School of Psychology, Cardiff University, Cardiff, UK.
Division of Psychological Medicine and Clinical Neurosciences and Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Genes Brain Behav. 2024 Jun;23(3):e12893. doi: 10.1111/gbb.12893.
Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and steroid (sulphate) levels correlate with mood and age-related cognitive decline. 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-related processes in humans. We investigated self-reported memory performance (Multifactorial Memory Questionnaire), word-picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X-linked ichthyosis (XLI; n = 41) and in adult female carriers of XLI-associated genetic variants (n = 79); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, n = 98) or recruited from the general population (n = 250)]. Using the UK Biobank, we compared mood/memory-related neuroanatomy in carriers of genetic deletions encompassing STS (n = 28) and non-carriers (n = 34,522). We found poorer word-picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI-associated 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-significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non-carriers. In humans, constitutive STS deficiency appears associated with mood-independent 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.
甾体硫酸酯酶 (STS) 可从甾体激素中去除硫酸盐基团，而甾体（硫酸盐）水平与情绪和与年龄相关的认知能力下降相关。在动物中，STS 抑制或相关基因缺失可增强记忆/神经保护作用，并改变海马神经化学。关于 STS 缺陷对人类记忆相关过程的影响，我们知之甚少。我们调查了患有性连锁鱼鳞病 (XLI；n = 41) 的男性 STS 缺乏症患者和 XLI 相关遗传变异携带者的成年女性 (n = 79) 的自我报告记忆表现（多因素记忆问卷）、单词-图片回忆和近期情绪（Kessler 心理困扰量表，K10）；我们将结果与匹配的对照组（诊断为寻常性鱼鳞病 [IV，n = 98] 或从普通人群中招募 [n = 250]）进行了比较。我们使用英国生物库，比较了包含 STS 的遗传缺失携带者 (n = 28) 和非携带者 (n = 34,522) 的情绪/记忆相关神经解剖结构。我们发现与对照组相比，XLI 男性和女性携带者的单词-图片回忆和感知记忆能力较差。与普通人群对照组相比，XLI 相关变异携带者和 IV 患者报告的情绪症状更差，记忆满意度降低，记忆辅助工具使用更多。情绪和记忆发现似乎在很大程度上是独立的。神经解剖分析仅表明，与非携带者相比，缺失携带者右侧海马体的分子层稍大。在人类中，STS 缺陷与记忆相关的情绪独立性损伤有关，但与大脑结构的大影响无关；可能会在 XLI 患者和缺乏 STS 发育的新哺乳动物模型中进一步探索潜在的中介心理生物学机制。
