iCAAD London 2019 - Prof Wulf Rossler - NUTRITION, SLEEP AND PHYSICAL EXERCISE: IMPACT ON MENTAL HEALTH

Nutrition, Sleep, Physical
Exercise: Impact on Mental
Health
Wulf Rössler
Berlin | Zürich | São Paulo
ICAAD, London, May 6, 2019
On behalf of “The Kusnacht Practice“

Member of the board of Directors of
„The Kusnacht Practice“

The role of diet and nutrition on
mental health and wellbeing
 Mental, neurological and substance-use disorders presently
represent the greatest global burden of disease
 Likewise, depression and other psychopathologies are elevated risk
comorbidities of other health hazards, such as obesity
 Nutrition has been implicated in behaviour, mood and in the
pathology and treatment of mental illness.
 There is compelling support for nutrition as a modifiable risk factor.
Owen L, Corfe B. The role of diet and nutrition on mental health and wellbeing. Proc
Nutr Soc. 2017 Nov;76(4):425-426

Nutrition and Mental Health
 Background:
 In recent years psychopharmacology achieved only mixed
results in treatment of mental disorders
 non-pharmacological treatment approaches receive increasing
attention
 extensive epidemiological evidence for associations between
habitual diet quality and mental disorders
Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial
severity and antidepressant benefits: a meta-analysis of data submitted to the Food and
Drug Administration. PLoS Med. 2008 Feb;5(2)

Nutritional medicine as mainstream
in psychiatry
Sarris J, Logan AC, Akbaraly TN, Amminger GP, Balanzá-Martínez V, Freeman MP,
Hibbeln J, Matsuoka Y, Mischoulon D, Mizoue T, Nanri A, Nishi D, Ramsey D,Rucklidge
JJ, Sanchez-Villegas A, Scholey A, Su KP, Jacka FN; International Society for Nutritional
Psychiatry Research. Lancet Psychiatry. 2015 Mar;2(3):271-4.
 Rapid urbanisation, and transition from traditional lifestyles
(concerning diet, physical activity, and social structures) have
been linked to increases in depression and other mental
disorders
 depression and other common mental disorders are part of an
epidemic of comorbidity between physical and mental ill health,
with diet being crucial determinant
 shift towards high, less nutritious foods instead of traditional,
more healthful diets
 many people are both overfed and undernourished

in psychiatry (cont’d)
 many individuals in affluent nations do not meet recommended
intakes of several brain-essential nutrients, including B-vitamins,
zinc, and magnesium
 although slight improvements have been detected in dietary intakes
of sugar and fats, documented intakes of nutrient-rich and fibre-rich
vegetables and whole grains are far lower than recommended
 these profound changes in dietary habits, along with tobacco use,
insufficient physical activity, and harmful alcohol and recreational
drug use, have resulted in an epidemic of ill health
Sarris Jet al., International Society for Nutritional Psychiatry Research. Lancet Psychiatry.
2015 Mar;2(3):271-4.

in psychiatry (cont’d 2)
 mechanisms by which nutrition might affect mental health are obvious:
 the human brain operates at a very high metabolic rate, and uses a
substantial proportion of total energy and nutrient intake; in both
structure and function
 it is reliant on amino-acids, fats, vitamins, and minerals or trace elements
 Dietary habits modulate functioning of the immune system, which also
moderates the risk for depression
 The antioxidant defence system, which is also implicated in mental
disorders, operates with support of nutrient cofactors and
phytochemicals
 Additionally, neurotrophic factors make essential contributions to
neuronal plasticity and repair mechanisms throughout life, and these too
are affected by nutritional factors
Sarris Jet al., International Society for Nutritional Psychiatry Research. Lancet Psychiatry.
2015 Mar;2(3):271-4.

in psychiatry (cont’d 3)
 selected nutrient-based supplements might provide many neurochemical
modulatory activities beneficial in the management of mental disorders
 Examples of these nutrient-based supplements include:
 omega-3 fatty acids
 S-adenosyl methionine (SAMe)
 N-acetyl cysteine (NAC)
 zinc
 B vitamins (including folic acid), and
 vitamin D
 Various clinical investigations support usefulness of omega-3 fatty acids
for disorders including BPD ,PTSD, and major depression, and they are
indicated in the prevention of psychosis

L-Dopa
Tyrosine
Phenylalanin-
Decarboxylase
Vit B6
CO2
SAM-e
SAHom
THB
Phenylalanin- Hydroxylase
Folic acid,
Magnesium
THB
Tyrosin-
Hydroxylase
Folic acid, SAM-e
DHB
NAD(P)H+H+
Tyrosin-
Hydroxylase
Calcium
NAD(P)+
Dopa-
Decarboxylase
Vit B6
CO2
O2
Dopamin-B
Hydroxylase
Vit C, Iron, Copper
H2O
Phenylethanolamin-
N-Methyltransferase
Vit B6, B12,
Folic acid
Dopamine
Adrenaline
Noradrenaline
Phenylalanine
Antoinette Sarasin/Adapted based on specialist brochure,
Ganzimmun, Labor für funktionelle Medizin AG
Co-factors in the synthesis of
neurotransmitters:
Dopamine

Serotonin
Acetylserotonin
Serotonin
Melatonin
NAD(P)H+H+
Tyrosin-
Hydroxylase
Calcium, SAM-e
NAD(P)+
Kynurenine
1% 9% 90%
Darkness
Acetyl-CoA
AANAT
Pantothenic acid
CoA
SAM-e
HIOMT
SAHom
Vit B6, B12,
Folic acid
Tetrahydro-
biopterin
Dihydro-biopterin
AAD
Vit B6,
Magnesium, Folic
acid, Omega-3
fatty acids
CO2
Tryptophan
5-Hydroxytryptophan (5-HTP)

Vit B6, Vit B12, Mg
Glutamat-
Decarboxylase
CO2
NH2
Glutamin-
synthetase
Glutamat-
dehydrogenase
NH2
Transaminierung
Vit B6, Vit B12, Mg
a-Ketoglutarat
Glutamat
Glutamine GABA
GABA

Epigenetics, nutrition and mental
health. Is there a relationship?
 Many aspects of human development and disease are influenced by the interaction
between genetic and environmental factors.
 Understanding how our genes respond to the environment is central to managing
health and disease and is one of the major contemporary challenges in human
genetics.
 Various epigenetic processes affect chromosome structure and accessibility of
deoxyribonucleic acid (DNA) to the enzymatic machinery that leads to expression of
genes.
 One important epigenetic mechanism that appears to underlie the interaction
between environmental factors, including diet, and our genome, is chemical
modification of the DNA.
 The best understood of these modifications is methylation of cytosine residues in
DNA.
 It is now recognized that the pattern of methylated cytosines throughout our genomes
(the ‘methylome’) can change during development and in response to environmental
cues, often with profound effects on gene expression.
Aaron J. Stevens, Julia J. Rucklidge & Martin A. Kennedy (2018) Epigenetics, nutrition
and mental health. Is there a relationship?, Nutritional Neuroscience, 21:9, 602-613

The Relationship between Nutrition
in Infancy and Cognitive
Performance during Adolescence.
Nyaradi A, Oddy WH, Hickling S, Li J, Foster JK. Front Nutr.2015 Feb 11;2:2.
 investigate the long-term associations between breastfeeding
duration during infancy, diet quality and cognitive performance
during adolescence.
 Results: Higher diet scores at 1 year representing better diet quality
were significantly associated with faster reaction times in cognitive
performance at 17 years

impact of diet-based glycaemic response and
glucose regulation on cognition: evidence across
the lifespan
 The brain has high metabolic rate and its metabolism is almost entirely
restricted to oxidative utilisation of glucose
 Thisemphasises extreme dependence of neural tissue on a stable and
adequate supply of glucose.
 initially thought that only glucose deprivation (i.e. under hypoglycaemic
conditions) can affect brain function, it has become apparent that low-level
fluctuations in central availability can affect neural and consequently,
cognitive performance
 although acute rise in blood glucose levels has some short-term
improvements of cognitive function, a more stable blood glucose profile,
which avoids greater peaks and troughs in circulating glucose is associated
with better cognitive function and a lower risk of cognitive impairments in the
longer term.
 Therefore, a habitual diet that secures optimal glucose delivery to the brain
in the fed and fasting states should be most advantageous for the
Sünram-Lea SI, Owen L. The impact of diet-based glycaemic response and glucose regulation on
cognition: evidence across the lifespan. Proc Nutr Soc. 2017 Nov;76(4):466-477 Review

Potential for primary prevention of
Alzheimer’s disease: an analysis of
population-based data
 Reduction of risk factors:
 Diabetes mellitus
 Midlife hypertension
 Midlife obesity
 Physical inactivity
 Depression
 Smoking
 Low educational attainment
 Conclusion:
 around a third of Alzheimer’s diseases
cases worldwide might be attributable to
potentially modifiable risk factors
 Alzheimer’s disease incidence might be
reduced through
 improved access to education and
 use of effective methods targeted at
reducing prevalence of vascular risk
factors (e.g. physical inactivity, smoking,
midlife hypertension, midlife obesity,
and diabetes) and depression)
Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. LancetNeurol. 2014
Aug;13(8):788-94.

The role of diet and nutrition in dementia
 The consequences of poor diet also impact on a global health
hazard: obesity.
 Alzheimer’s disease and depression are comorbidities of obesity,
leading to the theory that vascular impairments may have a role in
the development of dementia and psychiatric pathologies.
 As a result of these observations, Alzheimer’s disease and other
dementias are now being thought of as potentially preventable
diseases.
 In a 27-year longitudinal study, obesity in mid-life was shown to
double the risk of developing dementia at later age
 Moreover, while cognitive deficits have been associated with
glycaemic regulation in diabetes, only in the recent years observed
that cognitive deficits exist in young healthy, normal weight
individuals with poor glucoregulation,
 This exemplifies need for early, rather than later life, preventative
nutrition measures
Owen L, Corfe B. The role of diet and nutrition on mental health and wellbeing. Proc
Nutr Soc. 2017 Nov;76(4):425-426

Neural Signaling of Food Healthiness
Associated with Emotion Processing
Front Aging Neurosci. 2016 Feb 10;8:16..2016.
Herwig U, Dhum M, Hittmeyer A, Opialla , Scherpiet S, KellerC, Brühl AB, Siegrist M
 The ability to differentiate healthy from unhealthy foods important in order
to promote good health
 Food, however, may have an emotional connotation, which could be
inversely related to healthiness
 Compared individual evaluations of high and low healthiness of food items
 found increased activation when food was evaluated to be healthy in the
left DLPC
 perceived and rated higher healthiness was associated with lower amygdala
activity and higher ventral striatal and orbitofrontal cortex activity.

Under Stress we choose unhealthy food
Neuron. 2015 Aug 5;87(3):621-31. Acute Stress Impairs Self-Control in Goal-Directed
Choice by Altering Multiple Functional Connections within the Brain's Decision Circuits.
Maier SU, Makwana AB, Hare TA
 Important decisions are often made under stressful circumstances that
might compromise self-regulatory behaviour
 investigated mechanisms in human participants who faced self-control
dilemmas over food reward while undergoing fMRI following stress
 found that stress increased the influence of immediately rewarding
taste attributes on choice and reduced self-control
 results indicate that stress may compromise self-control decisions by
both enhancing the impact of immediately rewarding attributes and
reducing the efficacy of regions promoting behaviours that are
consistent with long-term goals

Gut–brain axis: how the
microbiome
influences anxiety and depression
Foster JA, McVey Neufeld
KA. Trends Neurosci. 2013
May;36(5):305-12. Review.
reciprocal relationship,
with the CNS moderating, e.g.
gut motility and secretion
manipulation of the gut microbiota
with specific probiotics or with
antibiotics can influence
depression-like behaviours
prenatal and early life stress
modulates the microbial
composition of the gut in
infants and suggests
implications for vulnerability to
mental disorders
in children

Stress and Microbiota
 depressive episodes associated with dysregulation of the hypothalamic–
pituitary–adrenal axis, resolution of depressive systems with normalization of
the HPA axis
 Gut microbiota play role in programming of the HPA axis early in life and stress
reactivity over lifespan
 neonatal stress leads to long-term changes in diversity and composition of gut
microbiota, which contribute to long-term alterations in stress reactivity
 concurrent treatment with probiotics (Lactobacillus sp.) during the early stress
period has been shown to normalize basal cortisol levels
 Stress known to increase intestinal permeability (leaky gut)
 bacteria directly access both immune cells and neuronal cells of the ENS
 potential pathway whereby microbiota can influence CNS via immune system
and ENS in presence of stress
Foster JA, McVey Neufeld KA. Trends Neurosci. 2013 May;36(5):305-12. Review.

Leaky Gut
 gut barrier controls flow of molecules between gastrointestinal tract and
bloodstream
 Compromised integrity of barrier been termed ‘leaky gut’
 associated with a wide range of intestinal and systemic diseases, including
allergies, autoimmune disorders, asthma, IBD and, speculatively, to mental health
 consequence of leaky gut, is increase in circulating bacteria derived
lipopolysaccharide which triggers immunological and inflammatory response
 increased systemic pro-inflammatory cytokines
 Inflammation suggested causative factor in depression
 Bacterial translocation across the gut wall induces an autoimmune response to
serotonin associated with fatigue and illness behaviour
Dash S, Clarke G, Berk M, Jacka FN. The gut microbiome and diet in psychiatry:
focus on depression. Curr Opin Psychiatry. 2015 Jan;28(1):1-6.

Biomarkers and clinical staging in
Psychiatry
McGorry P, Keshavan M, Goldstone S, Amminger P, Allott K, Berk M, Lavoie S,Pantelis
C, Yung A, Wood S, Hickie I. Biomarkers and clinical staging in psychiatry. World
Psychiatry. 2014 Oct;13(3):211-23.
 it is during the early stages of a disorder that interventions have the potential
to offer the greatest benefit
 progression of illness is by no means inevitable, but can be altered by
providing appropriate interventions that target individual modifiable risks and
protective factors

Biomarkers and clinical staging in
Psychiatry
McGorry et al. Biomarkers and clinical staging in psychiatry. World Psychiatry. 2014
Oct;13(3):211-23.
Possible targets of interventions

Inflammatory and oxidative stress
marker
 increasing evidence to implicate inflammatory processes in the
pathophysiology of major psychiatric disorders
 Elevated levels of cytokines are a well-replicated finding in most major
mental illnesses
 Elevated levels of pro-inflammatory cytokines appear to precede the
development of de novo disorder, suggesting that they play a role in its
genesis
 consistent body of evidence for an increase in oxidative stress in mood
and psychotic disorders, including reduction in brain glutathione levels,
changes in antioxidant enzymes, lipid peroxidation
Oct;13(3):211-23.

Inflammatory and oxidative stress
marker (cont’d)
 Evidence that most established psychotropic agents, including mood stabilizers and atypical
antipsychotics, have substantive impacts on oxidative and inflammatory pathways
 selective COX-2 blocker displays potential efficacy in the treatment of bipolar disorder
 and schizophrenia
 use of statins, which have anti-inflammatory and antioxidant properties, associated with
lowered risks of mood disorders in community studies
 N-acetylcysteine, which has antioxidant and anti-inflammatory properties, shows preclinical
and clinical efficacy in bipolar disorder and schizophrenia and is a potential neuroprotective
candidate
 Aspirin appeared to reduce the symptoms of schizophrenia in a placebo-controlled trial and
was linked to less progression of disease in bipolar disorder
 in a pharmaco-epidemiological study Minocycline, which has antioxidant and anti-
inflammatory properties, has potential in diverse illness models
McGorry et al. Biomarkers and clinical staging inpsychiatry. World Psychiatry. 2014
Oct;13(3):211-23.

Fatty acids marker (cont‘d)
 Phospholipids are main structural elements of all cell membranes
 polyunsaturated fatty acids (PUFAs) play central roles in broad range
of physiological functions e.g. signal transduction, receptor sensitivity
 Are precursors, which mediate inflammatory response
 have neuro-protective effect.
 PUFAs are essential fatty acids
 since humans are unable to synthesize them de novo, they must be
sourced in diet
 Typical Western diet contains low levels of anti-inflammatory omega-
3 fatty acids and high levels of pro-inflammatory omega-6 fatty acids
and saturated fatty acids, leading to increased production of pro-
inflammatory eicosanoids
 This imbalance has pathological consequences, and is a promoter of
chronic disease
Oct;13(3):211-23.

Fatty acids marker (cont‘d 2)
Oct;13(3):211-23.
 In relation to mental health, omega-3 PUFAs may play role in pathogenesis
of major affective and psychotic disorders
 patterns of these fatty acid alterations are not specific to depression, but
are also found in other conditions accompanied by increased oxidative
stress, such as Alzheimer’s disease, bipolar disorder, schizophrenia, and
during normal ageing
 study in a cohort of 33,000 women from the general population found
relationship between dietary intake of fish (the richest dietary source of PUFAs)
and vitamin D and psychotic-like symptoms
 also preliminary evidence that fatty acid deficits may be present during the early
of psychotic disorders.

Sleep and chronobiological
markers
 characteristic of onset of most major psychiatric disorders is disruption of
sleep, often accompanied by shifts in the sleep-wake cycle
 Shortened sleep duration appears to be a risk factor to the onset of common
forms of psychological distress
 Poly-somnographic studies have received relatively little attention in recent
years, because of lack of diagnostic specificity
 There appear to be distinct sleep “signatures”, with consistent reductions in
slow wave sleep in schizophrenia, and shortened rapid eye movement
latency and increases in REM density in depression
Oct;13(3):211-23.

Sleep problems in the general
population (age 20-40)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Class 1: NO
Class 2: SM
Class 3: SI
 Roughly ¼ suffers from sleep problems (approx. 18% sleep misperception, 7% severe
insomnia)
 mental health problems strongly related to patterns of sleep disturbances, e.g. affective disorders,
in particular major depression and dysthymia
 also concomitant with a broad range of mental health problems below the diagnostic threshold
(e.g. Burnout).
Sleep misperception:
symptoms of initiating
sleep, frequent
awakening during the
night and to a lesser
degree early awakening
Severe insomnia: broad
range of symptoms,
such as difficulties to get
up in the morning,
initiating sleep, frequent
awakening, early
awakening, anxiety
during the night and
nightmares,
Rössler et al. Sleep disturbances in young adults. Empirical patterns and related factors from an
epidemiological survey, Compr Psychiatry. 2017 Oct;78:83-90

Diet, Sleep, Exercise and
DepressionLopresti AL, Hood SD, Drummond PD. A review of lifestyle factors that contribute to
important pathways associated with major depression: diet, sleep heightened cortisol
secretion and exercise. J Affect Disord. 2013 May 15;148(1):12-27.
 heightened cortisol
secretion
 hypersecretion of
corticotropin-releasing
hormone (CRH)
 Successful treatment with
antidepressants is
associated with a
normalisation of HPA axis
activity and restoration in
glucocorticoid receptor
function
 reduced plasma concentrations of important antioxidants (vitamin C,
vitamin E and coenzyme Q10)
 reduced antioxidant enzyme activity such as glutathione peroxidase
 these deficiencies in antioxidant defenses impair protection against
reactive oxygen species (ROS), leading to damage to fatty acids, proteins
and DNA
 Elevated levels of C-reactive protein (CRP), interleukin-1 (IL-1), and
interleukin-6 (IL-6) reported in a meta-analysis on depression in clinic
and community samples

Relationship between Diet an
Depression
Lopresti et al. A review of lifestyle factors that contribute to important pathways
associated with major depression: diet, sleep heightened cortisol secretion and exercise. J
Affect Disord. 2013 May 15;148(1):12-27.
association between diet and depression has now been confirmed in prospective and
epidemiological studies:
 consumption of fish, vegetables, olive oil, and cereal correlated negatively
with the severity of depressive symptoms
 adherence to Mediterranean diet comprising high levels of vegetables, fruit,
nuts, cereal, legumes, and fish, moderate alcohol intake, and low
consumption of meat or meat products and whole-fat dairy, was protective
against the development of depression
 Depressive symptoms are positively associated with the consumption of
sweets
 Similarly, high intake of fast food (hamburgers, sausages, pizza) and processed
pastries (muffins, doughnuts, croissants) are associated with increased risk of
depression up to 6 years later investigations on the relationship between
nutrients and depression have demonstrated a role of folate and omega-3
essential fatty acids

Diet and its effect on
inflammation
 strong evidence in human studies that adherence to a Mediterranean diet is
associated with reduced inflammatory markers
 In a study on people with metabolic syndrome, five weeks on a Mediterranean
diet corresponded with lowered plasma CRP and an arbitrary inflammatory score
that included CRP, IL-6, IL-18, and TNF-a
 CRP levels were lower in an elderly population on a Mediterranean diet compared
to a standard ‘healthy diet’ comprising a high intake of fruits and low
consumption of eggs, spirits or liqueurs, and meats such as bacon, pork, lamb,
and sausages
 fatty acids were able to partly inhibit a number of aspects of inflammation

Diet and its effect on oxidative
stress
 Given the crucial role that diet plays in antioxidant intake, diet quality also
influences levels of oxidative stress
 In obese adults with metabolic syndrome, reducing energy intake by 2000
kJ, mainly via carbohydrate restriction, was associated with decreased
oxidative stress and increased levels of antioxidant markers
 Mediterranean diet is associated with increased circulating plasma
antioxidant levels and decreased oxidative stress

Sleep and its effect on
inflammation, oxidative stress and
HPA axisLopresti et al. A review of lifestyle factors that contribute to important pathways
 Inflammation
 Sleep difficulties increase inflammatory mediators; conversely elevated
inflammatory molecules heighten the risk of sleep problems
 IL-1, IL-6 and TNF-a may be directly involved in sleep regulation
cytokines are sleep regulatory, as they support the regulation of
spontaneous sleep–wake behaviour
 In patients with major depression, difficulty initiating sleep correlated
with increased pre-sleep levels of IL-6
 oxidative stress:
 difficulty falling asleep was related to higher morning levels of CRP and
IL-6
 proposed that cerebral free radicals accumulate during wakefulness
and are removed during sleep
 HPA axis
 Cortisol levels were also positively correlated with the severity of
reported sleep disturbance

The relationship between Exercise
& Depression
 investigations into sedentary behaviours largely confirmed a positive
relationship with depression
 Depression is commonly associated with low levels of physical activity
 studies do not necessarily confirm causation, but consistent relationship
does exist
 In adults, active lifestyle associated with reduced depressive symptoms
 In overweight/obese adults, reduced risk of depression was associated with
increasing moderate-to vigorous-intensity physical activity and decreasing
sedentary time
 In a longitudinal study of over 9000 people, regular physical activity was
associated with a reduced likelihood of depressive symptoms at follow-up

Exercise and its effect on
Inflammation, oxidative Stress and
HPA Axis
 exercise is followed by an increase in anti-inflammatory cytokines and a
decreased production of the pro-inflammatory cytokines TNF-a and IL-1b
 exercise results in an up-regulation of antioxidant enzymes, thus exercise
itself can be considered an antioxidant despite generating free radicals
 In a study on female adolescents with mild-to-moderate depression, 8 weeks
of an exercise regimen improved depressive symptoms and was associated
with reductions in 24 h urinary cortisol levels

Assessing the Potential and Limitations of Leveraging Food Sovereignty to Improve
Human Health Andrew D. Jones1 , Lilly Fink Shapiro and Mark L. Wilson REVIEW
published: 23 November 2015
Food Sovereignty to improve Human
(mental) Health
 Food sovereignty has been defined as "the right of
peoples to healthy and culturally appropriate food
produced through ecologically sound and sustainable
methods, and their right to define their own food and
agriculture systems”
 Human health is an implied component of this definition
through the principle of healthy food
 concerted effort to generate new empirical evidence on the
health implications of these domains of food sovereignty is
urgently needed

Conclusions
 While the importance of lifestyle factors such as diet, exercise and sleep are
generally acknowledged in research literature, the mechanisms of their potential
influence are often not fully understood
 exercise and sleep can influence several physiological pathways
 A bi-directional relationship likely exists between several mental disorders and
these lifestyle factors
 a multitude of other lifestyle influences may also be important e.g. chronic stress,
social influences, mental and physical effects associated with medical diseases,
alcohol and other drug use, chronic pain or even exposure to sunlight/vitamin D. It
is these influences, plus array of psychological, genetic and biological factors that
 Basic interventions comprising attention towards one cause and/or one
biochemical mechanism (e.g., targeting a single neurotransmitter disturbance)
makes goal of remission or recovery less likely

iCAAD London 2019 - Prof Wulf Rossler - NUTRITION, SLEEP AND PHYSICAL EXERCISE: IMPACT ON MENTAL HEALTH

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