The genetic and biological indices indicate the role of inflammation in mental health

A major study in the Netherlands has shown that inflammation is systematically linked to the symptoms of depression and anxiety, as well as subtle deficiencies in cognitive function – in particular memory and attention. Researchers have used observational and genetic approaches to better understand if these associations could be causal. While most associations were weak, the results offer convincing support for the idea that chronic low-grade inflammation can influence emotional well-being and mental performance. The results were published in the journal Translational psychiatry.

Depression is one of the most common and invalidating mental health problems in the world. It is often accompanied by memory, attention and decision -making problems. These cognitive problems are not only minor symptoms – they contribute to a long -term handicap and a reduced quality of life. However, current treatments for depression and cognitive symptoms are often only modestly effective.

A winning hypothesis of the field is that inflammation, in particular low-level systemic inflammation, can underlie certain cases of depression and related cognitive problems. Inflammation is the natural response of the body to infection or injuries, but when it becomes chronic, it can start to interfere with brain function. Previous studies have shown that people with depression tend to have higher levels of inflammatory protein such as interleukin-6 and C-reactive proteins in their blood. But that these proteins cause depression or that it is simply a by-product of poor health is not yet settled.

“There is more and more evidence that some people are developing depression due to an underlying immune dysfunction. Scientific evaluation is difficult because there are many factors that are associated with both depression and immune dysfunction (substance relations, has declared a diet, stress, adiposity), which makes relations with a medical and a medical-psycho-psycho-psychoto of the Naoise Giollabhui, a medical medical school mass and a Harvard medical. School.

“This article was an opportunity to explore the association between inflammatory biomarkers and a range of mental health results by using a very large Dutch cohort study and to use an approach that would allow us to determine whether certain specific immune biomarkers are linked due to causality to specific mental health results.”

The study used data from the rescue cohort, a major population-based study in the Netherlands following tens of thousands of individuals over time. More than 55,000 adults participated in the observational part of the study, which examined the levels of C-reactive protein in the blood, as well as symptoms of depression, anxiety and performance on cognitive tests. In addition, genetic data were available for more than 57,000 participants, allowing researchers to calculate the genetic scores linked to several inflammatory markers, including interleukin-6, its receiver and a compound called glyca.

Researchers first examined whether C-reactive protein levels were associated with mental health symptoms and cognitive operation. They found that higher levels of this immune marker were linked to an increased probability of depression, a lower positive effect, a higher negative effect and slightly worse performance on the tasks measuring executive functioning, attention and psychomotor speed. These associations were statistically significant even after adjustment for significant factors such as age, body mass index and existing health conditions, although the size of the effects is relatively low.

Then, the team examined whether individuals with genetic predisposition to higher inflammation also had a greater risk of mental health symptoms. They calculated genetic risk scores based on known variants that influence proteins linked to inflammation. Here, they found that individuals with a higher genetic tendency to a C-reactive protein or high glyca were more likely to feel a negative effect and, in some cases, to meet the criteria of depression or anxious disorders. For example, the genetic score linked to the C-reactive protein was associated with a higher risk of anxiety, while the glyca score was linked to a higher risk of major depressive disorder.

Interestingly, most genetic risk scores were not linked to cognitive results, with an exception. Individuals with genetic variants associated with higher levels of interleukin-6 soluble receptor- a key component of the immune system signaling- have formulated slightly lower memory performance. This discovery suggests a possible role for specific inflammatory paths in the memory function.

The third method used by researchers was Mendelian randomization, which helps to deduce if a factor like inflammation could cause certain results rather than simply being correlated with them. This method uses the random heritage of genetic lines to minimize confusion variables. Using this approach, researchers have found provisional evidence that high C-reactive proteins could causally increase the risk of anxiety. However, the association was just unless there is a statistical meaning, suggesting the need for more studies to confirm this result.

One of the most coherent results in all methods was the link between inflammation – in particular C -reactive protein – and negative affect. This refers to a general tendency to experience unpleasant emotions such as anger, sadness or fear. The fact that the inflammation measured and the genetic risk of inflammation has been linked to negative affect adds weight to the idea that the activity of the immune system can influence emotional states beyond traditional diagnostic categories such as depression or anxiety.

Although the results support the idea that inflammation contributes to psychological symptoms, the authors point out that the effects observed were small. They suggest that inflammation can play a role in a subset of individuals or in specific types of symptoms, such as anhedonia, fatigue or irritability. These symptoms have previously been linked to the activity of the immune system and can define a distinct depression subtype with biological foundations.

The study also adds to an increasing set of research suggesting that inflammatory paths can be more important to understand emotional well-being than to understand cognitive performance. Limited associations between inflammation and the results of cognitive tests, in particular in genetic analyzes, imply that the cognitive effects of inflammation can be more subtle or dependent on the context. However, the notable exception involving the signaling and memory of the interleukin-6 highlights the need for more research on specific immune paths and their cognitive effects.

“These results have found fairly coherent associations between an immune marker measured in the blood and depression, anxiety, cognitive capacities and negative affect,” Mac Giollabhui told Psypost. “We have also found evidence that genetic predisposition at higher levels of immune markers was linked to depression, anxiety, memory and negative affect, which suggests that these associations can be causal.”

But as for any study, there are limits. The sample was largely made up of individuals of European origin, which can limit the way in which the results can be applied. “More work is necessary to determine whether these results are generalized to other groups,” said Mac Giollabhui. “Secondly, the impact of genetics as operationalized in this study on our biomarkers was quite modest size and it is difficult to know if greater increases in immune biomarkers could have a cumulative and potentially more important effect on the results we are looking for.”

“Our study focused on associations of the general population, which have generally shown that small associations between immune markers and mental health results. Future studies are necessary to reproduce these results and focus on specific subgroups and life stages (for example, older populations),” added the co-author Chloe Slaney, a main research partner at the University of Bristol.

Despite these limits, the results provide new evidence that inflammation can play a small but measurable role in the formation of emotional experiences and mental health risks. Above all, the consistency of the results between different types of analyzes reinforces confidence in the idea that immune activity contributes to certain psychological features and symptoms.

“The long -term objective is to better understand the role played by immune dysfunction in depression in order to identify treatment targets,” said Mac Giollabhui. “I currently manage a mechanistic clinical trial which examines whether the experimental inhibition of immune signaling in depressed individuals with high levels of inflammation leads to a change in mood and cognition as well as underlying immune mechanisms. I hope we can harass this information to develop new and more effective treatments. ”.

The study, “Role of inflammation in depressive and anxious disorders, affect and cognition: genetic and non -genetic results in the cohort study of lines“, Was written by Naoise Mac Giollabhui, Chloe Slaney, Gibran Hemani, Eimear M. Foley, Peter J. Van Der Most, Ilja M. Nolte, Harold Snederder, George Davey Smith, Ghus Khandaker and Catharina A. Hartman.