Finally, we detected that CSF content in the region of the left Palbociclib side effects Sylvian fissure was inversely related to clinical improvement, which provided our findings with clinical significance. CSF volume increases in the left Sylvian fissure have been previously reported in other studies with samples of depressive patients. Furthermore, such a finding complements other reports of gray and white matter volume decreases in the insular cortex of depressive samples. More specifically, findings reported here are in agreement with the reduced gray matter volume in the left insular region reported for the same sample of patients in a previous study by our group. In this sense, results from previous anatomical and functional neuroimaging studies support the idea that the insular cortex is relevantly involved in the pathogenesis of depressive illness. Thus ventral striatum and orbitofrontal cortex and it is particularly implicated in the awareness and representation of emotions. Likewise, data from functional studies in MDD patients have also shown the implication of this area in the abnormal processing of emotions in depression. Interestingly, lateralization of structural abnormalities to the left insular region has been also reported in previous studies with melancholic samples, although the significance of such a finding is not fully clear. By contrast, significant volume decreases in the CSF spaces surrounding medial and lateral parietal cortices have not been observed in previous studies with melancholic or general depressive samples, in part because this region has not been typically evaluated in region of interest studies. There are, however, some reports of gray matter alterations in medial and lateral parietal areas in depressive patients, both in terms of volume reductions and increases. Interestingly, Shah et al. reported that gray matter volume increases in the precuneus differentiated between chronic and recovered depressive patients, suggesting that inconsistencies between studies may be partially accounted for by clinical differences between the assessed samples. In addition to complementing the description of putative structural alterations in gray and white matter, and thus providing a more comprehensive characterization of the structural abnormalities associated to psychiatric conditions, the identification of CSF abnormalities with reliable whole-brain automated approaches may assist the development of etiopathogenic hypotheses relating to the disorders. For example, CSF alterations located in regions with concomitant gray and/or white matter abnormalities may fit within neurodegenerative disease models, while larger CSF volumes without gray and/or white matter alterations may relate to neurodevelopmental disturbances, in terms of an abnormal gray/white matter volume increase during early development that is normalized with aging, resulting in larger CSF volumes in adult life, as has been proposed for schizophrenia. According to the above notions, our findings relating to an increased CSF content in the left insular region of melancholic patients.