The neurotransmitter serotonin plays a crucial role in our emotional balance. As the main player in the highly complex, endogenous serotonin system, this messenger substance is subject to our individual genetic predisposition, but is also directly influenced by experiences and other external factors.
serotalin®: What is known today about how genetic differences in the serotonin system influence whether people tend to remain calm or become unbalanced under stress?
Prof. Dr. Lesch: A person's composure and susceptibility to stress are determined, among other things, by genetic differences in the serotonin system. The serotonin system consists of numerous components, all of which are subject to genetic influence. For example, one of the tryptophan hydroxylases plays a major role in the synthesis of serotonin in nerve cells. The serotonin transporter, which itself can be genetically variable and thus modulates the entire system, is responsible for the reuptake of serotonin.
Furthermore, there are at least 14 different receptors and their corresponding signal transduction cascades, which in turn contain numerous genetically regulated components. These different receptor types to which serotonin binds also exhibit genetic differences.
In addition, the serotonin system is also influenced directly via ion currents, indirectly via potassium channels, and by numerous other genes. In summary, the serotonin system is a highly complex mechanism on which individual genes may have only a minor effect, but which collectively determine the stability of a person's emotional balance.
However, current research knowledge is not sufficient to make reliable predictions at the individual level, i.e., for individual people – too many factors are involved, both genetic and external.
serotalin®: Serotonin is often associated with mood – but it also plays a role in how flexible and adaptable our brain is. What does this mean, for example, for people who constantly have to switch between focus, creativity, and decision-making?
Prof. Dr. Lesch: Serotonin not only influences our mood, but also plays a central role in the flexibility and adaptability of our brain. It affects various cognitive processes such as perception, emotional processing, decision-making, and creative thinking. These functions are closely linked to the ability to switch flexibly between different mental states—such as focus, creativity, and action planning.
Even in early brain development, serotonin helps to build neural networks that enable our mental and emotional adaptability later in life. It modulates the activity of certain cell types and networks in the brain, thus acting like a kind of internal regulatory system.
Mood is a current state comprised of numerous facets. Factors such as how we perceive things, how we process them emotionally, and above all, how we think, play a particularly important role. These fundamental abilities make our brain flexible and adaptable and are established very early in brain development.
This means that serotonin not only regulates brain function while we are in a current situation, but our entire life is subject to the influence of serotonin – at the molecular and cellular level and in the area of networks in the brain that are modulated and balanced.
In short: Serotonin plays a crucial role in ensuring that our brain does not function rigidly, but reacts dynamically to changing demands – a capability that is particularly important in complex, fast-paced work and life environments.
serotalin®: You have spent decades studying the so-called serotonin transporter – a key factor in communication between nerve cells. Why does this system play such a central role in our mood, inner balance, and adaptability?
Prof. Dr. Lesch: The serotonin transporter is a central control unit in the serotonin system within the context of neuronal communication. There is only one gene that controls the transporter, which is extremely rare in the genetic coding of biochemical mechanisms. The serotonin transporter determines how much serotonin is taken up and thus also the concentration in the synaptic cleft or in the extracellular space.
The serotonin transporter also acts as a primary target molecule for various psychotropic drugs such as antidepressants, for drugs like ecstasy, and for hallucinogens, especially LSD, in the sense of neuronal modulation. Our sensitivity to this is variable, and the effects on behavior differ from person to person.
serotalin®: In your research, you show that people differ genetically in how they react to pressure or emotional stress. What is the reason for this – and why does one person remain calm when another is thrown off balance?
Prof. Dr. Lesch: A person's genetic makeup merely provides the framework within which their emotional reactions can unfold; it does not prescribe fixed behavioral patterns, but rather influences how receptive and adaptable we are in specific situations. Crucial in this regard is how well someone is able to recognize social signals, communicate appropriately in specific contexts, and control impulses.
The brain's key function is to perceive our environment, make rational decisions, and express emotions. Additionally, factors such as self-control—or the ability to assess the consequences of our actions—play a central role. The same applies to the ability to adapt to social and societal demands.
All these functions are governed by the serotonin system – depending on genetic predisposition. A healthy brain must fundamentally be balanced between activating and inhibitory processes: it is crucial that the neural network is in equilibrium. For stable social interaction, genetic predisposition is therefore decisive, determining whether someone remains calm in a situation or whether their individual stress level rises.
serotalin®: You say that not only genes, but also early experiences shape how we later deal with challenges. What role does this play in a daily life that is constantly geared towards performance – such as for students or entrepreneurs?
Prof. Dr. Lesch: Genes have only a very indirect influence on a person's personality. The same applies to the resulting behaviors. The effect of genes, that is, gene expression, is subject to external factors: for example, during pregnancy and early childhood, but also throughout life. In this regard, the respective social environment, especially the mother's behavior, is particularly important.
Early childhood is a period of significant sensitivity, characterized by numerous cellular toxins such as nicotine or alcohol during pregnancy, as well as child abuse, which can lead to epigenetic reprogramming of gene function via biochemical signals through stressors or environmental stimuli. The result is a change in gene expression.
These processes offer hope that we are not at the mercy of our genes, but rather that we can influence our serotonin system and ultimately our behavior. Through learning, reflection, social relationships, and conscious lifestyle choices, we can influence our gene functions—down to the very depths of our emotional experience. This is a particularly important insight in performance-oriented environments: inner stability is not solely a matter of genetic predisposition, but also of lifestyle and the opportunities for self-regulation and personal development.
serotalin®: You research how life experiences influence our stress system in the long term – even on a physical level. What do we know today about how, for example, persistent stress or changes in mindset affect our inner balance?
Prof. Dr. Lesch: Our inner balance is like a biological and psychological ecosystem. It is prepared by genetic predispositions, but decisively shaped by experiences throughout life – by stress as well as by how we deal with it.
Our experiences – especially under prolonged stress or during times of great change – profoundly influence our stress system, not only psychologically, but also on a physical and neurobiological level. Serotonin and its effect on personality traits play a central role in this. Certain characteristics – such as emotional stability, self-esteem, and problem-solving skills – are closely linked to regulation by the serotonin system.
Resilience, the ability to remain mentally healthy despite adverse circumstances, is therefore not solely determined by genes, but rather shaped by an interplay of genetic predisposition and lifelong experience. Genetically influenced personality traits that we ourselves perceive as positive can contribute to better stress management.
A high level of activity, combined with flexibility, self-confidence, openness, and tolerance, is crucial for developing creative coping strategies and problem-solving abilities. The same applies to social competence, curiosity towards others, self-esteem, and intelligence, which lead to a positive outlook on life and optimism.
“On top of that,” external factors such as experiences and reliable, trustworthy, and appreciative role models who shape us play an important role in enabling us to build autonomy, stability, constructive communication, and a social network. Additionally, a certain ethical standard is necessary for a minimum level of spirituality, for our stress resilience, and for our inner contentment.
serotalin®: Personalized approaches to mental health are increasingly discussed. What role can knowledge about individual differences in the serotonin system play in this – for example, when it comes to focus, stress regulation, or emotional stability?
Prof. Dr. Lesch: As already mentioned, the way we deal with stress or emotional strain is highly individual. The serotonin system acts as a biological mediator in this process: It influences how we perceive stimuli, how we process emotional impulses, and how well we can exercise cognitive control.
There are numerous strategies for developing resilience in any situation. Ultimately, one can focus on the knowledge that crises are a part of life and that they can be overcome. It is helpful to approach these challenges proactively with a positive outlook. This involves resolving conflicts and accepting change. A certain amount of stress is even necessary to develop resilience. The important thing is to focus on one's positive strengths and, for example, not to ask oneself why others are doing better.
Ideally, one should continually engage in new activities, constantly challenging one's body and mind in a unique way and developing resources: regularly setting personal goals and achieving them. Start small and don't aim for a huge goal right away, but rather tackle the main objective in manageable chunks; be proactive in order to stand up for oneself, take initiative, and continuously develop by learning.
Factors such as intuition, self-esteem, and the ability to listen to one's own needs also play a role. Last but not least, general recommendations such as a healthy lifestyle, including a balanced diet, physical activity, and sufficient sleep and regeneration, should be considered. The same applies to a positive outlook on life, with harmony and sustainability in the here and now, and a focus on social connections – especially during stressful periods with little free time.
About the author: Psychiatrist and behavioral scientist Prof. Dr. Klaus-Peter Lesch works at the Center for Mental Health at the University of Würzburg and at Maastricht University in the Netherlands. The emeritus chair of Molecular Psychiatry researches, among other things, attention deficit hyperactivity disorder (ADHD) in adults.
