IMPACT OF THE PROJECT FOR PATIENTS: A future scenario 

It’s a realistic scenario that in the 2020’s we will be able to give a personalised treatment of patients with psychiatric disorders like depressions, based on the immune signatures in these patients. Four (fictive) cases of patients illustrate what could be the impact of the current research. We describe what would happen to these patients before and after the development of new diagnostic methods and treatments in the EU-funded project Moodstratification:

 

The year 2016

In Rotterdam, the main port of Europe, Samantha, Fatima, Jan and Rose have appointments with Sigmund, a psychiatrist, all of them because of severe fatigue, loss of energy, irritability, sleeping problems and difficulties with concentrating. Samantha never had these complaints before, the other three had a previous mild episode. After a consult, assessing current complaints and symptoms as well as psychiatric and physical illness history, all four are diagnosed with a major depressive disorder in the course of probably a unipolar major depressive disorder. Sigmund starts with pharmacological treatment, i.e. as the first step with the serotonin-re-uptake inhibitor (SSRI) sertraline in all patients. 

Four weeks later, Samantha, Fatima, Jan and Rose have a follow-up appointment with Sigmund. In Samantha the depressive symptoms have reduced considerably, in the three others not. Sigmund switches to augmentation with lithium in all three. 

Another 4 weeks later only Jan has responded. The other two are now prescribed the tricyclic antidepressant (TCA) amitryptiline. 

After another 4 weeks only Fatima has improved, but she also reports considerable side effects. Sigmund discusses with Rose the possibility of electroconvulsive therapy (ECT). Rose is afraid of this treatment, has lost her motivation after now 4-5 months of depression, and decides to look elsewhere.

 

The year 2024

In Rotterdam, the main port of Europe, Samantha, Fatima, Jan and Rose have appointments with Sigmund, a psychiatrist, all of them because of severe fatigue, loss of energy, irritability, sleeping problems and difficulties with concentrating. Samantha never had these complaints before, the other three had a previous mild episode. After a consult, assessing current complaints and symptoms as well as psychiatric and physical illness history, all four are diagnosed with a major depressive disorder in the course of probably a unipolar major depressive disorder. Sigmund starts with pharmacological treatment, i.e. as the first step with the serotonin-re-uptake inhibitor (SSRI) sertraline in all patients.

Sigmund also sends Samantha, Fatima, Jan and Rose to Koch, the clinical immunologist, for blood tests. The blood samples are analysed in the following days, using routine diagnostic tools. After 5 days Sigmund receives the results of the tests. The tests show that:

• Samantha (26 years) does not have any immunological abnormalities. The clinical and immune profile predicts that she will respond to a SSRI, like sertraline;

• Rose (38 years) has a clear monocyte inflammatory profile, high serum hCRP and IL-6 and clear signs of a relatively strong CD4+ T helper cell defect (reduced naïve T helper cells, more memory T helper cells, reduced Th17 and T regulator cells). This profile is known to predict a chronic course of her depression and non-response to at least most of the regular pharmacological treatments. A small trial in 2018 (funded in EU Horizon 2020) has shown that in such patients augmentation of a SSRI with an anti-inflammatory agent (e.g. anti TNF) and a T cell enforcing therapy (e.g. low dose IL-2 therapy) is successful to get a rapid response;

• Fatima (28 years) has a clear monocyte inflammatory profile and raised serum IL-6 levels, but she does not have a T cell defect. On the contrary she has normal to high levels of activated CD3+ T cells and normal levels of T helper cells. This immune profile predicts that she requires a pharmacological treatment with the SSRI sertraline enforced with an anti-inflammatory agent (e.g. low dose aspirin) for a proper clinical response. She does not need T cell enforcing therapy;

• Jan (32 years) also has a strong monocyte inflammatory profile and high hCRP, reduced CD3+ T cells, yet without signs of a CD4+ T helper cell defect. In contrast he has high numbers of Th2 and Th17 cells, and also BDNF and SCF are high in serum. On the basis of this profile his depression is probably an early episode within an evolving bipolar disorder, which suggests that adding lithium would be a better option than an SSRI alone. For a further optimal response the lithium need to be enforced by an anti-inflammatory therapy, e.g. anti-TNF.

The next week, Samantha, Fatima, Jan and Rose visit the clinic of Sigmund again to discuss the lab outcomes. Sigmund explains the diagnosis to the patients and also discusses the reason for the various add-on pharmacological and immune medications he will prescribe.

Four weeks later, Samantha, Fatima, Jan and Rose have a follow-up appointment with Sigmund. In two of them almost all symptoms have disappeared, while in the two other symptoms have reduced considerably. Sigmund suggest to continue medication to all four patients and they agree.