The cost-of-illness and burden-of-disease of treatment-resistant depression in Austria.

BACKGROUND: Treatment-resistant depression (TRD) in major depressive disorder (MDD) is most commonly defined as the failure to respond to at least two antidepressant (AD) treatments of adequate duration and adherence. While the health care utilization (RU) and costs of patients with MDD are well documented, little is known about patients with TRD. Therefore, the aim of this study was to determine the direct medical RU of complex therapy pathways and to analyze the total cost-of-illness and the burden-of-disease in Austria. METHODS: In order to quantify the cost-of-illness and burden-of-disease of TRD, the analysis was designed with two steps. First, RU data were collected through an extensive survey of Austrian experts and a systematic literature review. Second, direct, indirect, and intangible costs were calculated using the micro-costing method. The results are presented per patient and based on a patient flow for the entire cohort of TRD patients. RESULTS: In Austria, the derived prevalence of TRD is 43,732 patients or 583 per 100,000 population. For 2021, the annual direct costs of TRD were estimated at 345.0 million €. At 684.7 million €, the estimated indirect costs were higher than the direct costs, representing 66.5% of the total cost-of-illness. The average annual cost per TRD patient is 23,547 €, of which direct costs are 7,890 €. Adding the years lived with a disability to the years lost due to premature death attributed to TRD resulted in a total of 29,884 disability-adjusted life years (DALYs) for the Austrian society. CONCLUSION: Although TRD accounts for only 0.7% (range: 0.6%-1%) of the total health care budget, it represents a significant burden-of-disease. In addition, TRD is associated with a high level of lost productivity in the Austrian economy. These findings support efforts to prioritize TRD as a focus area to achieve health-related goals.

Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response.

Very long-chain fatty acids (VLCFA) are critical for human cytomegalovirus replication and accumulate upon infection. Here, we used Epstein-Barr virus (EBV) infection of human B cells to elucidate how herpesviruses target VLCFA metabolism. Gene expression profiling revealed that, despite a general induction of peroxisome-related genes, EBV early infection decreased expression of the peroxisomal VLCFA transporters ABCD1 and ABCD2, thus impairing VLCFA degradation. The mechanism underlying ABCD1 and ABCD2 repression involved RNA interference by the EBV-induced microRNAs miR-9-5p and miR-155, respectively, causing significantly increased VLCFA levels. Treatment with 25-hydroxycholesterol, an antiviral innate immune modulator produced by macrophages, restored ABCD1 expression and reduced VLCFA accumulation in EBV-infected B-lymphocytes, and, upon lytic reactivation, reduced virus production in control but not ABCD1-deficient cells. Finally, also other herpesviruses and coronaviruses target ABCD1 expression. Because viral infection might trigger neuroinflammation in X-linked adrenoleukodystrophy (X-ALD, inherited ABCD1 deficiency), we explored a possible link between EBV infection and cerebral X-ALD. However, neither immunohistochemistry of post-mortem brains nor analysis of EBV seropositivity in 35 X-ALD children supported involvement of EBV in the onset of neuroinflammation. Collectively, our findings indicate a previously unrecognized, pivotal role of ABCD1 in viral infection and host defence, prompting consideration of other viral triggers in cerebral X-ALD.