Abstract
BackgroundSchizophrenia 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.MethodsDiffusion 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.ResultsTwelve 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.ConclusionsWhile 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.
Highlights
Schizophrenia is thought to be a neurodevelopmental disorder with pathophysiological processes beginning in the brain prior to the emergence of clinical symptoms
While those with schizophrenia were found to have significantly reduced fractional anisotropy (FA) in the left frontal and bilateral temporal and parietal regions compared to controls, no significant differences were identified between ultra-high risk (UHR) and schizophrenia patients
Epstein et al [24] found lowered FA in the bilateral corticospinal tract, left inferior longitudinal fasciculus and left inferior fronto-occipital fasciculus in UHR adolescents and those with schizophrenia compared to healthy controls, though no significant differences were identified between the two groups
Summary
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. Though it has long been postulated to be a disorder of neurodevelopment with pathophysiological processes beginning in the brain prior to the onset of clinical symptoms [1, 2], the advent of neuroimaging techniques has been instrumental in probing these neurobiological processes While these techniques have provided unique insights into various aspects of brain morphometry and function, of particular relevance to psychosis is diffusion tensor imaging (DTI) studies on white matter integrity in fibre tracts connecting brain regions. We highlight the need to examine these relationships in further detail among UHR samples to better understand the pathophysiology of the disorder, and potentially assist in the development of novel treatment and early intervention strategies
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