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In animals, STS inhibition or deletion of the associated gene, enhances memory\/neuroprotection and alters hippocampal neurochemistry. Little is known about the consequences of constitutive STS deficiency on memory\u2010related processes in humans. We investigated self\u2010reported memory performance (Multifactorial Memory Questionnaire), word\u2010picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X\u2010linked ichthyosis (XLI; <jats:italic>n<\/jats:italic>\u2009=\u200941) and in adult female carriers of XLI\u2010associated genetic variants (<jats:italic>n<\/jats:italic>\u2009=\u200979); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, <jats:italic>n<\/jats:italic>\u2009=\u200998) or recruited from the general population (<jats:italic>n<\/jats:italic>\u2009=\u2009250)]. Using the UK Biobank, we compared mood\/memory\u2010related neuroanatomy in carriers of genetic deletions encompassing <jats:italic>STS<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u200928) and non\u2010carriers (<jats:italic>n<\/jats:italic>\u2009=\u200934,522). We found poorer word\u2010picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI\u2010associated variant carriers and individuals with IV reported more adverse mood symptoms, reduced memory contentment and greater use of memory aids, compared with general population controls. Mood and memory findings appeared largely independent. Neuroanatomical analysis only indicated a nominally\u2010significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non\u2010carriers. In humans, constitutive STS deficiency appears associated with mood\u2010independent impairments in memory but not with large effects on underlying brain structure; the mediating psychobiological mechanisms might be explored further in individuals with XLI and in new mammalian models lacking STS developmentally.<\/jats:p>","DOI":"10.1111\/gbb.12893","type":"journal-article","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T09:58:59Z","timestamp":1714903139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Memory, mood and associated neuroanatomy in individuals with steroid sulphatase deficiency (X\u2010linked ichthyosis)"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-136X","authenticated-orcid":false,"given":"Georgina H.","family":"Wren","sequence":"first","affiliation":[{"name":"School of Psychology Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences and Centre for Neuropsychiatric Genetics and Genomics School of Medicine, Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1731-6039","authenticated-orcid":false,"given":"Jack F. 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