Saturday, 28 May 2016

Urban neighbourhood, food and risk of psychosis?

It's another research mash-up today as I bring to your attention two papers talking about potential correlates associated with psychosis and/or psychotic symptoms.

First up are the findings reported by Joanne Newbury and colleagues [1] (open-access here) who observed that urban residency and certain factors associated with urban residency might link into a higher risk of childhood psychotic symptoms. A second paper by Tomasz Pawełczyk and colleagues [2] provides some further food for thought and the suggestion that "dietary patterns of PUFA [polyunsaturated fatty acidsconsumption may play a role in the conversion to psychosis of HR [ultra high-risk] individuals."

Newbury et al report findings from the Environmental Risk (E-Risk) Longitudinal Twin Study and specifically the idea of "whether specific features of urban neighborhoods increase children's risk for psychotic symptoms." Aside from finding a potential association between urban residency at aged 5 and aged 12 and psychotic symptoms at aged 12, researchers also suggested that: "Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders."

Pawełczyk et al continued a research theme suggesting that what we do or do not eat might have implications for some with regards to transition to psychosis (see here). Focusing specifically on a group of HR individuals, they looked at the diet of those who did and did not transition into psychosis. They reported: "C-HR [converted into psychosis] individuals reported significantly higher consumption of n-6 fatty acids (linoleic acid, LA and arachidonic acid, AA) in comparison with individuals who did not develop psychosis (NC-HR)."

Although not seemingly covering the same factors when it comes to psychosis/psychotic symptoms, one of the things that I thought might also unite both these findings is food. Yes, Pawełczyk et al already talk about food (albeit based on the warts and all use of "a validated Food-Frequency Questionnaire") but the Newbury paper might also include a food element insofar as what types of food might be more readily available and eaten in urban vs. not-so-urban environments.

Bearing in mind that sweeping generalisations about food availability and importantly, what types of food are available depending on where one lives, are not required, I would like to suggest that spatial patterning of say, supermarkets vs. fast food outlets might be something that could potentially unite results. The paper by Lamichhane and colleagues [3] for example found that: "the availability of supermarkets and fast food outlets differed significantly by neighborhood characteristics; neighborhoods with supermarkets and with fast food outlets were significantly higher in socio-economic status." Research looking at the causes and/or drivers of obesity have tended to predominate in the area of how neighbourhood might influence eating patterns [4] but similar modelling could be done with more psychiatric outcomes in mind. Indeed to quote Newbury et al: "Neighborhood-level physical exposures such as noise, light, and air pollution, as well as exposure to viral infections warrant research in relation to early psychotic symptoms." Who says that food should not also be included?

I don't want to gloss over just how complicated the factors might be bringing someone to clinically relevant psychotic symptoms nor to say that food is somehow the 'missing' element for all cases. But it's not outside of the realms of possibility that in these days of nutritional psychiatry, food might exert an important effect for some people and food availability (certain food availability) could be one factor contributing to the idea that where you live might affect your risk of psychosis...

And if that wasn't enough speculating, how about sweeping generalisations about maternal smoking habits and prenatal nicotine exposure as a risk factor for psychosis+ [5] as something else potentially linked to urban living?

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[1] Newbury J. et al. Why are Children in Urban Neighborhoods at Increased Risk for Psychotic Symptoms? Findings From a UK Longitudinal Cohort Study. Schizophr Bull. 2016 May 6. pii: sbw052.

[2] Pawełczyk T. et al. The association between polyunsaturated fatty acid consumption and the transition to psychosis in ultra-high risk individuals. Prostaglandins Leukot Essent Fatty Acids. 2016 May;108:30-7.

[3] Lamichhane AP. et al. Spatial patterning of supermarkets and fast food outlets with respect to neighborhood characteristics. Health & place. 2013;23:10.1016/j.healthplace.2013.07.002.

[4] Macdonald L. et al. Neighbourhood fast food environment and area deprivation—substitution or concentration? Appetite. 2007; 49: 251-254.

[5] Niemelä S. et al. Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort. American Journal of Psychiatry. 2016. May 24.

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ResearchBlogging.org Pawełczyk, T., Trafalska, E., Kotlicka-Antczak, M., & Pawełczyk, A. (2016). The association between polyunsaturated fatty acid consumption and the transition to psychosis in ultra-high risk individuals Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 108, 30-37 DOI: 10.1016/j.plefa.2016.03.010




ResearchBlogging.org Newbury J, Arseneault L, Caspi A, Moffitt TE, Odgers CL, & Fisher HL (2016). Why are Children in Urban Neighborhoods at Increased Risk for Psychotic Symptoms? Findings From a UK Longitudinal Cohort Study. Schizophrenia bulletin PMID: 27153864

Friday, 27 May 2016

Wandering and autism continued... yet again

I know that I'm probably starting to sound like a broken record on the topic of wandering (elopement) and autism on this blog (see here and see here and see here) but I am yet again going to briefly talk about peer-reviewed research in this area simply because it's just too damned important not to.

This time around the results from Catherine Rice and colleagues [1] are the source of my musings and the conclusion that: "wandering among children with ASD [autism spectrum disorder], regardless of intellectual disability status, is relatively common." Based on the analysis of data from The Survey of Pathways to Diagnosis and Services (SPDS) initiative, where specific questions about 'wandering and wandering prevention' are asked (see page 29) researchers reported that: "For children with special healthcare needs diagnosed with either ASD, intellectual disability, or both, wandering or becoming lost during the previous year was reported for more than 1 in 4 children." A diagnosis of ASD seemed to be a key factor in the frequency of wandering, where those with additional learning disability were the most likely to wander (37% of the sample) and figures for those without intellectual disability came in at about 32%.

As per previous occasions when I've blogged about this topic, the differences (kingdoms) that might divide various groups/people when it comes to autism tend to take second place when it comes to tackling this issue and preventing (yes, preventing) wandering from turning into something rather more ominous. After all, there are a range of measures that can be employed to reduce the frequency of wandering/elopement and, if and when it does happen, reduce the probability of 'adverse outcomes' for the wanderer. First and foremost I would say, is for more people to take note of actual accounts about wandering as per those discussed by Solomon and Lawlor [2] for example. One can learn a lot about the circumstances around why wandering occurs and the different types of wandering (including the issue of bolting) from listening to parent and caregiver accounts. They are the experts on their own children and no doubt some of those accounts might generalise to more than just one child.

Next up are the various instruments that could be used to help find wanderers in a timely fashion. I'm thinking specifically about technology such as GPS trackers and the need for science to provide some further insight into the effectiveness of such items and what needs to be done to improve their effectiveness. I appreciate that 'tracking people' might have implications for things like civil liberties but just remember that the mobile (cell) phone you're carrying might not also be bad at telling others where you are. Improving autism awareness among first responders such as police and related agencies may also help them in their efforts if and when wandering becomes an issue.

Finally and bearing in mind that 'if you've met one person with autism, you've met one autistic person' (or words to that effect) is the importance of teaching things like road and water safety to those on the autism spectrum. I appreciate that the concept of 'danger' might not be something easily taught to some children and communication issues can be barriers to effective teaching. But, one should not assume that it is impossible to do [2], alongside the strategies for making lessons like swimming classes for example 'fun' as well as potentially lifesaving. And yes, swimming lessons can be particularly fun for many children on the autism spectrum [3].

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[1] Rice CE. et al. Reported Wandering Behavior among Children with Autism Spectrum Disorder and/or Intellectual Disability. J Pediatr. 2016 May 2. pii: S0022-3476(16)00428-5.

[2] Call NA. et al. Clinical outcomes of behavioral treatments for elopement in individuals with autism spectrum disorder and other developmental disabilities. Autism. 2016 May 12. pii: 1362361316644732.

[3] Eversole M. et al. Leisure Activity Enjoyment of Children with Autism Spectrum Disorders. J Autism Dev Disord. 2016 Jan;46(1):10-20.

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ResearchBlogging.org Rice, C., Zablotsky, B., Avila, R., Colpe, L., Schieve, L., Pringle, B., & Blumberg, S. (2016). Reported Wandering Behavior among Children with Autism Spectrum Disorder and/or Intellectual Disability The Journal of Pediatrics DOI: 10.1016/j.jpeds.2016.03.047

Thursday, 26 May 2016

CRISPR-Cas9 and autism research

If you feel brave enough, today I will direct your reading attention to the paper by Michael Williams and colleagues [1] detailing the application of a particularly important genome editing technique called CRISPR-Cas9 [2] to autism-related science.

Titled: "A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons" the Williams paper probably won't win any awards for plain English but don't be fooled about just how important this paper might be in the grand era of 'we can edit genomes' and how this might translate into modelling particular types of autism or genetic issues linked to autism in mice or other animals for example.

I really wish that I could say I was an expert on CRISPR-Cas9 and understood every detail included in the Williams paper but alas, I'm not and I didn't. Bearing in mind my non-expertise ('a cobbler should stick to his last') I did want to include it on this blog given the excitement in this area. Take my observations however, with a large pinch of salt...

So a definition of CRISPR [clustered regularly interspaced short palindromic repeats] -Cas9 - well, I don't want to reinvent the wheel so I'll use that offered in reference [2] with full credit given to the writer (Steph Yin): "Here’s how CRISPR/Cas works in bacteria: When bacteria encounter an invading source of DNA, such as from a virus, they can copy and incorporate segments of the foreign DNA into their genome as “spacers” between the short DNA repeats in CRISPR. These spacers enhance the bacteria’s immune response by providing a template for RNA molecules to quickly identify and target the same DNA sequence in the event of future viral infections. If the RNA molecules recognize an incoming sequence of foreign DNA, they guide the CRISPR complex to that sequence. There, the bacteria’s Cas proteins, which are specialized for cutting DNA, splice and disable the invading gene." The application of this process outside of just bacteria was subsequently recognised and a 'gene editing tool' was eventually born whereby a CRISPR-Cas9 system could replace any gene sequence.

Clear as mud right?

Well, Williams et al add to a small but emerging peer-reviewed research base at the time of writing suggesting that CRISPR-Cas9 might provide some important insights into at least 'some' autism. Their particular idea was to "mimic nonsense PTEN mutations from autism patients in developing mouse neurons" on the back of some previous research suggesting that various genetic issues with PTEN might be present in some autism [2]. Nonsense mutation by the way, normally ends in 'nonfunctional proteins' based on the knowledge that [some] genes provide the template to make proteins.

To achieve such mutations in PTEN authors used "retroviral implementation of the CRISPR-Cas9 system" where engineered retroviruses were purposed to deliver something mimicking a genetic mutation previously noted in cases of autism that were then injected into "the hippocampus of postnatal day 7 (P7) mice." Researchers then monitored the retrovirus infected cells to see what they looked like in terms of carrying the mutation and hence showing loss of PTEN function or not. They noted that there was a degree of 'hit-and-miss' based on their approach but were "able to clearly discern the established hypertrophic phenotype due to loss of Pten function across the cell population on average."

Not content with such molecular engineering, authors also turned their attention to designing viruses "to target a gene that has recently been associated with autism, KATNAL2." KATNAL2 has been described by other authors as a 'genuine' autism risk factor [3] (er, right...) and on that basis researchers designed a retrovirus carrying a mutation designed to disrupt expression of the gene. After some preliminary work to test out how successful their retrovirus delivered mutation was in the test tube, they injected it and/or a control retrovirus into the brain of another set of mice. They found some interesting changes in the experimental retrovirus-infected brains pertinent to "decreased dendritic arborization of developing neurons." In layman's terms this equates as evidence of "disruption of normal neuronal development" that "may lead to synaptic circuit dysfunction underlying the autism phenotype."

As per my earlier 'pinch of salt' sentiments I am not offering any authoritative opinion about the Williams paper and the techniques included. My interpretation is just that; interested readers are advised to do a little more reading around this subject before quoting my text as 'truth'. What I do hope that I've got across is the message that CRISPR-Cas9 and the delivery of engineered genetic mutations via something like a retrovirus is already here and will no doubt be impacting on autism research in times to come. In an era where 'the autism gene' has been replaced by a more general model of many different genes potentially producing many different autisms (see here), one can perhaps see how focusing in on specific genes linked to 'some' autism might be ripe for this kind of analysis (see here). I say all that recognising that whilst many would love to be able to say that autism is solely a genetic condition, the role of non-genetic factors variably affecting risk is not to be forgotten (see here).

We will see what else emerges in the peer-reviewed domain in this brave new world...

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[1] Williams MR. et al. A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons. Sci Rep. 2016 May 10;6:25611.

[2] Yin S. What Is CRISPR/Cas9 and Why Is It Suddenly Everywhere? Motherboard. 2015. April 30.

[3] Neale BM. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012 Apr 4;485(7397):242-5.

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ResearchBlogging.org Williams MR, Fricano-Kugler CJ, Getz SA, Skelton PD, Lee J, Rizzuto CP, Geller JS, Li M, & Luikart BW (2016). A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons. Scientific reports, 6 PMID: 27161796

Wednesday, 25 May 2016

The persistence of self-injury in relation to autism

Some behaviours associated with a diagnosis of autism don't make for great dinner table discussion. Self-injurious behaviours (SIBs), as exemplified by head banging, hair pulling and eye gouging must rank as some of the more distressing facets of [some] autism insofar as their potential effect on the person and also the people around them.

These and other types of behaviour commonly headed under the category of so-called 'challenging behaviours' have tended not to be too evident when it comes to the public depiction of autism it has to be said. I can appreciate why, but what this can mean is that such issues tend to get 'brushed under the carpet'. In recent times however, there does seem to be a greater willingness for research to delve into such behaviours [1].

The paper by Caroline Richards and colleagues [2] (open-access) looking at the persistence of such behaviour(s) and the potential correlates associated with their persistence is a welcome piece of research added to the research interest. Highlighting how for a small research sample of 67 children/young adults with autism over three-quarters reported SIB persisting over a 3-year period, the data provide some interesting insights into the nature of this issue and, potentially how it should be screened for and managed.

Based here in Blighty, researchers initially managed to recruit 190 participants, the data for some of whom were previously published [3]. As perhaps one might expect, the follow-up after on average 36.4 months had elapsed was not so well-populated. No mind, various findings are reported including that "the presence, topography and severity of self-injury were persistent and stable over three years" and that "individuals with self-injury were significantly more likely to be non-verbal than those who did not engage in self-injury." Further: "individuals with self-injury were significantly more likely to be less able and non-verbal and to show higher levels of stereotyped behaviour, compulsive behaviour, insistence on sameness, overactivity, impulsivity, repetitive behaviour and impairments in social interaction."

There is quite a bit more to do on this topic including facing up to issues around the small (eventual) participant size and the reliance on 'a questionnaire pack' as the chosen method of assessment. The authors also talk quite a bit about how some of the behaviours observed in connection with self-injury - impaired behavioural inhibition - might overlap with other diagnoses such as attention-deficit hyperactivity disorder (ADHD) but as far as I can see, they did not directly screen for ADHD outside of the use of something called The Activity Questionnaire (TAQ). I might also have liked to have seen a little more information about how parents/professionals had 'tackled' SIB in this cohort and what effect that might have had on results. Investigations remain.

Having said all that, the insights provided by the Richards article are important and provide plenty of food for thought when it comes to SIB and autism. Without trying to generalise SIB to all autism nor to come across as portraying too negative an image of what autism can mean to someone, recognition and management (dare I say treatment) of such behaviours when present should really be a priority [4].

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[1] Maddox BB. et al. Untended wounds: Non-suicidal self-injury in adults with autism spectrum disorder. Autism. 2016 May 12. pii: 1362361316644731.

[2] Richards C. et al. Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers. Journal of Neurodevelopmental Disorders 2016; 8: 21.

[3] Richards C. et al. Self-injurious behaviour in individuals with autism spectrum disorder and intellectual disability. J Intellect Disabil Res. 2012 May;56(5):476-89.

[4] Lee Y-H. et al. Cataract secondary to self-inflicted blunt trauma in children with autism spectrum disorder. Journal of American Association for Pediatric Ophthalmology and Strabismus. 2016. May 17.

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ResearchBlogging.org Richards, C., Moss, J., Nelson, L., & Oliver, C. (2016). Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers Journal of Neurodevelopmental Disorders, 8 (1) DOI: 10.1186/s11689-016-9153-x

Tuesday, 24 May 2016

Around 1 in 5 with autism will experience seizure or seizure disorder

The paper by Jennifer Jaskiewicz and colleagues [1] recently offered a further important insight into the relationship between autism and seizure or seizure disorder (i.e. epilepsy).

Based on the examination of records of nearly 50,000 children and young adults diagnosed with an autism spectrum disorder (ASD) compared with approximately quarter of a million 'not-autism' participants, authors reported some interesting trends. Concluding that some 19% of participants with autism experienced "some kind of seizure or seizure disorder", the study in particular reaffirms something of an important relationship between [some] autism and [some] epilepsy or seizure disorder.

Drawing on data derived from the US Military Health System database between 2000-2013, the records of children and young adults aged 0-18 years were the focus of analysis, where those with autism were age and sex-matched with asymptomatic (not autism) controls. Alongside the heightened risk of a general description of 'seizure or seizure disorder' in the autism group, authors also reported that specific issues such as status epilepticus and absence seizures were over-represented in the autism group. Febrile seizures - seizures that accompany fever - were also over-represented in the autism group although to a slightly lower extent than other seizure types. The authors conclude that: "Rates of epilepsy in children with autism are vastly increased in a wide variety of seizure types, known to have different etiologies, genetic and otherwise." Compare also the estimate of epilepsy or seizure disorder shown here with other population figures [2] and you get a flavour for how advanced the risk might be...

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[1] Jaskiewicz J. et al. Quantification of Risks of Seizure in Autism. Neurology. 2016; 86: suppl. S32.003.

[2] Russ SA. et al. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012 Feb;129(2):256-64

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ResearchBlogging.org Jennifer Jaskiewicz, Apryl Susi, Elizabeth Hisle-Gorman, David Dennison, Gregory Gorman, Cade Nylund, & Christine Erdie-Lalena (2016). Quantification of Risks of Seizure in Autism Neurology

Monday, 23 May 2016

Sex-specific immune response to Candida albicans in schizophrenia and beyond

I have quite a bit of time for the various members of the Stanley Division of Developmental Neurovirology at Johns Hopkins on this blog. Not least because of the interesting work of one researcher in particular - Emily Severance - as a name behind some potentially very important research on how food, infection and immune function might come together in complicated conditions such as [some] schizophrenia and [some] bipolar disorder (see here and see here).

Continuing their 'gut-brain' theme (oh, yes) new research from Prof/Dr Severance and colleagues [1] has been published observing that "sex-specific C. albicans immune responses were evident in psychiatric disorder subsets." C. albicans refers to Candida albicans, a fungus that I'm sure most people will have heard of at one time or another if not only as a function of those TV adverts for preparations to combat C. albicans when tied into yeast infection.

On this most recent occasion, researchers were testing the idea of "C. albicans as a new candidate infectious disease target for studies of schizophrenia and bipolar disorder" as a extension of other research talking about 'bacterial dysbioses' potentially contributing "to C. albicans overgrowth by failing to provide the competition needed to keep the fungus in check." If you're furrowing your brow about the thought that the trillions of wee beasties that call us home (the gut microbiome) might exert an effect on behavioural or psychiatric presentation, relax yourself slightly: interest is growing in this area [2] following on from other investigations in other areas (see here).

So, researchers: "measured and compared IgG antibodies directed against this fungus in two psychiatric cohorts: one composed of 261 people with schizophrenia, 270 with bipolar disorder and 277 individuals without a history of psychiatric disorder; the other cohort was composed of 139 people with first-episode schizophrenia, 78 of whom were antipsychotic naive." They also examined cognitive symptoms and took into account various factors that might act as confounders onwards to the idea that IgG antibodies to C. albicans *might* be considered a risk factor for either schizophrenia or bipolar disorder.

Results: well it wasn't as straight-forward as blanket saying that the presence of IgG antibodies (seropositivity) or quantitative levels of these antibodies to C. albicans equals schizophrenia or bipolar disorder (or not-schizophrenia or not-bipolar disorder). There was nothing statistically significant between the various groupings in the cohorts included for study. But... when the groups were categorised according to sex (gender), researchers reported "significant elevations of C. albicans IgG in males with schizophrenia and bipolar disorder compared with male controls."

Further analyses suggested that there may be some 'associations' with other variables examined across the sexes when it came to those IgG antibodies ("females with schizophrenia who were C. albicans IgG-seropositive performed more poorly on these [cognitive] tests than did females with schizophrenia who were C. albicans IgG-seronegative or than female controls") and it appeared that antipsychotic medication use did little to impact on the findings. The bottom line: "antibodies directed against the opportunistic fungal pathogen, C. albicans, were elevated in distinct subsets of individuals with psychiatric disorders" and minus any sweeping generalisations, a research agenda incorporating brain, immune function, gut and also contents of the gut could be indicated in future study. This of course set among the idea that schizophrenia might be better represented by the more plural 'schizophrenias'.

Some of the media around this study and its findings are perhaps a little 'sensational' as per the headline asking: Is a sexually transmitted yeast infection making people mentally ill? I perhaps wouldn't go as far as that at the moment given that C. albicans is present in everyone(?) and overgrowth of such a yeast is not necessarily due to sex or related activities. Yes, certain sexual diseases can manifest as psychological symptoms but an important basis of the Severance study is that intrinsic factors such as gut dysbiosis might start a chain reaction whereby C. albicans is able to flourish and becomes rather more systemic and pathogenic linked to the presentation of behavioural symptoms. Or at least that is part of the hypothesis requiring further testing...

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[1] Severance EG. et al. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia 2016; 2: 16018.

[2] Dinan TG. et al. Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry. 2014 Dec;19(12):1252-7.

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ResearchBlogging.org Severance, E., Gressitt, K., Stallings, C., Katsafanas, E., Schweinfurth, L., Savage, C., Adamos, M., Sweeney, K., Origoni, A., Khushalani, S., Leweke, F., Dickerson, F., & Yolken, R. (2016). Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder npj Schizophrenia, 2 DOI: 10.1038/npjschz.2016.18

Saturday, 21 May 2016

Add-on nutraceuticals for depression?

It came as no surprise to me that the systematic review and meta-analysis article by Jerome Sarris and colleagues [1] found what it did in relation to the use of [certain] adjunctive (add-on) nutraceuticals alongside antidepressants to reduce depressive symptoms: some of them might actually be clinically useful.

With no medical or clinical advice given or intended, the authors report that "adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants" might be something to consider "for improving inadequate response to antidepressants." Dr Sarris was one among many authors who contributed to the 'personal view' paper titled: 'Nutritional medicine as mainstream in psychiatry' [2] which was also covered a while back on this blog (see here). This latest addition to that and other opinions [3] which covered the peer-reviewed literature on a variety of nutrients also found something of a mixed bag of results for various other compounds including the aromatic amino acid tryptophan, zinc, folic acid and vitamin C.

Quite a bit more science needs to be done in this area, not least around the hows and whys that the various preparations might exert some effect. Vitamin D has of course been covered quite a bit on this blog in relation to something like depression (see here for example) so that particular nutraceutical might already have a research head start compared to others. I'm also minded to suggest that the involvement of something like SAMe (S-adenosylmethionine) as an add-on treatment might also imply a role for epigenetic variables in relation to at least some depression [4]. And then there is the question of who might be best responders to such nutraceutical use which implies heterogeneity and possible plural depressions...

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[1] Sarris J. et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. American Journal of Psychiatry. 2016. April 26.

[2] Sarris J. et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015 Mar;2(3):271-4.

[3] Sarris J. et al. International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry. World Psychiatry. 2015 Oct;14(3):370-1.

[4] McGowan PO. & Kato T. Epigenetics in mood disorders. Environ Health Prev Med. 2008 Jan;13(1):16-24.

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ResearchBlogging.org Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, & Ng CH (2016). Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. The American journal of psychiatry PMID: 27113121