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Mental health, depression and

bipolar disorder
Dr Mhairi Morris
mhairi.morris@dmu.ac.uk

Learning outcomes
By the end of this lecture you will:
1.Be able to describe the symptoms and diagnosis of
depression
2.Be able to discuss the evolving classifications of
depression
3.Be able to describe the overlap and differences between
depression and other similar disorders such as bipolar
disorder and addiction
4.Be able to discuss a number of different hypotheses
belying the cause of depression
5.Be able to describe the methods to treat depression,
including natural remedies and drug therapy

Introduction
Mental health:
Depression symptoms, facts, classification
Overlap with other disorders bipolar disorder, addiction
Areas of the brain involved and neurotransmission
Causes:

Stress!
Genetics?
Non-shared environment
Monoamine hypothesis
Gut microbiome

Treatment

Introduction to mental health

Depression
15% of population affected
Memory
impairment

Feelings of
worthlessness

Reward/
motivation

Anhedonia

Symptoms
Anxiety

Cognitive
aspects

Guilt
Doom

Emotional
memory

Feelings of
hopelessness
Suicidality

Neurovegetative
symptoms
Too much/too
little sleep
Lack of
energy

Loss of
interest

Loss of
appetite

http://www.nimh.nih.gov/news/science-news/2006/mice-lackingsocial-memory-molecule-take-bullying-in-stride.shtml

Body map energy (sensory activity)

Diagnosis
Five of the following 9 for at least 2 weeks:
1.
2.
3.
4.
5.
6.
7.
8.

Depressed mood
Loss of interest/pleasure
Significant weight or appetite alteration
Insomnia or hyposomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Feelings of worthlessness
Diminished ability to think or concentrate or
indecisiveness
9. Suicidal ideation

The facts
75% of patients will have another episode
within 10 years
Suicide = high risk for mortality
High between age of 15 and 24 years

Strong link between depression and CVD


Anxiety generally precedes depression
Alcohol misuse is equally likely to pre- or
postdate onset of depression

Types of depression
Early 20th Century two concepts:
Emil Kraepelin depression as a disease
Sigmund Freud depression as a manifestation of
internalised anger and loss

Sir Martin Roth and the Newcastle Group:


Endogenous independent of precipitating events
Reactive exaggerated reaction to life events

Recent classification:
Unipolar (depression)
Bipolar (manic depressive) disorder

Separation between depression


and other disorders
Two disorders that overlap (diagnostically):
Anxiety
Bipolar disorder

How linked are they?


60% of depressed patients report one or more anxiety
disorders
Bipolar is actually separate
MD neuroticism
Age of onset is ~15 years earlier
Recurs more frequently
Linked with certain personality types

Bipolar sensation
seeking and
extraversion

Bipolar disorder
Highs and lows (mania and depression)
Heritable
Also linked to stress (or physical illness)
Treatment:
Lithium mood stabiliser
Sodium valproate anti-convulsant
Anti-psychotics e.g. Olanzapine

Areas of the brain

limbic system

cingulate gyrus

Neurotransmission
Nor-adrenaline
(nor-epinephrine)
Serotonin

Chronic stress
depletion of
neurotransmitters
https://www.youtube.com/watch?v=InNhDfDfl5c

Molecular basis of addiction


Loss of control over drug intake
Heritable 50% of risk is genetic
Similar regions of brain involved:
Amygdala
Hippocampus
Frontal cortex

Alterations in dopamine system


Repeated, extreme perturbation of neurons
dramatic alterations in reward mechanisms
and motivational state...

Back to depression:
what causes it?
Numerous hypotheses:
1.Stress!
2.Genetics?
3.Non-shared environment
4.Monoamine hypothesis
5.Gut microbiome

Stress!
Neurotransmitter depletion

Stress
Chronic stress fire off neurons at rapid rate to
solve problem and escape from the stress
If individual cannot escape chronic stress body
becomes depleted in one of the neurotransmitters
Excitatory

Inhibitory

Dopamine

Dopamine

Noradrenaline

Serotonin

Adrenaline

GABA

Genetics?
But the evidence is sketchy

Genetic epidemiology
Aggregates within families
Meta-analysis estimates heritability at 37%
More prevalent in women
Women reported more interpersonal stresses
Men reported more legal- or work-related stressful
life events
BUT this cannot be attributed to greater prevalence
in women

Genetic epidemiology
Genome-wide association studies (GWAS)
Nothing significant has been found!

No evidence that shared environmental factors


contribute significantly
More likelymodel of a complex disorder

Candidate genes
Lots of studies few in agreement!
Evidence points to genetic heterogeneity
Different diseases similar symptoms (incorrectly
identified as the same illness)
OR different pathways same outcome (different
environmental precipitants trigger MD in different
ways, according to the genetic susceptibility of the
individual)

Non-shared environment
Nature vs nurture

Non-shared environment
Aspects of the association of
parenting
Punitive and constructive discipline
Negative life events (independent
and dependent)
Peers (antisocial and prosocial)

The monoamine hypothesis


Noradrenaline and dopamine

http://tinyurl.com/ok526zu

http://tinyurl.com/powmb5z

http://tinyurl.com/om32t2n

http://tinyurl.com/q9so6ue

http://tinyurl.com/q695jpf

Monoamine hypothesis
Monoaminergic systems affect:

Mood
Vigilance
Motivation
Fatigue
Psychomotor agitation or retardation

Abnormal function and behaviour


Altered synthesis, storage or release
Disturbed sensitivity of receptors or subcellular
messenger functions

Monoamine hypothesis
Depletion of monoamines did not induce or
worsen the symptoms of depression in
healthy controls or unmedicated patients
monoamine deficiency alone is not sufficient
for clinical syndrome
However, antidepressants require an intact
monoamine system for their therapeutic
action

Gut microbiome
Bacteria in GI tract

Gut microbiome

10x more microbial cells


Symbiotic (commensal)
Stress alters balance
Alterations in microbiota
influence stress-related
behaviours
Bacteria in GI tract can activate neural pathways and
CNS signalling systems

Clinical studies microbiota-gut-brain axis


prevention and treatment of mental illness

Treatment and therapies

Prevention and treatment


Diet eat a rainbow! (and a banana a day)
Probiotics! (generate GABA and enhance brain
receptors for GABA)

Lower levels of
corticosterone mouse
version of cortisol, our
stress hormone (Bravo
et al., 2011)
Conventional treatment SSRIs, NERIs
In combination with psychotherapy

Summary
Mental health:
Depression symptoms, facts, classification
Overlap with other disorders bipolar disorder, addiction
Areas of the brain involved and neurotransmission
Causes:

Stress!
Genetics?
Non-shared environment
Monoamine hypothesis
Gut microbiome

Treatment

Additional reading and resources


Interesting video:
https://www.ted.com/talks/andres_lozano_parkinson_s_depr
ession_and_the_switch_that_might_turn_them_off

Genetic associations:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919201/

A nice, easy to understand review of depression:


https://michiganpsychotherapy.com/wordpress/biochemicaldepression

Pathophysiology and treatment:


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181668/