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

Schizophr Res. 2018 May;195:168-175. doi: 10.1016/j.schres.2017.10.013. Epub 2017 Nov 2.


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 2.2g/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.

Keywords: Antipsychotics; Docosahexaenoic acid; Eicosapentaenoic acid; Magnetic resonance imaging; Neurodegeneration; Neuroprotection; Randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology*
  • Dietary Supplements
  • Docosahexaenoic Acids / therapeutic use*
  • Double-Blind Method
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Functional Laterality / drug effects
  • Gray Matter / diagnostic imaging
  • Gray Matter / drug effects*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Psychiatric Status Rating Scales
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / pathology*
  • Schizophrenia / therapy*
  • Young Adult


  • Antipsychotic Agents
  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids