Thread by @FeliceJacka

@dnunan79 @ellenfallows Lots to discuss here and I'd strongly welcome input. Will address qs and issues in a thread here:
SMILES was the only RCT conducted in a depressed population included in our recent meta-analysis (ncbi.nlm.nih.gov/pubmed/30720698)

@dnunan79 @ellenfallows Findings are consistent with the observational evidence (e.g. ncbi.nlm.nih.gov/pubmed/30254236)

@dnunan79 @ellenfallows Plenty of limitations (I’ll put links to papers at the end)

1. Small sample size. We’d hoped/intended to recruit nearly 170 and managed less than n=70 after three years of trying. A shoe-string budget didn’t help

@dnunan79 @ellenfallows 2. Participants not blinded to their condition (diet support or social support). We kept the assessors blinded, but people obvs knew what condition they were receiving. Those in the social support condition were more likely to drop out
3. Expectation bias is an obvious issue here

@dnunan79 @ellenfallows An RCT that was completed after SMILES, the HELFIMED study, was superior in many ways. They were adequately powered and used a group-based approach (the diet workshops had also been piloted extensively in people with SMI).

@dnunan79 @ellenfallows In that study, both the diet groups and the social groups were popular, so they had less of an issue with drop-outs. The problem with theirs from a scientific perspective was that they also gave N3 supps, which muddied the waters and meant it wasn’t included in our meta-analysis

@dnunan79 @ellenfallows In support of a ‘real’ impact however:
Both studies showed a close correlation between the degree of dietary change and the degree of improvement in depression scores (and the fact that people could and did improve their dietary intakes quite substantially was very encouraging)

@dnunan79 @ellenfallows Both studies showed evidence of high cost-effectiveness. I think that this is critical. In our SMILES trial, there was an average cost saving of roughly $3k per participant in the diet group comp to the social support group.

@dnunan79 @ellenfallows Savings arose from people losing less ‘time out of role’ and from fewer visits to health professionals. The HE evaluation of HELFIMED also showed that it was a very cost-effective approach to treatment (links all to come)

@dnunan79 @ellenfallows So the big problems to solve are around expectation bias and blinding. We have no reason to think that one form of ‘healthy’ diet is superior to another so comparing two different diets is challenging. (And we can’t randomise people to an unhealthy diet)

@dnunan79 @ellenfallows We need to collect data and better data on biomarkers - blood and gut microbiota in particular - in order to get insights into mechanistic pathways.

@dnunan79 @ellenfallows We need funds - it’s been very very challenging to get funding and it is a challenge we continue to face here in Australia with a desperate dearth of funding for medical research.

@dnunan79 @ellenfallows Our @foodmoodcentre immediate plans/applications focus on:
1. An online RCT that we are developing and piloting where we hope to be able to address the expectation bias issue
2. A large-scale pragmatic trial in primary care in Australia.

@dnunan79 @ellenfallows @foodmoodcentre The arguments for a scaled pragmatic trial, where people with depression are randomly assigned to TAU (psychological support through Medicare) or dietetics support (in addition to meds if wanted/warranted), are strong:

@dnunan79 @ellenfallows @foodmoodcentre Depression and chronic (diet-related) disease are highly comorbid and mutually reinforcing, with many common pathways including aberrant immune function and metabolism - both strongly influenced by diet quality.

@dnunan79 @ellenfallows @foodmoodcentre Moreover, in extensive animal experiments (and now human correlational studies), diet influences brain plasticity and brain health.

@dnunan79 @ellenfallows @foodmoodcentre We have good evidence of cost-effectiveness. Depression and chronic disease cost the economy billions every year. Tackling both through a Lifestyle Med approach offers the potential for massive cost-savings, quite apart from benefits to patients.

@dnunan79 @ellenfallows @foodmoodcentre Moreover, the RANZCP clinical guidelines for Mood Disorders in Australia have Lifestyle Med as step zero, yet this is not routinely implemented. (We're running some online training, with more to come)

@dnunan79 @ellenfallows @foodmoodcentre I and many of my colleagues strongly believe that we should be immediately routinely implementing Lifestyle Med as a fundamental of care across mental health conditions, as recommended in the recent Lancet Psychiatry Commission Report.

@dnunan79 @ellenfallows @foodmoodcentre There are demonstrable benefits of diet and exercise for physical health as well as mental and brain health, including cognition. The drastically shortened lifespan in those with SMI is largely down to chronic disease

@dnunan79 @ellenfallows @foodmoodcentre - we shouldn’t wait until people are obese or have cardiac/diabetes before implementing lifestyle support. It should be the stepping off point for treatment.

@dnunan79 @ellenfallows @foodmoodcentre It’s worth pointing to a new small RCT that found similar encouraging results in young people - again on a shoe-string budget:

journals.plos.org/plosone/articl…

@dnunan79 @ellenfallows @foodmoodcentre It would be wonderful if all the clever methods and dietetics people out there on Twitter such as yourself and ( will tag a few for good luck) would jump in with ideas and thoughts suggestions for advancing and improving the science in Nutritional Psychiatry going forward!

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan Links to papers: bmcmedicine.biomedcentral.com/articles/10.11…
(SMILES)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan tandfonline.com/doi/full/10.10…
(HELFIMED)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan ncbi.nlm.nih.gov/pubmed/29783983
(Chatterton Economic Evaluation of SMILES)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan tandfonline.com/doi/full/10.10…
(Economic Evaluation HELFIMED)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan bmcmedicine.biomedcentral.com/articles/10.11…
Diet and brain plasticity humans

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan sciencedirect.com/science/articl… (another diet and brain plasticity paper)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan n.neurology.org/content/early/… (another one)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan n.neurology.org/content/early/…

(the Rotterdam study)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan ncbi.nlm.nih.gov/pmc/articles/P… (animal experiments)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan ncbi.nlm.nih.gov/pubmed/26643054

(RANZCP Clinical Guidelines for Mood Disorders)

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan thelancet.com/journals/lanps…

Lancet Psych commission

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan thelancet.com/article/S2352-…

A review of mine on the topic

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan Finally, a more recent one: ncbi.nlm.nih.gov/pubmed/28942748

Sorry for the endless thread - I really do want input and I'm stuck at home in sickbed with more time than usual, so this seemed like a good opportunity! Value your thoughts

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan Whoops - posted it twice sorry

@dnunan79 @ellenfallows @foodmoodcentre @KCKlatt @kevinnbass @ProfWhelan Actually, my final points would be: Poor diet now leading contributor to illness and early death globally (GBD study) and mental disorders leading cause of disability. The fact that they're linked has potentially very large implications for prevention, public health & treatment