Impulse Control Disorders – The Continuum Hypothesis

Abstract

The group Parkinson Inside Out is composed of health professionals and academic researchers who have been diagnosed with Parkinson’s Disease. In our discussions we try to make use of both our inside perspective as patients, and our outside perspective as professionals. In this paper, we apply the two perspectives to the Impulse Control Disorders. These impulsive behaviour patterns are thought to be relatively uncommon side effects of some of the medication used in dopamine replacement therapy. The phenomenon is usually described as relatively rare (<15%), and mainly confined to patients with special vulnerabilities. In contrast, we propose that having some problems with controlling impulses is a very common experience for patients undergoing dopamine replacement therapy. They result from difficulties in decision making engendered by variations in dopamine accessibility in the reward centre of the brain. Only in a minority do the consequences grow to the damaging proportions of a disorder, but most patients are probably affected to some degree. Seeing, and measuring, decision difficulties as a continuous dimension, rather than as a discrete category, brings increased possibilities for early detection and continuous monitoring. With reliable measures of the propensity for impulsive decision making, it may become possible to both reap the benefits and avoid the dangers of the dopamine agonists. We point to ways of empirically testing our continuity hypothesis.

INTRODUCTION

How we worked

The group Parkinson Inside Out is more fully presented elsewhere in this issue (see: “Parkinson’s Inside Out”, by Stamford, Scheller and Jenner). Briefly, we are an international group of academic researchers and health professionals, who all have a diagnosis of Parkinson’s Disease. We have decided to apply whatever relevant skills or knowledge we bring to the problem of understanding this disease. We exploit our unique advantage, our intimate knowledge of (at least) one patient, whom we tenderly keep under constant surveillance. By observing ourselves so closely, it is possible, perhaps even likely, that we stumble upon something hitherto neglected.

Introspection has a precarious position in science. It can be seen as a boundless generator of new ideas and hypotheses, but a poor judge of their value. Hypotheses should be tested empirically, i.e. ultimately by what the world tells our senses. We have been led by this belief not only to examine our own inner experience, and share our findings with each other, but also to formulate a hypothesis. From this we have derived a prediction, in the humble hope that it can and will be put to the test.

Impulse control disorders

Impulse control disorders (ICD) form a class of behaviours in which a habit of making fast decisions without considering the long-term consequences develops in response to a desire for something subjectively valuable. Binge eating is a common example. In a typical sequence of events, an opportunity arises; a very short deliberation intervenes or is immediately short-circuited; and the desired object is acquired/consumed, often followed by remorse and guilt feelings. Addictive behaviours, besides eating, can be e.g. gambling, shopping, or sex. Having an Impulse Control Disorder means living in a world where Oscar Wilde’s observation applies: “The only way of getting rid of a temptation is giving in to it.”

The whole sequence of events quickly escapes the reach of voluntary control. For this reason, it is sometimes called “compulsive”. However, the term “compulsive” should be reserved for the obsessive-compulsive disorders, which are driven by a different sort of motivation. Compulsive behaviour aims to avoid negative feelings, such as when some people wash their hands excessively to master an exaggerated fear of being contaminated by dirt. Compulsive behaviour escapes anxiety, whereas impulsive behaviour seeks pleasure.

In Parkinson’s disease, some patients develop poor impulse control to the extent that it seriously threatens their basic values in life, such as having a reliable economy and a happy family. This is especially paradoxical, because this patient group has a reputation for being unusually cautious, conservative and conscientious [1, 2].

The four most typical forms of ICDs in Parkinson patients concern gambling, sex, buying and eating. These will be described in greater detail in the following. A few related, repetitive and stereotyped behaviours, designated punding, hobbyism and walkabout, show some of the same addictive characteristics.

The related behaviours share with impulse control disorders the mental absorption that effectively shuts out disturbances from outside. Unlike both impulse and compulsive behaviours, they are affectivelyneutral.

The core impulsive behaviours, hypersexuality, pathological gambling, overeating and impulsive buying, seem rooted in evolutionary motives. Food and sex are desirable for obvious biological reasons, and acquiring things by excessive buying is related to the hoarding instinct that would be useful for hunter-gatherers. The adrenaline rush of the gambler seems related to the sense of imminent danger and the exhilaration of the kill that the hunter experiences, and which he probably trains to deal with by simulating it in games and play.

We will describe these phenomena from two perspectives. One is the perspective from the outside, which is the usual viewpoint taken in scientific writing on the subject. The other is the inside perspective, based on subjective experience, hence one that only persons with the disease are privy to. Having experienced the disease, members of the PIO group have an opportunity to compare, align and reconcile these two perspectives.

THE OUTSIDE VIEW

The prevalence of Impulse Control Disorders (ICD) in Parkinson patients has been the centre of interest in some recent studies, shown in Table 1. Nineteen studies, published up to 2010, were summarized in an analysis by Ambermoon et al. [3], in the form of median values which are presented in the top row of Table 1. Sharma [4] presented an overview of some later studies and these are also presented in Table 1. Two studies of de novo, drug-naïve patients, and one group of healthy controls are added in the bottom rows.

The overall impression of the data in Table 1 is that of great variation between studies. Estimates of the presence of at least one ICD vary from 7% to 25%. If related behaviours are also included, the prevalence may rise to 42%. There seem to be great differences between cultures, perhaps caused by different norms concerning reporting of these behaviours. Even if only one particular type of impulse control disorder is selected, there is large variation, e.g. concerning hypersexuality going from 3% to 23%.

The difficulty of getting reliable self-reports is illustrated by a Swiss study [5] where both patients and caregivers responded to a questionnaire concerning impulsive behaviours. Reported hypersexuality was 55% in caregivers’ reports, but only 17% in patients’ self-reports. Other questions, such as presence of punding also elicited large differences between caregivers (22%) and patients (9%).

The factors that are correlated with occurrence of ICDs were computed by Ambermoon et al. [3]. Effect sizes in the form of odds ratios were found to be 2.5 for young age (under 65 years) and 2.7 for treatment with dopamine agonists. A family history of gambling can contribute with an effect size of 2.1. Treatment with L-dopa, although not as risky as that with agonists, contributes an effect of 1.5. In addition, we computed from data in [6] that having one ICD increases the risk of acquiring another one, with the odds-ratio 2.6.

It is now generally recognized that dopamine replacement therapy can increase the risk of ICDs [7]. The prevalence of ICDs is not higher in untreated Parkinson patients than in the general population, but it rises significantly in patients under treatment. Both levodopa and dopamine agonists constitute risks, although not of equal size [6].

A further indication of the role of dopamine agonists is the fact that patients who take them against other ailments, such as restless legs, also run an increased risk of impulse control disorders [8].

The pathophysiology is believed to be connected to the reward centre in the ventral striatum. During the years preceding diagnosis, cell destruction has been more extensive in the dorsal, motor part of the striatum than in the ventral part. When dopamine replacement therapy sets in, the relatively well preserved ventral part may be overstimulated, resulting in heightened feelings of good mood and reward in the subject [9].

But other parts of the brain may be involved as well. The mesocortical circuits connecting the basal ganglia to prefrontal cortex and the cingulate gyrus may be affected by the disease, resulting in impaired inhibition of impulsive behaviours from cortical centres [10].

The reason that dopamine agonists constitute a greater risk than L-dopa is that some of the agonists have a special affinity for D3 receptors which are densely distributed in the limbic system, whereas dopamine made from L-dopa has its effects mainly on D1 and D2-receptors [11]. The highest D3-affinity is found in pramipexole, followed by ropinirole and rotigotine, with bromocriptine at the low end. That is also the order in which risk for ICDs places them.

THE INSIDE VIEW

These questions were discussed in the group Parkinson Inside Out, presented elsewhere in this issue. Discussions in the group initially centred on the changes brought about by the disease in the lives of the participants. Several had experienced changes in their personalities after they had received the diagnosis. Most of them described themselves as having been cautious, risk-avoiding, rather withdrawn and introverted before the diagnosis. Changes that were brought about by the knowledge of having the disease, or the treatment given for it, were in the direction of greater sensation seeking, more risk-taking, and more extraversion. All reported having had heightened positive mood and spontaneity. To nearly all, the changes included an increase in creativity, a greater flow of ideas and greater ease in expressing them. In the increased positive mood, the subjectively heightened creativity could have been just a self-flattering illusion. However, available objective data, e.g. citation rates for scientific articles authored by group members, support the assertion that the quality was genuine. Retrospective judgements made by group members on their own creative products likewise judged them to represent their personal best level.

In the expansive mood created by this productivity, it is easy to lose one’s bearings. When things go so well and tasks are so easy, why dwell on cautious decision-making when your instinctive reflexes seem to serve you so well?

In the group discussions on these sensitive matters, all participants had some experience of impaired impulse control, a majority rating their impairment to be of a high degree. The area most often affected was that of sexual impulses, over which a majority acknowledged having, or having had, impaired control. Other areas that challenged impulse control were buying expensive articles, such as cars or high-fashion clothing, or collector’s items according to individual interests.

The heightened mood inspires a more forthright and direct approach to the social environment. Nowhere is this waywardness more clearly seen than in the field of personal and intimate relationships. Contacts may be taken more easily, and relations opened with less afterthought. In addition, the drive for sex is, in many patients, directly affected by the treatment. It is common knowledge in patient groups that the medication, especially the agonists, often enhance the experience of sex and augment the sex drive. Jokes and nudge-and-wink banter frequently refer to these facts.

In the generally understanding atmosphere of fellow sufferers in networks, either in local club meetings or in online social media, many relation problems transpire that probably never find their way to the physician in charge. Once the dam is broken, much can gush forth that has apparently been held back for a long time. The impression gleaned from patient fora on web sites directed at PD patients is that relation problems are many and varied, often stemming from an imbalance in the relation caused by the disease, the medication or both. The intensity and frequency of sex in a marriage is reputedly a perennial cause of disagreement, even in healthy couples. What is a nuisance in a marriage of healthy people can be grounds for divorce in a marriage that is already under the burden of disease. Increased sex drive in one of the parties can, in the lucky cases, be welcome, but may just as often become a stress factor for the other party, who may feel implicitly accused of inadequacy. A party who feels rejected may seek solace in extramarital affairs, often with disastrous consequences for the marriage. The divorce rate is high, especially among those who are afflicted at anearly age.

Ironically, the increased drive and lust for sex often arrive at a stage in life when the body is preparing to close down this area of activity. Erectile dysfunction in men, menopause in women, and increasing difficulty of reaching orgasm in both, are factors that complicate living with the increase in libido.

A walk on the wild side

The optimistic, euphoric feeling that the medication often induces builds courage and confidence, whether well founded or not. It encourages forays into uncharted territories. Some sexual practices that would have been deemed too outlandish before the change may be incorporated into the repertoire. In general, a more wide-ranging, less discriminate choice of partners and practices may appear. Exhibitionism and voyeurism may be tempting, especially as they can find outlets on the Internet.

The Internet, and IT in general, poses threats that the human psyche is not prepared for, because they are recent arrivals on the scene. Every development of apps and web pages in recent years seems to aim at making the time for decisions ever shorter, and placing everything “just a click away”. IT might just as well stand for Impulsivity Technology. The danger this presents for people with poor impulse control is no less grave for being obvious.

There is perhaps no other area where the Internet poses greater dangers than in addictions to gambling, or its financial equivalent, day trading. Some of the most publicized cases of failed impulse control have lost exorbitant sums of money to on-line casinos. The speed and ease with which bets can be made lower the threshold and leave no pause for afterthought. In desperate attempts to cover up for earlier losses, stakes are sometimes raised and devastatingly bad decisions can be made. In a case well known to one of the group members, a gambler trying to win back his huge losses took a loan in a bank, forging his wife’s signature. He was sentenced to prison, and lost his highly qualified job.

The desire to acquire things can take on many forms, some of them approaching impulse control disorders. Most group members know people with Parkinson’s who tend to get carried away when shopping, buying things they can’t afford, or even shop-lifting. The objects can range from everyday goods to luxury items.

The freewheeling behaviours ultimately take a toll on resources, marriages and stability. The most often reported negative consequence was emotional harm inflicted upon loved ones. This was reported from a majority of participants in the group. Losses of time and money were also a serious concern. One group member expressed his experience of taking pramipexole for a long period and then quitting, as similar to being drunk for a very long time, and then waking up with a terrible hangover.

For reasons such as adverse reactions from family, or draining of economic resources, some patients with impaired impulse control wish to terminate treatment with dopamine agonists totally and immediately. One group member had ceased agonist intake abruptly and experienced a period of apathy and depression which forced a return to the agonist, albeit at a lower dose than before. This withdrawal difficulty makes use of the drug look very much like an addiction.

SYNTHESIS

Comparisons of the inside and the outside view show that there are differences in the emphasis and the importance given to the impulse control disorders. Whereas the outside view treats the disorders as relatively infrequent deviations based partly on a pre-existing vulnerability in a minority of patients, the inside view sees the disorders as one part of a broad spectrum involving practically all patients treated with DRT (dopamine replacement therapy). The surprising finding in our admittedly small, but well-informed group was that all the participants had some experience with difficulties in controlling impulses induced by the treatment.

Published data suggest that the frequency of ICDs among PD patients is low (<15%), but it is hard to shake off the suspicion that the data are only showing the tip of an iceberg. The large differences between prevalence estimates reported in different cultures show that cultural norms can exert an influence on what is reported, and how much (see Table 1). The motivation for a patient to report socially embarrassing behaviours is not great, especially if there are no prima facie reasons to connect them with the disease or the medication. Differences in the extent to which caregivers and patients report ICDs suggest that underreporting is very common, perhaps due to both social taboos and lack of self-insight.

The problem in impulse control disorders is one of deficient decision-making [12]. Decisions are made hastily, the whole field of facts is not taken in, and so behaviours that become addictions live on in spite of their deleterious consequences.

The cognitive psychology of decision-making assigns a large role to emotions [13]. Emotions influence decision-making in many ways, one being through valence, i.e. the positive or negative mood level. In a negative mood, decisions are made after deliberation and thorough examination of the facts. It makes sense to tread carefully if mood is negative, because it indicates that something has recently gone wrong. On the other hand, positive mood is a sign that things are going well; that you are probably doing the right thing and that you can continue doing so without too much afterthought.

Much research shows that positive mood does indeed invite shallow examination of alternatives, quicker decisions, and a larger reliance on quick-and-dirty-solutions or heuristics, including stereotypes [13]. On the other hand, positive mood favours creativity, by increasing the flow of ideas [14].

Tests have been developed for impulsive decision making. One is the Bechara task, a.k.a. the IowaGambling task [15]. The player/patient is asked repeatedly to draw a card from one of four decks. Each card can bring a gain or a loss, and the task of the player is to win as much as possible. The player usually finds out after a while that two of the decks are more advantageous than the others, in that they bring net gains in the long run. But some players are more systematic than others and find out sooner. Additionally, there is the temptation to be seduced by early large gains from decks that in the long run bring mainly losses. Pramipexole has been found to increase risky decision making in this task [16]. There are also other test tasks that capture impulsivity in decision-making, for example the Beads task [17], or reversal learning experiments [18].

It seems natural to think of a dimension ranging from one extreme of impulsive decision making to another extreme of restrained, brooding decision-making (see Fig. 1). The impulsive end of the dimension is often evoked by positive mood, as is the other end by negative mood. This is a useful arrangement under normal circumstances, but it may become dysfunctional when the mood is artificially created, as it is by disease and medication. The onset of dopamine replacement therapy raises the mood level, and with it the impulsivity of decision making. The new position on the dimension is determined as the sum of the earlier position and the contribution of the treatment.

In contrast, the categorical view of the disorder admits no general treatment effect on impulsive decision-making across the board. Only individuals with a predisposing vulnerability are affected. An experiment to test the two hypotheses is outlined in Fig. 2.

A pre-test of cognitive impulsivity, e.g. Bechara or Beads, forms the basis of forming three groups of participants, with High, Medium and Low levels of impulsivity. All three groups are tested again, under two conditions, Control and with Pramipexole. The predictions are illustrated in Fig. 2. The Continuum hypothesis predicts that the influence of the agonist is independent of baseline impulsivity, whereas the Categorical view predicts that the agonist affects only the High impulsivity group.

Changes with time

In the life history of Parkinson patients, there is a long period before diagnosis where a gradual decline of dopaminergic function, including that in the reward centre of the ventral striatum takes place. Lack of dopamine reduces the level of signalling from the basal ganglia to the frontal lobes where it is interpreted as a lack of rewards, leading to low mood. The natural reaction to this state of affairs is to be cautious in one’s decision-making and relatively withdrawn to avoid risks. We see this reflected in the premorbid Parkinson personality [1] as well as in the group participants’ self-reports in the inside view.

When dopamine replacement therapy sets in, the drastic change of restored function in the reward system radically alters mood and decision making. Increased positive mood in a period after the start of treatment was reported by all the members of our group in the inside view. For a time, the benefits of positive mood are reaped as a harvest of creativity [19]. But soon, some drawbacks begin to appear. Euphoria gives its stamp of approval to many behaviours that the value system had previously deemed undignified or immoral. Dopamine agonists may release the limbic areas involved in hedonic pleasure from inhibition, as suggested by a recent brain activation study [20]. Decision making becomes increasingly rapid, making use of only a cursory view of possible consequences. Weakened cortical control over the striatum makes it harder to inhibit impulses [10].

Through the actions of the agonists, which are completely desynchronized with the actions the individual performs, social learning is thrown out of gear, and it becomes increasingly difficult to take corrective action when the environment disapproves. The honeymoon with positive mood may last a couple of years. With time, fluctuations develop, as they do in the motor system. Positive and negative mood may begin to alternate rapidly.

When faced with adverse consequences of the medication, patients may wish to terminate treatment with agonists, especially if they can receive some form of advanced therapy that can be expected to relieve the therapeutic burden. However, instantaneous cessation can cause withdrawal symptoms, as experienced by one group member, and as documented in clinical cases [21].

The spectrum of consequences following the post-diagnostic changes is very broad, depending on the individual patient’s starting position on the impulsive-to-restrained decision-making dimension [22]. Those near the impulsive end run the risk of developing impulse control disorders. In the special cases where a dependency on a particular source of satisfaction has developed earlier in life, this weak point is where the rift will become apparent.

Many others, with positions closer to the safe end of the dimension, will live on with altered behaviour patterns that may, in mild cases take the form of a more easy-going personality that may be welcomed by the environment. In other cases, they cause friction because of a more selfish, pleasure-seeking attitude to life than the social net expected. In still others, it may wreak havoc in more serious ways, wrecking a marriage here, ruining a family economy there.

Ideally, if a valid and reliable test of impulsive vs. restrained decision-making becomes widely available, predictive testing can be made before dopamine replacement therapy begins. It would then be possible to titrate the dosage to minimize the costs and maximize the benefits, by using the knowledge that speeding up and simplifying decision-making is dangerous for those who are already impulsive sensation seekers, but may bring an improvement for the obsessive-compulsive and depressive patients. There should be follow-up questions about impulsive behaviours at each interview, a task that admittedly makes great demands on the doctor’s tact anddiscretion.

There are consequences for research as well. Ideally, even the basic pharmacological research on animal models of Parkinson should take into account the effect of each tested compound on the risk for ICD. There are experimental paradigms, such as reversal learning, that test the flexibility of reward conditioning^rmboxi and therefore seem relevant as analogues to the formation of ICDs [23].

SUMMARY

We set out to examine the treatment complications related to Impulse Control Disorders, and found that, in spite of increasing interest in recent years, they still tend to be roundly underestimated and poorly understood. Drawing on our own experience as well as published studies, we suggest that difficulties in decision making, and the attendant replacement of well-considered decisions by pleasure-driven impulses, is a very common phenomenon in patients undergoing Dopamine Replacement Therapy. Understanding the psychological mechanism behind this enables us to measure the state of the mechanism in the patient both before and during treatment, thus permitting us to benefit from the advantages of the medication without incurring any of its dangers.

CONFLICT OF INTEREST

I have no conflict of interest.