Depression: Are there genetic risk markers of risk and response to treatment?

Because if these genetic markers. However, polygenic scores of the results of the treatments of the main psychiatric disorders present a modest predictive potential, they reflect well of coherent therapeutic trends, underlines one of the main authors, Professor Alessandro Serretti, of the University of Kore of Enna (Italy).

Genetic signatures for coherent therapeutic patterns – Depression: there genetic risk markers

The study is a meta-analysis of the data published over the period 2013-2025. In addition, relating to the link between the polygenic scores of the major depressive disorder (TDM) and the bipolar disorder (TB) and the therapeutic results. Consequently, These scores bring together the effects of hundreds. Consequently, even thousands of current genetic variants and combine them in the form of a single measure of genetic predisposition to psychiatric disorders. Meanwhile, The analysis reveals that:

• High polygenic scores for depression are systematically correlated depression: there genetic risk markers with less good therapeutic results for many other disorders. Therefore,
• Patients with high genetic risk of depression have an increased probability of non-response to antidepressants, thymoregulators, antipsychotics, lower remission rates and greater resistance to treatment in major depression, bipolar disorder and schizophrenia;
• This trend is validated for many population groups and many therapeutic approaches, which seems to confirm a real biological (or molecular) relationship;
• The relationship is modest, but constant, between the polygenic scores of major depressive disorder and the results of antidepressant treatments: a higher polygenic score for depression is correlated with an increased probability of non-response, non-reproduction or resistance to conventional antidepressant treatments;
• This effect is also observed for the results of bipolar disorder treatments and schizophrenia.

Genetics reveals nevertheless complex therapeutic relationships: Indeed, in particular for bipolar disorder, polygenet scores are associated with more nuanced effects. For example, If these markers have a depression: there genetic risk markers predictive value of the response to antidepressants in depression. they suggest “intriguing” trends in the treatment of bipolar disorder: they can, on the one hand, be associated with higher cognitive operation and on the other hand, predispose to psychotic traits in certain specific contexts. Clear.

• A genetic predisposition to bipolar disorder does not systematically lead to negative results

• And can even, in some contexts, be advantageous.

The role of environmental interactions: Environmental factors add to clinical complexity. The analysis highlights evidence of the interaction between the genetic risk of mood disorders and environmental factors. Thus. people with a higher genetic risk of depression also report more exposure to stressful life events and increased vulnerability to unfavorable environmental conditions.

• Conversely. again, the genetic risk of bipolar disorder is sometimes associated with positive results, including a higher level of education and better depression: there genetic risk markers cognitive performance. Conclusions which confirm “the complexity of psychiatric genetics”. where
• The same genetic variants can have different effects, depending on the context.
• Could these genes-environment interactions explain why some patients with similar genetic profiles experience very different clinical trajectories.

Finally, if these multiple and complex results find a certain coherence, the researchers note that their clinical implementation remains premature. Thus, the clinical utility of current polygenic scores remains limited. Even when they are statistically significant, these genetic markers generally explain less than 1 % of the variance of therapeutic results. This modest effect size reflects the persistent challenge of “missing inheritance” In psychiatric genomics. where identified variants represent only a fraction of genetic influence on complex traits.

These polygenic scores should therefore rather be considered as additional predictive markers rather than clinical decision -making tools. This highlights a critical limit of current research and depression: there genetic risk markers calls for large -scale and ethnically heterogeneous studies.

Automatic learning can allow better prediction: New approaches combining polygenic scores. clinical data thanks to automatic learning techniques already show substantial improvements in the prediction of results. Some studies have explained the variance of 4 to 5 % by integrating genetic and clinical information vs 1 to 2 % for genetic markers alone.

Developments that will eventually allow precision psychiatry.