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Deepen your understanding of alcohol use disorders

Webinar – Part 1: The addicted brain

Part 1 Neurobiology

Presentation: Wim van den Brink and Steve Brinksman

Moderator: Simon Graham

Duration: 0:16:53

The views expressed in this webinar are those of the presenters. This presentation may also include scientific discussions not necessarily consistent with a product’s specific label for a given country.

Transcript – Part 1: Alcohol dependence is a common brain disease

THE ADDICTED BRAIN – Wim van den Brink

THE ADDICTED BRAIN – Wim van den Brink

Thank you, Simon. I will very briefly introduce you to what we now know about the addicted brain.

Alcohol use disorders: DSM-IV →DSM-5

As you may know, we are talking not so much about alcohol abuse and alcohol dependence any more. This was in the DSM-IV. Now, with the new classification system, we use the term ‘alcohol use disorder’, which actually embraces both alcohol abuse and alcohol dependence – but they have been merged in one disorder, with different levels of severity – mild, moderate or severe. It is good to realise that, in clinical practice, you might see patients in all kinds of severity levels, and that it might change over time – they might move from mild or moderate to severe but, at the same time, they might improve and move back from severe to mild or completely recovered.

Alcohol dependence is a long-term disease

It is important to realise that addiction is not an acute disorder. In many cases, alcohol use disorders are rather chronic and here, you can see the results of long-term studies with seven to 10 years of follow-up, of patients who came to treatment. Even after seven to 10 years, about one-third were still drinking heavily and most of them still meet the criteria for alcohol use disorder. Long-term attention is thus needed in many of these patients.

Genetic vulnerability

Alcohol use disorder or addiction has long been thought about as a moral weakness but, with our knowledge of the neurobiology, we have started to look at addiction much more as a brain disease. Why do we do so? We now know that genetics plays an important role in the development of alcohol use disorders. For example, this slide shows you that about 50 to 70 per cent of all the causal factors are due to genetic differences in people. You might not be interested in that as genetics, but genetic factors are related to biological risk factors. What do we know about the relationship between genetics and biological risk factors?

[Slide]

At the bottom of this slide, you see that the genotype is represented by these lines representing chromosomes. On these chromosomes, you can see the dots – and these are the genes.

Certain combinations of genes are responsible for the development of certain brain abnormalities, and that is what we call the endophenotype. You cannot directly observe it, but you can measure it. For example, a certain combination of genes is responsible for the fact that, for example, the children of alcoholics have a low alcohol response. This means that, if they use alcohol, they do not become intoxicated so quickly and they do not develop hangovers. This genetically determined mechanism actually makes people – young kids of alcoholic parents – tend to use more alcohol because it seems, at a superficial level, that they are better able to digest it.

Another factor that is genetically determined is what we call ‘reward deficiency’. This means that certain people, with certain genetic factors, have less dopamine receptors in their nucleus accumbens, the reward centre of the brain, and so they need stronger stimuli to get a pleasant feeling and reward. Alcohol and drugs are just the strongest stimulants for that.

Another factor is impulsivity and, finally, different people have a different tendency to develop craving – the urge to use alcohol – once they have started to use it. These genotypes, and the risk increase in the endophenotype, may, in the end, under certain social circumstances, lead to the phenotype of alcohol dependence.

Brain Abnormalities [Table]

How do we know that? We know that from a great deal of animal research and recently also from neuro-imaging studies. Here, again, you can see the different brain functions on the left. I have told you a little about reward deficiency and impulsivity already. Conditioning and craving are also important issues in the development of alcohol use disorders. We know now that these functions are related to certain brain structures and, in these brain structures, we have certain neurotransmitters that are responsible for these abnormal functions. This is nice to know, but it mainly comes from animal research: is it really true in the human brain?

Brain abnormalities [Imaging]

These are just two examples. On the left-hand of the slide, on the left, you can see the brains of normal people and, on the right, you see patients who are using alcohol, metamphetamine or cocaine. What you can see is that, the more red there is, the more dopamine receptors there are in the ventral striatum – the reward centre. These people have been abstinent for at least three months but still the number of dopamine receptors is much lower than in the non-patients.

On the right-hand side, you can see the response. There is the control person on the right-hand side and, if he watches pictures of alcohol, you can see that the back of the brain has lightened up a little. However, if you look at the early abstinent people, who were addicted to alcohol, you see the same activity at the back of the brain, in the occipital cortex but, at the same time, you see activations in the ventral striatum. That is an indication that their reward centre is activated, although there is not a drop of alcohol in their brain. That is probably representing cue reactivity, or craving, in terms of the patient.

From reward to relief and from impulsive to compulsive

With time, alcohol use changes in character. Most alcohol-dependent patients actually start drinking because it gives them a very good feeling. They feel relaxed and they feel happy but, in the course of the disease, you see that this positive feeling becomes less and less and it is replaced by using alcohol just to get relief from the negative feelings, like stress and dysphoria. People move from an impulsive, reward-driven alcohol use, slowly to a compulsive, relief-driven alcohol use, and this also goes together with different activations of neurotransmitter systems.

These are a few indications of what can happen in the brain of people who will become addicted.

DEEPEN YOUR UNDERSTANDING OF ALCOHOL USE DISORDERS – Panel Discussion

DEEPEN YOUR UNDERSTANDING OF ALCOHOL USE DISORDERS – Panel Discussion

Simon Graham: Thank you very much for those insights, Wim.

We will now have a discussion on some of those concepts that you have raised. I would like to open up by asking you if you could summarise: does this just happen, or does the condition take time to build up?

Wim van den Brink: I have already mentioned that a little. It is definitely not the case that people become addicted to alcohol from one day to the other. Many people, definitely in Western society, start to drink when they are 16, 17 or 18. Most people can actually keep drinking and keep control over their alcohol use, so that they use small amounts and not every day. Then some people start to use more and you see that some people, especially at weekends, start to run out of control a little, and they start binge-drinking. That may be temporary, as in adolescence, but some of these kids carry on with that.

You then see some of these kids and adolescents who develop what we call craving, and they want to drink all the time. They want to do drinking more than anything else. With years, most of the time, you see it developing from recreational use to sometimes binge-drinking and into full-blown alcohol dependence, where craving and loss of control are the essence of the developing disorder.

Steve Brinksman: Do you feel that, by trying to intervene earlier, and screening and looking for these people who are likely to have this as a risk factor, we can start to prevent some of these people from progressing on to the moderate and severe alcohol dependency which is the stereotypical picture that people have in their minds, rather than the milder form of the disease?

Wim van den Brink: On the one hand, it is very nice to identify them much earlier, because there are good indications that, the earlier you catch these people in this process of increasing problems, the better success you have. On the other hand you have to realise that, in the very early stage, it is not always so easy to make a distinction between normal adolescent behaviour, and out-of-control drinking. The issues really are the craving and the urge and the need to use more and more, and the loss of control. These are very essential things but, the earlier you can catch them, absolutely the better. In that sense, primary care is probably a much better place than mental health care or specialised addiction treatment services.

Simon Graham: Wim, would you say that there are differences between men and women, in terms of how the disease develops?

Wim van den Brink: Right now, I think the differences are quite substantial. If you think about the people who come to specialised alcohol treatment centres, it is about three-quarters men and just a quarter are women. However, there are big changes going on in society and now, in Sweden for example, adolescent girls are actually drinking more than boys of the same age. The same is going on in Britain right now. The sex differences are going to change.

I have to say that if women develop alcohol dependence, as of now it is a little lower than with men but the ones who develop alcohol dependence do so at a much greater pace and it develops much more quickly than in men. That is sometimes called the ‘telescoping’ phenomenon. There are differences between males and females, both in the prevalence and the way they develop the disorder.

Simon Graham: Do you see this in the UK?

Steve Brinksman: Certainly, and it is very worrying for me. We have seen a huge rise in the increase of alcohol consumed by women. Basically, the drinking of wine has become normalised in the UK now, and I am sure in many other parts of Europe as well. It is not unusual to come home from a busy day at work, put the children to bed, and open a bottle of wine. We see women drinking much more than they used to. If they are going to progress to alcohol dependency more quickly than men in a similar situation, then I worry that we are at the start of a huge curve that will see many problems for this generation of women.

Simon Graham: Perhaps you could summarise for our audience what the main risk factors are for the development of this disease?

Wim van den Brink: We know a good deal about risk factors now. One of the most important – let’s say that starting to use alcohol is very strongly socially determined, but for the development of alcohol dependence there are genetic factors that play an important role. As I showed you, genetic factors contribute about 60 per cent of all the risk, but that means that there is a further 40 or 50 per cent for psychological and social factors. With regard to the psychological factors, these can be early childhood trauma and neglect, and we have to realise that that is much more common than we generally believe. Many of our patients have serious histories of adverse consequences of abuse and neglect.

It is also of course the social factors such as peer pressure. As you were saying, the way that we consume alcohol is changing and the ones with the risk factors are at a higher risk, and these risk factors really get into the phenotype also. That is peer pressure, but also the availability of alcohol.

Steve Brinksman: It is not just peer pressure but people look at their drinking and they compare themselves to the people around them. It is peer-referenced, rather than looking at your risk compared to everybody else in society. Often people will say to me, ‘I’m not at risk – I don’t drink any more than my friends and in fact I am the lightweight and I am the one who drinks the least.’

Wim van den Brink: I only drink 15 beers!

Steve Brinksman: When you talk to them, they are meeting their friends at the pub, or they are drinking wine at home with them. It is one of those things that we can be very disambiguous about, by covering up – that we are no worse than anybody else. That is a huge problem when it comes to trying to get patients to address this for themselves.

Wim van den Brink: It is also a very important message for doctors because doctors tend to drink quite seriously. A patient is not only a patient when he drinks more than you do.

Simon Graham: I would like to take this opportunity to encourage the audience to submit their questions. Some have actually come through already. How will the latest technology in neurobiology affect clinical management? Can you comment on that question?

Wim van den Brink: Definitely, yes. First of all, I would say that the neurobiology has shown us ways to develop new medications. Later on in this webinar, I will talk a little about these new medications. For many years, we had only one medication but, in the last five or 10 years we have had an explosion of new medications that have become available.

In addition, we are starting to use new ‘neuromodulation’ techniques. I will not say much about that, but we have things like transcranial magnetic stimulation, and there is deep brain stimulation. There is a great deal going on in the field of treatment of addiction as a neurobiological disorder.

Simon Graham: Perhaps this is a question for you, Steve. What is the social burden of alcohol use disorders?

Steve Brinksman: Across Europe it is a huge burden but, particularly within the UK, estimates are that it is something like £21 billion-worth, which would be about €28 billion per year. That is broken down to the costs upon the health service of about £3.5 billion; costs in lost productivity, and costs within the criminal justice system. Alcohol is still a significant factor in assaults, domestic violence and road traffic accidents, and pedestrian injuries.

Simon Graham: Before we move on to the next presentation, Wim, could you let us know how patient management should be approached?

Wim van den Brink: Patient management: first of all, it is how to identify the patients. Sometimes this is very easy and most doctors would actually recognise these patients. Sometimes, however, alcohol problems are hidden behind sleep problems, or behind working problems. The first point is about how to recognise these patients. The one single point is just to start to ask questions when the patient comes to your practice – and I guess that Steve will talk about that later.

The second stage is about how to motivate people to work on that problem. You have to realise that, for many patients, using alcohol is not the biggest problem. Some regard it as one of the solutions of their problems and so, to move from thinking about alcohol as normal or as the solution to your problems, to it being the problem itself, and how to move, is very important. Motivational interviewing is the way to go there. It is not a matter of saying, ‘You are a drunkard and you have to change’, but how to move from the early and fast positive effects, and start to think about the long-term negative effects. Creating this ambivalence in patients is a very important statement.

The next thing is about how to address the future: is it a future with reduced drinking, or is it a future with total abstinence? We will come to that in the last part of the webinar, but these are probably some of the most important issues about how to proceed. The very important thing is that we must not think of it as a moral weakness but that it is an illness and that we have to be very empathic about the problems that our patients have, and treat them with dignity.


Webinar – Part 2: Patients with alcohol use disorders in clinical practice

Webinar – Part 3: Treatment goals in alcohol use disorders


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