The Australian Doctorby Clare Pain28 November, 2016Leading psychiatrist Professor Patrick McGorry’s hopes that fish oil may protect young people from developing psychosis have proved to be unfounded. In a follow-up study of more than 300 young people at high risk of psychosis, omega-3 polyunsaturated fatty acid supplements were no better than placebo in reducing transition to psychosis.
The multinational study led by Professor McGorry failed to replicate preliminary findings from a 2010 trial in 81 patients that had shown fish oil could prevent transition to psychosis among young people who took supplements for 12 weeks. At the time, Professor McGorry, executive director of Orygen, the National Centre of Excellence in Youth Mental Health, described the results as "almost too good to be true".
Nevertheless, he suggested that clinicians considered using fish oil supplementation without waiting for further trial results, and included them as an appropriate treatment recommendation in Orygen’s Australian Clinical Guidelines for Early Psychosis. However, Professor McGorry and co-researchers conceded that the new trial had “clearly failed to replicate the findings of the original”. Low rates of transition to psychosis in the new trial may have made it difficult to show a beneficial effect of omega-3 fatty acids above and beyond the background treatments such as CBT and antidepressants, Professor McGorry said.
Commenting on the finding, Professor David Castle, Chair of Psychiatry at St Vincent’s Health and the University of Melbourne, said it was what he had expecting. “I always found the original paper very difficult to accept as the final word on [prevention of psychosis with fish oil]. The proof of science is in replication," he told Australian Doctor. "There is a complete inability to change rates of conversion [to psychosis] using any intervention. Nobody has proved anything works," he added. The failure of the fish oil trial is a further setback for Professor McGorry’s push for early interventions to prevent psychosis.
In 2011, a planned trial of antipsychotics as preventive therapy against psychosis in young people was abandoned, before it was started. And in June 2016, the Federal Government announced it would phase out funding of seven Early Psychosis Youth Services run by Headspace, of which Professor McGorry is a board member. Professor McGorry has been contacted for comment
by Morrison AP, French P, Stewart SL, Birchwood M, Fowler D, Gumley AI, Jones PB, Bentall RP, Lewis SW, Murray GK, Patterson P, Brunet K, Conroy J, Parker S, Reilly T, Byrne R, Davies LM, Dunn G.British Medical Journal. 2012 Apr 5;344
OBJECTIVE: To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia.DESIGN: Multisite single blind randomised controlled trial.SETTING: Diverse services at five UK sites.PARTICIPANTS: 288 participants aged 14-35 years [mean 20.74, SD 4.34 years] at high riskof psychosis: 144 were assigned to cognitive therapy plus monitoring of mental state and 144 to monitoring of mental state only. Participants were followed-up for a minimum of 12 months and a maximum of 24 months.INTERVENTION: Cognitive therapy [up to 26 [mean 9.1] sessions over six months] plus monitoring of mental state compared with monitoring of mental state only.MAIN OUTCOME MEASURES: Primary outcome was scores on the comprehensive assessment of at risk mental states [CAARMS], which provides a dichotomous transition to psychosis score and ordinal scores for severity of psychotic symptoms and distress. Secondary outcomes included emotional dysfunction and quality of life.RESULTS: Transition to psychosis based on intention to treat was analysed using discrete time survival models. Overall, the prevalence of transition was lower than expected [23/288; 8%], with no significant difference between the two groups [proportional odds ratio 0.73, 95% confidence interval 0.32 to 1.68]. Changes in severity of symptoms and distress, as well as secondary outcomes, were analysed using random effects regression [analysis of covariance] adjusted for site and baseline symptoms. Distress from psychotic symptoms did not differ [estimated difference at 12 months -3.00, 95% confidence interval -6.95 to 0.94] but their severity was significantly reduced in the group assigned to cognitive therapy [estimated between group effect size at 12 months -3.67, -6.71 to -0.64, P=0.018].CONCLUSIONS: Cognitive therapy plus monitoring did not significantly reduce transition to psychosis or symptom related distress but reduced the severity of psychotic symptoms in young people at high risk. Most participants in both groups improved over time. The results have important implications for the at risk mental state concept.
by Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, and McGorry PD.Nature Communication. 2015 6:7934.
Long-chain omega-3 polyunsaturated fatty acids (PUFAs) are essential for neural development and function. As key components of brain tissue, omega-3 PUFAs play critical roles in brain development and function, and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan, including schizophrenia. We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo. We have now completed a longer-term follow-up of this randomized, double-blind, placebo-controlled trial, at a median of 6.7 years. Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study. The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow-up.
The multinational study led by Professor McGorry failed to replicate preliminary findings from a 2010 trial in 81 patients that had shown fish oil could prevent transition to psychosis among young people who took supplements for 12 weeks.
Translational Medicine is a rapidly growing discipline in biomedical research and aims to expedite the discovery of new diagnostic tools and treatments by using a multi-disciplinary, highly collaborative, "bench-to-bedside" approach.
… and what’s wrong with it. If there is a prepsychotic personality [and I happen to think there might be], obviously the current criteria to define it are not ready for prime time. And the rationales for either CBT or Fish Oil as preventive treatments are based mostly on speculations. Like much of our modern research, they were in a hurry to hit a home run and were not paying enough attention to simply getting on first base. Our recently departed NIMH Director, Tom Insel, was a Translational Medicine aficionado, requiring NIMH grants to be Translational, establishing Translational Centers all over the country. And he left behind a string of fly balls that never made it over the fence. I’m afraid that these efforts have the same fate.
:{ -how disappointing!
Hello all,
As usual I am helicoptering into Mickey’s blog while on the lam between teaching classes, so I’ll be brief here.
The October 2016 issue of The American Journal of Psychiatry contains some interesting articles on the efforts to identify psychosis-proneness. I’ll let all of you make your own judgments about the new claims.
On both Researchgate and Academia.edu I have posted the manuscript of a book chapter on “Psychosis” that will appear in a few months in Greg Eghigian’s The Routledge History of Madness and Mental Health. It is sort of a “keyword” approach to “psychosis,” geared mainly to those in the humanities. However, a guiding thread in my chapter is this very issue of how problematic making determinations of “latent” or “prodromal” or “attenuated” or “proneness” can be, and I broaden my criticisms with some tentative ideas from the anthropological literature. Here is the Academia link to the manuscript::
https://www.academia.edu/13557839/Psychosis._In_Greg_Eghigian_ed._The_Routledge_History_of_Madness_and_Mental_Health_forthcoming_January_2017_
To Sally: it may be disappointing but not surprising.
Dr. Mickey emphasized “they were in a hurry to hit a home run and were not paying enough attention to simply getting on first base.” The Nobel Prize winner Peter Medawar taught us that research is the art of the soluble. The PUFA and the CBT efforts against transition to psychosis are so speculative that there was little chance they would pan out. But they do a lot for the careerism of the investigators….
Have you looked at the study on prenatal supplementation with choline? Their claims are much more modest, and the babies and children they have studied so far aren’t anywhere near the age when they would develop psychosis.
It isn’t anywhere near prime time, but if the risks were negligible and a woman had a strong family history it might not be a bad thing to do – even if it weren’t appropriate to recommend it routinely (i.e. not the level of evidence for widespread folic acid supplementation during pregnancy to prevent neural tube defects).
Initial Paper
Follow up at 40 months
Thoughts?
Initial Paper
East Coaster
Neither link made it through.
Thanks for commenting. Interesting chapter.
I don’t know the etiology of “schizophrenia” or if there even is a “schizophrenia” to have an etiology. But it does strike me that within that matrix of cases, there is a group that follow a monotonous syndromatic course. The various attempts at defining a prepsychotic “type” often go for crazy-ish thinking. I think if I were to take a shot at it, I’d look at the more primary, less dramatic symptoms:
Mickey,
Do you mean that the person’s ability for abstract thought becomes more diminished in a type of prodromol period, or do you mean they always had a relatively disminish ability for abstract thinking?
I don’t know the answer to that, but I think it’s a good question. Since Bleuler, the cognitive difficulty with abstractin has been known as a hallmark of the picture. I’ve always wondered if that might be primary. The psychotic ideas are dramatic and have always been the focus of attention, but I wonder if they’re not the consequences of a more fundamental cognitive deficit. Speculations of an old man…
Mickey that’s weird. At another eclectic web magazine (aka a blog) I frequent, html tags do work.
Slightly less elegant:
They were trying to improve cerebral inhibition in babies and young children.
1st paper
http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.12070940
2nd paper 40 months later
http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2015.15091188?trendmd-shared=0
“The PUFA and the CBT efforts against transition to psychosis are so speculative that there was little chance they would pan out. But they do a lot for the careerism of the investigators….”
I have no idea anyone would think treatment would work all that well for the mostly negative symptoms in the prodromal phase (that they can’t really define) when it doesn’t work all that well for negative symptoms in the florid stage.
But what do I know, I don’t even have an honorarium…