Introduction
Major Depressive Disorder
Bipolar Disorder
Serious mood disorder
characterized by alternating
periods of mania and depression.
Symptoms of mania including
feeling euphoric, exhibiting
increased speech, motor activity,
and grandiosity.
(MDD)
Serious mood disorder that consists of
unremitting depression or periods of
depression that do not alternate with periods
of mania people with MDD feel sad,
unworthy, guilty and have an increase
incidence of suicide.
 Female, Chronic or
Adverse life
adolescent and severe medical
events
young adult illness

Divorced, Substance Low

separated, or Abuse, & history Socioeconomic
widowed of smoking status
 Hereditability
– Heritable characteristic: Rosenthal (1971) found 10 times greater risk
in close relatives

– Monozygotic twins afflicted with affective disorder, might afflicted 69%

on another twins.

– Genetics studies suggest certain genes on several chromosomes may

be implicated in the development of the affective disorder
– RORA gene: control of circadian rhythms and major depression
– GRM8: codes for metabotropic glutamate receptor
– RORB: circadian gene and involves with rapid alternating bipolar
disorder in children
 Psychological Treatment
Biological Treatment (Psychotherapy:
(Drugs, ECT, DBS, TMS, Behaviour, CBT,
VNS) interpersonal, & families
therapies)
Patient
Education
 Biological Treatments
1. Antidepressant drugs
Treatment
a. Tricyclic Antidepressant
• Class of drugs used to treat
depression; inhibits reuptake of
norepinephrine and serotonin,
without affecting reuptake of
other neurotransmitters
• Selective Serotonin Reuptake Inhibitor
(SSRI) – fluoxetine, citalopram, and
paroxetine
• Reduce symptoms OCD and social
phobia
• Serotonin and Norepinephrine Reuptake
Inhibitor (SNRI) – milnacipran, duloxetine,
and venlafaxine
• Widely use than SSRIs
b) Ketamine
–

increase brain level of

glutamate
c) Lithium
-

low therapeutic
index,

Toxic doses
2) Electroconvulsive Therapy (ECT) –
mania and depression only - Rapid effect than medications with less
adverse effects. However, prolonged use
- Electroconvulsive therapy (ECT) is a
can cause cognitive impairment & memory
procedure, done under general
loss.
anesthesia, in which small electric
currents are passed through the brain,
intentionally triggering a brief seizure.

- ECT decreases brain activity and

raises the seizures threshold for the
brain, making less likely for another
seizure to occur, and this changes
associated with this effect maybe
responsible for reducing the symptoms
of depression. https://youtu.be/-T0mwzXHgvI
3) Transcranial magnetic stimulation (TMS)
Noninvasive procedure that uses magnetic
fields to stimulate nerve cells in the brain to
improve symptoms of depression.
TMS is typically used when other depression
treatments haven't been effective.
- Aims to provide ECT without risk of cognitive
impairment
- TMS applied to the prefrontal cortex reduces
the symptoms of depression without
producing any apparent negative side effects
- Response rate less than 30%, with relapse
similar with ECT
4) Deep brain stimulation (DBS)
Preliminary research suggest its useful for
treatment-resistant depression (Mayberg
et al 2005 & Lozano, 2008)

• Deep brain stimulation involves

implanting electrodes below the
subgenual anterior cingulate cortex
(subgenual ACC), and targeting the
nucleus accumbens.

• Research suggests these electrodes

produce electrical impulses of the brain
to provide significant improvement in
symptoms, 6 months after surgery, 60%
showed improvement and 35% showed
remission.
5) Vagal nerve stimulation

• Vagus nerve
stimulation (VNS) is a
treatment that involves
delivering electrical impulses to
the vagus nerve, by implanting
similar device as DBS but the
simulating electrodes are
attached to vagus nerve.

• It is painless and does not elicit

seizure
Physiological Role in Depression
frontal cortex
monoamine hypothesis
5-HT Transporter (5-HTT)
Neurogenesis
circadian rhythm
– REM sleep deprivation as treatment
– Slow-wave sleep deprivation
– Total sleep deprivation
– Zeitgebers in affective disorders
 1. Role of the Frontal Cortex
in depression
• Research findings:

subgenual ACC

decrease

successful antidepressant treatment.

Mayberg et al. (2005) implanted stimulating electrodes in the subgenual ACC of patients with treatment-resistant
depression. The figure shows functional imaging scans of the patients ongoing for deep brain stimulation (DBS)
(a) before DBS,
(b) after three months of DBS, and
(c) after six months of DBS.
Increased activity is shown in red; decreased activity is shown in blue. The subgenual ACC initially showed
increased activity, which decreased during the course of stimulation, and also reduced the symptoms of
depression. Concurrently increase other activity in other brain region.
Successful treatment of the frontal cortex
on depression

How?

decrease
2. Role of the Monoamine Hypothesis
in depression
• Monoamine hypothesis: Depression is caused by low level activity of monoaminergic
neurons (serotonin and norepinephrine). Monoamine antagonists produce depression
symptoms, and monoamine agonists can reduce them.

1) Reserpine – Monoamine antagonist

 Blocks the activity of transporters that fill synaptic vesicles in monoaminergic terminals
with the neurotransmitter and interfered with the release of serotonin and norepinephrine in
brain causing depression.

2) Tryptophan depletion
Trytophan is the precursor of 5-HT (serotonin receptors), or serotonin. By taking low
tryptophan diet caused little tryptophan in brain of the depressed patients to relapse back
into depression. However, after normal eating, they recovered.
 Trytophan depletion has no effect on the mood of healthy people, but it does lower the
mood of people with a personal or family history of affective disorders.
 3. Role of the Stressful Life Event,
5-HT Transporter (5HTT) and Depression

no significant effects
4. Role of Neurogenesis
• Neurogenesis

absent

• Based on animal laboratory study (Pereira et al. 2007)

suppress
increases

exercise induces neurogenesis in the

human brain.
 5. Role of Circadian Rhythms
• One of most prominent symptoms of
depression is disordered sleep.
• Evidence suggests that up to 90% of people
who experience an episode of depression
report changes in their pattern of sleep, and
having difficulty in initiating and maintaining a
good night’s sleep (Wulff et al. 2010).
• As in the diagram illustrates patterns of the
stages of sleep comparing between depressed
and healthy participant. The sleep of people
with depression tends to be shallow, slow wave
sleep is reduced, and stage 1 is increased.
Sleep is fragmented, and depressed people
tend to awaken more frequently especially
toward the morning.
Antidepressant Treatment Through Role of
Changes in Circadian Rhythm

(seasonal affective disorder) through bright light exposure