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University of Basel

“Stress is a public health problem”

Interview: Christoph Dieffenbacher

Neuroscientist Pasquale Calabrese discusses a widespread health problem, its physical and psychological aspects, and how people assess threats differently.

Prof. Pasquale Calabrese. (Image: University of Basel, Christian Flierl)
Prof. Pasquale Calabrese. (Image: University of Basel, Christian Flierl)

UNI NOVA: Professor Calabrese, do you recall a time when you felt particularly stressed?

PASQUALE CALABRESE: Yes, it was a few years ago, when I moved to Basel after accepting a new job here. My circumstances changed completely at that point. I wasn’t yet able to gauge my situation and found myself in an uncertain position. This is quite normal: People feel stressed if they cannot control a situation; if they aren’t sure if their own resources are enough to cope with the demands they are facing. As a neuroscientist, I would put this a bit differently: Stress occurs when an organism receives stimuli that it perceives and interprets as a threat – one that the organism cannot evade. The less controllable the situation, the more stressful it is perceived to be.

UNI NOVA: What exactly happens to the body when it experiences stress?

CALABRESE: We know from brain research that there are still structures in our brain whose alarm systems were key to our ancestors’ survival – for example if they were suddenly faced with a potential predator, such as a saber-toothed tiger. These networks have survived for millions of years because they have proven their worth over the course of evolution and helped to ensure our survival. In these biological systems, the crucial thing was to act extremely quickly – according to the motto “fight or flight”. From a physiological perspective, the threat is first registered by the thalamus, in the diencephalon region of the brain, which forwards the stimulus to other switching points in the brain. The stimulus is then processed firstly via an – in evolutionary terms – “old” route, which is faster, as well as via a “newer” route, which operates more slowly. Whereas the first route provides approximate but rapid processing, the evolutionarily younger route processes the stimulus more slowly but with greater accuracy and in greater detail. The first route activates the amygdala, which relays the signals to the hypothalamus, causing it to release specific control hormones. These arrive at the pituitary gland, where so-called glandotropic hormones are formed, leading to the release of stress hormones such as cortisol and adrenaline from the adrenal glands. The blood pressure rises and the bronchi become wider to allow more oxygen to reach the muscles. The immune system and sensitivity to pain are temporarily suppressed. This activation of the stress axis, as we call it, takes place within fractions of a second.

UNI NOVA: And what about the slower stimulus processing route?

CALABRESE: Well, as evolution progressed, the cerebral cortex developed in humans and took on a specific function, allowing us to process complex information. One result of this is that humans are able not only to perceive threats that appear directly in front of them but also to detect more distant – and merely potential – sources of danger. In other words, we have the capacity to imagine a specific situation and to begin responding to it already …

UNI NOVA: … and perhaps also to experience stress as a result of dangers that we have simply imagined?

CALABRESE: Exactly. Our more advanced brain allows us to perceive potential dangers through association and anticipation. As a result, even simply imagining a dangerous situation that we expect to occur, or have already experienced, can trigger the same physical responses as the real threat: a pounding heartbeat, breaking out into a sweat, increased muscle tension. The slower route for stimulus processing triggers essentially the same stress axis as the faster route, but whether and how strongly we become stressed in response to a situation depends primarily on our assessment of the situation.

UNI NOVA: Are some people therefore more susceptible to stress?

CALABRESE: In principle, one can say that there are various options for coping with stress. Broadly speaking, there are the “fighters”, who face the situation head on and call upon their resources. Then there are those who run away, avoiding the threatening situation, and lastly those who play dead and act as if nothing is happening. A person’s assessment of a situation depends partly on how they evaluate it cognitively. In humans, strategies for coping with stress are largely learned. However, we also know from brain research that stress can be transferred in the womb: If the mother is put under significant pressure, this can lead to programming errors in the child’s brain – with potential consequences such as attention disorders, ADHD, or learning difficulties later in life.

UNI NOVA: Can stress be measured?

CALABRESE: Yes. Stress has not only a psychological but also a physiological/endocrinological and behavioral dimension. The first of these can be measured using questionnaires and psychometric tests, for example; the second using measurements of hormone concentrations, brain waves, or cardiac activity, for example. The third dimension can be deduced indirectly through observations, for example if someone suddenly speaks in a high or shaky voice. There are therefore a series of direct and indirect methods for recording an individual’s state of stress.

UNI NOVA: Today, even children actively use the terms “stress” and “burnout” as part of their vocabulary. Has stress truly become a public health problem, as you said in a recent talk?

CALABRESE: Numerous health issues, such as cardiovascular diseases, diabetes, and obesity can be traced back to stress. Stress-related loss of working hours costs our economy huge sums of money. For many people, stress also entails psychological and social pressures. We use the term “public health problem” to describe health phenomena that have become so widespread as to lead to huge economic consequences, as is clearly the case here.

UNI NOVA: Why are stress and the diseases associated with it becoming more prevalent, at least in Western societies?

CALABRESE: In my opinion, this is related to the ever-rising tide of data that we are required to process in our daily lives. Today, people are confronted with information of all kinds far more often than before. Our environment has become more complex. In almost all occupations and jobs nowadays, there is a constant stream of new things to learn. At the same time, people face growing pressure on performance and work intensification. But increased quantity of information does not necessarily mean increased quality – there is always a need to review and weigh up what is important or useful and what is not. This can lead to stress in many people. However, it is important to add that short-term and temporary stress also has positive effects: This “good” stress – eustress as opposed to distress – produces a temporary boost in physical and mental performance. It can be viewed as a challenge.

UNI NOVA: But the big problem is probably chronic stress, which stops many people from relaxing …

CALABRESE: Correct. Stress – a word that actually comes from mechanics and originally referred to wear and tear on a material – can have fatal consequences. These not only relate to the rising incidence of the diseases of modern civilization we mentioned earlier. It is also important to consider the effects on the brain: Persistent pressure and demands on the individuals can lead to a state of chronic stress, in which the hippocampus – a brain structure with a vital role in learning and memory processes and one that can curb the production of stress hormones in a feedback loop – is flooded with the hormone cortisol. The nerve endings are damaged, and the connections between the nerve cells recede. In the medium term, the consequences of this include altered brain function: The powers of concentration are impaired, and the affected individuals have problems recalling information. Stress also has an adverse effect in conjunction with other diseases: For example, it exacerbates the condition of patients with multiple sclerosis or dementia, as well as those with affective disorders.

UNI NOVA: Stress-related diseases and health complaints are hard to treat – what options are available?

CALABRESE: The best way to treat stress is through a two-pronged approach. On the one hand, it is important to curb the physical responses within the stress axis. For example, this can be done using medicines that have a moderating effect, at the same time as avoiding or reducing the consumption of alcohol and stimulants such as caffeine. On the other hand, these steps should also be supplemented with coaching methods – or, in the event of pathological effects, with certain forms of psychotherapy. In this way, the affected individuals can learn to reassess or reevaluate certain situations. Other preventive measures include consciously deciding to take things easier, or learning to say no more and to use your resources more sensibly and economically.

UNI NOVA: What do you think of the alternative medicines on offer on the healthcare market?

CALABRESE: Instead of alternative medicine, I prefer to talk of complementary medicine. As a complement to traditional medicine, methods of this kind can also assist with treatment for stress. As we know, good results have been achieved by incorporating aspects such as exercise, diet, coaching, resilience training, meditation, and mindfulness. At the same time, it is always important to raise awareness of these techniques among affected individuals. Sufferers of stress often come to the experts far too late, i.e. only when their stress has already become a chronic condition.

UNI NOVA: What are the key outstanding research questions at the moment?

CALABRESE: For example, it remains unclear what role stress plays in the development of affective disorders, such as cases of depression. Moreover, although the highly regulated stress axis is known to have an adverse effect on the emergence and development of certain neuroimmunological diseases, such as multiple sclerosis. This is another area where there is a need to examine the cause-effect relationship in greater detail. After all, it must be assumed that, in line with the biopsychosocial model, all of these examples involve an interplay between hereditary factors – that is, specific individual genetic conditions – and environmental influences. These combine with social circumstances in the individual case to produce an organic “loss of control”, which we experience as a stress-associated disorder. There is still a great deal of research to be done in this area.

UNI NOVA: Going back to your earlier experience with stress when you arrived in Basel: How did you cope with the stress at the time?

CALABRESE: Firstly, I was helped by the social environment and by the fact that I felt comfortable in my new job in Basel. Later, my family came to join me, and my wife also found a job here. Social and communicative elements are very important when it comes to stress – after all, humans are social beings, and their brains are also social brains.

Pasquale Calabrese is Professor of Neurosciences at the University of Basel’s Faculty of Psychology, where he leads the Neuropsychology and Behavioral Neurology group within the Transfaculty Research Platform Molecular and Cognitive Neurosciences (MCN). At the same time, he also works in the clinical setting and conducts research into, among other things, the neuropsychiatric aspects of multiple sclerosis, Parkinson’s disease, dementia, depression, stress, and perception.

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