{"id":69298,"date":"2016-12-01T12:00:10","date_gmt":"2016-12-01T17:00:10","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=69298"},"modified":"2016-12-01T11:58:41","modified_gmt":"2016-12-01T16:58:41","slug":"in-the-realm-of-hypothesis","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/12\/01\/in-the-realm-of-hypothesis\/","title":{"rendered":"in the realm of hypothesis…"},"content":{"rendered":"
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Hopes of preventing psychosis with fish oil flounders: study<\/a><\/div>\n
The Australian Doctor<\/font><\/strong><\/div>\n
by Clare Pain<\/div>\n
28 November, 2016<\/div>\n

Leading 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.<\/p>\n

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".<\/p>\n

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.<\/p>\n

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.<\/p>\n

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<\/div>\n<\/blockquote>\n
Over a century ago, Eugen Bleuler described a premorbid personality type [the Schizoid Personality] seen in many [but not all] patients who developed Schizophrenia. Since then, the hope for heading off a psychotic decompensations has rested in identifying the at risk population in advance. A few years back, there was much excitement about identifying patients at risk for psychosis in advance. Both Patrick McGorry’s group in Australia and Anthony Morrison’sand colleagues in the UK had reported success in defining a prepsychotic personality profile and were working on interventions that appeared to decrease the conversion rates. But Morrison’s definitive study was negative: <\/div>\n
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Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial.<\/a><\/div>\n
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.<\/div>\n
British Medical Journal<\/font><\/strong>. 2012 Apr 5;344 <\/div>\n
[full text on-line<\/font><\/u><\/a><\/strong>]<\/div>\n

<\/p>\n

OBJECTIVE<\/font><\/strong>: 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.<\/div>\n
DESIGN<\/font><\/u><\/strong>: Multisite single blind randomised controlled trial.<\/div>\n
SETTING<\/font><\/strong><\/u>: Diverse services at five UK sites.<\/div>\n
PARTICIPANTS<\/font><\/strong><\/u>: 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.<\/div>\n
INTERVENTION<\/font><\/strong><\/u>: Cognitive therapy [up to 26 [mean 9.1] sessions over six months] plus monitoring of mental state compared with monitoring of mental state only.<\/div>\n
MAIN OUTCOME MEASURES<\/font><\/strong><\/u>: 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.<\/div>\n
RESULTS<\/font><\/strong><\/u>: 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].<\/div>\n
CONCLUSIONS<\/font><\/strong><\/u>: 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.<\/div>\n
<\/div>\n<\/blockquote>\n
While a smaller study of the fish oil treatment was reported as successful…<\/div>\n
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Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study.<\/a><\/div>\n
by Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, and McGorry PD.<\/div>\n
Nature Communication<\/font><\/strong>. 2015 6:7934.<\/div>\n
[full text on-line<\/font><\/a>]<\/div>\n

<\/p>\n

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.<\/div>\n<\/blockquote>\n
…however, in the report in the The Australian Doctor<\/font><\/strong>, Dr. McGorry announced that the definitive study did not confirm those results:<\/div>\n
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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.<\/div>\n<\/blockquote>\n
In both instances, the larger clinical trials failed to replicate not only the success in preventing psychosis, but also the validity of the target population selection criteria<\/font><\/strong><\/em>. These were both large clinical trials with a lot riding on the results. In the Australian effort, early detection programs were already in place [now being un<\/em><\/font>funded<\/font><\/em>]. While it’s always easy to criticize failed research in retrospect, in this case it’s important to take a careful look at what happened with both the CBT and Fish Oil Clinical Trials. In my opinion, they are both examples of Translational Medicine<\/font><\/em>… <\/div>\n
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Translational Medicine<\/font><\/strong><\/em> 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.<\/div>\n<\/blockquote>\n

… 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<\/font><\/em>. 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<\/font><\/em>, requiring NIMH grants to be Translational<\/font><\/em>, establishing Translational<\/font><\/em> 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.<\/p>\n

In this case, it would seem a better use of our research funds and talent to continue to work on defining and characterizing the prepsychotic personality’s clinical characteristics using case studies, epidemiology, psychometric techniques, etc – basic research aiming towards finding a more reliable set of criteria. The existence of such a clinical entity itself still remains in the realm of hypothesis at this point.<\/div>\n","protected":false},"excerpt":{"rendered":"

Hopes of preventing psychosis with fish oil flounders: study The Australian Doctor by Clare Pain 28 November, 2016 Leading 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 […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-69298","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/69298","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=69298"}],"version-history":[{"count":18,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/69298\/revisions"}],"predecessor-version":[{"id":69316,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/69298\/revisions\/69316"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=69298"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=69298"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=69298"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}