Structural and functional MRI correlates of inflammation in bipolar disorder: a systematic review

Abstract

Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI abnormalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1’233 BD patients). Despite heterogeneity between studies, a qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between stress, the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.

Applications of Mendelian randomization in psychiatry: a comprehensive systematic review

“…Overall, the causal relationships between depression and cardiovascular risk (of stroke in particular) that have been identified (Cai et al, 2019;Gill et al, 2019;Lu et al, 2021) are particularly interesting considering the increasing evidence on depression and serotoninergic axis dysregulation as important players in stroke physiopathology (Colpo et al, 2019;Damsbo et al, 2019;Saccaro et al, 2022a). While the present review did not identify a definitive causal link between systemic inflammation and psychiatric disorders (the results on SCZ, MDD, or BD patients, for example, are not conclusive), the link between inflammation and psychiatric disorders is another topic of major interest in recent years (Wium-Andersen et al, 2016;Han and Ham, 2021;Murphy et al, 2021;Saccaro et al, 2021aSaccaro et al, , 2021bSaccaro et al, 2022b), and further studies, employing MR as well, could unravel the pathophysiological role of inflammation in psychiatric disorders, with diagnostic, prognostic or therapeutic potential. To do so, however, it is important to focus on the right targets and to correctly interpret results.…”

“…Interestingly, two articles focused on causal risk factors for early-onset MDD (Michalek et al , 2017; Sequeira et al , 2017). The latter (Sequeira et al , 2017) showed that genetic liability to early menarche was causally associated with higher levels of depressive symptoms at 14 years but not after 14 years. The first one (Michalek et al , 2017) found that genetic predisposition to shorter telomere lengths was causally associated with increased risk for childhood-onset MDD.…”

“…We included 15 studies on MR in MDD (Table 2) including data from populations ranging between 500 and 143 265 MDD patients (Wium-Andersen et al , 2014; Hung et al , 2014; Wium-Andersen et al , 2015a; Wium-Andersen et al , 2015b; Kwok et al , 2016; Sequeira et al , 2017; Clarke et al , 2017; Michalek et al , 2017; Cai et al , 2019; Choi et al , 2019; Milaneschi et al , 2019; Gill et al , 2019; Huang et al , 2020; Lu et al , 2021; Maharjan et al , 2021). Studies employed most often inverse variance–weighted analysis, and they all accounted for pleiotropic effects, apart from (Michalek et al , 2017).…”

“…Interestingly, two articles focused on causal risk factors for early-onset MDD (Michalek et al , 2017; Sequeira et al , 2017). The latter (Sequeira et al , 2017) showed that genetic liability to early menarche was causally associated with higher levels of depressive symptoms at 14 years but not after 14 years.…”