Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression

Abstract

Background: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. Methods: 51 depressed participants (HDRS score >13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. Results: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r=0.28, p=0.02), prefrontal cortex (r=0.24, p=0.04), and insular cortex (r=0.24, p=0.04), but not with the peripheral inflammatory markers: CRP levels (r=0.07, p=0.53), IL-6 (r=-0.08, p=0.61), and TNF-α (r=-0.06, p=0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r=0.34, p=0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. Conclusion: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.

Interoceptive pathways to understand and treat mental health conditions

“…Immune system dysfunction is commonly found in patients with current mental health disorders, including psychosis [52], trauma-and stressor-related disorders [53], and depression [54]. Crucially, increased peripheral inflammation can induce central nervous system inflammation via humoral and neural mechanisms, including recruitment of activated monocytes into the brain following cerebral microglial activation [55], which may be one cause of central neuroinflammation in psychiatric disorders [56].…”

Sickness Behaviour and Depression: An Updated Model of Peripheral-Central Immunity Interactions

“…Persistent disturbance of homeostasis affects brain activity and in particular the neotenic regions, such as prefrontal cortex, that in the adult cortex still retain high synaptic density and, for this reason, are the most metabolically active (75); disturbance in energetic homeostasis will then place these tissues under stress and elicit a microglia response. In fact, in our data on MDD subjects, CP volume correlated with TSPO-PET signal in prefrontal regions (74).…”

Choroid plexus volume is enlarged in clinically isolated syndrome patients with optic neuritis

“…Intriguingly, enlargement of the CP has also been reported in other neurological conditions including stroke (Egorova et al 2019), psychosis (Lizano et al 2019), schizophrenia(Y. F. Zhou et al 2020), depression (Althubaity et al 2022), Alzheimer disease (Choi et al 2022) and complex regional pain syndrome(G. Zhou et al 2015). Therefore, enlargement of the CP is not MSspecific, but instead is likely to be associated with general increase of neuroinflammation (Althubaity et al 2022) (Choi et al 2022). Indeed, functional dysregulation of the CP may reflect a common underlying mechanism in the pathophysiology of the chronic stage of neurodegenerative diseases (Schwartz and Cahalon 2022).…”

“…Intriguingly, enlargement of the CP has also been reported in other neurological conditions including stroke(Egorova et al 2019), psychosis(Lizano et al 2019), schizophrenia(Y. F. Zhou et al 2020), depression(Althubaity et al 2022), Alzheimer disease(Choi et al 2022) and complex regional pain syndrome(G. Zhou et al 2015).…”

“…Furthermore, it has been suggested that enlargement of the CP may occur before the development of pathological changes in the CNS and may even reflect an inherited or acquired susceptibility to neuroinflammation (Egorova et al 2019) (Althubaity et al 2022) (Y. F. Zhou et al 2020). For example, enlargement of the CP has been reported in stroke patients in the early, post-acute period.…”