What are some signs of behavior control

Recognize innate susceptibility to addiction

Not everyone becomes addicted immediately - not even when taking drugs with a high potential for addiction. Scientists are looking for biological causes for an increased susceptibility to addiction.

Whether a person becomes addicted to drugs, alcohol or nicotine in the course of their life depends on the interaction of many factors: the availability of addictive substances, emotional stress, stress or social group pressure, but also personality traits. The fact that children with an alcoholic parent are four times more likely to become alcoholics than the population average and that children of cocaine addicts even have an eight-fold higher risk of addiction also suggests a hereditary component. Twin and adoption studies confirm this. Scientists try to clarify the biological basis of the different susceptibility at different levels.

Genes and living conditions

In genetic studies, numerous gene variants have already been identified that are more common than average in patients with one or the other addictive disease. For example, they concern genes that code for receptors for dopamine, a neurotransmitter that plays a key role in the brain's reward system. But since the hereditary addiction propensity is probably based on the interplay of hundreds, if not thousands of genes, which only set the course in interplay with individual living conditions, isolated gene variants can only reflect a tiny part of the risk profile.

Also in the brain - at the actual scene of the addiction - there are signs of a family-related susceptibility to addiction, as a recently published study by British researchers shows. Based on the observation that the areas of the anterior cerebral cortex (prefrontal cortex) that are important for behavior control are often changed in addicts, the scientists at the University of Cambridge wanted to test whether such deficits only arise as a result of pathological drug use or whether they are also hereditary can.

Lack of self-control

Using a special brain-scanning method, they examined 50 pairs of siblings, of which only one sibling was addicted to drugs. Interestingly, in comparison to unrelated healthy individuals, both siblings showed a number of different characteristics in the fronto-striatal reward network of their brain: on the one hand, a lower nerve tract fiber density in the prefrontal cortex, on the other hand, enlarged areas in the basal ganglia that lie under the cerebral cortex especially in the striatum. In addition, a behavior test confirmed that both siblings had limited self-control. This trait has long been considered a risk factor for addictive diseases.

Since the aforementioned brain anomalies associated with a lack of self-control in siblings are most likely hereditary, the study authors believe that they could serve as a measurable characteristic of an increased risk of addiction. The fact that this feature does not mean a definite fate is proven by the fact that one of the two siblings in the study is not sick.

It is known that certain sections of the prefrontal cortex have an inhibitory effect on the basal ganglia. According to one accepted hypothesis, this inhibition helps a person to resist harmful temptations and, for example, to forego an inviting but high-calorie piece of cake or a dodgy cash win. If the function of the fronto-striatal network is restricted, as can be the case with addicts and, according to the study results mentioned, also with healthy people, there is an increased susceptibility to potentially dangerous behavior.

The fact that young people are particularly easy to get involved in experiments with addictive substances is also likely to be related to a lack of function of this neural network. In this case, however, the deficit is developmental; because the frontal lobe reaches its full functionality later than the brain structures that respond to reward stimuli. High-risk behaviors such as trying drugs, binge drinking or excessive speed in road traffic occur increasingly in the phase of separation from the parental home and the connection to peers, so are usually a temporary phenomenon.

Looking for markers

But especially with a view to those young people who eventually slide into drug addiction, it remains an important concern to find measurable markers for an increased susceptibility in order to ultimately be able to influence such factors in a targeted manner. When searching for appropriate hereditary indicators, there has been a veritable gold rush atmosphere since the sequencing of the human genome. Using high-quality techniques from genetic epidemiology and neuroimaging, scientists often use interdisciplinary consortia to search large patient groups for correlations between individual gene variants and physiological characteristics that could indicate a predisposition to addictive diseases.

This approach can be illustrated using the gene variant A118G, which correlates with an increased risk of alcoholism in many, but not all, studies. For example, a study found the variant in every second adolescent with alcohol problems, but only in every sixth without such problems.

The gene in which the mutation A118G can occur, codes for the so-called μ-opiate receptors of the body's own opioid system, which is not only important for pain control, but also seems to influence the reaction to alcohol in a way that has not yet been clarified. American scientists recently made an exciting contribution to the possible influence of this gene variant on susceptibility to alcoholism. In non-alcohol-dependent carriers of the A118G variant, they used PET scans to show that alcohol in the striatum triggers a significantly stronger release of dopamine than in people without this genetic characteristic. Previously, other studies had indicated that A118G carriers felt more intense feelings of euphoria after consuming alcohol and also suffered less from hangover symptoms. The increased response of the reward system to alcohol could result in an increased susceptibility to alcoholism.

Approaches can already be seen here for therapy. Carriers of the A118G variant react much better to naltrexone - one of the few active ingredients that are approved in Switzerland for the treatment of alcoholism - than people without this gene variant. Naltrexone blocks the μ-opiate receptors in the brain. Their structure is slightly changed by the A118G mutation, which means that naltrexone should bind more strongly to these receptors. The better responsiveness of A118G carriers to naltrexone is worth considering for the neurobiologist Rainer Spanagel from the Central Institute for Mental Health in Mannheim, to adapt the treatment of alcoholics with naltrexone to the individual genetic make-up.

In studies in which only carriers of this gene variant were specifically given naltrexone therapy, this approach has paid off. The patient groups selected according to genetic criteria show a better treatment success. According to Spanagel, there is currently considerable resistance to the introduction of this personalized treatment approach. The facts are too unclear, it is argued, not to mention the legal and ethical problems that the genetic tests necessary for patient selection could bring with them.

At the cellular level

Of course, correlations between certain gene variants and brain abnormalities occurring in addicts do not yet provide any causal relationships. This requires precise knowledge of the cell biological processes that lead from the gene to the disease characteristic, as the neurobiologist Christian Lüscher from the University of Geneva emphasizes. By means of studies on mice, he and his colleagues have made important contributions to clarifying these processes. Even if substances such as alcohol, cocaine or nicotine intervene in brain physiology in very different ways, they all seem to ultimately trigger a dopamine signal in the brain's reward network. This signal can trigger neural learning processes that lead to addictive behavior. With the method of so-called optogenetics, Lüscher and others succeeded in stimulating neurons that release dopamine in living mice with light and thus triggering addictive behavior in the animals.

The still young optogenetics makes it possible to use molecular biological methods to smuggle light-sensitive molecules into certain types of nerve cells, where they can act as light switches that can be manipulated externally in the cell membrane. These nerve cells can then be excited by light impulses of a suitable wavelength. Ultimately, according to Lüscher, it is only on the basis of such approaches, with which the processes in the reward system can be traced on a cellular level, that one learns to understand how the brain disease that we call addiction develops; and why some people stay healthy despite prolonged use of drugs and others become addicted.