Major Depression in Children with β-Thalassemia Major is Strongly Associated with the Number of Blood Transfusions, Iron Overload and Increased Levels of Interleukin-1β

Abstract

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

Depression, Anxiety, and Stress Symptoms in Patients With Beta Thalassemia Major in Almadinah Almunawwarah, Saudi Arabia

“…In Arab communities, in 2012, a study reported similar findings from 80 patients in Lebanon where 35% of patients were depressed [ 19 ]. In the study by Al-Hakeim et al, it was reported that major depression in children with BTM was strongly associated with the number of blood transfusions, iron overload, and increased levels of interleukin-1ß [ 5 ].…”

“…Depression, anxiety, and stress (DAS) are psychological disorders, which can complicate BTM patients' condition and cause multiple comorbidities if they were not diagnosed early and managed appropriately [5][6][7][8].…”

“…It is expected and well documented in the literature that the diagnosis of BTM patients with DAS can affect the course of the thalassemia disease and if detected early and managed appropriately will improve the outcome including compliance with treatment and hence improve the quality of life of affected patients [7]. Thalassemia is a chronic disease with a lot of psychological impact on patients, such as coming to the hospital every month and being afraid of blood-transmitted infections, having to take iron chelators every day, getting complications of iron overload, missing school and work to attend the blood transfusion sessions, financial burden, loss of friends and family members from the disease, hormonal abnormalities, and disfiguring abnormalities from bone marrow expansion [5][6][7][8].…”

“…Thalassemia is a chronic disease with a lot of psychological impact on patients, such as coming to the hospital every month and being afraid of blood-transmitted infections, having to take iron chelators every day, getting complications of iron overload, missing school and work to attend the blood transfusion sessions, financial burden, loss of friends and family members from the disease, hormonal abnormalities, and disfiguring abnormalities from bone marrow expansion [ 5 - 8 ].…”

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

“…The current therapies for β-TM include blood transfusion yielding almost normal life expectations 4,5 . Since the human body has no regulated mechanism to excrete excess iron, secondary iron overload occurs rapidly in patients, who are on chronic blood transfusion programs.…”