|1

Introduction to Clinical Psychology

(BE2-22)

Mood disorders: depressive disorder

Marije aan het Rot

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About a (common) black dog

› https://www.youtube.com/watch?v=vA2b0_Plwbk

› “Depression is more than just feeling down, sad, or blue”

› “If you never experienced depression, it may be hard to

imagine”

› Be aware of reification!
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Place of the lecture in the course

› Mood disorders
› Anxiety disorders
› Psychotic disorders
› Substance use disorders
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After today you can…

10. Recognize the symptoms of the different types of mood

disorders, using diagnostic criteria

11. Apply the theories that may help explain mood disorders

12. Discuss the use of the psychological and biological interventions

available to people with mood disorders

14. Discuss the psychological characteristics of suicide and

deliberate self-harm
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Case description - I
Dean is a 28-year-old married man with a 2-year-old daughter and a
3-month-old son. He works as a manager in his parents’ food business.
He was referred by his family doctor after his wife had called the
doctor to express concern over her observations that Dean was
becoming increasingly despondent.

Over the prior 2-3 months, Dean’s symptoms had indeed escalated.
These symptoms included feeling down all the time, a lack of energy,
awakening very early in the day, difficulties concentrating at work,
withdrawal from family activities, and a decreased interest in sexual
relations with his wife. While Dean had previously been very energetic
and devoted to his work, he now found it difficult to get up in the
morning and go to the office.
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Hallmarks of a major depressive episode

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Additional DSM-5 criteria

“The symptoms cause clinically significant distress or impairment in

social, occupational or other important areas of functioning.”

“The symptoms are not due to the direct physiological effects of a

substance or a general medical condition.”

“The symptoms are not better accounted for by bereavement after the
loss of a loved one.”
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Depressive disorders in the DSM-5

or

Major depressive Major depressive

disorder (MDD), disorder (MDD),
Single episode Recurrent episodes

>50% of patients who recover from a first

episode will relapse
80% of patients with a history of two episodes
will relapse
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Depressive disorders in the DSM-5

› Persistent depressive disorder

and

DSM-IV: DSM-IV:
Dysthymic disorder Double depression
(fewer symptoms, longer duration) (MDD + dysthymic disorder)

› Disruptive mood dysregulation disorder

› Premenstrual dysphoric disorder
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Treatment options

› Guidelines
• NL: Trimbos Institute
• DE: German Association for Psychiatry, Psychotherapy and
Neurology (DGPPN)
• UK: National Institute for Health and Care Excellence (NICE)
• US: American Psychiatric Association (APA)

› Psychotherapy, pharmacotherapy, combination, other

Stepped care
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Other biological interventions for depression

› Physical activity/exercise

› Bright light therapy

› Electroconvulsive therapy (ECT)

• http://www.youtube.com/watch?v=EGZv2wbYV7U

› Transcranial magnetic stimulation (TMS)

› Experimental drugs, e.g. ketamine?

• Will return to this…
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Physical activity: Evidence-based?

Lawlor, D.A. & Hopker, S.W. (2001) BMJ 322(7289): 763-767

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Physical activity: not for everyone?

Rosmalen, J., et al (2012) Psychosomatic Medicine 74: 377-86.

 Latitude: N53°
SAD: 3%, winter blues: 9%
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Bright light therapy: why does it work?

› Less sunlight exposure in
winter due to shorter days
› Particularly at higher latitudes

› SAD = seasonal affective

disorder (“winter depression”)
› Winter blues = mild SAD

› More depressive symptoms

with less sunlight exposure

› Other factors also involved!

Molin, J., et al. (1996) J Affective Disorders 37: 151-155

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Bright light therapy: pros and cons

+ 50-60% of patients respond
+ As effective as SSRIs
+ Onset of action within 1 week
+ Few side effects
+ Alternative for people who
cannot take medications

- Rapid relapse after

discontinuation?
- Risk of (hypo)mania in
vulnerable individuals
- Evidence-based?
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Introduction to Clinical Psychology

(BE2-22)

Mood disorders: bipolar disorder

Marije aan het Rot

 | 18

Case description - II
When Dean was in his senior university year, he also had symptoms of
depression. During this time, he was under a great deal of stress arising
from his parents, and very concerned about what he would do for a
career after graduation.
However, these symptoms were followed by more dramatic changes.
Dean’s mood became persistently elevated and he experienced
hyperactivity and a decreased need for sleep. He had always been a
sensible drinker, but now he engaged in several alcohol binges. Most
significantly, his sexual desire markedly increased. He was even found
naked in his student room with an underage girl. For this he was first
arrested and then hospitalized. He never received formal charges, but he
never returned to university to complete his degree.
Bipolar disorder
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Bipolar disorders in the DSM-5

2% 10%
or or

Bipolar disorder I: Bipolar disorder II:

mania hypomania
(+ or - major depression!) (fewer symptoms, longer duration)
+ major depression
4% 84%
Bipolar disorder
Not Otherwise
Specified
(DSM-IV)
Cyclothymic disorder
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Treatment options
› Guidelines (NL, DE, UK, US, …)

› Focus on pharmacotherapy
• Lithium
• “Antidepressants”
• “Antipsychotics”
• “Anticonvulsants”
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Lithium for mood stabilisation

› Alleviates both mania and (bipolar) depression

› Commonly used for prevention of relapse (=prophylaxis)

› Alters serotonin / dopamine / norepinephrine receptor function

› Low therapeutic index!

› Often in combination with ...

(=augmentation)
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“Antidepressants” for bipolar depression

› Depression medications are commonly prescribed

› Tricyclics and MAO inhibitors may also induce mood

destabilisation!
• Rapid cycling
• Increased agitation
• Risk of suicidality
• Antidepressant-induced mania (AIM)

› SSRIs are safer, but remain less effective than lithium

and may be ineffective for prophylaxis
 Stepped care?
| 24

› N = 4107 patients › Adding “antidepressants” to

lithium during bipolar
› n = 1380 depressed depression makes no difference
• ~65% had concomitant manic
symptoms (=mixed features)
› Psychotherapy for (severe)
› n = 1469 symptomatic bipolar depression worked
• After 2 years, only ~25% had better than expected !
recovered and not relapsed
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Mood disorders: from DSM-IV to DSM-5

› Separate sections for depressive disorders versus bipolar disorders

› At the same time, a more dimensional approach!

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Bipolar vs. unipolar depression?

Yes? No!
Number of manic symptoms

Number of manic symptoms

ZONE OF
RARITY

Number of depressed patients Number of depressed patients

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Bipolar disorder vs. schizophrenia?

Elanjithara, T.E., et al (2011) Advances in Psychiatric Treatment 17(4): 283-91

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Summary – Part 1

› Depression is characterized by multiple emotional,

cognitive, behavioral, and physiological changes.

› Major depressive disorder is unipolar and often recurrent.

› Bipolar disorders are considered categorically distinct

from unipolar depressive disorders but there is overlap.

› Several biological interventions are available for treating

depressive and bipolar disorders; all have pros and cons.
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Break
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Introduction to Clinical Psychology

(BE2-22)

Mood disorders: suicide

 | 31

Case description - III

Despite his recent escalating symptoms of depression, Dean had been
hesitant to see a mental health care professional for fear of being
revealed as “weak.” However, at some point his symptoms began to
interfere with his work and marriage and he started having suicidal
thoughts. These thoughts were triggered largely by conflicts at work.
After such conflicts, Dean would isolate himself and become
preoccupied with his dislike of himself. Specifically, Dean would feel
like the world was coming down on him. He would think about what
he could do to escape that feeling. When Dean told his wife that he had
considered suicide, she persuaded him to seek help.
Although Dean had not decided to see a psychologist on his own, he
felt relieved by opportunity to express the feelings he had been having.
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Suicide: numbers
› Annual prevalence worldwide is high:
• Completions: >1 million (men > women)
• Attempts: 10-20 million (women > men)

› Around 10-20% of attempts is completed

› Every other completion involves a first attempt

› About 90% involves mental illness

• Often depression (80%?)
 Seasonality
| 33

Woo, J.-M., et al. (2012) Int J Environ Res Public Health 9(2): 531-547
 | 34

Diathesis-stress model

Predisposing factors, Precipitating factors,

vulnerabilities triggers

Turecki, G., et al. (2012) Trends in Neurosciences 35: 14-23

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Developments in suicide prevention

› From: Overall symptom reduction
• Psychological interventions
• Biological interventions

› To: Specific symptom targeting

• Problem-solving therapy (PST)
• Suicide hotlines
• 113online.nl, zelfmoordlijn.be
• Experimental drug treatment
• Intravenous ketamine?
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Experimental psychopharmacology: Acute

treatment with intravenous ketamine (K)

› Problem: How to assess effects on suicidal

thoughts?

› Solution: Multimethod approach

- Explicit: MADRS, BSSI (questionnaires)
- Implicit: IAT (computer test)

Price, R.B., et al. (2009) Biol Psychiatry 66(5): 522-526.

Price, R.B., et al. (2014) Depress Anx 31: 335-343.
 MADRS
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Montgomery-Asberg Depression Rating Scale

› Suicide item:
0 Enjoys life, or takes it as it comes.

2 Weary of life. Only fleeting suicidal thoughts.

4 Probably better off dead. Suicidal thoughts are common, and suicide is
considered as a possible solution, but without specific plans or intentions.

6 Explicit plans for suicide when there is an opportunity. Active preparation

for suicide.

Price, R.B., et al. (2009) Biol Psychiatry 66(5): 522-526.

 BSSI
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Beck Scale for Suicidal Ideation

› 21 items

• Duration and frequency of ideation

• Sense of control over an attempt

• Number of deterrents

• Amount of planning involved into a contemplated attempt

Price, R.B., et al. (2009) Biol Psychiatry 66(5): 522-526.

 MADRS
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Post-K: rapid decrease in suicide item score

Price, R.B., et al. (2009) Biol Psychiatry 66(5): 522-526.

 BSSI
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Post-K: rapid decrease in total score

Midazolam (placebo; n=21) Ketamine (n=36)
7
6
5
4
3
2
1
0
Baseline 24-hours post single infusion

Price, R.B., et al. (2014) Depress Anx 31: 335-353

 IAT
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Implicit Association Test

› Reaction time measure to detect subconscious self-
identification with various topics, incl. social taboos
• https://implicit.harvard.edu/implicit/demo/selectatest.html

› Relevant finding in suicide attempters:

• Greater self-identification with death than with life
• Greater self-identification with escaping than with staying

Nock, M.K, and Banaji, M.R. (2007) J Consult Clin Psychol 75(5): 707-715.
 IAT
| 42

COFFIN

E I
 IAT
| 43

DEATH LIFE
ME NOT ME

E I
 IAT
| 44

E
?

E I
 IAT
| 45

BREATHING

E I
 IAT
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DEATH LIFE
NOT ME ME

E I
 IAT
| 47

?I

E I
 IAT
| 48

QUIT

E I
 IAT
| 49

ESCAPE STAY
ME NOT ME

E I
 IAT
| 50

E I
 IAT
| 51

PERSIST

E I
 IAT
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ESCAPE STAY
NOT ME ME

E I
 IAT
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E I
 IAT
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Post-K: decreased preference for escape

Ketamine (n=26)

-0.1
Escape=Me
association

-0.2

-0.3

-0.4

-0.5

-0.6

Baseline 24-hours post single infusion

Price, R.B., et al. (2009) Biol Psychiatry 66(5): 522-526.

 IAT
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Post-K: decreased preference for escape

Midazolam (placebo; n=21) Midazolam (placebo; n=21)
Ketamine (n=36) Ketamine (n=36)
0 0
Escape=Me association

Death=Me association
-0.1 -0.1
-0.2 -0.2
-0.3 -0.3
-0.4 -0.4
-0.5 * -0.5
-0.6 -0.6
Baseline 24-hours post Baseline 24-hours post
single infusion single infusion

Price, R.B., et al. (2014) Depress Anx 31: 335-343

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Introduction to Clinical Psychology

(BE2-22)

Mood disorders: role of serotonin

| 58

| 58
 Depression medications
| 59

MAO inhibitors
(e.g., tranylcypromine)

Tricyclics/TCAs
(e.g., nortryptiline)
SSRIs
(e.g., sertraline)

aan het Rot, M., et al. (2009) CMAJ 180(3): 305-313

 | 60

Brain serotonin synthesis during depression

Rosa-Neto, P., et al. (2004) Arch Gen Psychiatry 61: 556-563

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aan het Rot, M., et al. (2009) CMAJ 180(3): 305-313

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Cowen (2008) Trends in Pharmacological Sciences 29(9): 433-6

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aan het Rot, M., et al. (2009) CMAJ 180(3): 305-313

 Experimental psychopharmacology

| 64

Tryptophan depletion (TD)

  5-hour waiting period   

8 8:30 9 2:30
 3:30 4:30
AM AM AM PM PM PM

 Mood assessment
Amino acid mixture (with or without tryptophan)  Other assessments
 | 65

Effects of TD on brain serotonin synthesis

MALE in FEMALE
control in control
condition condition

-87% -97%

MALE FEMALE
after after
TD TD

Nishizawa, S., et al. (1997) Proc Natl Acad Sci 94(10): 5308-5313
 | 66

aan het Rot, M., et al. (2009) CMAJ 180(3): 305-313

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Effects of TD on mood: overview

› In never-depressed men: -

› In never-depressed women: 

› In remitted patients with MDD: 

› In remitted patients with BD: -

› In symptomatic patients with MDD: -

› In never-depressed relatives of patients with MDD: 

Ruhe, H.G., et al. (2007) Mol Psychiatry 12: 331-359

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Relatives: shared genes and environment

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aan het Rot, M., et al. (2009) CMAJ 180(3): 305-313

 Serotonin transporter gene
| 70

Polymorphism

Variable
Possible genotypes: serotonin
S/S - S/L - L/L transporter
synthesis rate
 | 71

Effects of TD on mood: impact of 5-HTTLPR

Genotype No MDD among relatives MDD among relatives
S/S
low mood low mood low mood

low mood low mood low mood

S/L

L/L

Neumeister, A., et al. (2002) Archives of General Psychiatry 59: 613-620

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Depression risk: impact of 5-HTTLPR

Leonardo, E.D., and Hen, R. (2006) Annual Review of Psychology 57: 117-137
 | 73

Genes may alter environment!

 | 74

Experiments in rhesus monkeys

Mother-reared Peer-reared
Mother always present Temporary maternal separation

Suomi, S. (2003) Ann N Y Acad Sci 1008: 132-139

 | 75

Gene Environment
(=Diathesis) (=Stress)

Canli, T., and Lesch, K.P. (2007) Nature Neurosci 10: 1103-1109
 13-12-2010 | 76 | 76

Depression phenotype:
SL (SS) genotype + peer-reared
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Summary – Part 2
› Suicide risk is elevated during depression and determined
by multiple biological, psychological, and social factors.

› Suicide prevention is difficult to study due to the nature of

the phenomenon, but progress is being made.

› Neurotransmitter theories of MDD continue to focus on

brain serotonin; less remains known about BD.

› Experimental psychopharmacology and nonhuman studies

help elucidate the biological causes of psychopathology.
 | 79

Thank you for your attention