., 2011). The prefrontal cortex and serotoninergic system have a “controller function” on behaviours. The controller inhibits the emotional drive and it is the centre of decision-making (problem analysis and problem solving) and of coping
function. Motivation at the basis of behaviour implies the involvement also of thalamus,
prefrontal cortex, striatum, nucleus accumbens and ventral and tegmental area. Amygdala, hippocampus and perception- motor areas of cortex are also implied (Chambers & Potenza, 2003). The motivation of gambling derives from a balance between the drive system and the inhibitory system but also from salience/attention to a stimulus for the person in a particular contest (Goldstein & Volkow, 2011). In an “ Addicted brain” salience is exaggerated compared to healthy people. The Addicted person put in the centre of his life the looking for the rewarding stimulus in spite of negative consequences that gambling determines (Goudriaan et al., 2004). Amygdala, insula and noradrenergic system have “emotional function” as “drive”. These systems are influenced by dopaminergic reward system (nucleus accumbens and ventral tegmental area) and are engaged besides endocannabinoid system, opioidergic system and GABAergic one, engaged in stress response, depression, aggressive behaviour and euphoria (Potenza, 2001). The current literature explains that, in gambling affected people, there is an anomalous reaction to winning or losing reward or a mixture of the two, like in substance use disorder (SUD) (Volkow et al., 2002).
Dopamine seems important in abstinence and craving, noradrenaline and serotonin take part in control of the arousal and the aggressive behaviour, the circadian cyclicity and
reaction to stress (dos Santos Coura & Granon, 2012) while the opioid system, works through the modulation of the GABAergic system in the tegmental ventral area (VTA), and is capable of controlling the activities of the dopaminergic cortical-mesolimbic system projecting towards the nucleus accumbens and the striatum control. In GD, as in the other addictions, craving is the core of relapsing behaviour. Craving is a strong desire and research of the gambling activity, sometimes not only in gambling called “urge”. Brain structures engaged in craving are cingulate gyrus, prefrontal and orbitofrontal cortex. Thalamus is another important brain structure for motivation of a human behaviour. To better explain how rewarding stimuli can induce a maladaptive behaviour, it’s better to remember that reward circuits always imply a memory of brain circuits and a cognitive modulation on which the person learns and than tries to reproduce the rewarding behaviour. The features of the stimulus are: a core, derived of endogenous attendance (craving, game skills, anxiety level) and peripherals that are factors that can inhibit or increase the perceive reward. Dickerson et al (Dickerson et al., 1987) found that pathological gamblers had a higher arousal compared to occasional gamblers. Peripheral factors are environmental as the location, the lights, the music, alcohol assumption, etc. Dixon et al. have shown that the rhythm of music (e.g. fast music) significantly influenced betting speed. The sound associated with the pay-out has a strong connotation on memory sedimentation and the re-enhancement of the rewarding in contrast of the unpleasant one (Spenwyn J., 2010). Stark et al. have shown that gambling in red light (compared to blue light) has led to an increase in risk gambling, higher bets, and more frequent bets. Indeed, Spenwyn and co-workers (Spenwyn J., 2010) noted that the combined effect of high rhythm music and red light produced bets faster in a computerized version of roulette. Alcohol consumption can alter the cognitive abilities of choice (thinking skill and attention) resulting in decision-making alteration (Baron & Dickerson, 1999) and an increase in the level of behavioural risk (Breslin & Sobell, 1999).
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The dopamine system is crucial in addiction, it codes for reward anticipation and outcome evaluation. Reward anticipation is dopaminergic activation prior to reward, while outcome evaluation refers to dopaminergic activation after reward. In GD have been found alterations, but existing data are heterogeneous: some studies report higher levels of
dopamine metabolites (homovanillinic acid and DOPAC) versus healthy people
suggesting a reduction in reward sensitivity in the disorder, other studies don’t confirm these data (Linnet et al., 2010; Linnet et al., 2011). Clark and colleagues, studying striatal dopamine D(2)/D(3) receptor availability, as a premorbid vulnerability marker for addictive disorders, in PG, found no significant difference between groups in contrast to previous reports in drug addiction (Clark et al., 2012); studies by Fiorillo et al. and Preuschoff et al. (Fiorillo et al., 2003; Preuschoff et al., 2006) support the knowledge of sustained anticipatory dopamine activation toward uncertainty, but a lower one, during the winning phase. Indeed, unexpected outcome determines a smaller reduction in dopamine, in GD patients, compared to healthy people. More investigations are needed to determine whether or not this mechanism is associated with dopaminergic dysfunctions in GD. This is consistent with the incentive-sensitization model’s suggestion of increased “wanting” but decreased “liking” in addiction and the knowledge of sustained
anticipatory dopamine activation in reward prediction (Linnet, 2014).
In gamblers, high level of norepinephrine has been identified, so that there is a higher stimulation and searching for sensations with sympathetic and para- sympathetic involvement and neural-endocrine stress response. This engagement is different in winning and in losing (Fowles, 1980; Leeman & Potenza, 2013). Arousal and risk taking behaviour may be linked to noradrenergic system dysfunction i.e. increased levels of norepinephrine metabolites (Roy et al., 1988): during casino black- jack gambling, heart rate and noradrenergic measures become elevated to a greater degree in men with gambling problems as compared to those without (Meyer et al., 2004).
The major system implicated in impulse control disorders is the serotoninergic one and findings in this field corroborate similarity between GD and SUD: low levels of the serotonin metabolite 5-hydroxy-indole-acetic acid have been found in the cerebrospinal fluids of individuals with GD and alcoholism. Behavioural responses to the partial serotonin 5HT1/5HT2 agonist meta-chloral-phenyl-piperazine (m-CPP) have been found to distinguish individuals with impaired impulse control, including those with GD and alcohol abuse/dependence, from those without. Specifically, affected individuals report a euphoric response following m-CPP administration whereas unaffected subjects do not. Levels of platelet monoamine oxidase, considered a peripheral marker of serotonin function, are decreased in subjects with GD, and similar findings have been observed in individuals with SUD and behaviours characterized by impaired impulse control (Potenza, 2008).
Also serotoninergic system is involved and (Potenza, 2001; Potenza et al., 2013) Potenza and coll. found lower level of this neurotransmitter post stimulus, probably responsible for the deficit in inhibitory control. Low platelet mono-amine oxidase (MAO) activity reported in these patients indicates dysfunction in serotonergic systems (Carrasco et al., 1994). The severity of pathological gambling in humans is linked to increased levels of 5-HT (1B) receptors in the ventral striatum and anterior cingulate cortex regions of brain (Potenza et al., 2013). Serotonin has been linked to behavioural initiation and stop which are important in the onset of the gambling cycle and difficulty in decreasing the behaviour (Hollander et al., 2000). Indeed, clinical evidence has shown the efficacy of selective serotonin inhibitors (SSRIs) in reducing symptoms and impulsive and compulsive behaviours, regardless of the simultaneous presence of depressive disease in GD (Lupi et al., 2014).
Glutamatergic system is another system involved: it has a crucial role in satisfaction, craving and relapse with the neural ways that origin in prefrontal cortex and go to nucleus
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accumbens. There are empirical evaluations: manipulation of glutamatergic neurotransmission appears to be promising in developing therapeutic agents for the treatment of GDs (Pettorruso et al., 2014).
Koob and Le Moal (Koob & Le Moal, 2008) supposed the existence of a disrupted HPA axis with chronic exposure to substances, as well as during engagement in gambling, which alters its ability to function effectively and efficiently (Zhou et al., 2010). The changes to the HPA axis resulting from repeated substance use include increases in circulating adrenocorticotropic and corticosterone hormones. These changes cause individuals with addictions to experience stress more intensely and for longer periods than others (Koob & Le Moal, 2008) and lead to a long term increase in their susceptibility to the negative effects of stress, factors that can encourage relapses.
3.1.1 Neuroimaging
The literature explored brain activity during winning or losing a game in healthy subjects. The two different outcomes induced identic response patterns in the frontal-striatal-limbic matrix (main peaks in ventral striatum), amygdala, insular cortex and hippocampus based on endogenous-related potentials; but during losses, the connectivity of the amygdala appeared more pronounced (Camara et al., 2008).
In problem gamblers the circumstances of winning or losing determined different frontal-parietal activation pattern versus occasional gamblers (this might be interpreted as a signal-triggered addiction memory matrix induced by playing linked signals) (Miedl et al., 2010). Both groups however showed a raised response in the caudal cingulate cortex and the inferior striatum (Miedl et al., 2010).
FMRI studies explored also problem and occasional gamblers during high- versus low-risk conditions (Miedl et al., 2010): in high-risk situations, problem gamblers showed a higher response in the thalamus and inferior rostral and superior temporal zones compared to
occasional gamblers. On the other hand, during low-risk situations, problem gamblers showed a lower response in the thalamus and inferior rostral and superior temporal zones compared to occasional gamblers.
Reuter et al. studying Pathological Gamblers compared with control subjects in a fMRI study during a task that simulate Gambling, observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that was negatively correlated with gambling severity, linking reduced activation of these areas to disease severity (Reuter et al., 2005). Similarly, Hommer et al. (Hommer et al., 2011) in a study carried out in adult subjects with alcohol-related disorders and controls found that subjects with alcoholism activate ventral striatum less robustly in anticipation of working for monetary reward. Diminished ventral striatal activation in addictions also appears relevant to craving. In a study of gambling urges in PG and cocaine cravings in cocaine dependence, diminished activation of ventral striatum similarly distinguished addicted from control subjects during viewing of the respective gambling or drug videotapes (Kober et al., 2016).
In a recent meta-analysis Lujiten et al. support the decreased striatal activation during reward anticipation in both individuals with substance and gambling addictions compared with healthy control individuals. However, during reward outcome, addictions differ: individuals with substance addiction showed increased activation in the ventral striatum, whereas individuals with GD showed decreased activation in the dorsal striatum compared with healthy control individuals (Luijten et al., 2017). However, reports of relatively increased activation of striatum exist, particularly in response to gambling cues, although the findings are not uniform across studies (Potenza, 2014).
Romanczuk-Seiferth et al (Romanczuk-Seiferth et al., 2015) in one fMRI study evaluated grey matter volume between three groups: GD patients, alcohol-dependent patients and
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controls using a monetary incentive delay task. GD groups demonstrated increased activity in the right ventral striatum during loss anticipation compared with controls and alcohol-dependent patients, and decreased activity in the right ventral striatum and right medial prefrontal cortex during successful loss avoidance compared with controls. These results suggest relevant differences with respect to the anticipation of loss as well as its avoidance (negative reinforcement) in GD. Moreover, functional magnetic resonance studies have clearly demonstrated that in patients with pathological gambling, during the pay out expectation, increased activity is manifested in the reward system (Clark et al., 2009). After the payout, there would be a lower level of activity in the areas of gratification than normal players and during the game a minor activation of control areas. This imbalance in problem gamers can explain the persisting of a maladaptive behaviour like gambling.
Indeed, another study of resting fMRI (Jung et al., 2014), demonstrated default mode networks alterations in GD, similar to those present in SUD.
Koehler et al (Koehler et al., 2013) carried out another resting state fMRI study of GD using seed-based functional connectivity analyses. They demonstrated increased connectivity between the prefrontal cortex and striatum and decreased connectivity within prefrontal areas compared with controls. This study suggests that network alterations exist between prefrontal regions and reward-related areas during rest. Gamblers showed, indeed, a lower level of activity in the brain region related to impulse control (ventromedial prefrontal cortex) compared to controls, based on event-related fMRI; however, there were no discrepancies in the responses of the rostral cingulate cortex or dorsolateral frontal cortex (Potenza et al., 2003).
While neuroimaging data suggest similarities between PG and SUD, they suggest differences between PG and Obsessive Compulsive Disorder (Potenza, 2006).
Observations of brain volume seem to depend on a methodological approach: VBM whole-brain analyses found no alterations, whereas region-of-interest analyses found volumetric changes in subcortical brain areas.
Gamblers displayed bigger grey-matter volume compared to healthy volunteers, according to structural MRI technology (Fuentes et al., 2015). Moreover, healthy volunteers had larger volumes of the right hippocampus, right thalamus, and left putamen compared to gamblers (Fuentes et al., 2015).
Since GD is as an addiction without the neurotoxic effect of a drug of abuse, these alterations might be related to addiction-related processes. Results of functional connectivity studies are in accordance with task-related findings in decision making and reward processing, because these studies found changes in reward- and control-related brain networks (Grant et al., 2006).
Another brain area emerging as playing a specific role in gambling cognitive distortions is the insula: patients with brain injury affecting the insula (patients with vmPFC and amygdala damage) were insensitive to the effects of gambling ‘near-misses’ on a slot machine task, and did not display the gambler’s fallacy (the tendency to avoid recent outcomes) in sequential roulette predictions, compared to the comparison groups (Clark et al., 2014).
Electroencephalography studies highlighted major alterations in brain activity (particularly in temporal areas and the back region) (Regard et al., 2003) that lead to persistence in gambling despite the negative consequences.
3.2 Genetic factors
Family cohort studies find that GD runs in families and families with GD frequently have histories of substance use disorder (Black et al., 2003). GD’s heritability is similar to
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‘Taq1A’ allele of the dopamine receptor D2 polymorphism has been linked to both GD and SUD (Comings et al., 2001). This allele has been associated with increases in impulsivity on neurocognitive tasks (Rodriguez-Jimenez et al., 2006), suggesting the possibility that at least part of the shared genetic variance between GD and alcohol dependence (12%–20%) (Slutske et al., 2000) is due to a genetic predisposition toward the
underlying construct of impulsivity.
Only a study investigating the serotonin transporter showed that the serotonin receptors 1B and 2A are implied in the diagnosis of PG. They found a significant association of the C/C genotype of the serotonin receptor 2A T102C (receptor 6313) polymorphism and PG. This was a preliminary result confirming what have been reported for nicotine and alcohol dependence but similar studies need to be done in future (Wilson et al., 2013).
3.3 Psychosocial factors
3.3.1 Gender
Many etiological studies focused on Gamblers anonymous groups inappropriately generalize findings about men to women, although females seem (1) to start gambling later than men, (2) appear to experience the onset of problem gambling earlier in the course of their life (Mark & Lesieur, 1992). This phenomenon is called “telescoping” (Potenza et al., 2001) although the biological factors underlying this process have yet to be examined systematically.
The American Psychiatric Association reports that the rate of pathological gambling is twice as high among men than among women and some clinical gender differences. Gambling type seems different: cards, sports and horse races seems more prevalent in males and slot machine and bingo among females. Besides, females with GD tend to have more depressive, bipolar and anxiety disorders (American Psychiatric Association, 2013).
3.3.2 Cognition
In GD there is an increased relevance of rewarding stimuli linked with gambling witch is associated with an altered way of punishment and reward related also to behavioural conditioning. The high impulsivity, due to diminished prefrontal self-control, compromises also the decision-making efficacy and the evaluation of winning
probability. Another constant is, indeed, novelty seeking (Shaffer, 1996).
Usually, GD starts with a first period of voluntary research and experimental of incentive, the phase of recreational gambling. In this period there is just the exciting side of game. In that way, vulnerable people to develop the disorder, continues gambling, that, in this people, leads to:
1. A neural and plastic effect where there is, at one side, the augmentation of emotional drive (in the amygdala) and in the other side, reduced inhibitory control of prefrontal cortex.
2. A cognitive modulation that the subject structures around gambling, his winning and losing experiences and to his skills.
That pathway leads to cerebral autonomous mechanisms that free themselves from voluntary control of the subject himself.
Gratification in GD is more linked to winning anticipation than to winning it-self as proved by some studies of dopaminergic release in the striatum (Joutsa et al., 2011). The dopamine release during gaming to the slots machines, in fact, is equivalent to healthy controls.
A number of neuropsychological distortions have been found in GD: they refer to how the gambler thinks about randomness, chance, and skill (Dube et al., 1996; Clark et al., 2009) and foster an inappropriately high expectation of winning during the game and an underestimate of losing. There is, at the PET imaging, a lower density of D1 and D2
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receptors in striatum correlated to decision making during gambling activity (Ito et al., 2011).
The activation of the amygdala and the orbitofrontal cortex, occurred during the selection process, impairs decision making related to working memory deficit in individual with SUD (Coricelli et al., 2007). Moreover, the insula was fundamental in altered cognitive interpretation of near-miss results and trial sequences in gambling-related tasks (Clark et al., 2014).
Cognition distortions in GD patients are, compared with healthy controls: - Bias in processing of random sequences;
- Illusion of control;
- Near miss results (Clark et al., 2014);
- Diminished executive functioning: poorer results in planning tests, poorer inhibition, less accurate temporal estimation, poorer results in planning tests (Goudriaan et al., 2006);
- Reward-based cognitive flexibility (Boog et al., 2014)
- Concentration, memory, and executive functions (deficits in selection of the decision process (Regard et al., 2003; Bechara & Martin, 2004; Ledgerwood et al., 2012)
- Cognitive rigidity, impulsivity, and compulsivity, related to the region of prefrontal cortex: GD patients displayed deficits in discovering alternative ways of resolving problems, had decreased efficiency (WCST test), were unable to learn from errors and to search for alternative responses (Marazziti et al., 2008);
- Risky decisions (Brand et al., 2005);
- Response speed, motor-impulse control and cognitive plasticity (Odlaug et al., 2011). GD were slower, less accurate, and had impaired performance on the reverse Stroop-test (Kertzman et al., 2006).
Tang et al. found that gambling-related cognitive biases were related to the severity of gambling problem. The probable pathological gambling group had greater cognitive deficits than probable problem gambling group witch in turn had greater cognitive biases than non-problem-gambling group. The youth patients were, indeed, the age group of pathological gamblers with higher cognitive biases (Tang & Wu, 2012).
Cognition influenced by gambling skills (illusion of control, fostered by internal factors such as reappraisal of losses, or perceived outcome sequences) but not cognition influenced by rituals (such as illusion of control fostered by external factors such as luck or superstitions) predicted desire for play following near-miss results; furthermore, a lack of personal control predicted perseverance on the slot-machine test (on laboratory conditions) (Billieux et al., 2012).
In GD, as in SUD, features of impulsivity and sensation-seeking have been found to be elevated (Blaszczynski et al., 1997; Petry, 2001; 2001; Potenza et al., 2003; Brewer & Potenza, 2008) and people with GD tend to prefer immediately available rewards even if smaller, compared to greater reward delayed, in delay discounting paradigms (Petry, 2001) and to make disadvantageous choices on decision-making tasks like the Iowa Gambling Task (Cavedini et al., 2002; Bechara, 2003).
The relationship between impulsivity and addiction is strong as evidenced by self-report measures and laboratory tests of impulsive behaviour. Otherwise, this relationship has been investigated in terms of its temporality: impulsiveness precedes addiction, follows it or both? It is important to clarify that impulsivity itself is not a unitary construct; one distinction is between impulsive choice (as in the temporal discounting of reward and
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delayed gratification) and impulsive action (as in Go-No Go paradigm) and another is between ‘waiting’ and ‘stopping’, which refers to whether the inhibitory process occurs before or after response initiation, respectively (Dalley et al., 2011). In at least two cohort studies, impulsivity preceded and facilitated gambling behaviours (Mischel et al., 1989; Vitaro et al., 1999) and several studies in GD and alcohol dependence generally support this hypothesis (Lawrence et al., 2009). Moreover, convergent with neurocognitive findings, self-report data show that trait impulsivity tends to be elevated in GD, providing independent, multimodal evidence for pre-existing inhibitory control deficits in addictive disorders (Fuentes et al., 2006). In GD, as in SUD, features of impulsivity and sensation-seeking have been found to be elevated (Blaszczynski et al., 1997; Petry, 2001; 2001; Potenza et al., 2003; Brewer & Potenza, 2008); GD patients tend to prefer immediately available rewards (Petry, 2001) and to make disadvantageous choices (Cavedini et al., 2002; Bechara, 2003). Trait impulsivity and impulsive choice predict treatment dropout in pathological gamblers, whereas impulsive action (Stroop-test) and executive inhibitory tasks did not (Alvarez-Moya et al., 2011).
4 Clinical aspects
4.1 Clinical picture
Usually, GD starts with a first period of voluntary research and experimental of incentive, the phase of recreational game.
The developmental pathway that can involve people vulnerable of developing GD can manifest in different ways (Figure 1). The behavioural pathway of GD can be conceptualized in 7 phases (Rosenthal, 1987 ):
• The second phase: of the unexpected losses and run after desired win but characterized by continue losses with a spiral trend (sporadic winnings worth substantial and regular losses);
• The desperation phase with illegal acts, fantasies of escape and often suicide ideation;
• The surrender phase and seeking for treatments; • The treatment phase and follow up with craving;
• The relapse phase: this phase can be conceptualized in 2 roads: continuation of gambling behaviour with financial and legal consequences or prolonged abstinence during treatment.
In Italy the gambler is mainly a man (86,4%) that lives in the Centre-South of the State, has a secondary school degree, often use alcohol (56,4% Alcohol use disorder) and nicotine (34,6% heavy smokers) (Dipartimento Politiche Antidroga, 2009). In 2011 in our country has been spent in gambling 80 billion euro. Most money spent on slot machine and video-lottery (56,3%), than scratch and win (12,7%), lotteries (8,5%), sports (4,9%) and than bingo and horse races. Gambling can occur in multiple venues (e.g., in casinos, convenience stores or bars or on the Internet), either legally or illegally.
It is also relevant to find out the game preferred by the subject (Cocco et al., 1995) because games can differ greatly in the amount of stakes and odds, the concentration needed, the skills required, and the degree of anxious and excitatory involvement that they are able to evoke. It has been noted that there are several sub-groups of players that can be selected according to the typology and the "magnitude of the game" (both financially and emotionally) required to complete the game. It is evident that the enjoyment of stimuli requires a higher level of commitment to the player, and thus a higher degree of stress, and greater severity of the clinical picture. There are also a number of features of gaming that make them particularly risky to cause loss of control, such as accessibility, anonymity,
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comfort, the use of a virtual currency. These elements favour the presence of cognitive distortions, such as the illusion of control, which fuel the desire to "beat the system", in young people (Caillon et al., 2012). There are, in fact, games that have a relative negligible risk of harm (e.g. lotteries) versus those more “addictive” (e.g. electronic gaming machines or fixed odds betting terminals) based on their structural features (Griffiths & Auer, 2012). Welte has noted that participation in more types of gambling is highly predictive of pathological gambling (Welte et al., 2004). Most individuals with GD have one or two types of gambling that are more problematic for them, although some individuals
participate in many forms of gambling. The frequency of gambling can be related more to
the type of gambling than to the severity of the overall GD. The amounts of money spent wagering are not in themselves indicative of the disorder: some individuals can wager thousands of dollars per month not having problem with gambling, while others may wager much smaller amounts but experience substantial gambling-related difficulties (American Psychiatric Association, 2013).
GD is more common among younger and middle-age persons than among older adults. Among adolescents and young adults, the disorder is more prevalent in males than in females. Younger individuals are more involved in sports betting, while older adults are more likely to gambles at slot machine and bingo. The treatment seekers among gamblers are low, especially between younger individuals (American Psychiatric Association, 2013).
Individuals with GD experience a euphoric state similar to a drug-induced “high” (Kyngdon & Dickerson, 1999), symptoms of withdrawal (including restlessness, headaches, and irritability) at comparable levels to individuals with alcohol use disorder (AUD) (Nower & Blaszczynski, 2008). 91 % of a sample of 222 GD reported “craving” which were not related to other drug use (de Castro et al., 2007). Craving in PG may be associated with depressive symptoms (Tavares et al., 2005) potentially suggesting an
influence of negative reinforcement, a process that is often suggested to underlie substance addiction (Koob & Volkow, 2010). In terms of tolerance, individuals with PG demonstrate changes in heart rate responses to gambling activities (Griffiths, 1993) and report increasing levels of gambling or bet size over time (Nower & Blaszczynski, 2008). This latter effect was linked with an aim of increasing chances of winning rather than increasing or maintaining excitement levels (Nower & Blaszczynski, 2008).
Pfund et al. (Pfund et al., 2016) found that gamblers with greater elevations of psychological distress evidenced greater severity of gambling pathology. Clinically significant elevations were present for symptoms of depression, deviancy, and anxiety, but not substance abuse. Greater scores of psychological distress significantly predicted elevations of depression, deviancy, and anxiety.
20% of individuals seeking treatment for GD have a history of suicidal attempts. Interestingly, 1.7% of all suicides are gambling related (Linden et al., 1986).
4.2 Longitudinal aspects
The natural history of GD is characterized by exacerbations and remissions, often related to life events (Prakash et al., 2012): individuals can fluctuate between problematic phases to period in which they do not gamble. Gambling patterns can be regular or episodic, and persistent or in remission. Gambling can increase during periods of stress or depression and during periods of substance use or abstinence. Sometimes it is associated with spontaneous, long-term remissions (American Psychiatric Association, 2013).
Usually, GD starts with a first period of voluntary research and experimental of incentive in adolescence or young adulthood, and could be several years of recreational gambling. The majority of patient’s evidences a pattern of gambling that gradually increases in both frequency and amount of money spent. Milder forms can develop into more severe cases.
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The developmental pathway that can involve people vulnerable of developing GD can manifest in different ways, so it is important to establish some predictors of progression to GD and to develop early interventions that target high-risk internet gamblers for prevention efforts.
“Gambling to escape problems” was one of the most stable symptoms and “reliance on others to support gambling” was also important among participants at-risk for PG (LaPlante et al., 2011). Braverman and Shaffer analysed the characteristic of this high-risk subgroup and found: (1) frequent and (2) intensive betting combined with (3) high variability across wager amount and (4) an increasing wager size during the first month of betting (Braverman & Shaffer, 2012). However, literature is insufficient, so additional researches are necessary to identify markers that can classify subset of high-risk
gamblers.
Male gender and low depression has been identified as predictors of successful treatment outcomes across multiple time-points. Other predictors of successful treatment outcomes included older age, lower gambling symptom severity, lower levels of gambling behaviours and alcohol use, and higher treatment session attendance (Merkouris et al., 2016). On the other hand, predictors of relapse were: more time of the disease before looking for treatment and neurocognitive markers of impairment on executive functions (Goudriaan et al., 2008).
Development of early-life GD appears to be associated with impulsivity and substance abuse. Many high school and college students who develop GD grow out of the disorder over time, although it remains a lifelong problem for some (American Psychiatric Association, 2013).
4.3 Diagnosis
To meet criteria for a DSM-IV PG diagnosis, subjects had to endorse at least 5 out of 10 criteria. In the DSM-5, 9 of the criteria are the same, but the ' illegal act criterion' was removed and diagnostic threshold was lowered to 4 criteria out of 9.
The DSM-V eliminates any distinction between substance abuse and addiction diagnosis to unify them in a syndrome that assigned a gradient of severity based on the number of criteria that are met in the specific clinical picture.
The essential feature of GD is persistent (at least 12 months) and recurrent maladaptive gambling behaviour that results in maladaptive consequences in social, family and working areas (Criterion A). A pattern of "chasing one's losses" may develop, with an urgent need to keep gambling (often with increasing bets or taking of greater risks) to undo a loss or series of losses. The patient may abandon his or her gambling strategy and try to win back losses all at once. Although many gamblers may "chase" for short periods of time, it is the frequent, and often long-term, "chase" that is characteristic of GD (Criterion A6). Individuals may lie to family members, therapists, or others to conceal the extent of involvement with gambling (Criterion A7). Another important feature is engaging in "bailout" behaviour, turning to family or others for help with a desperate financial situation that was caused by gambling (Criterion A9).
The inclusionary criteria for GD share similarities with those for substance abuse,
dependence and use disorders across DSM-IV and DSM-5. For example, the inclusionary
criteria for GD as those for SUD include criteria targeting tolerance, withdrawal, repeated unsuccessful attempts to cut back or quit and interference in major areas of life functioning. Although certain criteria are specifically listed for gambling and SUD, they often have applicability to both. For example, cravings are listed in the inclusionary criteria for SUD but not for GD although gambling urges are present. On the other hand, gambling
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when feeling distressed is an inclusionary criterion for gambling but not for SUD.
The Differential diagnosis is between Problematic gambling (professional or social gambling), with the Manic Episode where the loss of judgment and risky behaviour are due to the mood elevation, Personality disorders especially with antisocial personality disorder and other medical conditions. Some patients taking dopaminergic medications (e.g., for Parkinson's disease) may experience urges to gamble. If such symptoms dissipate when dopaminergic medications are reduced in dosage or ceased, then a diagnosis of GD would not be indicated (American Psychiatric Association, 2013).
Passing from DSM-IV to DSM-5 the following differences are observed: (1) reclassification of pathological gambling from Impulse Control Disorders to a newly created category labelled “Substance-Related and Addictive Disorders” that also includes substance use disorders. (2) Renaming of pathological gambling to GD, (3) removal of the 'illegal acts criterion', and (4) lowering the diagnostic threshold for diagnosis from five to four criteria.
4.4 Substance Use Disorder Comorbidity with special reference to Heroin Use Disorder
GD, as diagnosed with DSM-5 criteria, has prevalence in SUD patients at about 20,4% (Rennert et al., 2014). High rates of co-occurrence between SUDs and GD are present in
both directions (Potenza, 2006): in GD samples, 50% have a lifetime SUD (Lorains et al.,
2011). Prevalence rates are higher in treatment seeking samples (Cowlishaw et al., 2014).
This is important in a prognostic way becauseindividuals with comorbid GD and alcohol
tend to have more severe problems (Rash et al., 2011). Indeed, a history of a comorbid SUD often hampers efforts to achieve gambling abstinence, and a current alcohol use disorder increases the risk of relapse after gambling treatment and those with no lifetime
history of SUD are 2.6 times more likely to achieve a 3-month period of gambling abstinence compared to those with lifetime SUD (Hodgins & el-Guebaly, 2010).
GD among heroin addicts in maintenance treatment seems to be a frequent diagnosis with percentage variable between 7 and 29% among the different studies (Spunt, 2002; Toneatto & Brennan, 2002; Weinstock et al., 2006; Peles et al., 2009; Peles et al., 2010; Castren et al., 2015; Bonnaire et al., 2016). Weinstock et al. (Weinstock et al., 2006) found a percentage even higher: 52,7% of their patient receiving
methadone maintenance treatment (MMT), has PG and the majority of them have
gambled during the past 2 years. Italian studies are lacking in this sense but it seems that comorbidity between GD and SUD is frequent: about 50% with alcohol and 60% with tobacco. Like with substance dependence, high prevalence estimates have been reported for pathological gambling amongst adolescents and young adults and lower estimates amongst older adults (Potenza, 2006).
Literature concerning GD and SUD comorbidity is centered on epidemiology amongst
treatment seeking patients, especially MMT and CBT patients.
The few studies highlighting psychopathology found that methadone maintenance patients with GD had significantly poorer mental and physical health than patients without this comorbidity (Peles et al., 2010) Indeed, PG patients tended to be male and older on admission to MMT. (Weinstock et al., 2006) HUD patients with comorbid GD tend to respond less to substance abuse treatment (Ledgerwood & Downey, 2002).
To better investigate the relationship between these disorders, further studies are needed.
Similarities between GD and SUD are:
1. Euphoric state/ excitement or arousal-state; euphoric state such as ‘‘high’’. 2. Loss of control/ impaired control
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3. Craving/failure to resist an impulse, drive, or temptation to perform an act 4. Recidivism/exacerbations and remissions
5. Alteration in global functioning/impaired control
4.5 Comorbidity
4.5.1 Psychiatric Comorbidity
96% of individuals with lifetime GD also meet criteria for at least one other lifetime psychiatric disorder (Kessler et al., 2008). Literature estimates axis I disorders comorbidity 74.8% current and 75.5% lifetime. The higher rates are of current mood disorders (23.1%) with high incidence of depression (McCormick et al., 1984; Bergh & Kuhlhorn, 1994), alcohol use disorders (AUD) (21.2%), anxiety disorders (17.6%) and substance (non-alcohol) use disorders (7.0%) (Dowling et al., 2015). Lifetime rates are higher: mood disorders (49%–56%), anxiety (41%–60%), disorders, AUD (73%) and DUD (38%) (Kessler et al., 2008) being particularly prevalent. Personality disorders are also more common among those with GD (Petry et al., 2005) and the prevalence of multiple comorbid disorders is increased as well.
The majority of this comorbidity (74%) precedes and may be a risk factor for the development of GD. However, longitudinal prospective studies (Chou & Afifi, 2011; Parhami et al., 2014) suggest that past-year GD is associated with the subsequent development of new psychiatric conditions including mood, anxiety, and AUD. The risk of developing new disorders appears to be associated with the severity of gambling behaviour (Parhami et al., 2014) with diagnosed gamblers at greatest risk for onset of a new comorbid disorder compared to problem or recreational gamblers. Overall, the literature supports a bidirectional relationship with respect to comorbidity such that psychiatric disorders can serve as risk factors in the development of, can serve as maintenance factors in GD, and can arise as consequences of GD (Dussault et al., 2011). HUD patients with comorbid GD
tend to respond less to substance abuse treatment (Ledgerwood & Downey, 2002).
4.6 Medical Comorbidity
Some specific medical diagnoses, such as tachycardia and angina, are more common among individuals with GD than in the general population, even when excluded other substance use disorders, including tobacco use disorder (American Psychiatric Association, 2013).
5 Treatment of GD
5.1 Pharmacological treatment
Currently, exist three main pharmacological approaches for GD derived from the psychopathological and phenomenological perspectives of the disorder itself: considering GD as a behavioural addiction, as belonging to the obsessive- compulsive disorder spectrum, or as the result of an emotional dysregulation related to mood disorders (Dell'Osso et al., 2005; Angelucci et al., 2013).
According to the first perspective, pharmacological approach use opioid antagonists, as in the treatment of alcoholism or other forms of addiction. In particular, controlled studies have been conducted for naltrexone and nalmefene on larger samples and with the best results (Kim & Grant, 2001; Grant et al., 2006).
In the second case, anti-obsessive or antidepressant drugs in order to improve serotoninergic transmission are the most used drugs, usually at medium-high dose and for longer period than in depression. Controlled trials have shown positive results, in particular for fluvoxamine, paroxetine, escitalopram, and sertraline (Hollander et al., 2000; Kim et al., 2002; Saiz-Ruiz et al., 2005; Grant et al., 2006).
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atypical antipsychotics, as in the treatment of resistant depression and bipolar disorder (Hollander et al., 2005; Fong et al., 2008; McElroy et al., 2008). Published data, although limited by brief duration of the studies and small number of enrolled subjects, shows mixed evidence for serotonergic antidepressants, opioid antagonists, and mood stabilizers. Other compounds, such as glutamatergic agents and psychostimulants, deserve further studies (Lupi et al., 2014).
The coexistence of a GD and a SUD makes the treatment more challenging (Quintero, 2017).
5.2 Psychosocial treatment
A Cochrane review of 2012 on psychological therapies for pathological and problem gambling supports the efficacy of Cognitive Behavioural Therapy in
reducing gambling behaviour and other symptoms of pathological and
problem gambling immediately following therapy but the majority of studies included in the meta analysis, had risk of bias so the authors concludes that the treatment efficacy could be overestimated. Indeed, the durability of therapeutic gain is still unknown. Preliminary evidence for some benefits from motivational interviewing therapy in terms of reduced gambling behaviour were found (Cowlishaw et al., 2012).
Schuler and co-workers in a review indicate that the evidence for the effectiveness of Gamblers Anonymous either as a control condition or in conjunction with formal treatment or medication is inconsistent (Linden et al., 1986).
Part B
Specific Psychopathology of Addiction
Comparison between Heroin Use Disorder and Gambling Disorder patients
6 Introduction
In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Pathological Gambling become Gambling Disorder (GD) and it moved from “Impulse Control Disorder” to the chapter of “Substance-Related and Addictive Disorders” (Rash & Petry, 2016). In this way, DSM-5 is the first diagnostic system to recognize a behavioural addiction. In the GD there isn’t an exogenous drug administration that is the central core of traditional meaning of addiction, but people compulsively and dysfunctionally engage in behaviours that can be conceptualized within an addiction framework as different expressions of the same underlying syndrome. As in addiction to substances, there are similar elements in terms of clinical expression (e.g., craving, tolerance, withdrawal symptoms), comorbidity, neurobiological profile, heritability, and treatment (Yau & Potenza, 2015). Further similarities are found between GD and substance use disorders (SUD) in life course, treatment outcome, diagnostic criteria (with some differences) (Weinstock & Rash, 2014) although scepticism remains (Schuckit, 2013).
A specific psychopathology of Substance Use Disorders (SUD) has been proposed recently. By applying an exploratory principal component factor analysis (PCA) to the Self-Report Symptom Inventory (SCL-90) checklist in a sample of Heroin Use Disorder (HUD) patients entering agonist opioid treatment, it became possible to identify a group of 5 mutually exclusive psychopathological/psychiatric dimensions: (1) “worthlessness and
being trapped”, (2) “somatic symptoms”, (3) sensitivity-psychoticism”, (4) “panic anxiety”
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performed in a different sample of HUD patients. The studies in question led to the identification of the same 5-factor solution, which proved not to be substantially influenced by confounding factors such as active heroin use, lifetime psychiatric problems, kind of treatment received or specific drug of abuse (heroin, cocaine or alcohol) (Pani et al., 2014; Pani et al., 2015; Pani et al., 2016; Pani et al., 2016). Moreover, these five psychopathological dimensions appeared to be also correlated with the outcome of a variety of agonist opioid treatments (Maremmani et al., 2008) and residential treatments (Maremmani et al., 2016). In addition, these five psychopathological dimensions have demonstrated their capability to discriminate HUD patients from other psychiatric patients, specifically those affected by Major Depression (Maremmani et al., 2015). Accordingly, it is possible to speculate that these 5 dimensions can delineate the specific psychopathology of substance use disorder (Maremmani et al., 2017)
Aims: To further support the hypothesis of the existence of a specific psychopathology of addiction, in this study, we compared psychopathological symptoms of GD and HUD patients. We expected no differences or little differences between the two addictive behaviours.
7 Methods
7.1 Design of the study
Information on patients included in the present study comes from two different datasets. Data regarding heroin-dependent patients came from the Pisa Addiction dataset, a database including anonymous individual information originally collected for clinical or other research purposes at the Dual Diagnosis Unit, Santa Chiara University Hospital in Pisa, Italy. Data regarding PG individuals were extracted from a pluriannual dataset of patients treated at the Drug Addiction Unit, in Castelfranco Veneto, Treviso, Italy.
