Summary
Schizophrenia is a psychiatric disorder that is perhaps best known for episodes of psychosis. During these episodes, schizophrenic individuals lose touch with reality, often experiencing hallucinations and delusions, which can result in impulsive and aggressive behavior. Research has shown that persons with schizophrenia have reduced levels of omega-3 fatty acids EPA and DHA in their brains. Studies investigating DHA + EPA supplementation in persons with schizophrenia or at risk of its development report a positive impact on both psychiatric and physical symptoms.
 
Introduction
Schizophrenia symptoms
Schizophrenia is a psychiatric condition that can have a wide range of behavioral and cognitive symptoms, which may present themselves in different combinations per affected individual. These symptoms include hallucinations, delusions, lack of willpower, lack of capacity for emotion, but also impairments in cognitive skills such as logical thought, memory or speech. A well-known aspect of schizophrenia is the occurrence of psychoses. These are (temporary) states of being wherein schizophrenic individuals “lose their grip on reality”. During psychoses, schizophrenic individuals can display behavior such as agitation, aggressiveness, hostility and impulsivity. Needless to say, this often leads to dangerous health situations for the schizophrenic person and those around them. The initial occurrence of a psychotic state is called first-episode psychosis; the schizophrenic disorder starts to develop years prior to this. Next to these psychoses, persons with schizophrenia often suffer from cognitive dysfunctions,  depression and anxiety, which precede the first-episode psychosis and can impact their lives in very negative ways. Symptom severity assessment of schizophrenia is commonly done by means of the Positive and Negative Syndrome Scale or the MATRICS Cognitive Consensus Battery (MCCB). Psychological symptoms in schizophrenia are often assessed according to the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale or Montgomery–Asberg Depression Rating Scale. These scales are widely used in research trials studying schizophrenia, allowing for comparison of results between studies.
 
Cardiometabolic health in schizophrenia
In addition to the psychological effects of schizophrenia, individuals with this disorder have a reduced life expectancy of up to 10 years. This is mostly because of cardiometabolic conditions such as metabolic syndrome that are commonly seen in schizophrenia.
 
 
Treatment and diagnosis
Current treatment methods include antipsychotic medication and various forms of therapy, both of which are focused on management of schizophrenia rather than curing it. Around the turn of the century, criteria were determined for elevated risk of psychosis, referred to as ultra-high risk or at-risk mental state. These criteria are used as a tool to detect and prevent progression of psychotic symptoms into psychiatric disorders with psychotic episodes, such as schizophrenia, by means of preventative treatment.
 
Schizophrenia and DHA
Although the cause of schizophrenia remains unknown, scientific studies point out that DHA is involved in schizophrenia. Namely, research has shown that persons with psychiatric disorder typically have lower levels of DHA in their blood plasma, and that these low levels are associated with an increased risk of psychotic episodes. Following up on these findings, randomized clinical trials have been carried out where scientists sought to reduce risk and prevalence of psychotic episodes for schizophrenic persons with omega-3 fatty acid supplementation. Moreover, the connection between omega-3 fatty acids and cardiometabolic health in people with schizophrenia has been investigated as well. Findings from these studies can be found below.   
 
Research findings
In a longitudinal study that followed participants from birth throughout early adulthood, Mongan and colleagues investigated the relation between omega-3 fatty acids and psychotic disorders and episodes (Mongan et al., 2024). Data from 3635 participants collected at ages of 7, 15, 17, and 24 was used, though not every participant had data available for every time point. The collected data included participant’s blood plasma, as well as a score from a Psychosis-Like Symptoms Interview conducted at 24 years of age. This data was then used to investigate suspected connections between levels of omega-3 fatty acids in blood plasma and psychotic symptom/disorder status.  The authors found that a persistent high ratio of omega-6 to omega-3 fatty acids, as well as a persistent low level of DHA, was associated with an increased risk of psychotic episodes and psychotic disorder occurrence at age 24. Moreover, persistent low levels of DHA were associated with an increase in number of psychotic episodes and negative symptoms of psychotic disorders.
 
Robinson and collaborators set out to examine the effects of omega-3 supplementation in persons receiving antipsychotic medication (Risperidone) with current psychotic symptoms and schizophrenia or bipolar disorder (Robinson et al., 2019). A total of 46 persons with schizophrenia and 4 people with bipolar disorder aged 15-40 years participated in the randomized placebo-controlled trial. Participants were evenly divided into two groups and received either a placebo (corn/soybean oil blend) or 740mg EPA + 400mg DHA per day, for a period of 16 weeks. Every participant received the antipsychotic medicine Risperidone throughout the study. Half the participants took Lorazepam (medication given to, among others, treat anxiety) before the onset of the study and were allowed to continue this treatment. The authors conducted the Brief Psychiatric Rating Scale (BPRS) at the beginning and end of the study to assess presence and severity of schizophrenic psychological symptoms such as depression and anxiety. It was found that there was a trend towards greater improvement in BRPS scores following EPA + DHA supplementation compared to the placebo group, though this was not significant. Then, the authors conducted a sub-group analysis comparing participants who took Lorazepam to those who did not. Interestingly, it was found that EPA + DHA supplementation caused a significant improvement in the BRPS score in participants who did not take Lorazepam, signified by a decrease in depression-anxiety in this group. Therefore, the authors concluded that supplementation with EPA and DHA can reduce psychological symptoms in persons with schizophrenia.
 
Szeszko and colleagues set out to investigate the effect of omega-3 fatty acid supplementation in persons with a recent psychotic episode and treated with the antipsychotic medicine Risperidone (Szeszko et al., 2021). They used data from a clinical trial by Robinson and collaborators (Robinson et al., 2019). In this study, a group of men and women with recent onset-psychosis on Risperidone treatment was randomly divided into two groups and given either EPA + DHA or a placebo for a period of 16 weeks. The fish oil group received 740mg EPA + 400mg DHA per day next to the Risperidone treatment, the placebo group received a soybean/corn oil blend in addition to their Risperidone treatment. At the start and end of the 16 week supplementation period, levels of omega-3 and omega-6 fatty acids in red blood cells were assessed. Furthermore, two types of psychological assessments were conducted at the beginning and end of the study: the MATRICS Cognitive Consensus Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS). The MCCB tests cognitive capacities such as learning capability, memory, reasoning and social cognition, all of which can be affected in schizophrenia. The BPRS is a scale to determine the presence and severity of psychiatric symptoms commonly present in schizophrenia such as depression, anxiety and psychotic episodes. Szeszko and colleagues investigated the data of these psychological assessments and omega-3 / omega-6 levels in red blood cells to determine if there were any connections. This way, they aimed to establish if EPA + DHA supplementation influences treatment effect of Risperidone in recent-onset psychosis patients. They found that higher levels of EPA and DHA at the baseline correlated with a better social cognition score. Accordingly, the EPA + DHA supplementation group showed a greater increase in social cognition scores compared to the placebo group after 16 weeks. Crucially, the DHA levels in red blood cells had a significant positive correlation with social cognition scores at 16 weeks. A trend towards a greater improvement on the BPRS score was also found for the supplementation group, though this was not significant. The authors concluded that omega-3 fatty acids, especially DHA, have a positive effect on social cognition in recent-onset psychosis patients given Risperidone treatment.
 
In a follow-up study on their previous trial on omega-3 supplementation in persons at risk of developing psychotic disorders, Amminger and colleagues investigated progression to psychotic disorders and psychiatric symptoms in the original participant groups (Amminger et al., 2015). A total of 81 participants aged 13-25 and at ultra-high risk of psychosis were divided into two groups of 40 and 41, respectively receiving 700mg EPA + 480mg DHA or a placebo (coconut oil in a capsule) every day for 12 weeks. In their original study they reported that at 12 months after the supplementation period, 4.9% of the participants progressed to a psychotic disorder, compared to 27.5% in the placebo group (Amminger et al., 2010). In this follow-up study, 16 out of 40 participants (40%) in the placebo group compared to a psychotic disorder 7 years after the supplementation period, 13 of these cases were a type of schizophrenia. In stark contrast, 4 out of 41 participants (9.8%) of the EPA+DHA group progressed to a psychotic disorder, a type of schizophrenia in every case. In agreement with this finding, antipsychotic medication prescription rate was significantly lower in the omega-3 supplementation group. Moreover, the prevalence of psychiatric symptoms was significantly reduced in the omega-3 supplementation group compared to the placebo group, based on scores from the Positive and Negative Syndrome Scale and Montgomery–Asberg Depression Rating Scale. The authors concluded that omega-3 supplementation has a long-lasting positive effect in this study cohort by reducing psychiatric symptoms and prevalence of psychotic disorder progression.
 
Conclusion
Schizophrenia can be a devastating psychiatric disorder for the person with this condition and those around them, such as during psychotic episodes. No cure for this disorder exists, current therapy and pharmacological treatment options are focused on management of the disorder and prevention of psychotic episodes. Research highlights the importance of DHA in schizophrenia, it is reported that persons with schizophrenia often have lower levels of DHA. This is emphasized by the increased risk of psychotic episodes in young adults with low circulating DHA levels.
Accordingly, giving EPA + DHA supplementation to persons with schizophrenia who take the antipsychotic Risperidone improves social cognition, which is often negatively affected in schizophrenia. Persons with schizophrenia who take Risperidone but not the anti-anxiety medication Lorazepam benefit from EPA + DHA supplementation as well; a decrease in anxiety-depression scores as a result of supplementation with EPA + DHA has been proven. The most striking evidence for the positive role of EPA and DHA has perhaps come from Amminger and colleagues. They showed that giving EPA + DHA supplementation to persons at risk of developing psychotic disorders such as schizophrenia is an effective way to reduce prevalence of psychotic symptoms and progression to psychotic disorders.
Finally, treatment with EPA and DHA is proven to have a positive impact on the cardiometabolic health of men and women with schizophrenia by reducing the risk of developing metabolic syndrome.
DHA has also been found to play a positive role in cardiovascular symptoms associated with schizophrenia. To read more, click here to visit healthDHA’s cardiovascular theme page.
 
References
Amminger, G. P., Schäfer, M. R., Papageorgiou, K., Klier, C. M., Cotton, S. M., Harrigan, S. M., Mackinnon, A., McGorry, P. D., & Berger, G. E. (2010). Long-Chain ω-3 Fatty Acids for Indicated Prevention of Psychotic Disorders: A Randomized, Placebo-Controlled Trial. Archives of General Psychiatry, 67(2), 146–154. https://doi.org/10.1001/archgenpsychiatry.2009.192
 
Amminger, G. P., Schäfer, M. R., Schlögelhofer, M., Klier, C. M., & McGorry, P. D. (2015). Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nature Communications, 6(1), 7934. https://doi.org/10.1038/ncomms8934
 
Mongan, D., Perry, B. I., Healy, C., Susai, S. R., Zammit, S., Cannon, M., & Cotter, D. R. (2024). Longitudinal Trajectories of Plasma Polyunsaturated Fatty Acids and Associations With Psychosis Spectrum Outcomes in Early Adulthood. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2024.04.004
 
Pawełczyk, T., Grancow-Grabka, M., Żurner, N., & Pawełczyk, A. (2021). Omega-3 fatty acids reduce cardiometabolic risk in first-episode schizophrenia patients treated with antipsychotics: Findings from the OFFER randomized controlled study. Schizophrenia Research, 230, 61–68. https://doi.org/10.1016/j.schres.2021.02.012
 
Robinson, D. G., Gallego, J. A., John, M., Hanna, L. A., Zhang, J.-P., Birnbaum, M. L., Greenberg, J., Nariane, M., Peters, B., McNamara, R. K., Malhotra, A. K., & Szeszko, P. R. (2019). A Potential Role for Adjunctive Omega-3 Polyunsaturated Fatty Acids for Depression and Anxiety Symptoms in Recent Onset Psychosis: Results from a 16 Week Randomized Placebo-Controlled Trial for Participants Concurrently Treated With Risperidone. Schizophrenia Research, 204, 295–303. https://doi.org/10.1016/j.schres.2018.09.006
 
Szeszko, P. R., McNamara, R. K., Gallego, J. A., Malhotra, A. K., Govindarajulu, U., Peters, B. D., & Robinson, D. G. (2021). LONGITUDINAL INVESTIGATION OF THE RELATIONSHIP BETWEEN OMEGA-3 POLYUNSATURATED FATTY ACIDS AND NEUROPSYCHOLOGICAL FUNCTIONING IN RECENT-ONSET PSYCHOSIS: A RANDOMIZED CLINICAL TRIAL. Schizophrenia Research, 228, 180–187. https://doi.org/10.1016/j.schres.2020.11.050
 
Taha, A. Y., Cheon, Y., Ma, K., Rapoport, S. I., & Rao, J. S. (2013). Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients. Journal of Psychiatric Research, 47(5), 636–643. https://doi.org/10.1016/j.jpsychires.2013.01.016