Food and Mood

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Food and Mood

• Ted Dinan MD, PhD, DSc
• Department of Psychiatry
• and Alimentary Pharmabiotic Centre
• University College Cork

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Depression

• What is it?
• What causes it?
• What impact does it have?

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How is depression treated?

• SSRIs
• SNRIs
• Tricyclics
• Cognitive behaviour therapy

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AVP
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Cytokine Balance

• Anti-
• Inflammatory
• TGFß
• IL-10
• IFN a
• IL-11

• Pro-
• Inflammatory
• TNFa
• IFN?
• IL-8
• IL-12

ZEFE905
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CRP in Depression
OBrien et al, 2005
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Treatment Impact on CRP
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OBrien et al, 2005
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Which food components have potential as
antidepressants?

• Tryptophan
• Omega-3 fatty acid
• Folate
• Probiotics

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Serotonin synthesis
Tryptophan
?
5HTP
?
5HT
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Serotonin Anatomy
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Tryptophan

• Little storage capacity in brain
• The breakdown of tryptophan is regulated by two
  key enzymes namely, indoleamine, 2, 3-dioxygenase
  (IDO) and tryptophan 2, 3-dioxygenase (TDO).
• IDO is the enzyme in the kynurenine pathway,
  which converts tryptophan to kynurenine.

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Tryptophan depletion studies

• Using drinks rich in competing amino acids
  reduces tryptophan passage across the blood brain
  barrier.
• The effect of acute tryptophan depletion has been
  studied in patients with a history of depression
  who are currently free of symptoms.
• Tryptophan depletion results in a transient
  return of depressive symptoms

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Is tryptophan an antidepressant?

• Numerous studies have been conducted but the
  answer at this point is less than clear-cut
• Most of the studies had design flaws and
  conclusive evidence of antidepressant effect is
  not available
• There is no definite evidence that taking a
  daily supplement of tryptophan is of benefit to
  the average depressive (Shaw et al, 2002)

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Polyunsaturated fatty acids

• The main PUFAs in the brain are
• docosahexaenoic acid (DHA) derived
• from the omega 3 fatty acid, alpha-
  linolenic acid
• arachidonic acid (AA) and docosatetraenoic acid
  both derived from the omega 6 fatty acid,
  linoleic acid

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Omega-3

• Omega-3 fatty acid is derived from fish oil
• There is evidence that those with a diet rich in
  fish have a lower incidence of cardiovascular
  disease
• Studies suggest that in countries where there is
  a high consumption of fish there are lower rates
  of depression (Sanchez-Villegas et al, 2006
  Muskiet Kemperman, 2006)

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Treatment Responders
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Treatment Non-Responders
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Omega-3 treatment of depression

• N22 depressed patients
• All failed to respond to antidepressant treatment
• 4 weeks of omega-3 (E-EPA) or placebo
• Highly significant benefits of the addition of
  the omega-3 fatty acid compared with placebo were
  found by week three of treatment.

Nemets et al (2002)
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Omega-3 treatment study

• N70 antidepressant non-responding patients
• The patients were randomised to receive either
  placebo or E-EPA in doses of 1, 2 or 4 grams per
  day for 12 weeks in addition to their
  antidepressant.
• The 1 gram per day group showed a significantly
  better outcome than the placebo group.

Peet et al, 2002
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How does omega-3 work?

• The mechanism through which E-EPA impacts on the
  symptoms of depression is not fully understood.
• It is know that E-EPA has a general
  immuno-suppressive effect with a capacity to
  suppress inflammatory states.

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Folic acid

• Studies report that patients with major
  depression have low plasma, serum or red blood
  cell folate levels
• Papakostas et al (2004) followed 71 patients with
  major depression who had responded to therapy
  with fluoxetine. Over 40 of patients with low
  folate levels relapsed, whilst, only 3 of those
  with higher levels of folate relapased over 28
  weeks.

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Community study of folic acid

• Sachdev et al (2005) examined the relationship
  between folic acid and depression in a sample of
  412 individuals between the ages of 60 and 64
  years of age.
• Low serum folate was significantly associated
  with the presence of depressive symptoms.

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Folic acid treatment study

• Placebo controlled study in a general practice
  setting.
• N127 randomly allocated to receive either
  fluoxetine 20mg daily plus placebo or fluoxetine
  20mg daily plus folic acid 500mcg daily.
• Ninety-four percent of the women showed a
  response to folic acid as compared with only 61
  of the women who received fluoxetine alone.

Coppen Bailey, 2000
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Probiotics

• Probiotics are defined as living
  micro-organisms, which upon ingestion in certain
  numbers exert health benefits beyond general
  nutrition
• Numerous unsubstantiated claims
• Demonstrated efficacy in IBS

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Probiotics in depression

• The principal rationale for the use of probiotics
  in treating major depression rests on their
  potential for suppressing the pro-inflammatory
  component of depression.

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Evidence in maternal separation model of
depression

• Bifidobacteria have the capacity to
• suppress corticosterone levels
• reduce pro-inflammatory cytokines
• alter central 5HT transmission
• increase exploratory behaviour in the open field

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Vaillant Study (1998)

• 55 year prospective study
• Examined the relationship between mood disorder
  and physical health
• 237 men were followed from College entry

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Vaillant Study Results

• 45 of those with poor psychological health were
  dead
• 5 of those with good psychological health were
  dead

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Ford et al Study (1994)

• 35 year prospective study of 1198 male university
  students
• Depressive illness significantly increased risk
  of heart disease
• On average there was a lag of ten years between
  the first depressive episode and evidence of
  heart disease

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Epidemiological Catchment Area Study

• Prospective study in Baltimore
• 1551 physically healthy subjects at baseline were
  studied
• Following an episode of major depression the risk
  of myocardial infarction increases 3-4 fold

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Is the link between depression and heart
disease gender specific?(Barefoot and Schroll
1996)

• 409 men and 321 women born in 1914
• Physical and psychiatric assessments were
  conducted in 1964 and 1974 and 1991
• Depression increased risk of heart disease
• Risk is not gender specific

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Conclusions

• Good mental health is dependent on a balanced
  diet and exercise
• As yet no food component has been conclusively
  demonstrated to have antidepressant properties
• Depression can result in poor cardiovascular
  health