Mood Disorders

Hussein Sabit, Ph.D 2009

The picture was painted by: Vincent Willem van Gogh
 Mood Episodes
• Major Depressive Episode:
– Severely depressed mood characterized by loss
of interest in typical activities, self-deprecation,
inability to concentrate
• Manic Episode:
– elevated and expansive mood characterized by
grandiosity, distractability, excessive
involvement in pleasurable activities
Major depressive episode
is a key symptom of major depressive disorder. It is
characterized by severe, highly persistent
depression, which is often manifested by lack of
appetite, chronic fatigue, lethargy, and
sleep disturbances (somnipathy).

The victim may think about suicide, and in fact an

increased risk of actual suicide is present.
In addition to the emotional pain endured by those
suffering from depression, significant economic
costs are associated with depression.
 Manic episode
• Mania is generally characterized by a distinct period
of an elevated, expansive, or irritable mood state.

• People commonly experience an increase in energy

and a decreased need for sleep.

• Attention span is low and a person in a manic state

may be easily distracted.

• Judgment may become impaired; sufferers may go on

spending sprees or engage in behavior that is quite
abnormal for them.
Cont..
• They may indulge in substance abuse,
particularly alcohol or other depressants,
cocaine or other stimulants, or sleeping pills.

• Their behavior may become aggressive,

intolerant or intrusive. People may feel out of
control or unstoppable.

• People may feel they have been "chosen", are

"on a special mission", or other grandiose or
delusional ideas.
 Signs of depressive episode
• In order to be diagnosed as suffering from a major
depressive episode, the patient must meet the
following criteria:
• Over a two week period, the patient has
consistently experienced five or more of the
following symptoms, and these behaviours must
be outside the parameters of the patient's normal
behaviour. Either depressed mood or decreased
interest or pleasure must be one of the five
(although both are frequently concomitant).
[] Eating disorders and weight gain/loss
[] Sleep
[] Motor activity
[] Fatigue
[] Concentration
[] Thoughts of death
Biological clock human being
 Mood Disorders

• Major Depression
• (Unipolar depression):
– one or more major depressive episodes.
• Bipolar Disorder:
– One or more manic episodes
 major depressive disorder
Unipolar disorders

• Major Depressive Disorder

• Major depressive disorder is diagnosed after a single episode of major
depression. It is characterized by emotional changes, primarily
depressed mood, and by so-called vegetative changes, consisting of
alterations in sleep, appetite, and energy levels.

• Epidemiology
The lifetime prevalence (will occur at some point in a person’s life)
rate for major depressive disorder is 5% to 20%. The female-male
ratio is 2: 1.
• Race distributions appear equal, and socioeconomic variables do not
seem to be a factor.
• The incidence (rate of new cases) is greatest between the ages of 20
and 40 and decreases after the age of 65.
 bipolar disorders
• There are two types; bipolar 1 disorder, bipolar II disorder.
• Bipolar I Disorder
• Bipolar I disorder is the most serious of the bipolar disorders and is
diagnosed after at least one episode of mania. Patients with bipolar I
disorder typically also have major depressive episodes in the course of
their lives

• Bipolar II disorder
• is similar to bipolar I disorder except that mania is absent in bipolar II
disorder and hypomania (a milder form of elevated mood than mania)
is the essential diagnostic finding.
• Epidemiology
Lifetime prevalence is about 0.5%. Bipolar II disorder may be more
common in women.
 Definition of Bipolar Disorder

• Bipolar Disorder, or BP, was previously called

manic-depression or manic depressive disorder.
BP is characterized by extreme moods - highs and
lows.
• Symptoms cycle from clinical or major
depression, to mania and manic behavior.
• Bipolar Disorder can significantly affect a patient's
ability to function, and can result in strained or
broken relationships, poor job performance, and
poor performance in school or group settings.
• Symptoms do not go away in a week or two. If left
untreated, the disorder can even result in suicide.
 Causes of Bipolar Disorder

• Mental health disorders typically stem from more than one

cause, and Bipolar Disorder (BP) is no exception to this
rule.
• Research on Bipolar Disorder indicates links to hereditary
or genetic factors and environmental factors.
• Those with a family history of depression, bipolar disorder
or other mental disorders seem more likely to suffer from a
mental disorder, and specifically from depression or
bipolar disorder. Other research indicates a chemical
imbalance in the brain of the bipolar patient. In some
patients, symptoms appear after a stressful event in the
patient's life, e.g. the death of a spouse, a divorce, or the
loss of a job.
 Symptoms of Bipolar Disorder

• There are two types of Bipolar Disorder. Bipolar I is characterized by

severe, debilitating symptoms, with extreme episodes, including some
or all of the following:
• Manic Symptoms
• Agitation, nervousness, irritability, feeling edgy, short-tempered,
• Feeling you can 'do no wrong', inflated sense of self, grandiose
feelings, inappropriate or poor judgment
• Increased sex drive or desire, loss of inhibition
• Dressing or speaking in an extreme, or unusual manner
• Inability to focus
• Delusions, hallucinations
• Euphoria, or feeling 'high'
• Heavy use of drugs or alcohol
• Boundless energy, sleeplessness, insomnia
• Rage, aggression or combative behavior
• Racing or disassociated thoughts, extreme talkativeness, rapid speech
• Reckless spending, high speed driving, high risk activities, decisions
made without considering consequences
Basic Epidemiology of UP and BP

• Typical age of onset

– Late 20s to 30s for UP
– Late teens to early 20s for BP
• Lifetime Morbid Risk – greater for UP than
BP
• Sex Difference for UP but not BP
• Cross-cultural stability for BP not UP
 Cross-national Rates of Depression

25
Men
20
Women
15

10

0
Italy
CA

NZ
Taiwan
PR

France

Korea
Lebanon
Ger
U.S.
 Cross-national Rates of Bipolar

5
Men
4 Women

0
CA

Taiwan

NZ
PR

Korea
Ger
U.S.
Cohort Effects on Depression
 Conclusions re Epidemiology
• UP and BP are distinguished in terms of
their:
– Typical age of onset
– Frequency
– Sex ratio
– Cross-cultural stability
Evidence For Genetic Influence
• Twin studies have consistently reported
greater MZ than DZ concordance
• Adoption studies indicate affective disorder
is associated with biological not adoptive
family background
Investigating Overlap of BP & UP

• Are two disorders differentially heritable?

• Is there cross-family transmission?

• Is there cross-MZ twin transmission?

If there is it would  shared etiology

Family Studies of Mood Disorders

• Risk to Relatives of UP
Proband:
– Clear excess UP
– Slight excess BP
• Risk to Relatives of BP
Proband
– Clear excess risk of BP
– Clear excess risk of UP
 Rates of Affective Disorder in
MZ Cotwins
50

40
BP
30 UP

20

10

0
Population Cotwins of UP Cotwins of BP
McGuffin, P. (2003). Heritability of bipolar affective disorder and the
Genetic relationship to unipolar depression. Arch Gen Psychiatry, 6: 497-502.
 Summary of Overlap Data

• Evidence supporting shared etiology

– Cross-family transmission
– Cross-MZ twin transmission
• Evidence supporting distinct etiologies
– Differential heritability
– UP MZ twins tend to be concordant for polarity
 Two Types of Mood Disorder
• Less common, more severe and more
heritable. Typically manifested as BP, but
can also manifest as UP

• More common, less heritable, and

manifested as UP only.
 Sex Differences in UP Depression

• Differential heritability

• Cross-sex transmission

• Variable Expressivity? Substance Use

disorders in men and depression in women?
 Risk of Depression in Male and
Female First Degree Relatives
(Kendler et al., 1999)
0.5
LMR
0.4
Female Proband
Male Proband
0.3

0.2

0.1

0
Men Women

Relatives
 Gene Identification in Depression
• Serotonin (5-HT) system
–Serotonin Transporter (SERT, 5-HTT)
• Serotonin Transporter Gene (SLC6A4)
–Serotonin transporter gene-linked polymorphic region (5-HTTLPR)
• 20-23bp repeated either 16 (=long) or 14 (=short) times
• s allele produces fewer 5-HTT molecules
–Lesch (1996) showed that s was associated with
neuroticism in two samples
–Recent meta-analyses suggest a modest effect of the s allele
on neuroticism; association with depression less clear
(Schinka et al. 2004)
G x E Interaction and Depression

Caspi, A. et al. (2003). Influence of life stress on depression: Moderation

By a polymorphism in the 5-HTT gene. Science, 301: 386-389.
 Is the GxE Replicable?
• Kendler et al. (2005) showed that only s-
carriers susceptible to low-threat events
• Hariri et al. (2005) – s allele on amygdala
reactivity to angry faces
• Serretti et al. (2007) meta-analysis of SSRI
tretament response
Linkage Analyses in Depression
 Gene Identification for BP
• Multiple rather than a single gene
• X-linked Hypothesis
– Reduced father-son transmission (Winokur,
1969)
• Anticipation?
– Age of onset earlier in successive generations
– No evidence of trinucleotide repeat expansion
• Linkage studies
Multiple Genes
 Regions/Genes Implicated in BP
Genome-Wide Chromosomal Candidate
Linkage Anomalies Gene
1q31-32 1q31-32
4p16
6pter-p24 11q21-25
10p14
10q25-26 15q11-13
12q23-24
13q31-32 21q22
18p11
18q21-23 22q11-13
21q22
22q11-13 Xq27-28
Xq24-28

Highlighted – regions also implicated in schizophrenia

 Summary
• Although in some cases UP does appear to be assoc with BP, the two
are generally distinct:
– Distinct epidemiology
– Differentially heritable
– UP MZs are generally concordant for polarity

• UP is more common in women than men

– More heritable in women than men
– Greater like-sex versus unlike-sex transmission implies genetic factors
differ in two sexes
– Recent molecular genetic research gives preliminary support to this
hypothesis
• Gene identification in Depression
– SLC6A4 and GxE interaction
– “Genome-wide” LD mapping
• Gene identification efforts for BP
– Multiple genes
– Anticipation, unstable mutation
– Multiple regions have been implicated