Figure 4.

Summary of our findings about miR-132 dysregulation in unmedicated depression. (A) Mapping of three MRI components in the same brain with three colours. Note that prefrontal cortex, hippocampus and amygdala are all identified in both fALFF and grey matter, constituting the fronto-limbic system that has been implicated in mediating emotional processing (Phillips et al., 2003) and the pathophysiology of MDD in adults (Drevets, 1999; Sinclair, 2013). Note that these regions were also touched or linked by the identified white matter tracts such as the anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF), forceps minor (FMIN) and forceps major (FMAJ) (green arrows); while this is all data-driven, it further validates the effectiveness of multimodal fusion. (B) Inference and summary based on our results. Here higher miR-132 expression levels are related with lower fALFF and grey matter in the fronto-limbic circuits and result in poorer attention and executive functions in MDD. Note that forceps minor interconnects the left and right prefrontal cortex across hemispheres (detected in both fALFF and grey matter), anterior thalamic radiation links prefrontal cortex (PFC) with the thalamus, providing evidence for disrupted anatomical connections in fronto-limbic circuitry. Our results clearly support that key depression-associated brain areas, previously implicated in functional, anatomical and structural brain-imaging studies, may be affected by miR-132 dysregulation. AMY = amygdala; DLPFC = dorsolateral prefrontal cortex; FA = fractional anisotropy; GM = grey matter; HIPP = hippocampus; MPFC = medial prefrontal cortex.