ArticlePDF AvailableLiterature Review

Abstract

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n -3 fatty acids, folate, S -adenosylmethionine, N -acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.
The Joint Winter Meeting between the Nutrition Society and the Royal Society of Medicine held at The Royal Society of Medicine,
London on 67 December 2016
Conference on Diet, nutrition and mental health and wellbeing
Plenary Lecture: Mental health as an emerging public health problem
Nutritional psychiatry: the present state of the evidence
Wolfgang Marx
1
, Genevieve Moseley
2
, Michael Berk
2,3,4,5
and Felice Jacka
2,3,6,7
*
1
School of Allied Health, La Trobe University, Bundoora, Australia
2
Deakin University, Food & Mood Centre, IMPACT Strategic Research Centre, School of Medicine,
Barwon Health, Geelong, Australia
3
Department of Psychiatry, University of Melbourne, Parkville, Australia
4
Orygen, The National Centre of Excellence in Youth Health, Melbourne, Australia
5
Florey Institute for Neuroscience and Mental Health, Melbourne, Australia
6
Centre for Adolescent Health, Murdoch Childrens Research Institute, Melbourne, Australia
7
Black Dog Institute, Sydney, NSW, Australia
Mental illness, including depression, anxiety and bipolar disorder, accounts for a signicant
proportion of global disability and poses a substantial social, economic and heath burden.
Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psy-
chotherapy, such as cognitive behavioural therapy; however, such treatments avert less
than half of the disease burden, suggesting that additional strategies are needed to prevent
and treat mental disorders. There are now consistent mechanistic, observational and inter-
ventional data to suggest diet quality may be a modiable risk factor for mental illness.
This review provides an overview of the nutritional psychiatry eld. It includes a discussion
of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutra-
ceutical interventions in mental disorders, and recommendations for further research.
Potential biological pathways related to mental disorders include inammation, oxidative
stress, the gut microbiome, epigenetic modications and neuroplasticity. Consistent epi-
demiological evidence, particularly for depression, suggests an association between measures
of diet quality and mental health, across multiple populations and age groups; these do not
appear to be explained by other demographic, lifestyle factors or reverse causality. Our
recently published intervention trial provides preliminary clinical evidence that dietary inter-
ventions in clinically diagnosed populations are feasible and can provide signicant clinical
benet. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine,
N-acetyl cysteine and probiotics, among others, are promising avenues for future research.
Continued research is now required to investigate the efcacy of intervention studies in large
cohorts and within clinically relevant populations, particularly in patients with schizophre-
nia, bipolar and anxiety disorders.
Diet: Nutrition: Mental health: Psychiatry: Treatment
Mental illness is among the leading causes of disability
worldwide, accounting for 18·9 % of years lived with a
disability
(1)
. Due to the high prevalence of common men-
tal disorders, the social, economic and heath burden
associated with these disorders is substantial, with up
to $8·5 trillion in lost output attributed to mental, neuro-
logical and substance use disorders
(2)
. Pharmacotherapy,
such as antidepressants, and psychotherapy, such as
*Corresponding author: F. Jacka, email f.jacka@deakin.edu.au
Abbreviations: BDNF, brain-derived neurotrophic factor; NAC, N-acetyl cysteine; RCT, randomised controlled trial.
Proceedings of the Nutrition Society, Page 1 of 10 doi:10.1017/S0029665117002026
© The Authors 2017
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
cognitive behavioural therapy, are cornerstones of treat-
ment; however, they avert less than half of the disease
burden, suggesting that additional strategies to prevent
and treat mental disorders are needed
(3,4)
. Indeed, recent
evidence suggests that despite a substantial increase in
the use of psychotropics and wider availability of psy-
chotherapies, the population burden of depression has
not reduced, and may be increasing
(5)
. If indeed this is
the case, it suggests the presence of operative environ-
mental risk factors for depression.
The new eld of nutritional psychiatry provides evidence
for diet quality as a modiable risk factor for mental ill-
nesses. Recent systematic reviews examining the association
between diet and common mental disorders have shown
healthy dietary patterns to be inversely associated with the
probability of, or risk for, depression
(68)
. Such diets are
characterised by the high intake of vegetables, fruit, whole-
grains, nuts, seeds and sh, with limited processed foods. In
contrast, unhealthy diets high in processed, high-fat, high-
sugar foods in adolescence and adulthood are shown to be
positively associated with the common mental disorders,
depression and anxiety
(6,9)
. Similar evidence exists in early
childhood, where poor maternal nutrition status and
early-life diet is associated with childhood emotional and
behavioural dysregulation
(912)
.
Research investigating the potential biological pro-
cesses involved in the diet and mental health relationship
has primarily implicated inammation, oxidative stress
and neuroplasticity, with the gut microbiome as a key
mediating pathway for each of these processes
(1316)
.
An understanding of these pathways has prompted
research into the adjunctive use of dietary and nutraceut-
ical (nutritional supplements) interventions that affect
these pathways for both common and severe psychiatric
disorders; such as n-3 fatty acids in depression and
N-acetyl cysteine (NAC) in schizophrenia
(1719)
.Critically,
the rst whole diet intervention studies in clinical depres-
sion are also now available
(20)
.
This review provides an overview of the eld of nutri-
tional psychiatry including discussion of the implicated
biological mechanisms that are likely modulated by
diet, the results of recent systematic reviews and meta-
analyses regarding the use of dietary and nutraceutical
interventions in mental disorders, and promising avenues
for further research. An executive summary of each sec-
tion can be found in Table 1.
For this narrative review, a systematic literature review
of ve electronic databases (Pubmed, PsychInfo, CiNAHL,
Cochrane Database and Embase) was conducted using key
search terms related to diet (e.g. diet*,nutrition), nutra-
ceuticals (e.g. diet* supplement) and mental illness (e.g.
depression,mental illness,mood). Results from system-
atic reviews, notable clinical and observational trials, and
meta-analyses were prioritised for this review.
Implicated pathways in diet and mental illness
There are several pathways implicated in mental illness
and that can be modulated by diet
(13,14,21)
. This section
will provide an overview of the evidence for the primary
pathways that have been studied to date. Although
described as distinct pathways, it is likely that these path-
ways overlap synergistically and are mutually interacting.
Inammation
Chronic low-grade inammation, characterised by an
elevationinpro-inammatory cytokines and acute phase
proteins, is implicated in the development of de novo
depression, schizophrenia and bipolar disorder
(13,22,23)
.
The causes of this inammation are multifaceted and
include several lifestyle factors, such as psychological
stress, smoking, obesity, lack of sleep and, of particular
relevance to the present discussion, poor diet
(13)
.Results
from large observational studies suggest that healthy diet-
ary patterns, such as the Mediterranean diet
(24)
,thatare
higher in PUFA, bre, fruit and vegetables are associated
with lower levels of inammatory markers
(25)
.Moreover,
Mediterranean dietary patterns signicantly improve mar-
kers of inammation in intervention studies
(26)
.
Oxidative stress
Oxidative and nitrosative stress are implicated in several
chronic diseases and appear to be relevant to mental ill-
ness
(14)
. Schizophrenic populations have decreased brain
glutathione levels, disordered glutamate metabolism and
increased oxidative stress
(27)
. Similar results are reported
in depressed populations, with higher levels of oxidative
stress markers observed, as well as lower levels of antioxi-
dants, such as vitamin E, vitamin C, coenzyme Q10 and
glutathione, when compared with healthy controls
(14)
.
Furthermore, a recent meta-analysis of 115 studies reported
lower antioxidant capacity in depressed patients during
acute episodes
(28)
. Given the abundance of antioxidant com-
pounds present in foods such as fruit and vegetables, this is a
pathway that could be modulated through dietary means.
Brain plasticity
Neurogenesis, particularly within the hippocampus, is
associated with learning, memory and mood regulation,
while altered neurogenesis is implicated in mental ill-
ness
(21)
. Brain-derived neurotrophic factor (BDNF) as
well as other neurotrophins (e.g. bcl-2 and vascular endo-
thelial growth factor) are suggested to mediate hippo-
campal neurogenesis
(29,30)
. There is presently limited
clinical investigation of the effect of diet on this pathway;
however, preliminary evidence supports the role of diet in
improving BDNF levels. For example, a 4-week dietary
intervention to increase consumption of carotenoid-rich
fruit and vegetables (eight servings daily) in people
with schizophrenia resulted in higher serum levels of
BDNF than in the control group
(31)
. Moreover, an epi-
demiological investigation in older adults has demon-
strated an association between poor diet and reduced
hippocampal volume
(15)
. In addition to possessing anti-
oxidant and anti-inammatory properties, nutrients,
such as n-3 fatty acids
(32)
, polyphenols
(33)
, l-theanine
(34)
and vitamin E
(35)
, can also stimulate neurogenesis while
energy-dense diets high in fat and sugar impair this
process
(21,36,37)
.
W. Marx et al.2
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Microbiotagutbrain axis
The role of gastrointestinal microbiota on chronic disease
is now a burgeoning area of research. Compelling evi-
dence, predominantly from animal studies, indicates the
gut microbiota can affect mental health-related beha-
viours via multiple pathways
(38)
.
The gastrointestinal microbiota has been implicated in
several neurobiological pathways related to mental
illness, including the modulation of BDNF
(39)
,serotonin
neurotransmission
(40)
, immune function
(41)
and the hypothal-
amicpituitaryadrenal axis-mediated stress response
(39,42)
.
For example, microbiota-decient germ-free mice exhibit
Table 1. Executive summary of present research areas within Nutrition Psychiatry
Executive summary Key references
Biological pathways mediating the dietmental health relationship
Several pathways implicated in mental illness can be modulated by diet. These include pathways related to
inammation, oxidative stress, brain plasticity, mitochondrial dysfunction and the gutbrain axis. Although
described as distinct pathways, it is likely that these pathways overlap synergistically and are mutually
interacting
Berk et al.
(13)
Estruch
(24)
Moylan et al.
(14)
Liu et al.
(28)
Zainuddin and Thuret
(21)
Fung et al.
(38)
Morris and Berk
(52)
Maes et al.
(54)
Observational data on diet and mental illness in adults
Several meta-analyses and systematic reviews have established a consistent relationship between diet and
depression in adults, across multiple populations, which does not appear to be explained by other demographic
factors or reverse causality
Li et al.
(64)
Lai et al.
(6)
Psaltopoulou et al.
(7)
Childhood and maternal perinatal mental illness observational data
Diet is also associated with mental health in children, adolescents and women in the antenatal period. The body
of research is relatively smaller compared with adult populations; however, research has identied an inverse
relationship between high-quality diet and mental health disturbances, as well as a positive relationship between
unhealthy diets and mental symptomatology such as internalising and externalising problems in children and
adolescents. Similarly, poor diet quality is associated with antenatal depression; however, evidence for an
association between diet quality and postnatal depression and anxiety is inconsistent
ONeil et al.
(9)
Sparling et al.
(66)
Baskin et al.
(67)
Specic dietary patterns, individual nutrients and mental illness
Nutrient dense dietary patterns that include plant foods and high-quality sources of protein are inversely
associated with mental illness, independent of body weight. There is evidence of an association between
depression and dietary patterns, such as a traditional Mediterranean diets, Norwegian diets and Japanese diets
Observational data suggest dietary intake of sh, magnesium, iron and zinc may be inversely associated with
depression; however, an association with intake of other micronutrients has not been denitively established
Quirk et al.
(62)
Murakami and Sasaki
(73)
Li et al.
(75)
Li et al.
(76)
Evidence from intervention studies
While observational studies have reported consistent evidence for an association between diet quality and
common mental disorders, relatively few intervention studies have investigated this relationship
Present evidence from intervention trials are mixed, with successful trials generally including at least one of the
following: single delivery mode (e.g. single or group face-to-face meetings only), employment of a dietitian,
explicit recommendation of a diet high in bre and/or fruits and vegetables. The SMILES trial provides
preliminary evidence that dietary interventions in clinically diagnosed depressed populations are feasible and
can provide clinical benet. Further studies in larger samples are now required to conrm these results
Opie et al.
(8)
Jacka et al.
(20)
Evidence for the use of nutraceuticals in mental illness
Numerous nutraceutical interventions have been conducted in a range of mentally ill populations, including
depression, bipolar and schizophrenia, with varying levels of efcacy. Supplementation has included ω-3 fatty
acids, vitamins (e.g. B vitamins, vitamin E, C and D), minerals (e.g. zinc, magnesium), herbal preparations (e.g. St
Johns wort, passionower, Kava) and amino acids (e.g. S-adenosylmethionine, N-acetyl cysteine). Presently,
there is a lack of studies that have evaluated the clinical efcacy and safety of these nutraceuticals in populations
with clinical mental disorders. Future studies are required to investigate these interventions using sufciently
powered randomised controlled trial study designs
Cui and Zheng
(82)
Sarris et al.
(17)
Sarris et al.
(86)
Fernandes et al.
(91)
Lakhan and Vieira
(106)
Firth et al.
(93)
Future directions in nutritional psychiatry
Continued research is required to elucidate the impact of various physiological pathways on mental health and to
develop optimal strategies for interventions. In addition, few studies have specically considered diet and its
effect on symptomology in patients with severe mental illness
The role of the gut microbiome in mental illness is an emerging area with promise. Further investigation into the
possible role of dietary factors and gut microbiota dysbiosis in psychosis and associated neurodegeneration is
warranted. Furthermore, probiotic supplementation may be an effective nutraceutical intervention; however,
future trials are required to resolve uncertainty regarding the optimal duration of intervention, dose and strains of
the probiotics
N-acetyl cysteine is a promising therapeutic intervention for addiction, bipolar disorder, schizophrenia and
depression. However, while N-acetyl cysteine has been investigated in a range of clinical populations, further
randomised controlled trials are required to conrm these results
Huang et al.
(100)
Wallace and Milev
(101)
Romijn and Rucklidge
(102)
Fernandes et al.
(91)
Asevedo et al.
(103)
Deepmala et al.
(104)
Jacka
(72)
Nutritional psychiatry 3
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
an exaggerated stress response
(39)
and lower BDNF and
serotonin receptor levels in the cortex and hippocampus of
the brain
(39,43)
compared with normal gut colonised mice.
At least some of these pathways appear bidirectional, with
stress activation of the hypothalamicpituitaryadrenal
axis found to modulate microbial composition in rats
(44)
.
Clinically, differences in patterns of faecal microbiota,
reecting decreased gut microbiota richness and diversity,
have been reported in depressed patients compared with
healthy controls
(45)
. Transplantation of microbes from
depressed patients into rodents results in depression-
related behaviours
(45,46)
and altering gut microbiota
through probiotic supplementation or food products
inuences depression-related behaviour in animals
(47)
.
Dietary-induced alterations in intestinal permeability
(such as via a high-fat diet
(48)
) may also affect mental
health. Integrity of the gut epithelial barrier by tight
junctions regulates the movement of substrates from the
gut into the blood stream and, when compromised, is
associated with depression
(49,50)
. Increased permeability
may allow bacteria-derived lipopolysaccharides to acti-
vate immune cells within the intestinal wall, promoting
the production of inammatory cytokines and activation
of nitro-oxidative stress pathways, resulting in elevated
systemic inammation
(50)
.
Mitochondrial dysfunction
Impaired mitochondrial energy production, size and distri-
bution are associated with depression, schizophrenia and
may be particularly relevant to bipolar disorder
(51,52)
.
These changes could be the result of reduced antioxidant
capacity and a pro-inammatory cytokine-mediated
increase in mitochondrial-derived oxygen and nitrogen-free
radicals, suggesting inammation and oxidative stress drive
mitochondrial dysfunction
(52)
. Dietary and nutraceutical
compounds such as coenzyme Q10, α-lipoic acid, carnitine,
creatine, resveratrol, NAC and some antidepressants
up-regulate mitochondrial respiratory function in animal
models
(5355)
.
Observational literature on diet and mental illness
There is now consistent epidemiological evidence for an
association between measures of diet quality and mental
health, across multiple populations,
(5658)
which do not
appear to be explained by other demographic factors or
reverse causality
(5961)
.
Adult data
Several meta-analyses and systematic reviews have estab-
lished a relationship between diet and depression in
adults
(6,7,6264)
. Lai et al.
(6)
conducted a meta-analysis
of thirteen observational studies (four cohorts and nine
cross-sectional) and reported that consumption of a
healthy diet was associated with reduced odds of depres-
sion (OR 0·84; 95 % CI 0·76, 0·92). It was, however,
unable to establish a statistically signicant relationship
between western diet and increased odds of depression,
likely due to insufcient power from the small number
of studies analysed. The second meta-analysis presented
similar results, showing moderate and high adherence
to a Mediterranean diet to be associated with reduced
likelihood of depression
(7)
. A more recent systematic
review and meta-analysis including data from twenty-one
studies and 117 229 participants has conrmed an inverse
relationship between dietary patterns characterised by
higher intakes of fruit, vegetables, whole grain, sh,
olive oil, low-fat dairy and the probability or risk for
depression, and a positive relationship between dietary
patterns characterised by a higher consumption of red
and/or processed meat, rened grains, sweets, high-fat
dairy products and an increased probability or risk of
depression
(64)
.
Childhood and maternal perinatal data
The association between diet and mental health has also
been studied in children, adolescents and women in the
perinatal period
(9,6567)
. A systematic review of nine
cross-sectional and three prospective studies reported
an inverse relationship between high-quality diet and
mental health disturbances and a positive relationship
between unhealthy diets and poorer mental health out-
comes in children and adolescents
(9)
. Since this system-
atic review, three prospective cohort studies have
reported maternal nutrition and early-life nutrition to
be independently associated with mental symptomatol-
ogy, such as internalising and externalising problems in
children aged 57 years, when controlling for prenatal
and postnatal confounders
(1012)
.
During pregnancy, women are more susceptible to
nutrient deciencies due to increased physiological stress
on the body and increased nutrient demand from a grow-
ing fetus. These deciencies are likely exacerbated by
poor quality diets. Given the potential role of dietary
nutrients in the biochemical pathways of mental illnesses,
generalised maternal nutrient deciency may explain
rates of perinatal depression. Baskin et al.
(67)
found asso-
ciations between poor diet quality and antenatal depres-
sion; however, evidence was inconsistent for an
association between diet quality and postnatal depression
and anxiety. Together this literature indicates diet is
likely relevant to mental health at all stages of life.
Specic dietary patterns and individual nutrients
A healthy diet is generally characterised as a higher intake
of fruit, vegetables, sh and wholegrains, while a western
diet, in contrast, is characterised by higher consumption
of processed foods, processed meats, rened grains, salty
and sugary snacks and beverages
(63)
. However, there is
still substantial heterogeneity in dening a healthy diet, as
many unique cultures have diverse but still healthy dietary
patterns
(68)
. At the core of these diets are nutrient-dense
plant foods and high-quality sources of protein, which
are likely to be a signicant contributor to the observed
results
(69)
.Raheet al.
(63)
differentiated between a healthy/
traditional diet and a Mediterranean diet, with a
Mediterranean diet having a greater emphasis on high
intake of legumes, moderate intake of meat and dairy,
and olive oil as the main fat source. They reported both
W. Marx et al.4
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
diets were protective against depression. Observational
studies have examined the association with other diets,
including the traditional Japanese diet
(70)
and the
Norwegian diet
(71)
; however, evidence is limited and
conicting
(62)
.
It is important to note that the favourable association
of healthy foods and mental health outcomes is consist-
ently independent of the association between unhealthy
foods and poorer mental health outcomes
(72)
, which sug-
gests that different physiological pathways may be medi-
ating the potential effects of these contrasting dietary
patterns. These associations are also independent of
body weight, suggesting dietary patterns can affect mental
illness via pathways that are independent of weight status.
A 2010 review of thirty-four publications investigating
a number of dietary variables, including long chain n-3
PUFA, sh, folate and B vitamins as markers of dietary
intake, did not establish a denitive association between
the intake of specic dietary components and depressive
symptoms
(73)
. However, more recent meta-analyses of
observational studies have identied sh consumption,
and dietary magnesium, iron and zinc as associated
with lower rates of depression
(7476)
.
While most observational studies have made appropri-
ate adjustments for potential confounding variables, such
as socioeconomic status, physical activity and smok-
ing
(59)
, residual confounding by these variables is likely.
Moreover, while reverse causality has been examined as
an explanatory factor (e.g.
(60)
), observational studies,
particularly when cross-sectional, are unable to establish
causality. Therefore, observational studies using pro-
spective and casecontrol cohorts and intervention ran-
domised controlled trials (RCT) should be prioritised in
future studies. Most studies to date have examined the
association between diet and depression, with only a lim-
ited exploration of anxiety and more severe mental ill-
nesses, such as schizophrenia and bipolar disorder.
There is now a need to extend observational nutritional
psychiatry research into these areas.
Dietary interventions for mental illness
While observational studies have reported consistent
evidence for an association between diet quality and
common mental disorders, there are relatively few inter-
ventions that have investigated this relationship. Our
2013 systematic review of seventeen previous interven-
tion studies provides an overview of existing dietary
intervention studies with depression, anxiety and mood
disturbance endpoints
(8)
. The results were mixed, with
approximately half the studies reporting improvements
in outcomes, with successful trials generally including
at least one of the following: single delivery mode (e.g.
single or group face-to-face meetings only), employment
of a dietitian, explicit recommendation of a diet high in
bre and/or fruit and vegetables. These trials were also
less likely to recommend weight loss, reduce red meat
intake or follow a low-cholesterol diet.
The review also identied multiple limitations within
the literature. Primarily, only one study recruited
participants with a depressive/anxiety diagnosis, while
others included other participant populations, such as
breast cancer and obese/overweight participants, and/or
excluded participants with pre-existing mental health
symptoms or disorders. Some studies included only one
gender or had a sample comprising primarily Caucasian
adults with a high education level. Hence, the ndings
may not be generalisable to other clinical and general
populations.
Since the publication of this review, the potential
impact of a Mediterranean diet on the incidence of de
novo depression has been assessed in a post hoc analysis
of the PREDIMED study
(77)
; this was a large RCT that
investigated the effect of Mediterranean diet on CVD
endpoints. While underpowered for the depression end-
point, the analysis suggested a non-signicant reduction
in the incidence of de novo depression for those rando-
mised to a Mediterranean diet with nuts, and signicant
reduction in a subset of those with type 2 diabetes.
Forsyth et al.
(78)
conducted a 12-week RCT in 119
individuals treated for depression and/or anxiety in pri-
mary care. The intervention group received motivational
interviewing, activity scheduling and an individualised
lifestyle programme focusing on changes in physical
activity and diet (e.g. reducing fat intake, increasing vege-
table intake and variety). The control group received
regular phone contact with research staff that did not
include dietary advice but asked participants about
changes to their diet or physical activity patterns. Both
groups reported improved symptoms of depression and/
or anxiety as well as dietary intake over time. However,
no signicant differences in symptoms were observed
between the two groups.
We have recently published the results of the SMILES
trial, an RCT that investigated a 12-week modied
Mediterranean diet intervention in sixty-seven participants
with major depression
(20)
. Participants in the intervention
group received personalised dietary and nutritional coun-
selling based on a traditional Mediterranean diet and the
Australian Dietary Guidelines. Participants in the control
group received the same number of scheduled visits but
received a befriendingprotocol (social support) whereby
research staff met with participants and discussed neutral
topics of interest (e.g. sport, hobbies). At 12 weeks, there
was a signicantly greater improvement in depression
scores in the dietary support group compared with the
social support control group. Furthermore, there was a
signicantly greater level of remission in the dietary sup-
port group (dened as a MontgomeryÅsberg
Depression Rating Scale score <10) with 32·3% (n10/
31) of the dietary support group reporting remission com-
paredwith8·0% (n2/25) in the social support control
group and a number needed to treat of 4·1. Participants
did not signicantly change their energy intake or body
weight during the trial, which suggests that these improve-
ments were not primarily related to weight status. The
results of the SMILES trial provide preliminary evidence
that dietary interventions in clinically diagnosed popula-
tions are feasible and can provide clinical benet.
Further studies in larger samples are now required to
conrm these results.
Nutritional psychiatry 5
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Nutraceutical interventions for mental illness
There is a broad array of nutraceutical interventions that
target pathways implicated in mental illness, including
inammation, oxidative stress, modulation of the methy-
lation cycle and prevention of hippocampal-associated
cognitive decline, as well as mitochondrial dysfunction
and neurotransmitter pathways
(7981)
. Due to their action
on these pathways, clinical trials have investigated
specic nutrients and herbal preparations for their effect
on mental illness. As this area of research is expansive,
this section will only provide an overview of recent sys-
tematic reviews and meta-analyses that have evaluated
intervention studies in this area.
St Johns Wort, a widely researched herbal nutraceut-
ical, has been reported in a recent meta-analysis to
achieve similar improvements in depression to selective
serotonin reuptake inhibitor medication controls
(82)
.
The n-3 PUFA are another supplement that have a
long history of investigation, with several meta-analyses
reporting mixed ndings
(17,83,84)
. However, interventions
that use n-3 formulations with a high EPA : DHA ratio
as an adjunctive to antidepressants might be benecial
to patients with depression
(17,84)
.S-adenosylmethionine,
methylfolate and vitamin D may also have a positive
effect on depression as adjunctive interventions, although
there are also large negative studies
(17,85)
. Furthermore,
some nutraceuticals, including creatine, folinic acid and
an amino acid combination, have yielded positive prelim-
inary data from single trials, while zinc, folic acid, vita-
min C, inositol and tryptophan have mixed or
non-signicant effects for depression
(86)
. The results of
additional meta-analyses also report no benet from fol-
ate, vitamin B
12(87)
and vitamin D supplementation for
depression
(88)
.
While not as extensively studied, clinical trials have
also investigated some nutraceuticals for other mental ill-
nesses. Three meta-analyses concluded that adjunctive
n-3 supplementation can be benecial for both unipolar
and bipolar depressions
(86,89,90)
. The results of a recent
meta-analysis suggest that NAC may be efcacious for
depression and depressive symptoms regardless of the
main clinical diagnosis, although again there are negative
studies
(91)
. Furthermore, L-tryptophan, magnesium, folic
acid and branched-chain amino acids may be effective
for bipolar disorder-related mania and chelated mineral
and vitamin formulas may be effective in improving
both bipolar disorder-related depression and mania
(86)
.
The use of micronutrient combinations for mental ill-
ness has also been investigated. A systematic review by
Rucklidge and Kaplan
(92)
reported limited evidence for
micronutrient combinations for stress, antisocial beha-
viours and depressed mood in healthy people, as well
as potentially for attention-decit hyperactive disorder
and autism. However, the review identied few studies
in this area and most studies were conducted in healthy
rather than clinically diagnosed populations.
A 2010 systematic review concluded that passionower,
kava and combinations of L-lysine and L-arginine were
promising interventions for anxiety and that more
research is required to make recommendations regarding
magnesium supplementation due to limited published
studies on this intervention. The results of a meta-analysis
reported that folate and other vitamin B supplementation
(including B
6
and B
12
) may be benecial for certain popu-
lations diagnosed with schizophrenia
(93)
.
Nutraceuticals including n-3 fatty acids, calcium,
multivitamin and B vitamins have been investigated for
perinatal depression; however, a recent review concluded
that there is presently limited support for nutraceutical
interventions in this population with few intervention
studies reporting signicant improvements and several
trials rated as having a medium or high risk of bias
(66)
.
Overall, clinical trials have evaluated numerous nutra-
ceutical interventions; however, there is a lack of trials
that have evaluated their clinical efcacy and safety in
populations with clinical mental disorders. Future studies
are required to investigate these interventions using suf-
ciently powered RCT study designs. Importantly, likely
effect modiers, including baseline diet, inammatory
status and gut microbiome composition, are essential
variables to include in future interventions.
Promising new avenues for investigation
The eld of nutritional psychiatry has provided a signi-
cant body of evidence to suggest that dietary patterns are
relevant to common mental illnesses. However, contin-
ued research is required to translate the evidence base
into clinical and public health recommendations.
Dietary patterns may modulate numerous biological
pathways involved in mental illness including inamma-
tion, oxidative stress, the gutbrain axis and neurogen-
esis. Continued research is required to elucidate the
impact of these as well as additional pathways, including
the role of homocysteine
(94)
, telomerase
(95)
and epigenet-
ics
(96)
, on mental health and to develop optimal strategies
for interventions.
Most observational data to date have focused on com-
mon mental disorders and there is now a need to examine
dietary patterns in those with severe mental illnesses.
Numerous systematic reviews and meta-analyses have
considered the effects of dietary patterns on weight loss
and metabolic diseases in individuals with severe mental
illnesses, namely schizophrenia and bipolar disorder, yet
few have specically considered diet and its possible
effect on psychiatric symptoms in these populations.
Limited evidence suggests a positive association between
obesity/weight gain and impaired functioning in indivi-
duals with bipolar disorder; however, the directionality
of this relationship has not been rmly established, indi-
cating the need for further research in this area
(97)
.
Schizophrenia is associated with gastrointestinal and
microbial dysfunction, immune and inammatory
mechanisms
(98,99)
. Further investigation into the possible
role of dietary factors and gut microbiota dysbiosis in
psychosis and associated neurodegeneration is warranted.
The microbiotagutbrain diet axis is a promising tar-
get that could be modied via dietary and nutraceutical
intervention, such as prebiotics (e.g. high-bre foods
and supplements) and probiotics (e.g. fermented foods
W. Marx et al.6
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
or supplements) directly targeting microbial populations.
A 2015 systematic review of ten RCT investigated pro-
biotic supplements for stress, mood, anxiety, schizo-
phrenic symptoms and externalising behaviours in
autism spectrum disorder. It concluded that few studies
reported signicant improvements from probiotic supple-
mentation. Alternatively, a more recent meta-analysis of
ve RCT reported that probiotic supplementation
decreased measures of depression (0·30, 95 % CI
0·51, 0·09; P=0·005)
(100)
, and an additional system-
atic review of ten RCT also concluded that probiotics
may be benecial to cognition, mood and anxiety
(101)
.
However, few studies included in these reviews were con-
ducted within populations with diagnosed mental illness
and the clinical relevance to psychiatry is thus far
unclear. Furthermore, all studies noted additional limita-
tions in the literature including uncertainty regarding the
optimal duration of intervention, dose and strains of the
probiotics
(100102)
. Future quality intervention studies are
required to improve the existing evidence base for pro-
biotic supplementation and to explore the role of dietary
manipulation (e.g. pro and prebiotic foods) on mental
health. Characterisation of changes in microbial signa-
ture and composition and gut permeability in response
to diet, and associated changes in mental health and
related behaviours are also needed.
NAC is an amino acid-derived glutathione precursor
that may modulate glutamatergic and neurotrophic
transmission, glutathione production for antioxidant
capacity, mitochondrial function and inammation
(19)
.
Recent reviews conclude that, while the present evidence
is preliminary, NAC is a promising therapeutic intervention
for addiction (e.g. substance dependence, gambling) and
bipolar, schizophrenic and depressed populations
(91,103,104)
.
However, while NAC has been investigated in a range of
these clinical populations, further RCT are required to
conrm these results
(55)
.
Conclusion
Nutritional psychiatry is a rapidly growing eld of
research that has the potential to provide clinically mean-
ingful interventions to both prevent and manage mental
illness. Observational research has demonstrated a con-
sistent relationship between diet quality and common
mental illnesses, while biological pathways including
inammation, oxidative stress, gastrointestinal micro-
biota and neurotrophic factors provide viable mechan-
isms of action for this observed effect. Preliminary
clinical evidence provides support for the feasibility and
efcacy of dietary and some nutraceutical interventions.
It is likely that changes to public policy are needed to
translate these ndings into population-wide changes in
eating behaviour to achieve associated benets
(105)
.
More research is now required to investigate the efcacy
of intervention studies in large cohorts and within clinic-
ally relevant populations, particularly in patients with
schizophrenia, bipolar and anxiety disorders, in order
to build on the existing evidence base and to inform clin-
ical practice.
Acknowledgements
M. B. is supported by an NHMRC Senior Principal
Research Fellowship (1059660). F. J. is supported by an
NHMRC Career Development Fellowship (2) (1108125).
Financial Support
None.
Conicts of Interest
None.
Authorship
W. M. and G. M. contributed equally, with primary
responsibility for writing this work. M. B. and F. J. con-
tributed to planning and editing this work.
References
1. Whiteford HA, Ferrari AJ, Degenhardt L et al. (2015) The
global burden of mental, neurological and substance use
disorders: an analysis from the global burden of disease
study 2010. PLoS ONE 10, e0116820.
2. Chisholm D, Sweeny K, Sheehan P et al. (2016) Scaling-up
treatment of depression and anxiety: a global return on
investment analysis. Lancet Psychiatry 3, 415424.
3. Olfson M, Druss BG & Marcus SC (2015) Trends in mental
health care among children and adolescents. N Engl J Med
372, 20292038.
4. Casacalenda N, Perry JC & Looper K (2002) Remission in
major depressive disorder: a comparison of pharmacother-
apy, psychotherapy, and control conditions. Am J
Psychiatry 159, 13541360.
5. Jorm AF, Patten SB, Brugha TS et al. (2017) Has increased
provision of treatment reduced the prevalence of common
mental disorders? Review of the evidence from four coun-
tries. World Psychiatry 16,9099.
6. Lai JS, Hiles S, Bisquera A et al. (2014) A systematic
review and meta-analysis of dietary patterns and depression
in community-dwelling adults. AmJClinNutr99,181197.
7. Psaltopoulou T, Sergentanis TN, Panagiotakos DB et al.
(2013) Mediterranean diet, stroke, cognitive impairment,
and depression: a meta-analysis. Ann Neurol 74, 580591.
8. Opie RS, ONeil A, Itsiopoulos C et al. (2015) The impact
of whole-of-diet interventions on depression and anxiety: a
systematic review of randomised controlled trials. Public
Health Nutr 18, 20472093.
9. ONeil A, Quirk SE, Housden S et al. (2014) Relationship
between diet and mental health in children and adolescents:
a systematic review. Am J Public Health 104, e31e42.
10. Jacka FN, Ystrom E, Brantsaeter AL et al. (2013)
Maternal and early postnatal nutrition and mental health
of offspring by age 5 years: a prospective cohort study. J
Am Acad Child Adolesc Psychiatry 52, 10381047.
11. Pina-Camacho L, Jensen SK, Gaysina D et al. (2015)
Maternal depression symptoms, unhealthy diet and child
emotional-behavioural dysregulation. Psychol Med 45,
18511860.
Nutritional psychiatry 7
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
12. Steenweg-de Graaff J, Tiemeier H, Steegers-Theunissen RP
et al. (2014) Maternal dietary patterns during pregnancy
and child internalising and externalising problems. Gener
R Study Clin Nutr 33, 115121.
13. Berk M, Williams LJ, Jacka FN et al. (2013) So depression
is an inammatory disease, but where does the inamma-
tion come from? BMC Med 11, 200.
14. Moylan S, Berk M, Dean OM et al. (2014) Oxidative &
nitrosative stress in depression: why so much stress?
Neurosci Biobehav Rev 45,4662.
15. Jacka FN, Cherbuin N, Anstey KJ et al. (2015) Western
diet is associated with a smaller hippocampus: a longitu-
dinal investigation. BMC Med 13, 215.
16. Slyepchenko A, Maes M, Jacka FN et al. (2017) Gut
microbiota, bacterial translocation, and interactions with
diet: pathophysiological links between major depressive
disorder and non-communicable medical comorbidities.
Psychother Psychosom 86,3146.
17. Sarris J, Murphy J, Mischoulon D et al. (2016) Adjunctive
nutraceuticals for depression: a systematic review and
meta-analyses. Am J Psychiatry 173, 575587.
18. Sarris J, Schoendorfer N & Kavanagh DJ (2009) Major
depressive disorder and nutritional medicine: a review of
monotherapies and adjuvant treatments. Nutr Rev 67,
125131.
19. Berk M, Malhi GS, Gray LJ et al. (2013) The promise of
N-acetylcysteine in neuropsychiatry. Trends Pharmacol
Sci 34, 167177.
20. Jacka FN, ONeil A, Opie R et al. (2017) A randomised
controlled trial of dietary improvement for adults with
major depression (the SMILEStrial). BMC Med 15, 23.
21. Zainuddin MS & Thuret S (2012) Nutrition, adult hippo-
campal neurogenesis and mental health. Br Med Bull 103,
89114.
22. Fernandes BS, Steiner J, Molendijk ML et al. (2016)
C-reactive protein concentrations across the mood spec-
trum in bipolar disorder: a systematic review and
meta-analysis. Lancet Psychiatry 3, 11471156.
23. Fernandes BS, Steiner J, Bernstein HG et al. (2016)
C-reactive protein is increased in schizophrenia but is not
altered by antipsychotics: meta-analysis and implications.
Mol Psychiatry 21, 554564.
24. Estruch R (2010) Anti-inammatory effects of the
Mediterranean diet: the experience of the PREDIMED
study. Proc Nutr Soc 69, 333340.
25. Watzl B, Kulling SE, Moseneder J et al. (2005) A 4-wk
intervention with high intake of carotenoid-rich vegetables
and fruit reduces plasma C-reactive protein in healthy,
nonsmoking men. Am J Clin Nutr 82, 10521058.
26. Schwingshackl L & Hoffmann G (2014) Mediterranean
dietary pattern, inammation and endothelial function: a
systematic review and meta-analysis of intervention trials.
Nutr Metab Cardiovasc Dis 24, 929939.
27. Dean OM, van den Buuse M, Bush AI et al. (2009) A role
for glutathione in the pathophysiology of bipolar disorder
and schizophrenia? Animal models and relevance to clinical
practice. Curr Med Chem 16, 29652976.
28. Liu T, Zhong S, Liao X et al. (2015) A meta-analysis of
oxidative stress markers in depression. PLoS ONE 10,
e0138904.
29. Fernandes BS, Berk M, Turck CW et al. (2014) Decreased
peripheral brain-derived neurotrophic factor levels are a
biomarker of disease activity in major psychiatric disorders:
a comparative meta-analysis. Mol Psychiatry 19, 750751.
30. Fernandes BS, Molendijk ML, Kohler CA et al. (2015)
Peripheral brain-derived neurotrophic factor (BDNF) as a
biomarker in bipolar disorder: a meta-analysis of 52 stud-
ies. BMC Med 13, 289.
31. Guimaraes LR, Jacka FN, Gama CS et al. (2008) Serum
levels of brain-derived neurotrophic factor in schizophrenia
on a hypocaloric diet. Prog Neuropsychopharmacol Biol
Psychiatry 32, 15951598.
32. Kawakita E, Hashimoto M & Shido O (2006)
Docosahexaenoic acid promotes neurogenesis in vitro and
in vivo. Neuroscience 139, 991997.
33. Williams CM, El Mohsen MA, Vauzour D et al. (2008)
Blueberry-induced changes in spatial working memory cor-
relate with changes in hippocampal CREB phosphoryl-
ation and brain-derived neurotrophic factor (BDNF)
levels. Free Radic Biol Med 45, 295305.
34. Wakabayashi C, Numakawa T, Ninomiya M et al. (2012)
Behavioral and molecular evidence for psychotropic effects
in L-theanine. Psychopharmacology (Berl) 219, 10991109.
35. Cecchini T, Ciaroni S, Ferri P et al. (2003) Alpha-
tocopherol, an exogenous factor of adult hippocampal
neurogenesis regulation. J Neurosci Res 73, 447455.
36. Molteni R, Barnard RJ, Ying Z et al. (2002) A high-fat,
rened sugar diet reduces hippocampal brain-derived
neurotrophic factor, neuronal plasticity, and learning.
Neuroscience 112, 803814.
37. Martire SI, Maniam J, South T et al. (2014) Extended
exposure to a palatable cafeteria diet alters gene expression
in brain regions implicated in reward, and withdrawal from
this diet alters gene expression in brain regions associated
with stress. Behav Brain Res 265, 132141.
38. Fung TC, Olson CA & Hsiao EY (2017) Interactions
between the microbiota, immune and nervous systems in
health and disease. Nat Neurosci 20, 145155.
39. Sudo N, Chida Y, Aiba Y et al. (2004) Postnatal microbial
colonization programs the hypothalamic-pituitary-adrenal
system for stress response in mice. J Physiol 558(Pt 1),
263275.
40. OMahony SM, Clarke G, Borre YE et al. (2015)
Serotonin, tryptophan metabolism and the brain-gut-
microbiome axis. Behav Brain Res 277,3248.
41. Hooper LV, Littman DR & Macpherson AJ (2012)
Interactions between the microbiota and the immune sys-
tem. Science (New York, NY) 336, 12681273.
42. Dinan TG & Cryan JF (2012) Regulation of the stress
response by the gut microbiota: implications for psychoneur-
oendocrinology. Psychoneuroendocrinology 37, 13691378.
43. Clarke G, Grenham S, Scully P et al. (2013) The
microbiome-gut-brain axis during early life regulates the hip-
pocampal serotonergic system in a sex-dependent manner.
Mol Psychiatry 18, 666673.
44. OMahony SM, Marchesi JR, Scully P et al. (2009) Early
life stress alters behavior, immunity, and microbiota in
rats: implications for irritable bowel syndrome and psychi-
atric illnesses. Biol Psychiatry 65, 263267.
45. Kelly JR, Borre Y, OBrien C et al. (2016) Transferring the
blues: depression-associated gut microbiota induces neurobe-
havioural changes in the rat. J Psychiatr Res 82,109118.
46. Zheng P, Zeng B, Zhou C et al. (2016) Gut microbiome
remodeling induces depressive-like behaviors through a
pathway mediated by the hosts metabolism. Mol
Psychiatry 21, 786796.
47. Bravo JA, Forsythe P, Chew MV et al. (2011) Ingestion of
Lactobacillus strain regulates emotional behavior and cen-
tral GABA receptor expression in a mouse via the vagus
nerve. Proc Natl Acad Sci USA 108, 1605016055.
48. Amar J, Chabo C, Waget A et al. (2011) Intestinal mucosal
adherence and translocation of commensal bacteria at the
W. Marx et al.8
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
early onset of type 2 diabetes: molecular mechanisms and
probiotic treatment. EMBO Mol Med 3, 559572.
49. Dantzer R, OConnor JC, Freund GG et al. (2008) From
inammation to sickness and depression: when the immune
system subjugates the brain. Nat Rev Neurosci 9,4656.
50. Maes M, Kubera M, Leunis JC et al. (2013) In depression,
bacterial translocation may drive inammatory responses,
oxidative and nitrosative stress (O&NS), and autoimmune
responses directed against O&NS-damaged neoepitopes.
Acta Psychiatr Scand 127, 344354.
51. Morris G, Walder K, McGee SL et al. (2017) A model of
the mitochondrial basis of bipolar disorder. Neurosci
Biobehav Rev 74(Pt A), 120.
52. Morris G & Berk M (2015) The many roads to mitochon-
drial dysfunction in neuroimmune and neuropsychiatric
disorders. BMC Med 13, 68.
53. Wright DJ, Renoir T, Smith ZM et al. (2015)
N-Acetylcysteine improves mitochondrial function and
ameliorates behavioral decits in the R6/1 mouse model
of Huntingtons disease. Transl Psychiatry 5, e492.
54. Maes M, Fisar Z, Medina M et al. (2012) New drug targets
in depression: inammatory, cell-mediated immune,
oxidative and nitrosative stress, mitochondrial, anti-
oxidant, and neuroprogressive pathways. And new drug
candidates Nrf2 activators and GSK-3 inhibitors.
Inammopharmacology 20, 127150.
55. Dean OM, Turner A, Malhi GS et al. (2015) Design and
rationale of a 16-week adjunctive randomized placebo-
controlled trial of mitochondrial agents for the treatment
of bipolar depression. Rev Bras Psiquiatr 37,312.
56. Jacka FN, Kremer PJ, Berk M et al. (2011) A prospective
study of diet quality and mental health in adolescents.
PLoS ONE 6, e24805.
57. Munoz MA, Fito M, Marrugat J et al. (2009) Adherence to
the Mediterranean diet is associated with better mental and
physical health. Br J Nutr 101, 18211827.
58. Oellingrath IM, Svendsen MV & Hestetun I (2014) Eating
patterns and mental health problems in early adolescence
a cross-sectional study of 1213-year-old Norwegian
schoolchildren. Public Health Nutr 17, 25542562.
59. Jacka FN, Cherbuin N, Anstey KJ et al. (2014) Dietary
patterns and depressive symptoms over time: examining
the relationships with socioeconomic position, health beha-
viours and cardiovascular risk. PLoS ONE 9, e87657.
60. Jacka FN, Cherbuin N, Anstey KJ et al. (2015) Does
reverse causality explain the relationship between diet and
depression? J Affect Disord 175, 248250.
61. Sanchez-Villegas A, Delgado-Rodriguez M, Alonso A
et al. (2009) Association of the Mediterranean dietary pat-
tern with the incidence of depression: the Seguimiento
Universidad de Navarra/University of Navarra follow-up
(SUN) cohort. Arch Gen Psychiatry 66, 10901098.
62. Quirk SE, Williams LJ, ONeil A et al. (2013) The
association between diet quality, dietary patterns and depres-
sion in adults: a systematic review. BMC Psychiatry 13,175.
63. Rahe C, Unrath M & Berger K (2014) Dietary patterns and
the risk of depression in adults: a systematic review of
observational studies. Eur J Nutr 53, 9971013.
64. Li Y, Lv MR, Wei YJ et al. (2017) Dietary patterns
and depression risk: a meta-analysis. Psychiatry Res 253,
373382.
65. Muhlig Y, Antel J, Focker M et al. (2016) Are bidirectional
associations of obesity and depression already apparent in
childhood and adolescence as based on high-quality stud-
ies? A systematic review. Obes Rev 17, 235249.
66. Sparling TM, Henschke N, Nesbitt RC et al. (2017) The
role of diet and nutritional supplementation in perinatal
depression: a systematic review. Matern Child Nutr 13,
e12235.
67. Baskin R, Hill B, Jacka FN et al. (2015) The association
between diet quality and mental health during the perinatal
period. A systematic review. Appetite 91,41
47.
68. Martinez-Gonzalez MA & Sanchez-Villegas A (2016)
Food patterns and the prevention of depression. Proc
Nutr Soc 75, 139146.
69. Jacka FN, Pasco JA, Mykletun A et al. (2010) Association
of Western and traditional diets with depression and anx-
iety in women. Am J Psychiatry 167, 305311.
70. Nanri A, Kimura Y, Matsushita Y et al. (2010) Dietary
patterns and depressive symptoms among Japanese men
and women. Eur J Clin Nutr 64, 832839.
71. Jacka FN, Mykletun A, Berk M et al. (2011) The associ-
ation between habitual diet quality and the common men-
tal disorders in community-dwelling adults: the Hordaland
Health Study. Psychosom Med 73, 483490.
72. Jacka FN (2017) Nutritional psychiatry: where to next?
EBio Med 17,2429.
73. Murakami K & Sasaki S (2010) Dietary intake and depres-
sive symptoms: a systematic review of observational stud-
ies. Mol Nutr Food Res 54, 471488.
74. Delgado-Lista J, Perez-Martinez P, Garcia-Rios A et al.
(2016) CORonary diet intervention with olive oil and car-
diovascular PREVention study (the CORDIOPREV
study): rationale, methods, and baseline characteristics.
Am Heart J 177,4250.
75. Li Z, Li B, Song X et al. (2017) Dietary zinc and iron
intake and risk of depression: a meta-analysis. Psychiatry
Res 251,4147.
76. Li F, Liu X & Zhang D (2016) Fish consumption and risk
of depression: a meta-analysis. J Epidemiol Commun
Health 70, 299304.
77. Sanchez-Villegas A, Martinez-Gonzalez MA, Estruch R
et al. (2013) Mediterranean dietary pattern and depression:
the PREDIMED randomized trial. BMC Med 11, 208.
78. Forsyth A, Deane FP & Williams P (2015) A lifestyle inter-
vention for primary care patients with depression and anx-
iety: a randomised controlled trial. Psychiatry Res 230,
537544.
79. Wu A, Ying Z & Gomez-Pinilla F (2004) Dietary omega-3
fatty acids normalize BDNF levels, reduce oxidative dam-
age, and counteract learning disability after traumatic brain
injury in rats. J Neurotrauma 21, 14571467.
80. Wu A, Ying Z & Gomez-Pinilla F (2004) The interplay
between oxidative stress and brain-derived neurotrophic
factor modulates the outcome of a saturated fat diet on
synaptic plasticity and cognition. Eur J Neurosci 19,
16991707.
81. Lim SY, Kim EJ, Kim A et al. (2016) Nutritional factors
affecting mental health. Clin Nutr Res 5, 143152.
82. Cui Y-h & Zheng Y (2016) A meta-analysis on the efcacy
and safety of St Johns wort extract in depression therapy in
comparison with selective serotonin reuptake inhibitors in
adults. Neuropsychiatr Dis Treat 12, 17151723.
83. Appleton KM, Sallis HM, Perry R et al. (2016) ω-3 Fatty
acids for major depressive disorder in adults: an abridged
Cochrane review. BMJ Open 6, e010172.
84. Sublette ME, Ellis SP, Geant AL et al. (2011) Meta-ana-
lysis of the effects of eicosapentaenoic acid (EPA) in clin-
ical trials in depression. J Clin Psychiatry 72, 15771584.
85. Sanders KM, Stuart AL, Williamson EJ et al. (2011)
Annual high-dose vitamin D3 and mental well-being: ran-
domised controlled trial. Br J Psychiatry 198, 357364.
86. Sarris J, Mischoulon D & Schweitzer I (2011) Adjunctive
nutraceuticals with standard pharmacotherapies in bipolar
Nutritional psychiatry 9
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
disorder: a systematic review of clinical trials. Bipolar Disord
13, 454465.
87. Almeida OP, Ford AH & Flicker L (2015) Systematic
review and meta-analysis of randomized placebo-controlled
trials of folate and vitamin B12 for depression. Int
Psychogeriatr 27, 727737.
88. Gowda U, Mutowo MP, Smith BJ et al. (2015) Vitamin D
supplementation to reduce depression in adults: meta-
analysis of randomized controlled trials. Nutrition 31,
421429.
89. Sarris J, Mischoulon D & Schweitzer I (2012) Omega-3 for
bipolar disorder: meta-analyses of use in mania and bipolar
depression. J Clin Psychiatry 73,8186.
90. Grosso G, Pajak A, Marventano S et al. (2014) Role of
omega-3 fatty acids in the treatment of depressive disor-
ders: a comprehensive meta-analysis of randomized clinical
trials. PLoS ONE 9, e96905.
91. Fernandes BS, Dean OM, Dodd S et al. (2016) N-
Acetylcysteine in depressive symptoms and functionality:
a systematic review and meta-analysis. J Clin Psychiatry
77, e457e466.
92. Rucklidge JJ & Kaplan BJ (2013) Broad-spectrum micro-
nutrient formulas for the treatment of psychiatric symp-
toms: a systematic review. Expert Rev Neurother 13,4973.
93. Firth J, Stubbs B, Sarris J et al. (2017) The effects of vitamin
and mineral supplementation on symptoms of schizophre-
nia: a systematic review and meta-analysis. Psychol Med
47, 15151527.
94. Salagre E, Vizuete AF, Leite M et al. (2017) Homocysteine
as a peripheral biomarker in bipolar disorder: a
meta-analysis. Eur Psychiatry 43,8191.
95. Deng W, Cheung ST, Tsao SW et al. (2016) Telomerase
activity and its association with psychological stress, men-
tal disorders, lifestyle factors and interventions: a system-
atic review. Psychoneuroendocrinology 64, 150163.
96. Januar V, Saffery R & Ryan J (2015) Epigenetics and
depressive disorders: a review of current progress and
future directions. Int J Epidemiol 44, 13641387.
97. Cerimele JM & Katon WJ (2013) Associations between
health risk behaviors and symptoms of schizophrenia and
bipolar disorder: a systematic review. Gen Hosp Psychiatry
35,1622.
98. Anderson G, Berk M, Dodd S et al.(2013)Immuno-inam-
matory, oxidative and nitrosative stress, and neuroprogressive
pathways in the etiology, course and treatment of schizophre-
nia. Prog Neuropsychopharmacol Biol Psychiatry 42,14.
99. Nemani K, Hosseini Ghomi R, McCormick B et al.
(2015) Schizophrenia and the gut-brain axis. Prog
Neuropsychopharmacol Biol Psychiatry 56, 155160.
100. Huang R, Wang K & Hu J (2016) Effect of probiotics on
depression: a systematic review and meta-analysis of ran-
domized controlled trials. Nutrients 8, e483.
101. Wallace CJK & Milev R (2017) The effects of probiotics
on depressive symptoms in humans: a systematic review.
Ann Gen Psychiatry 16, 14.
102. Romijn AR & Rucklidge JJ (2015) Systematic review of
evidence to support the theory of psychobiotics. Nutr
Rev 73, 675693.
103. Asevedo E, Mendes AC, Berk M et al. (2014) Systematic
review of N-acetylcysteine in the treatment of addictions.
Rev Bras Psiquiatr 36, 168175.
104. Deepmala D, Slattery J, Kumar N et al. (2015) Clinical
trials of N-acetylcysteine in psychiatry and neurology: a
systematic review. Neurosci Biobehav Rev 55,294321.
105. Dash SR, ONeil A & Jacka FN (2016) Diet and common
mental disorders: the imperative to translate evidence into
action. Frontiers in Public Health 4, 81.
106. Lakhan SE & Vieira KF (2010) Nutritional and herbal
supplements for anxiety and anxiety-related disorders:
systematic review. Nutr J 9, 42.
W. Marx et al.10
Proceedings of the Nutrition Society
https://doi.org/10.1017/S0029665117002026
Downloaded from https://www.cambridge.org/core. Monash University, on 28 Sep 2017 at 06:43:56, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
... Increasing evidence shows that fruit and vegetable-rich diets may have a protective role on stress, with consumption of whole fruit and vegetables (8), as well as some specific types (such as citrus fruits and leafy green vegetables) being linked with less stress (9). Moreover, healthy lifestyle factors, such as being active and adhering to a healthy diet (10,11), particularly a fruit and vegetable-rich diet, can help alleviate mental health issues (10,(12)(13)(14) and improve mental well-being (15). Therefore, greater intakes of FV could help reduce the estimated 7.8 million premature deaths worldwide, which have been associated with low intakes of fruit and vegetables (16), and consequently decrease the additional burden of chronic diseases and deaths caused by mental health worldwide (7). ...
... Bioactive compounds found in a healthy diet, particularly in a FV-rich diet, such as vitamins (i.e., B and C vitamins), minerals (i.e., zinc, magnesium) and fiber (i.e., resistant starch), have been linked to health and well-being (21). These constituents appear to play a protective role on mental health conditions (11), modulating some of the neurotransmitters in the brain, which regulate mood (21) and could potentially increase joy and happiness (64). Some neurochemicals (e.g., endorphin, dopamine, serotonin, norepinephrine, and melatonin) have been shown to cause feelings of happiness (22). ...
... Bioactive compounds in FV seem to protect against oxidative stress (23), inflammation (24) and brain plasticity (66), which are impaired in those with mental health issues (67). Dysbiosis of the gut microbiota is another potential pathway, with evidence showing the involvement of the microbiome in the modulation of stress response (11) and diet being an important modulator of gut health (68). ...
Article
Full-text available
Background and Aims Higher total fruit and vegetable (FV) intakes have been associated with lower perceived stress. However, the relationship of FV intake with domains of perceived stress is unclear. The aim of this cross-sectional study was to explore the relationship between consumption of FV and four perceived stress domains (worries, tension, lack of joy and demands) in a population-based cohort of Australian adults. Methods Participants (n = 8,640) were men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Dietary intake was assessed using a 74-item validated Food Frequency Questionnaire. Perceived stress domains were determined using a validated 20-item version of the Perceived Stress Questionnaire, with higher scores representing higher perceived stress. Cut-offs for high perceived stress domains were obtained from the highest quartiles of each domain for each sex. Multivariable-adjusted logistic regression was performed to investigate cross-sectional associations. Results The mean age of participants (50.1% females) was 47.8 (SD 15) years. Those with higher intakes of FV, combined and separately, had a significantly lower odds (16–36%) for higher worries, tension and lack of joy, independent of other lifestyle factors. Conclusion In Australian adults, higher consumption of FV was associated with lower odds of worries, tension and lack of joy. Following the dietary guidelines for the recommended intake of FV may help improve feelings of worries, tension and lack of joy, which are linked to mental health problems.
... Poor dietary quality is well established as a potentially modifiable risk factor for mental disorders [5,6]. Historically, the associations of poor dietary quality with mental disorders have largely focused on depression [7,8]. ...
... Our narrative syntheses of studies not eligible for meta-analysis showed that for 65% of analyses, intake of ultra-processed food was positively and cross-sectionally associated with depressive, anxiety, trauma and stress as well as addiction-related parameters. These findings build upon the extensive body of evidence that demonstrates healthier dietary patterns characterised by higher intakes of fruit, vegetables, whole grains, fish, olive oil and low-fat dairy, and lower levels of ultra-processed food, such as the Mediterranean and 'anti-inflammatory' diets [5,6,8,[51][52][53], are associated with reduced risk of mental disorders such as depression. ...
Article
Since previous meta-analyses, which were limited only to depression and by a small number of studies available for inclusion at the time of publication, several additional studies have been published assessing the link between ultra-processed food consumption and depression as well as other mental disorders. We aimed to build on previously conducted reviews to synthesise and meta-analyse the contemporary evidence base and clarify the associations between the consumption of ultra-processed food and mental disorders. A total of 17 observational studies were included (n = 385,541); 15 cross-sectional and 2 prospective. Greater ultra-processed food consumption was cross-sectionally associated with increased odds of depressive and anxiety symptoms, both when these outcomes were assessed together (common mental disorder symptoms odds ratio: 1.53, 95%CI 1.43 to 1.63) as well as separately (depressive symptoms odds ratio: 1.44, 95%CI 1.14 to 1.82; and, anxiety symptoms odds ratio: 1.48, 95%CI 1.37 to 1.59). Furthermore, a meta-analysis of prospective studies demonstrated that greater ultra-processed food intake was associated with increased risk of subsequent depression (hazard ratio: 1.22, 95%CI 1.16 to 1.28). While we found evidence for associations between ultra-processed food consumption and adverse mental health, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.
... Nutritional psychiatry is a rapidly expanding field of study, which has recently benefited from the advances of neurosciences, epidemiological research on risk factors as well as the renewed interest in the role of lifestyle in mental health [1]. Extensive observational evidence consistently demonstrates that diet quality is a predictor of depression riskindependent of other factors, such as education and body weight [2]. ...
... Considering that poor diet and dysfunctional eating behaviors are modifiable risk factors, it is possible that these will be converted into critical interventions for mental health [3,9,10]. Indeed, new clinical practice guidelines for mood disorders include diet, along with other aspects of lifestyle, as foundational and 'non-negotiable' treatment targets [1,11]. ...
Article
Introduction: Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD. Materials and methods: The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies. Results: There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC). Discussion: Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.
... Emerging research has demonstrated the importance of nutrient intake and dietary composition of whole foods for optimizing mental health (114)(115)(116)(117). The results of this study are in line with multiple meta-analyses, systematic reviews, and observational studies demonstrating positive effects of healthy dietary intake on mental health outcomes (118)(119)(120)(121). Additionally, a few RCT studies have also reported significant improvement in depression and anxiety symptoms from Mediterranean-style dietary interventions (122)(123)(124). ...
Article
Full-text available
The objective of this pilot study was to examine the effects of the low glutamate diet on anxiety, post-traumatic stress disorder (PTSD), and depression in veterans with Gulf War Illness (GWI). The low glutamate diet removes dietary excitotoxins and increases consumption of micronutrients which are protective against glutamatergic excitotoxicity. This study was registered at ClinicalTrials.gov (NCT#03342482). Forty veterans with GWI completed psychiatric questionnaires at baseline and after 1-month following the low glutamate diet. Participants were then randomized into a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG; a dietary excitotoxin) vs. placebo over three consecutive days per week, with assessments on day three. Data were analyzed across the full sample and with participants categorized by baseline symptom severity. Pre-post-dietary intervention change scores were analyzed with Wilcoxon signed-rank tests and paired sample t-tests across the full sample, and changes across symptom severity categories were analyzed using ANOVA. Crossover challenge results were analyzed with linear mixed modeling accounting for challenge material (MSG v. placebo), sequence (MSG/placebo v. placebo/MSG), period (challenge week 1 v. week 2), pre-diet baseline symptom severity category (minimal/mild, moderate, or severe), and the challenge material*symptom severity category interaction. A random effect of ID (sequence) was also included. All three measures showed significant improvement after 1 month on the diet, with significant differences between baseline severity categories. Individuals with severe psychological symptoms at baseline showed the most improvement after 1 month on the diet, while those with minimal/mild symptoms showed little to no change. Modeling results from the challenge period demonstrated a significant worsening of anxiety from MSG in only the most severe group, with no significant effects of MSG challenge on depression nor PTSD symptoms. These results suggest that the low glutamate diet may be an effective treatment for depression, anxiety, and PTSD, but that either (a) glutamate is only a direct cause of symptoms in anxiety, or (b) underlying nutrient intake may prevent negative psychiatric effects from glutamate exposure. Future, larger scale clinical trials are needed to confirm these findings and to further explore the potential influence of increased micronutrient intake on the improvements observed across anxiety, PTSD, and depression.
... A recent review suggested that the Mediterranean diet could provide a model for the reduction of dietary AGEs [163]. Consumption of foods with a low-glycaemic index that are naturally low in AGEs, including those derived from dietary patterns such as the Mediterranean and DASH (dietary approaches to stop hypertension) diet, have demonstrated potential for reducing cognitive decline and the incidence of mental disorders, particularly in those with T2DM [164][165][166]. As a result, healthy dietary interventions may represent affective strategies for avoiding the detrimental effects of AGE accumulation. ...
Article
Full-text available
Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.
... has increased (see Box 5 and Table 4). However, to warrant definitive recommendation, this dietary profile still requires further confirmation in well-designed clinical trials in clinical populations (Firth et al., 2019a;Li et al., 2017;Marx et al., 2017;Molendijk et al., 2018). ...
Article
Objective To rebut the claims made in an opinion piece by Anaf and colleagues regarding the recommendations for psychotherapy within the 2020 RANZCP Mood Disorders Clinical Practice Guidelines (CPG). Conclusions The CPG attaches importance to psychological interventions and recommends their administration as first-line in the treatment of depression. The concerns raised by Anaf and colleagues have no basis and are readily dismissed by referring to the guidelines. Therefore, we strongly encourage clinicians to formulate their own views by reading the guidelines for themselves.
Article
Deficiencies of nutrients, including vitamins, minerals and polyunsaturated fatty acids, and surpluses of food items, such as sucrose and artificial food additives, have not convincingly been shown to be involved in the etiology of ADHD. At group level, there is no conclusive evidence supporting dietary interventions for the treatment of ADHD. The identification of a role of food compounds in ADHD is hindered by the complex and ill-defined nature of ADHD. In view of the heterogeneity of the disorder, potential therapeutic benefits of nutritional interventions could be confined to subpopulations of children with ADHD as yet unidentified. The cumulative benefits of the range of ingredients comprising healthy diets may result in better outcomes compared to a supplementation of individual nutrients. Diet and nutrition interact with other lifestyle factors, such as physical activity, and the interrelationship between nutrition and lifestyle should play a more prominent role in research on treatment approaches to ADHD. The few-foods or oligoallergenic diet allows the design of individually tailored diets and may offer treatment opportunities in subgroups of children diagnosed with ADHD. Further research is required to demonstrate the utility of nutrition-related interventions alone or in combination with other treatment approaches in ADHD.
Article
Importance: Acupoint hot compress during the early postpartum period may benefit patients after a vaginal delivery, but the evidence of this effect is limited. Objective: To assess whether acupoint hot compress involving the abdominal, lumbosacral, and plantar regions could reduce the incidence of postpartum urinary retention, relieve postpartum uterine contraction pain, prevent emotional disorders, and promote lactation. Design, setting, and participants: This multicenter randomized clinical trial was conducted at 12 hospitals in China. Pregnant patients were screened for eligibility (n = 13 949) and enrolled after vaginal delivery (n = 1200) between January 17 and August 15, 2021; data collection was completed on August 18, 2021. After vaginal delivery, these participants were randomized 1:1 to either the intervention group or control group. Statistical analysis was based on per-protocol population. Interventions: Participants in the control group received routine postpartum care. Participants in the intervention group received routine postpartum care plus 3 sessions of a 4-hour acupoint hot compress involving the abdominal, lumbosacral, and plantar regions within 30 minutes, 24 hours, and 48 hours after delivery. Main outcomes and measures: The primary outcome was the incidence of postpartum urinary retention, defined as the first urination occurring more than 6.5 hours after delivery and/or use of an indwelling catheter within 72 hours after delivery. The secondary outcomes were postpartum uterine contraction pain intensity (assessed with the visual analog scale [VAS]), depressive symptoms (assessed with the Edinburgh Postnatal Depression Scale), and lactation conditions (including lactation initiation time, breastfeeding milk volume, feeding mood and times, and newborn weight). Results: Of the 1200 participants randomized, 1085 completed the study (537 in the intervention group and 548 in the control group, with a median [IQR] age of 26.0 [24.0-29.0] years). Participants in the intervention group compared with the control group had significantly decreased incidence of postpartum urinary retention (relative risk [RR], 0.58; 95% CI, 0.35-0.98; P = .03); improved postpartum uterine contraction pain when measured at 6.5 hours (median [IQR] VAS score, 1 [1-2] vs 2 [1-2]; P < .001), 28.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [1-2]; P < .001), 52.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [0-1]; P < .001), and 76.5 hours (median [IQR] VAS score, 0 [0-1] vs 0 [0-1]; P = .01) after delivery; reduced depressive symptoms (RR, 0.73; 95% CI, 0.54-0.98; P = .01); and increased breastfeeding milk volume measured at 28.5, 52.5, and 76.5 hours after delivery. No adverse events occurred in either of the 2 groups. Conclusions and relevance: Results of this trial showed that acupoint hot compress after vaginal delivery decreased postpartum urinary retention, uterine contraction pain, and depressive symptoms and increased breastfeeding milk volume. Acupoint hot compress may be considered as an adjunctive intervention in postnatal care that meets patient self-care needs. Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038417.
Article
When describing health care provider wellness, diet and nutrition are typically not addressed. This, in combination with the lack of decent food and diet resources typically available to the typically busy health care provider, exposes a significant gap in the road to advancing clinician wellness. This article aims to describe the relationship between nutrition and well-being, and potential barriers to optimal nutrition encountered by health care providers in the workplace. Readily available and practical strategies to improve physician diet and nutrition include: mindful eating practices, home meal preparation, food journaling, and mobile applications. From an organizational level, once physicians are making more informed food choices it is the hospital's responsibility to make nutritional options available in the workplace.
Article
Full-text available
The nascent field of ‘Nutritional Psychiatry’ offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and ‘psychobiotic’ interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.
Article
Full-text available
Background Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the “gut–brain axis.” Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans. MethodsA systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process. ResultsTen studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and duration of treatment varied widely and no studies assessed sleep. Conclusion The evidence for probiotics alleviating depressive symptoms is compelling but additional double-blind randomized control trials in clinical populations are warranted to further assess efficacy.
Article
Full-text available
Background The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes. Methods ‘SMILES’ was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses. Results We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen’s d = –1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ² (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3–27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions. Conclusions These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered on 29 February 2012.
Article
Although some studies have reported potential associations of dietary patterns with depression risk, a consistent perspective hasn’t been estimated to date. Therefore, we conducted this meta-analysis to evaluate the relation between dietary patterns and the risk of depression. A literature research was conducted searching MEDLINE and EMBASE databases up to September 2016. In total, 21 studies from ten countries met the inclusion criteria and were included in the present meta-analysis. A dietary pattern characterized by a high intakes of fruit, vegetables, whole grain, fish, olive oil, low-fat dairy and antioxidants and low intakes of animal foods was apparently associated with a decreased risk of depression.A dietary pattern characterized by a high consumption of red and/or processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes and high-fat gravy, and low intakes of fruits and vegetables is associated with an increased risk of depression. The results of this meta-analysis suggest that healthy pattern may decrease the risk of depression, whereas western-style may increase the risk of depression. However, more randomized controlled trails and cohort studies are urgently required to confirm this findings.
Article
Background: Bipolar disorder (BD) is a psychiatric disorder with an uncertain aetiology. Recently, special attention has been given to homocysteine (Hcy), as it has been suggested that alterations in 1-carbon metabolism might be implicated in diverse psychiatric disorders. However, there is uncertainty regarding possible alterations in peripheral Hcy levels in BD. Methods: This study comprises a meta-analysis comparing serum and plasma Hcy levels in persons with BD and healthy controls. We conducted a systematic search for all eligible English and non-English peer-reviewed articles. Results: Nine cross-sectional studies were included in the meta-analyses, providing data on 1547 participants. Random-effects meta-analysis showed that serum and plasma levels of Hcy were increased in subjects with BD in either mania or euthymia when compared to healthy controls, with a large effect size in the mania group (g=0.98, 95% CI: 0.8-1.17, P<0.001, n=495) and a small effect in the euthymia group (g=0.3, 95% CI: 0.11-0.48, P=0.002, n=1052). Conclusions: Our meta-analysis provides evidence that Hcy levels are elevated in persons with BD during mania and euthymia. Peripheral Hcy could be considered as a potential biomarker in BD, both of trait (since it is increased in euthymia), and also of state (since its increase is more accentuated in mania). Longitudinal studies are needed to clarify the relationship between bipolar disorder and Hcy, as well as the usefulness of peripheral Hcy as both a trait and state biomarker in BD.
Article
When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01–1.01, p = 0.047, I2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00–1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.
Article
The associations between dietary zinc and iron intake and risk of depression remain controversial. Thus, we carried out a meta-analysis to evaluate these associations. A systematic search was performed in PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for relevant studies up to January 2017. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. A total of 9 studies for dietary zinc intake and 3 studies for dietary iron intake were finally included in present meta-analysis. The pooled RRs with 95% CIs of depression for the highest versus lowest dietary zinc and iron intake were 0.67 (95% CI: 0.58-0.76) and 0.57 (95% CI: 0.34-0.95), respectively. In subgroup analysis by study design, the inverse association between dietary zinc intake and risk of depression remained significant in the cohort studies and cross-sectional studies. The pooled RRs (95% CIs) for depression did not substantially change in the influence analysis and subgroup analysis by adjustment for body mass index (BMI). The present meta-analysis indicates inverse associations between dietary zinc and iron intake and risk of depression.
Article
Many people identified as having common mental disorders in community surveys do not receive treatment. Modelling has suggested that closing this “treatment gap” should reduce the population prevalence of those disorders. To evaluate the effects of reducing the treatment gap in industrialized countries, data from 1990 to 2015 were reviewed from four English-speaking countries: Australia, Canada, England and the US. These data show that the prevalence of mood and anxiety disorders and symptoms has not decreased, despite substantial increases in the provision of treatment, particularly antidepressants. Several hypotheses for this lack of improvement were considered. There was no support for the hypothesis that reductions in prevalence due to treatment have been masked by increases in risk factors. However, there was little evidence relevant to the hypothesis that improvements have been masked by increased reporting of symptoms because of greater public awareness of common mental disorders or willingness to disclose. A more strongly supported hypothesis for the lack of improvement is that much of the treatment provided does not meet the minimal standards of clinical practice guidelines and is not targeted optimally to those in greatest need. Lack of attention to prevention of common mental disorders may also be a factor. Reducing the prevalence of common mental disorders remains an unsolved challenge for health systems globally, which may require greater attention to the “quality gap” and “prevention gap”. There is also a need for nations to monitor outcomes by using standardized measures of service provision and mental disorders over time.
Article
The diverse collection of microorganisms that inhabit the gastrointestinal tract, collectively called the gut microbiota, profoundly influences many aspects of host physiology, including nutrient metabolism, resistance to infection and immune system development. Studies investigating the gut–brain axis demonstrate a critical role for the gut microbiota in orchestrating brain development and behavior, and the immune system is emerging as an important regulator of these interactions. Intestinal microbes modulate the maturation and function of tissue-resident immune cells in the CNS. Microbes also influence the activation of peripheral immune cells, which regulate responses to neuroinflammation, brain injury, autoimmunity and neurogenesis. Accordingly, both the gut microbiota and immune system are implicated in the etiopathogenesis or manifestation of neurodevelopmental, psychiatric and neurodegenerative diseases, such as autism spectrum disorder, depression and Alzheimer's disease. In this review, we discuss the role of CNS-resident and peripheral immune pathways in microbiota–gut–brain communication during health and neurological disease.