Abstract

BackgroundCurrent pathophysiological models of psychotic disorders suggest that stress contributes to the aetiology and trajectory of the disorder. Allostatic load (AL), a multisystem index of immune, neuroendocrine and metabolic dysregulation, is thought to represent the cumulative biological impact of stress. Two recent studies suggest that AL is elevated in patients with first-episode psychosis and related to psychotic symptoms and poor social and occupational functioning. Here, we investigate the relationship between AL and clinical outcomes in individuals at ultra-high risk for psychosis.MethodsAL was measured in a sub-group of participants of the NEURAPRO study, a multicentre randomized-controlled trial of omega-3 polyunsaturated fatty acids versus placebo in people aged 13 - 40 at UHR for psychosis. A total of 106 participants who underwent additional biomarker analysis were included in the present study. Biomarkers for the AL index were selected based on (1) representation of several physiological systems including the cardiovascular, neuroendocrine, immune, and metabolic systems, (2) use in previous AL research, and (3) associations with disease risk. We adopted a scaled AL algorithm whereby each marker proportionally contributes to the overall AL index. Clinical outcomes were assessed 3 and 12 months after study intake using the Social and Occupational Functioning Assessment Scale (SOFAS), the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS). We hypothesised that AL would be (1) associated with higher symptoms scores and reduced functioning at baseline and (2) related to more severe symptoms and reduced functioning at the 3 and 12 month assessments. These hypotheses were tested by calculating Pearson correlation coefficients and by using linear regression modelling, respectively.ResultsNo significant correlations of AL with any of the psychometric scales are observed at study intake. AL at baseline was associated with lower SOFAS scores at 3 months (B=-1.436, p=0.042) but not at 12 months (B=-1.096, p=0.297). No prospective associations of AL were found with any of the other psychometric measures (all p>0.05).DiscussionOur data support the notion that multisystem dysregulation, indexed as AL, may be a potential predictor of early treatment response and warrants further investigation. These observations are consistent with recent research demonstrating elevated AL in patients with psychotic disorders that is related to reduced functioning.

Highlights

  • Life adversity has been identified as a potentially causal factor in the development of mental disorders

  • The majority of the studies demonstrated that various types of early life adversities, physical neglect, emotional and sexual abuse and insecure attachment, are significantly associated with social cognitive function

  • No significant correlations of Allostatic load (AL) with any of the psychometric scales are observed at study intake

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Summary

Background

Schizophrenia is a severe disorder affecting approximately 1% of the population. The disorder is associated with symptoms such as false perceptions and beliefs and disturbances in affect and language production. In 2004 the total direct healthcare and non-healthcare cost in Canada was estimated at $2 billion, with an additional productivity loss estimated at $5 billion. Methods: I will present a program of research into disease-specific and genetic risk factors associated with structural and functional brain abnormalities, including morphology (amount of grey matter), structural connectivity (amount of white matter integrity), and brain functioning (amount of brain activity) in individuals with schizophrenia, their family members, and community controls using magnetic resonance imaging.

Results
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