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World J Transl Med. Apr 12, 2013; 2(1): 1-12
Published online Apr 12, 2013. doi: 10.5528/wjtm.v2.i1.1
Cognitive, behavioural and psychiatric phenotypes associated with steroid sulfatase deficiency
Simon Trent, William Davies
Simon Trent, William Davies, Behavioural Genetics Group, Neuroscience and Mental Health Research Institute, Schools of Psychology and Medicine, Cardiff University, Cardiff CF10 3AT, United Kingdom
Simon Trent, William Davies, MRC Centre for Neuropsychiatric Genetics and Genomics and Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom
Simon Trent, William Davies, School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom
Author contributions: Trent S and Davies W contributed to this paper equally.
Supported by Medical Research Council United Kingdom New Investigator Research Grant (G0900636) to Davies W
Correspondence to: William Davies, PhD, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, Heath Park Campus, Cardiff CF14 4XN, United Kingdom. daviesw4@cardiff.ac.uk
Telephone: +44-29-20687047 Fax: +44-29-20687068
Received: December 19, 2012
Revised: January 24, 2013
Accepted: February 8, 2013
Published online: April 12, 2013
Processing time: 92 Days and 15.7 Hours
Abstract

The enzyme steroid sulfatase (STS) desulfates a variety of steroid compounds thereby altering their activity. STS is expressed in the skin, and its deficiency in this tissue has been linked to the dermatological condition X-linked ichthyosis. STS is also highly expressed in the developing and adult human brain, and in a variety of steroidogenic organs (including the placenta and gonads); therefore it has the potential to influence brain development and function directly and/or indirectly (through influencing the hormonal milieu). In this review, we first discuss evidence from human and animal model studies suggesting that STS deficiency might predispose to neurobehavioural abnormalities and certain psychiatric disorders. We subsequently discuss potential mechanisms that may underlie these vulnerabilities. The data described herein have potential implications for understanding the complete spectrum of clinical phenotypes associated with X-linked ichthyosis, and may indicate novel pathogenic mechanisms underlying psychological dysfunction in developmental disorders such as attention deficit hyperactivity disorder and Turner syndrome.

Keywords: Acetylcholine; Aggression; Attention; Attention deficit hyperactivity disorder; Dehydroepiandrosterone sulfate; Impulsivity; Hippocampus; Postpartum psychosis; Serotonin