Data from studies in patients with “classic” OCD also suggest an association with aberrant innate immune activation. This includes altered levels of systemic cytokines, such as tumor necrosis factor-α and interlelukin-1β (Gray and Bloch 2012; Mitchell and Goldstein 2014; Rao et al. 2015; Simsek et al. 2016) as well as lower-than-expected immunoglobulin titers (Kawikova et al. 2010; Williams 2016; Calaprice et al. 2017), including immunoglobulin A (IgA), which provides protection at mucosal surfaces and can be produced through T cell-independent mechanisms (Macpherson et al. 2011). Moreover, a recent positron emission tomography imaging study in adults with OCD—many with childhood-onset—showed increased volume of translocator protein-18 (TSPO) distribution in cortico-striato-thalamo-cortical circuits, implicating widespread microglial activation (Attwells et al. 2017). Further support for a potential causative or perpetuating role of inflammation due to abnormal innate immune cell activity was provided by a double-blind, placebo-controlled randomized controlled trial of 50 adult outpatients with moderate-to-severe OCD that found modest symptom improvement with the nonsteroidal anti-inflammatory drug (NSAID) celecoxib as an adjuvant to fluvoxamine (Shalbafan et al. 2015).
