Case

12Part 2Develo
pment
of
Depres
sion

L E A R N I N G O U TC O M E S

Glia- Protection repair mechanisms in the CNS

Serotonin and Dopamine receptors on elevated

levels of schizophrenia
Psychosis
Drugs, cocaine etc
Stigma
Interdisciplinary team and care issue
Continue care
Share experiences from placement, learning
points

GLIAL CELLS

WHAT ARE THE MAIN

GLIAL CELLS IN THE CNS?

4 main glial cells are ependymal,

oligodendrocytes, astrocytes and microglial

cells
The main Glial cells is the oligodendrocytes
and astrocytes

WHAT ARE THE FUNCTIONS OF ASTROCYTES?

The astrocytes, which are more numerous,

have many radiating processes that

interweave in complex and intimate ways between neuronal cell bodies and
bres
biochemical support of endothelial cells that form the bloodbrain barrier, provision of
nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the
repair and scarring process of the brain and spinal cord following traumatic injuries.
WHAT ARE THE FUNCTION OF OLIGRODENDROCYTES?

Their main functions are to provide support and insulation to axons in the central nervous
system of some vertebrates, equivalent to the function performed by Schwann cells in
the peripheral nervous system.

HOW IS THE CNS DAMAGED?

Nerves can be damaged through trauma and disease

Nerve trauma may be incurred through motor vehicle accidents, severe falls,

lacerations, and typing. Traumatic nerve injury, such as carpal tunnel

syndrome, is caused by the compression of nerves. Other trauma, such as
falls and motor vehicle accidents, may lead to the severance of nerves.
Diseases that damage nerves include multiple sclerosis, diabetes, spina
bifida, and polio. Multiple sclerosis, for example, causes the breakdown of
the insulating myelin surrounding axons.

WHAT ARE THE COMMON PATHOLOGICAL FEATURES OF THE CNS?

Intracranial pressure changes, refers to high or low( cerebral oedema,

vasogenic oedema, cytotoxic oedema, interstitial oedema

Neural tube defects ( Spina bida, anencepaly, Arnold-chiari malformation,
cerebral palsy

NAME SOME CAUSES OF CENTRAL NERVOUS SYSTEM TRAUMA?

They can come under 3 headings,

Penetrating injuries, crush injuries, acceleration/ decelerating injuries

NAME SOME OTHER CONDITIONS IN THE BRAIN THAT CAN BE DAMAGED?

Cerebrovascular disease, stroke, subarachnoid heamorrahages, Infections in

the brain such as meningitis , intracranial absecess, chronic
meningoencephalitis

HOW DOES MYELIN DISORDERS ARISE?

Myelin is inherently abnormal or was never formed appropriately

Normal myelin breaks down due to a pathological insult (MS)

NAME THE DEMYLINATION AND DEGENERATION CONDITIONS?

Multiple scleroisis ( demylinations)

Degenerating- Alzheimer disease, dementia, Picks disease(another form of
dementia)

WHY CANT THE CNS REPAIR THESE?

The central nervous system has limited ability to fix its damaged nerves, in

contrast to the peripheral nervous system.

When parts of the central nervous system are critically injured, the CNS

cannot generate new neurons nor regenerate new axons of previously

severed neurons.
Severed CNS tips initially try to grow, but eventually abort and ultimately
completely fail to regenerate.

Remarkably, almost 90% of cells in the CNS are not even neurons. Rather
they are glial cells, which play an important role in supporting neurons both
physically and metabolically.

GANGLIA

IN

CNS

WHAT ARE THE DIFFERENCE BETWEEN GANGLIA AND NUCLEI?

In the central nervous system, a collection of neuron cell bodies is called a nucleus. In
the peripheral nervous system, a collection of neuron cell bodies is called
a ganglion (plural: ganglia). The one exception to this rule that you may have encountered

is the basal ganglia in the brain.

The preganglionic motor neuron cell body may originate from the CNS but the post
ganglionic is normally always in the PNS

DOPAMINE

AND

SCHIZOPHRENIA

WHAT ARE THE TWO TYPES OF RECEPTORS FOR DOPAMINE?

The D1 and D5 receptors are members of the D1-like family of dopamine receptors,
whereas the D2, D3 and D4 receptors are members of the D2-like family.

There is at least 5 subtypes

WHAT DOES THE D1 FAMILY RECEPTORS DO?

Activation of D1-like family receptors is coupled to the G protein Gs, which subsequently
activates adenylyl cyclase, increasing the intracellular concentration of thesecond
messenger cyclic adenosine monophosphate (cAMP).

D1 is encoded by the Dopamine receptor D1 gene (DRD1).

D5 is encoded by the Dopamine receptor D5 gene (DRD5).

WHAT DOES THE D2 FAMILY RECEPTORS DO?

D2-like family Activation of D2-like family receptors is coupled to the G protein Gi,

which directly inhibits the formation of cAMP by inhibiting the enzyme adenylyl
cyclase.

By blocking the excess

What antipsychotical drugs target is the D2 receptor so less dopamine is made

In the mesolimbic dopaminerigic pathway the positive side effects of schizophrenia

occur, therefore blocking the excessive dopamine activity in the mesolimbic system.

D2 blockage at other sites contributes along with antagonism at other receptors

PSYCHOSIS

WHAT IS PSYCHOSIS?

Young people often worry that they may be going mad' when they are feeling
stressed, confused or very upset. In fact, worries like this are rarely a sign of
mental illness. Psychosis is when your thoughts are so disturbed that you lose
touch with reality. This type of problem can be severe and distressing.

WHAT CAUSES PSYCHOSIS?

When you have a psychotic episode, it can be a signal of another underlying

illness. You can have a psychotic episode after a stressful event like losing a close
friend or relative. It can also be the result of a physical illness ( like a severe
infection), the use of illegal drugs (like cannabis) or a severe mental illness
l(ike schizophrenia or bipolar disorder). Sometimes it is difficult to know what
caused the illness.

WHAT DOES MICHAEL HAVE?

Psychotic depression is characterized by not only depressive symptoms,
but also by hallucinations (seeing or hearing things that arent really there)
or delusions (irrational thoughts and fears). Often psychotically depressed
people become paranoid or come to believe that their thoughts are not
their own (thought insertion) or that others can hear their thoughts
(thought broadcasting).
WHAT IS THE TREATMENT FOR PSYCHOSIS?

Medications called antipsychotics are an important part of treatment. They may

need to be taken for a long time in order to stay well. As with medication of any
kind, there can be side-effects; the doctor you see will be able to advise you on
these and what can be done to help.

If the psychosis is related to drug use or an underlying physical illness, you may
need specic help and treatment to manage this.

WHAT ALSO CAN PSYCHOTIC ILLNESSES CAUSED BY?

Alcohol misuse and drug misuse can trigger a psychotic episode.

A person can also experience a psychotic episode if they suddenly stop

drinking alcohol or taking drugs after using them for a long time. This is known as
withdrawal.

It's also possible to experience psychosis after drinking large amounts of alcohol
or if you're high on drugs.
Drugs known to trigger psychotic episodes include:
cocaine
amphetamine (speed)
methamphetamine (crystal meth)
mephedrone (MCAT or miaow)
MDMA (ecstasy)
cannabis
LSD (acid)
psilocybins (magic mushrooms)
ketamine

Go back over Bipolar which is in other book

DRUGS

AND THEIR EFFECTS

Drug

Subgroup:

Specific drugs:
Examples:

Benzodiazepin
es

Benzodiazepin
e agonists

Barbiturates

Diazepam (Valium),
clonazepam (Klonopin),
lorazepam (Ativan),
temazepam (Restoril),
flunitrazepam
(Rohypnol), triazolam
(Halcion), alprazolam
(Xanax)
Zolpidem (Ambien),
eszopiclone (Lunesta),
zopiclone, zaleplon
(Sonata)

Sedatives

Mechanism:

Major
effects:

Side effects:

Any medical
use:

Agonist at
benzodiazepin
e site on the
GABA-A
receptor

Calm,
relaxed
muscles,
sleepy

Drowsiness,
falls, impaired
coordination,
impaired
memory,
dizziness

Anxiety,
insomnia,
epilepsy, many
other diseases

Same as above

Mainly just
sleepy,
sometimes
hallucination
s and sleeplike states
Calm,
euphoric,
sleepy

Same as
benzodiazepines

Insomnia

Same as
benzodiazepines
, plus breathing
suppressed,
terrible
withdrawal,
death
Same as
benzodiazepines
, plus nausea,
vomiting,
breathing
suppressed,
terrible
withdrawal
(including
psychosis and
seizures), brain
damage, various
diseases, death

Epilepsy, other
diseases in the
past and more
rarely today

Same as
benzodiazepines
, plus nausea,
vomiting,
breathing
suppressed,
psychosis,
seizures, death

Narcolepsy
(improves
cataplexy, not
simply a sleep
aid)

Phenobarbital,
pentobarbital, thiopental
(sodium pentothal,
sodium amytal),
secobarbital

Agonist at
barbiturate site
on the GABAA receptor

Alcohol

Opens BK
potassium
channels
(hyperpolarizi
ng neurons),
closes SK
potassium
channels in
reward center
of brain
(causing DA
release),
probably other
effects
Agonist at
GHB receptor
(may
desensitize it
or inhibit
GABA),
agonist at
GABA-B
receptor

Gammahydroxybutyrate (GHB), GBL,

1,4-butanediol

Calm,
euphoric,
loss of
inhibitions
(facilitates
socializing,
talking,
singing,
sex), relaxed

Euphoric,
energetic,
sleepy, calm
(mix of
stimulant
and sedative
effects)

Alcohol
withdrawal

Amphetamines

Amphetamine
(Adderall),
methamphetamine
(Desoxyn),
methylphenidate
(Ritalin),
phentermine, 4methylaminorex,
phenmetrazine
(Preludin),
methcathinone,
fenfluramine
(Pondimin, FenPhen),
dexfenfluramine
(Redux),
pseudoephedrine
(Sudafed),
ephedrine,
phenylpropanolam
ine (old
Triaminic),
phenylephrine
(Sudafed PE)
MDMA (ecstasy),
MDA, MDEA

Cocaine

Increase
release and
inhibit
reuptake of 5HT, DA, and
NE.

Euphoric,
energetic,
able to work,
concentrate,
stay awake.
Reduces
appetite.

Anxiety,
paranoia,
psychosis, high
blood pressure,
heart attack,
stroke, brain
damage when
used excessively

ADHD,
narcolepsy,
obesity, rarely
depression

Like above,
but releases a
lot more 5-HT

Euphoric,
energetic,
deep and
unusual
thoughts,
perceived
inspiration
and novelty,
enhances
sex, dancing,
music, art,
touch and
senses.
Contentment
. Connection
to other
people,
strong
emotions.
Same as
amphetamin
e (above)

Same as
amphetamine,
plus brain
damage,
confusion,
agitation,
frequently death
due to
hyperthermia,
heart attack,
water
intoxication,
and other
problems.

None

Same as
amphetamine,
plus a worse
risk of heart
attack

Local anesthesia
and bleeding
control,
diagnostic tests

Inhibits 5-HT,
NE, and DA
reuptake,
blocks
voltage-gated
sodium

S
t
i
m
u
l
a
n
t
s

channels

Full opioid agonists

Narcotics
Partial, selective, or
mixed opioid
agonists

Morphine, heroin
(diacetylmorphine
), hydrocodone
(Vicodin),
oxycodone
(Percocet,
Oxycontin),
fentanyl,
Demerol, codeine,
opium,
hydromorphone
(Dilaudid),
oxymorphone
(Opana),
methadone
Buprenorphine
(Suboxone),
pentazocine,
nalbuphine,
tramadol
(Ultram),
tifluadom

Cannabis

Active ingredient is mostly

tetrahydrocannabinol, some other active
ingredients like cannabidiol in smaller
quantities

Activate all
opioid
receptors
completely.
Reduce NE
release.

Euphoric,
pain relief,
calm,
relaxed,
sleepy,
appetite
suppression

Nausea,
constipation,
vomiting,
drowsiness,
breathing
suppressed

Pain relief,
rarely
depression and
diarrhea

Only activate
certain
subtypes of
opioid
receptors,
and/or do not
activate them
fully, and/or
block certain
subtypes.
Agonist at
cannabinoid
receptors

Pain relief,
not quite as
euphoric or
relaxing as
full agonists
(above)

Nausea,
constipation,
vomiting,
drowsiness

Pain relief,
rarely
depression,
opioid addiction

Unusual
thoughts and
feelings,
sometimes
calm, happy,
hungry,
enhanced
appreciation
of art

Memory,
thinking,
reflexes, and
coordination are
impaired. May
contribute to
psychosis in the
long term.

Might relieve
nausea,
vomiting, and
neuropathic
pain. Pills
already legal,
other forms
under
investigation.

Unknown,
probably
multiple
mechanisms

Nitrous oxide

Unknown, but
opioid
pathways are
necessary

Inhalants

Diethyl ether (starter fluid), toluene,

gasoline, glue, paint, xenon, freon,
halothane, sevoflurane

Nitrites

Isoamyl nitrite,
isobutyl nitrite

Nicotine (tobacco)

DIAGNOSIS

Nicotinic
acetylcholine
receptor
agonist
Adenosine
receptor
antagonist,
inhibits some
PDE enzymes
causing
increased
cAMP
signaling
Other

Caffeine (coffee, tea, other plants)

Stimulate NO
system (NO is
a
neurotransmitt
er)

Calm,
relaxed,
euphoric,
pain relief,
hallucination
s, strange
sensations
(different
inhalants
cause
different
effects from
this list)
Calm,
euphoric,
pain relief,
memory
loss,
unconscious
ness
"Head rush",
muscle
relaxation,
dizziness

Many diseases,
death, nausea,
vomiting,
accidental
asphyxiation,
falls, varies
depending on
particular drug

General
anesthesia

Similar to above

General or
partial
anesthesia

Dangerously
low blood
pressure,
fainting

Heart conditions

See Wikipedia, PubMed, Google

Alertness,
wakefullness
, energy,
appetite
suppression,
headache
relief

Insomnia,
anxiety,
headaches on
withdrawal,
diuresis

AND SPECIFIC ASSESSMENTS

Check for cognitive function. A patient may not interact with you
o Does the patient have signicant cognitive impairment?
o Is there a medical cause?

Headaches

If there is no obvious direct cause, is this dementia, delirium or

depression?
How to assess for psychosis?
o Find out if the person is sufferening from psychosis?
o If so what is the cause of psychosis?( could be psychiatric
o
o

problem or could be organic problem)

Take psychosis history
Infereing that it is schizophrenia and other pscyhoses relies on

detailed evaluation of number of symptoms and signs

Also using the patients appearance, behaviour, mood, speech,

thought content, flow and possession of thought, perception,

cognition, insight
How to assess for depression?
o Ask relevant questions such as
o Does the patient think they are depressed?
o Identify past and current stressors in life?
o How the patient has tried to cope?
o Does the patient have depressive or anxious traits in family?
o Is there a family history of psychiatric disorder?
o You would then use the MSE to assess the patient, e.g
appearance, behaviour as mentioned above

INTERDISCIPLINARY TEAM

Most Pyschiatric disorders are seen ad managed iun the general practise, the

most common involve depression and substance misuse

Other psychiatric patients are managed by pschiatrists and other patients are

seen in A and E as a result of self harm

Also one third of medical and surgical outpatient clinic attendees have a
psychiatric disorder.

HOW ELSE CAN PYSCHIATIC PROBLEMS BE CAUSED?

Many patients with medical conditions have psychiatric disorders, e.g medical
conditions such as cushing syndrome and hyperthyroidism

STAGES OF PATIENT CARE

1.
2.
3.
4.

The decision to consult the doctor

Recogition by the GP
Referral to psychiatrist
Admission to hospital

HOW IS THE PATIENT MANAGED?

Management of the psychiatric disorder is based on the general principals (A)
attention to the patients medical condition and treatment (B) necessary adaptation
to the medical setting.
WHY DOES GPS REFER ONTO THE PSYCHIATRISTS

Request for a second opinion

Failure of rst line management
Need for specialist treatment such as ECT
Serious suicide risk
Presence of a condition such as psychosis requiring specialist services
Severe substance misuse
Need for compulsory treatment

STIGMA
Stigma differs from discrimination. Discrimination is unfair treatment due to a
persons identity, which includes race, ancestry, place of origin, colour, ethnic origin,
citizenship, creed, sex, sexual orientation, gender identity, gender expression, age,
marital status, family status or disability, including mental disorder. Acts of
discrimination can be overt or take the form of systemic (covert) discrimination.
Under the Ontario Human Rights Code, every person has a right to equal treatment
with respect to services, goods and facilities, without discrimination due to the
identities listed above.
Stigma is the negative stereotype and discrimination is the behaviour that results
from this negative stereotype. Often, individuals with a mental illness are faced with
multiple, intersecting layers of discrimination as a result of their mental illness and
their identity. For example, a woman with a mental illness may experience
discrimination due to sexism as well as her illness, and a racialized individual may
experience discrimination due to racism in addition to their mental illness. In
addition, living with discrimination can have a negative impact on mental health.
MEDIA

INFLUENCE ON PUBLIC ATTITUDES

Many studies have found that media and the entertainment industry play a key role
in shaping public opinions about mental health and illness. People with mental
health conditions are often depicted as dangerous, violent and unpredictable. News
stories that sensationalize violent acts by a person with a mental health condition
are typically featured as headline news; while there are fewer articles that feature
stories of recovery or positive news concerning similar individuals. Entertainment
frequently features negative images and stereotypes about mental health conditions,

and these portrayals have been strongly linked to the development of fears and
misunderstanding.
IMPACT

OF NEGATIVE PUBLIC ATTITUDES

There are signicant consequences to the public misperceptions and fears.

Stereotypes about mental health conditions have been used to justify bullying.
Some individuals have been denied adequate housing, health insurance and jobs due
to their history of mental illness. Due to the stigma associated with the illness, many
people have found that they lose their self-esteem and have difficulty making
friends. Sometimes, the stigma attached to mental health conditions is so pervasive
that people who suspect that they might have a mental health condition are
unwilling to seek help for fear of what others may think. Experiences of stigma and
discrimination is one of their greatest barriers to a satisfying life.

WHAT

YOU CAN DO TO STOP STIGMA AND DISCRIMINATION

Use the STOP criteria to recognize attitudes and actions that support the stigma of
mental health conditions. Its easy, just ask yourself if what you hear:

Stereotypes people with mental health conditions (that is, assumes they are
all alike rather than individuals)?

Trivializes or belittles people with mental health conditions and/or the

condition itself?

Offends people with mental health conditions by insulting them?

Patronizes people with mental health conditions by treating them as if they

were not as good as other people?
If you see something in the media which does not pass the STOP criteria, speak up!
Call or write to the writer or publisher of the newspaper, magazine or book; the
radio, TV or movie producer; or the advertiser who used words which add to the
misunderstanding of mental illness. Help them realize how their words affect people
with mental health conditions.
Start with yourself. Be thoughtful about your own choice of words. Use accurate and
sensitive words when talking about people with mental health conditions.

NOTES

FROM

Synthesis and

PREVIOUS SESSION

Distribution

Receptors

Clinical

removal
Acetylcholine (Ach)

Link reaction to
produce acetyl
CoA which binds
to Choline via
acetyl
transferase,
packaged into
vesicles and
exocytosed.
Broken down by
acytylcholinester
ase

Glutamate

Converted from
glucose via
krebs cycle, then
converted to
glutamine in glial
cells, glutamine
synthetase, GLN
to GLU via
glutaminase

Significance
Basal
Forebrain
supply
neocortex,
hippocampus
, amygdala
Dorsolateral
tegmentum
of pons
basal
ganglia,
hypothalamu
s

Widespread,
most
abundant NT
in CNS.
4 tracks
corticospinal,
Corticostriate
,
hippocampus
, primary
afferents

mACh- g
protein
coupled,
more
widespread,
found on
smooth
muscle and
glands of
parasympat
hetic glands

Basal
Forebrain
learning and
memory
limbic system,
dementia and
alzheimers

NMDA Nmethyl-DAspartate

Ketamine and
ecstasy block
NMDA,
affecting short
term memory

Dorsolateral
sleep-wake
cycle,
promotes REM
nACh
in sleep cycle,
ionotropic,
controls
gangli at
electrical
neuromusc rhythms of the
ular junction hippocampus
and modulates
its functions

Kainate
AMPA
aminomethylisoxa
zole.
mGlu

Degeneration
of neurones in
anterior horn
cells can lead
to ALS

GABA

Synthesised
from glutamate
by glutamate
decarboxylase in
order to cross
the BBB

Major
inhibitoy

GABAa
ionotropic

Target for
drugs

Hyperpolaris
es axons

GABAb metabotropi
c

Inhibitory in
spinal
column,
retina and
grey matter

Ionotropic

Tetanus toxin
prevents
release of
glycine from
inhibitory
neurons,
muscular
spasm

Alpha and
beta
Norad does
not act on
beta 2

Times of
stress,
increased
cortisol,
increased
transmission of
norad in locus
coeruleus
affecting the
amygdala
affecting the
hypothalamus,
temperature,
feeding, sleep
and the limbic
system, mood
etc and the
cerebral cortex

Removed by
reuptake (see
glutamate)
Also converted
into succinate
and feeds into
krebs cycle
Glycine

See glutamate

Noradrenaline

Catecholamine
synthesis, see
lecture diagram
Removal
actively re
uptaken
Degradation MAO and COMT

Cerulean
nucleus on
floor of
4th ventricle
PNS NMJ
of
sympathetic
ANS

G-protein
Gated

Adren
aline

Upper part of
medulla
oblongata
due to
location of
phentolamine
nmethyltransfe
rase enzyme

Dopa
mine

Major
transmitter in
connections
between
basoganglia

D1
excitatory
D2 inhibits
cAMP

Parkinsons,
schizophrenia,
effects of
antipsychotic
medication

Found in
pathways
affecting the
limbic system
Produced in
substia nagra
and VTA
Serato
nin

See lecture
diagram

Raphe Nuclei
project into
the cerebral
cortex and
spinal cord
Caudal
system

Pathologies and management:

Depression

3 Core

Anhedonia

All 5HT are

G Protein
coupled

Vegetative
behaviour
Atypical
antipsychotics

Serotonin
works on all
Pineal gland,
but 5HT3,
ligand gated implicated in
ion channel circadian
rhythm
2 and 4
excitatory,
the rest
inhibitory

Low mood

Anergia
6 Associated

Reduced concentration

Reduced self confidence

Guilt and unworthiness

Pessimistic

Ideas or acts of self harm/suicide

Not eating/sleeping
Other symptoms

Loss of libido

Diurnal variation

Weight loss (5% in one month)

Psychomotor agitation
Under activity of monoamine transmitters eg. serotonin,
theory based on drug action
Autoreceptor sensitivity theory, inhibit uptake of
transmitter, has negative feedback of production
SSRIs, blocks transport proteins, and reduces the
number of receptors, increasing the firing rate of the neuron
Cushings syndrome, decreased serotonin increased
cortisol hippocampal damage severe depression
Brain derived neutrophic factor
Risk factors

Gender Females post natal and postmenopausal

Chronic illness

Chronic substance abuse

Lack of social support

Bereavement

Stress

Hypothyroidism

Anxiety 60% of those depressed have anxiety

Treatment

CBT 9 month waiting list, expensive

Talking to change the way you think and

behave

More on how you act not feel

Mindfulness

Psycho education understand condition more,

reduce stigma

Electroconvulsive therapy last resort, electrodes

induce an epileptic fit, free from serious side effects,
minor temporary memory loss and muscle soreness
Pharmacology

SSRIs

Inhibit the rate of firing by action on 5HT1a,

longer term exposure, down regulation of the
5HT1a receptors, and a dis inhibition of serotonin
release. inhibiting the inhibitor. Increased
serotonin on the post synaptic membrane

Inhibits the reuptake

Prozac fluoxetine

Citalopram

Better tolerated than other drugs

Side effects hangover, bleeding, dry

mouth, constipation, serotonin syndrome
overdose, synergistic effect with St. Johns wart

SNRIs

Used when SSRIs dont work, next level of

treatment

TCAs

Inhibit the uptake of monoamines by

competitively binding with the monoamine ATPase pump

More side effects, arrhythmias and weight

gain

Not first line due to side effects

Amitriptyline, Imyprymine (also anti

epileptics)

MAOI

Monoamine oxidase inhibitors, early ones

irreversible, now they are reversible

Avoid certain foods, cheese and red wine,

due to tyramine

Can increase blood pressure significantly

Dizziness

Carry round an MAOI card due to

interactions with other drugs

Withdrawal syndrome if taken of them too

quickly

Phenelezine