The Involvement of TNF-α in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments

Abstract

Abstract:Major depressive disorder is a highly prevalent, chronic and recurring disorder, associated with substantial impairment in cognitive and interpersonal functions. Accumulating evidence suggests that inflammatory processes play an important role in the etio-pathogenesis, phenomenology, comorbidity and treatment of MDD. Suboptimal remission rates and the persistence of cognitive deficits contribute to functional impairment in MDD inviting the need for the development of mechanistically novel and domain specific treatment approaches. The MEDLINE/ Pubmed database was searched from inception to February, 9 th , 2014 with combinations of the following search terms: 'TNF-alpha', 'depression', 'infliximab', 'etanercept', 'adalimumab', 'golimumab' and 'certolizumab'. Preclinical and clinical evidence linking TNF-α to MDD pathophysiology were reviewed as well as the current status of TNF-α modulators as novel agents for the treatment of MDD. Experimental models and clinical studies provide encouraging preliminary evidence for the efficacy of TNF-α antagonists in mitigating depressive symptoms and improving cognitive deficits. Further studies are warranted to confirm these data in larger randomized controlled trials in primary psychiatric populations. Translational research provides a promising perspective that may aid the development and/or repurposing of mechanism-based treatments for depressive symptoms and cognitive impairment in MDD.

Psoriasis, Depression, and Inflammatory Overlap: A Review

“…The current US Food and Drug Administration-approved TNF-a antagonists include infliximab, etanercept, adalimumab, golimumab, and certolizumab. Etanercept, adalimumab, and infliximab were efficacious in the treatment of depression, as evidenced by limited studies [24,[36][37][38]. In a retrospective Taiwanese database cohort study of 980 patients, a 47% reduction in depression and insomnia was noted in patients who were treated with anti-TNF-a biologics for psoriasis and psoriatic arthritis over a 2-year time period [39].…”

“…These results suggest that depression is reduced by anti-TNF-a biologics; however, the variability in depression screening tools hinders comparison between different medications in this treatment class (Table 1). Depression improved in patients treated with infliximab for Crohn's disease, ankylosing spondylitis, and psoriasis [36,[43][44][45][46][47][48]. However, the evidence for improved depression in the psoriasis category was from case reports and studies with small sample sizes [36].…”

“…Depression improved in patients treated with infliximab for Crohn's disease, ankylosing spondylitis, and psoriasis [36,[43][44][45][46][47][48]. However, the evidence for improved depression in the psoriasis category was from case reports and studies with small sample sizes [36]. Other areas of focus include IL-17 inhibitors such as brodalumab, secukinumab, and ixekizumab, and IL-12/23 inhibitors such as ustekinumab and kriakinumab.…”

Factors Associated With Anxiety and Depression Spectrum Disorders in Behchet’s Disease

“…Причина этого, наиболее вероятно, кроется в общем патогенезе: в условиях длительных РТДС поддерживается хроническое воспаление, а некоторые провоспалительные цитокины, в частности фактор некроза опухоли α, способ-ны усугублять КН [39]. То, что стрессовые факторы способствуют разви-тию РТДС, подтверждено множеством работ, но при ББ связь стрессовых факторов с развитием РТДС изучена недостаточно [17].…”

Effects of Synthetic Disease-Modifying Antirheumatic Drugs, Biological Agents, and Psychopharmacotherapy on the Mental Disorders in Patients With Rheumatoid Arthritis

“…В частности, хроническое воспаление иг-рает первостепенную роль в развитии как РА, так и де-прессии, а депрессия в последние годы все чаще рассмат-ривается как системное заболевание [20,21]. Кроме того, и РА, и депрессия ассоциируются с повышением уровней биомаркеров воспаления, таких как С-реактивный белок (СРБ), интерлейкин 1, интерлейкин 6 и фактор некроза опухоли α (ФНОα), а ингибиторы ФНОα, по данным не-которых исследователей, статистически значимо умень-шают выраженность симптомов депрессии у пациентов с хроническими заболеваниями, в том числе у больных РА [22][23][24].…”