title: White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids.
abstract: BACKGROUND
  Schizophrenia is thought to be a neurodevelopmental disorder with pathophysiological processes beginning in the brain prior to the emergence of clinical symptoms. Recent evidence from neuroimaging studies using techniques such as diffusion tensor imaging has identified white matter abnormalities that are suggestive of disrupted brain myelination and neuronal connectivity. Identifying whether such effects exist in individuals at high risk for developing psychosis may help with prevention and early intervention strategies. In addition, there is preliminary evidence for a role of lipid biology in the onset of psychosis, along with well-established evidence of its role in myelination of white matter tracts. As such, this article synthesises the literature on polyunsaturated fatty acids (PUFAs) in myelination and schizophrenia, hypothesizing that white matter abnormalities may potentially mediate the relationship between PUFAs and schizophrenia.
  
  
  METHODS
  Diffusion tensor imaging studies were identified through a systematic search of existing literature. Studies examined white matter integrity in ultra-high risk (UHR) samples, as assessed using structured diagnostic interviews. Data was extracted and summarised as a narrative review.
  
  
  RESULTS
  Twelve studies met inclusion criteria, and findings identified reduced fractional anisotropy and higher diffusivity. Although the exact location of abnormalities remains uncertain, fronto-temporal and fronto-limbic connections, including the superior longitudinal and uncinate fasiculus, cingulum, and corpus callosum appear to be implicated. Because of preliminary evidence suggesting lipid biology may be relevant for the onset of psychosis, a discussion is provided of the role of polyunsaturated fatty acids (PUFAs) in myelination and risk for psychosis.
  
  
  CONCLUSIONS
  While the function of PUFAs in myelination is well-established, there is growing evidence of reduced PUFA concentration in UHR samples, highlighting the need for research to examine the relationship between PUFA and white matter integrity in high-risk samples and age-matched healthy controls. Such investigations will help to better understand the pathophysiology of the disorder, and potentially assist in the development of novel treatment and early intervention strategies.
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.|Department of Psychology, University of Oregon, Eugene, USA.
authors: Nandita
authors: N
authors: Vijayakumar
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.
authors: Cali
authors: C
authors: Bartholomeusz
authors: Brain & Mind Research Institute, Central Clinical School, University of Sydney, Sydney, Australia.
authors: Thomas
authors: T
authors: Whitford
authors: School of Psychology, UNSW Australia, Sydney, Australia.
authors: Daniel F
authors: DF
authors: Hermens
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.
authors: Barnaby
authors: B
authors: Nelson
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.
authors: Simon
authors: S
authors: Rice
authors: Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Australia.
authors: Sarah
authors: S
authors: Whittle
authors: Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Australia.
authors: Christos
authors: C
authors: Pantelis
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.
authors: Patrick
authors: P
authors: McGorry
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia.
authors: Miriam R
authors: MR
authors: Schäfer
authors: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria, 3052, Australia. amminger@unimelb.edu.au.
authors: G Paul
authors: GP
authors: Amminger
mesh_terms: D000328:Adult; D056324:Diffusion Tensor Imaging; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D009422:Nervous System Diseases; D011618:Psychotic Disorders / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D066127:White Matter
chemical_list: D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated
keywords: Polyunsaturated fatty acids; Psychosis; Ultra-high risk; White matter; Youth