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
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.
Section snippets
Materials and methods
A scan dataset of patients enrolled to a randomized clinical trial was employed. The aim of the trial was to assess the efficacy of n-3 PUFA supplementation to antipsychotics in patients with first episode schizophrenia.
Study sample
No difference in MRI gray matter thickness was observed between the groups at the beginning of the study, which indicates that the process of patient exclusion was not biased. The treatment groups were similar in terms of socio-demographic variables and baseline characteristics (Table 1). Antipsychotic use at baseline and change in antipsychotic use, presented as chlorpromazine equivalents, is shown in Table 1. The mean rate for adherence with study intervention, based on pill count and
Summary of the results and relevance of the location
The study showed decreased cortical thickness loss related to concentrated fish oil supplementation (EPA + DHA) in comparison with placebo in schizophrenia patients treated with antipsychotics. The differences were observed in the left parieto-occipital cortex, specifically Brodmann areas 7 and 19, i.e. the cortical areas located near the temporo-parieto-occipital junction (TPOJ), which integrates information from both the external environment and from within the body (Abu-Akel and Shamay-Tsoory,
Conflict of interest
Authors declare no conflict of interest.
Contributors
Author TP was responsible for literature searches, study design, patient's enrollment and clinical assessments, drafting the manuscript. Authors EP-J and PB took part in MRI data preparation, statistical analyses of MRI data, prepared MRI figures, and drafted parts of the manuscript related to MRI data processing and analysis. Author PG was responsible for data acquisition and drafting parts of the manuscript related to data acquisition. Author MG-G took part in literature searches, enrollment
Funding body agreements and policies
This paper was supported by grant no. N N402 243435 obtained from the Polish National Science Centre.
Acknowledgement
The authors would like to express their special thanks to Prof. Jolanta Rabe-Jabłońska MD, PhD, the former head of the department who was deeply involved in study preparation, and who unfortunately died in May 2014.
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