“Prolonged waking alleviates depression in about 60% of patients”

Borbely 3

Alexander Borbély, one of the major international specialists in sleep study and depression, creator of the term “sleep homeostasis” and of the so-called 2-process model, gives an exclusive interview to iSleep, in which he unravels his theories and reveals that “one of the surprising aspects of sleep and depression is that prolonged waking alleviates depression in about 60% of patients”.

How did you come upon the notion of sleep homeostasis? Can you explain it?

I coined the term “sleep homeostasis” in a book chapter published in 1980 entitled “Sleep: circadian rhythm versus recovery process”. My data obtained in the rat showed that sleep deprivation gives rise to a compensatory increase in sleep intensity as indexed by a rise in EEG slow waves. The term indicates a regulatory principle that maintains sleep pressure within certain limits.

You and your team developed most of the conceptual and experimental work that proves the so called 2-process model. What is behind this interaction between homeostasis and circadian mechanisms?

I published the two-process model of human sleep regulation in 1982 and together with Serge Daan and Domien Beersma we published an extended quantitative version in 1984. The model posits that the timing of sleep is determined by the interaction of a homeostatic and circadian process.

The more time we remain awake, the more we increase sleep and slow wave intensity when asleep. Could this idea dangerously make people believe that they can push wakefulness to the limit in order to sleep better?

Although sleep intensity increases with sleep restriction, the recuperative action of sleep still requires a certain duration. If it declines below a certain limit, sleep propensity challenges the maintenance of waking.

What is the feeling of having established the dominant theory of sleep regulation?

I am glad that the model I had proposed together with my colleagues serves as a useful conceptual framework for the sleep science community.

You have been internationally distinguished by your research on depression. What role do sleep disturbances play in this condition? And, reversely, does depression affect sleep disturbances?

Disturbed sleep is a common symptom of depression. In the 1980s specific alterations of sleep architecture such a reduced REM sleep latency were considered to be pathognomonic for depression. In the mean time we know that these changes are not specific and occur also in other disorders. One of the surprising aspects of sleep and depression is that prolonged waking alleviates depression in about 60% of patients. Unfortunately, this effect is transitory and the next sleep episode causes a relapse into depression. Anna Wirz-Justice and I proposed in 1982 that a deficient Process S could underlie sleep disturbances in depression and the antidepressant action of prolonged waking.

What is there still to know about the role of adenosine as neurotransmitter involved in sleep mechanisms?

Adenosine has a sleep-promoting action. The adenosine-receptor blocker caffeine is the world’s most widely used psychostimulant and has a wake-promoting action. Adenosinergic mechanisms and their genetic underpinnings are presently a hot topic in sleep research.

In 1984 you published a book in German entitled “The Secrets of Sleep”, afterwards translated into English. Do you consider that some of the secrets were in the meanwhile unveiled?

To paraphrase Winston Churchill, sleep is a riddle wrapped in a mystery inside an enigma. Every new measurement device that is applied to monitor or explore sleep reveals new data. In the last 3 decades technology has made immense progress and a wealth of data has been generated. This allows us to view sleep and its secrets in new ways. We tend to call this progress.

You are Pharmacology Professor. Are medicines a necessary evil in the treatment of sleep disturbances?

I think they are a bliss if correctly administered. Countless sufferers of insomnia due to pain, worries or other reasons find repose after swallowing a sleep remedy.

Is the placebo effect in sleep a solution in treating some of the sleep disturbances?

No, placebos are not potent enough to treat serious sleep disorders.

Which scientific discovery could revolutionize the study of sleep and sleep disturbances?

I don’t see any revolution on the horizon, but then revolutions happen unexpectedly, don’t they?

You have dedicated many years to sleep research in animals. How did those experiments contribute to a better knowledge of the human sleep?

The basic features of sleep architecture and sleep regulation are similar in all mammals. Therefore studying sleep in animals may help understanding human sleep. However, there is an interest in animal sleep in its own right.

A tiger needs around 15 hours of sleep per day, and a giraffe 2. Can you explain this huge difference?

Even though my wife who is an expert in animal sleep does not agree with these figures, carnivores can afford sleeping much longer than herbivores. They are less threatened and are not obliged to spend most of their waking time with feeding.

Dolphins continue swimming during sleep, and I believe they do it with just one hemisphere working. Which process is there involved?

Dolphins exhibit deep sleep only in one hemisphere at a time which shows that the sleep process does not necessarily encompass the entire brain. These observations in the dolphin promoted the search for analogous phenomena in mammals. We know that also human sleep shows certain use-dependent regional modulations in intensity. They are referred to as “local sleep”.

Do you consider your scientific career to have different stages? Would they take the shape of a staircase, as stochastic process, as an oscillatory (sinusoidal) process, or any other?

My scientific career was dominated by my fascination with sleep science. I had the good fortune to find excellent collaborators and students who shared my enthusiasm. I see my scientific activities in terms of a continuum rather than stages.

Your paper on the 2 process model, published in 1982, has 2412 citations, a very impressive number. Did this fact have an important impact on your career?

No, it did not. However, I am pleased that the two-process model had a positive resonance.

Your scientific publications started in 1966; how did you manage to have such a long scientific career, which goes on even after your retirement?

I am still fascinated by the subject.

You were President of the ESRS (the European Sleep Research Society). Was is an enjoyable and challenging work?

It was enjoyable and challenging. One of the challenges at that time was to facilitate the participation of scientists in Eastern Europe who suffered from travel restrictions and other limitations. It was during my presidency that we decided to create a new journal, the “Journal of Sleep Research”. Another initiative was the “Young Scientists Symposium” on the first day of the ESRS Congresses to provide a forum for young talents. It was enjoyable to tackle the problems as a team with an international board and scientific committee comprising basic and clinical sleep scientists from various disciplines.

How do you envisage the function of ESRS at the present times?

Many national sleep societies have been established within Europe for which the ESRS assumes an integrating function. This is an important task in addition to promoting research and education. In addition, the ESRS must position itself with respect to global endeavours to organize and coordinate sleep research and sleep medicine. The biennial ESRS congresses being held in different European cities are outstanding in terms of science and attendance. It is fortunate that scientists enjoying a high international reputation are ready to serve as members of the board and scientific committee of the society.

Aristotle wrote extensively about sleep and wakefulness. This means that scientific curiosity about the mysteries of sleep started very early…

Aristotle declared that it is impossible that animals should be always asleep or always awake without intermission. “… for all organs which have a natural function must lose power when they work beyond the natural time-limit of their working period.” This is the principle of sleep homeostasis.

Descartes said that the brain is constantly thinking. Do you think he was referring to the sleep-wake thought? It is a very important discovery of the 18th century…

In his Metaphysical Meditations Descartes discusses the problem of distinguishing waking experiences from those occurring during sleep. After dwelling on the similarities of the two which render it almost impossible to decide whether one is waking or sleeping, he then argues that the capacity of linking the experiences together and relating them to our life can occur only during waking. Our memory is incapable of performing this integrating action with dream experiences.

You have lived many years in the United States. Does an American have a different approach to sleep than a European? What about sleep hygiene habits: are there many differences?

I don’t think there are basic differences. However, the medical and economic impact of sleep loss is more intensely discussed in the US than in Europe.

I know you don’t sleep much. Are you a short sleeper?

Yes, I am a short sleeper sleeping on average a bit more than 6 hours.

You were born in Budapest in 1939, in the beginning of World War II. Which memories do you have from this time?

I have very pleasant early childhood memories. However, I also remember the night-time sirens signalling approaching bomber aircraft and our hurried descent into the underground shelter.

You left the city very early. Why?

My parents emigrated due the political situation in spring 1944.

Why did you choose to live in Switzerland?

My parents wanted to go to a neutral country.

Have you ever been to Portugal? What do you think about our country? Did you know Budapest is a twin town of Lisbon – two beautiful cities?

I had several opportunities to visit Portugal. It is one of my favourite countries. I am fascinated by its history and culture. Lisbon is a beautiful city with a unique atmosphere. I was delighted to hear that it is a twin town of Budapest. My visits to Portugal were almost invariably related to a scientific event organized by Professor Teresa Paiva. She is for me the epitome of an outstanding scientist and humanist, and her initiatives related to sleep science and sleep medicine had a huge impact not only in Portugal, but also in Europe. She found time to publish wonderful children’s book on sleep promoting the curiosity of this topic at an early age. I have the greatest admiration for her and I am honoured to be invited for an interview on her webpage.