biostudies-literatureUnknown26(12)Seo JSMajor depressive disorder (MDD) is a severe, common mood disorder. While reduced cerebrospinal fluid (CSF) flow adversely affects brain metabolism and fluid balance in the aging population and during development, only indirect evidence links aberrant CSF circulation with many diseases including neurological, neurodegenerative, and psychiatric disorders, such as anxiety and depression. Here we show a very high concentration of p11 as a key molecular determinant for depression in ependymal cells, which is significantly decreased in patients with MDD, and in two mouse models of depression induced by chronic stress, such as restraint and social isolation. The loss of p11 in ependymal cells causes disoriented ependymal planar cell polarity (PCP), reduced CSF flow, and depression-like and anxietMolecular psychiatry7308-7315https://www.ebi.ac.uk/biostudies/studies/S-EPMC8873010biostudies-literatureEpendymal cells-CSF flow regulates stress-induced depression.PMC8873010Seo JSMantas IGreengard PSvenningsson PfalseEpendymal cells-CSF flow regulates stress-induced depression.Major depressive disorder (MDD) is a severe, common mood disorder. While reduced cerebrospinal fluid (CSF) flow adversely affects brain metabolism and fluid balance in the aging population and during development, only indirect evidence links aberrant CSF circulation with many diseases including neurological, neurodegenerative, and psychiatric disorders, such as anxiety and depression. Here we show a very high concentration of p11 as a key molecular determinant for depression in ependymal cells, which is significantly decreased in patients with MDD, and in two mouse models of depression induced by chronic stress, such as restraint and social isolation. The loss of p11 in ependymal cells causes disoriented ependymal planar cell polarity (PCP), reduced CSF flow, and depression-like and anxiet2021-01-01T00:00:00Z2021 Dec2025-04-25T22:57:06.478Z2025-04-06T09:15:16.528ZS-EPMC88730103423428010.1038/s41380-021-01202-1