Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia: A secondary outcome analysis of the OFFER randomized controlled study

Abstract

The aim of the study was to assess changes in cortical thickness related to the use of n-3 polyunsaturated fatty acids (PUFA) as add-on therapy in patients with first episode schizophrenia. A double-blind randomized controlled study was conducted using a 26-week intervention composed of concentrated fish oil containing 2.2 g/d of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) or placebo (olive oil). Participants underwent MRI scanning twice to assess changes in cortical thickness: at the beginning and at the end of intervention. Data of suitable quality was obtained from 29 participants. The T1-weighted images for each participant were analyzed using FreeSurfer methodology for longitudinal pipeline. Significant differences in cortical thickness loss were observed between the groups in the parieto-occipital regions of Brodmann areas 7 and 19 of the left hemisphere, dysfunctions in which may be involved in schizophrenia symptomatology. The results of the study support the previous observations carried out in older individuals and patients with mild cognitive impairment, indicating that n-3 PUFA may have neuroprotective properties, especially at early stages of neurodegenerative diseases, such as schizophrenia. If replicated, the results of the present study may encourage clinicians to consider n-3 PUFA as a promising addition to antipsychotics for long-term treatment of schizophrenia.

Introduction

Structural brain abnormalities are well established in schizophrenia. Magnetic resonance imaging (MRI) studies frequently show reduced brain volume and cortical thickness in patients with schizophrenia, especially of the fronto-temporal and hippocampal regions of the brain, as well as lateral ventricle enlargement, even in individuals at high clinical risk of schizophrenia (Benetti et al., 2013) and at early stages of the disease (Hýža et al., 2016). Moreover several studies have shown these changes to be progressive over time, with different loss patterns at every stage of the disease (Bois et al., 2016, Torres et al., 2016). It has been found that brain volume loss is partly related to disease severity, expressed as the number and frequency of relapses leading to excitotoxicity induced by glutamatergic overactivity, or by oxidative stress related to dopaminergic stimulation (Ho et al., 2011). There is also accumulating data suggesting a link between brain tissue loss and intensive antipsychotic therapy (Ahmed et al., 2015, Fusar-Poli et al., 2013). However, that extent to which these changes can be attributed to the pathological processes underlying the disease and the consequences of antipsychotic therapy is still a matter of debate (Andreasen et al., 2013, Goff et al., 2017). Studies also indicate the magnitude of brain volume loss to be directly related to worse clinical outcome (van Haren et al., 2008).

Deficiencies of n-3 polyunsaturated fatty acid (n-3 PUFA) levels have repeatedly been observed in schizophrenia, especially at early stages of disease (van der Kemp et al., 2012). MRI studies suggest that n-3 PUFA may be related to neuroprotective effects in patients with schizophrenia (Wood et al., 2010) and bipolar disorder (Hirashima et al., 2004), leading to decreased brain water proton transverse relaxation times (T2), which was shown to be indicative of increased neuronal membrane fluidity, and hence, increased neuronal health. A study of schizophrenia showed n-3 PUFA supplementation to have neuroprotective effects in hippocampi (Wood et al., 2010), and a bipolar study showed T2 reductions across the whole brain (Hirashima et al., 2004).

Both the disease itself and, possibly, treatment with antipsychotics are known to be related with GM loss (Ahmed et al., 2015, Fusar-Poli et al., 2013, Goff et al., 2017, Ho et al., 2011). The aim of the present study, therefore, is to confirm whether the use of adjunctive n-3 PUFA therapy, with its neuroprotective effects, may preserve this cortical volume loss in patients with schizophrenia.