Mood Disorders

PSY 348
Introduction

• Each of us experience periods of sadness, as well as periods in which

we feel on top of the world, of varying duration
• For some, these mood swings become prolonged and extreme,
conditions known as mood disorders or affective disorders
• These disorders have been recognized as clinical entities as early as
the 4th century BCE, when Hippocrates described both depression and
mania in detail
Major Depressive Episodes (MDE)

• Onset is typically gradual, occurring over a period of several weeks or

months, the episode lasts for several months, and ends gradually
• The characteristic features of a major depressive episode are:
1. Depressed mood: can range from mild melancholy to total
hopelessness
2. Loss of pleasure or interest in usual activities: known as
anhedonia
3. Disturbance of appetite: most depressed people have poor
appetite and lose weight, while others eat more and put on weight
MDEs continued

4. Sleep disturbances: insomnia is common, but increased sleep

can also occur
5. Psychomotor retardation or agitation: usually the depressed
person is fatigued (in extreme cases catatonia is seen); in other cases, the
person shows incessant activity like hand wringing and pacing
6. Loss of energy: the depressed person typically exhibits a
sharply reduced energy level
MDEs continued

7. Feelings of worthlessness and guilt: depressed people see

themselves as deficient in attributes they value, often accompanied by a
profound sense of guilt
8. Difficulties in thinking: depressed people have trouble
concentrating, remembering, and making decisions (even simple ones)
9. Recurring thoughts of death or suicide: many depressed people
have recurrent thoughts of death, ranging from passive ideation to intent
Manic Episode
• Typically manic episodes begin relatively suddenly, and are shorter than depressive
episodes, lasting from several days to several months
• The characteristic features of a manic episode are:
1. Elated, expansive, or irritable mood accompanied by abnormally and persistently
increased goal-directed behavior
2. Inflated self-esteem
3. Sleeplessness
4. Talkativeness
Manic Episode continued
5. Flight of ideas; potentially a reason for their pressured speech
6. Distractibility
7. Hyperactivity; restlessness and increased goal-directed activity (including sexual
activity)
8. Reckless behavior
Hypomanic Episode
• Briefer and less severe than a manic episode, and does not require impairment, but similar
symptoms
• Requires a change in functioning that must be observable by others
Major Depressive Disorder

• People who experience one or more major depressive episodes, with no mania or
hypomania, have major depressive disorder (MDD)
• 12 month prevalence is 7.1%, and lifetime risk is about 16.6%
• Second leading cause of years lived with disability worldwide; responsible for significant
financial burden due to both direct costs (medical and pharmacy services) and indirect cost
(work days lost, unemployment)
• Most people with major depression do not receive adequate treatment (Auerbach et al.,
2016)
• Each successive generation born since WWII has shown higher rates of depression
(Compton et al., 2006)
MDD: Course
• MDD is highly recurrent, with about 72% of those with first onset of major depression
experiencing at least one recurrence (Boland & Keller, 2009)
• Factors increasing likelihood of recurrence include previous episodes, younger age of first
onset, female gender, family history of depression, more stressful life events endured
recently, less social support, and more negative cognitions
• Median number of episodes per patient is 4, with median duration of 4.5 months per
episode
MDD Course continued
• Following a depressive episode, some return to previous level of functioning, while others
still show serious impairment 10 years later
• Many individuals experience a chronic course of the disorder, with high rates of
comorbidity with other conditions
Groups at Risk for Depression

• Research shows that Hispanic youth (especially girls) tend to have higher rates of
depression than White or African American youth (Twenge & Nolen-Hoeksma, 2002)
• African-American and Hispanic adults have higher rates of depression than White adults
(Dunlop et al., 2003)
• Never-married and formerly married individuals have higher depressive symptoms than
those who are married (Mirowsky & Ross, 2003)
• Later-born cohorts have a higher lifetime prevalence of depression (Mojtabai et al., 2016)
Groups at Risk for Depression continued

• Women are twice as likely to develop depression as men (Hankin et al., 2015)
• The gender difference in depression rates first emerges during adolescence, and lasts
through adulthood; prior to adolescence, boys and girls tend to have similar rates of
depression (Hankin et al., 2015)
• Discussion question: why might this gender difference exist?
Bipolar Disorder

• Involves both manic or hypomanic and depressive episodes

• Consists of two types:
• Bipolar I disorder: the person has had at least one manic episode,
and usually (but not always) one major depressive episode
• Bipolar II disorder: the person has had at least one hypomanic
episode and one major depressive episode, but has never met the
criteria for a manic episode
Bipolar Disorder continued

• Bipolar disorder is much less common than major depression, affecting

approximately 0.5 to 3.5% of the world population (Cia et al., 2018)
• BD occurs in the two sexes with approximately equal frequency, and is
more prevalent among higher socioeconomic groups
• Those who are married are not at decreased risk for BD
• BD is associated with greater impairment, heightened risk of suicide, and
worse long-term outcomes compared to MDD
Persistent Depressive Disorder

• Formerly known as dysthymia; involves a mild depression that may occur for two or more
years
• These individuals often have low energy, low self-esteem, and disturbances of eating,
sleeping, and thinking, but worse functioning than those with MDD
• Whereas MDD is episodic, PDD is chronic
• 2-3 times more common in women and unmarried people, with many of the same risk
factors as MDD
• Double depression: a MD episode may be superimposed on PDD
Cyclothymic Disorder
• Like PDD for MDD, this is a chronic manifestation of bipolar disorder
• Milder than bipolar II and bipolar I disorder
• Studies suggest a common genetic diathesis between cyclothymic disorder and BD
Life Events

• Depression is often precipitated by events involving failures of

interpersonal loss such as death, divorce, separation, or rejection
• By the same token, social supports are protective factors in stopping
individuals from succumbing to depression
• Kindling hypothesis: suggests that stressful life events are important for
the first onset of depression, but the association between events and
episodes becomes weaker as the number of episodes increases
Suicide

• Defined as death from a self-inflicted injury committed with the intent to die
• In addition to completed suicide, other suicidal behaviors include suicidal attempts and
suicidal ideation
• Most suicide ideators do not attempt suicide (May & Klonsky, 2016)
• MDD is the psychiatric diagnosis most commonly associated with suicide, with the risk of
suicide approximately 20x greater than in the general population
• Risk of suicide in individuals with BD is 60x greater than in the general population
• 54% of individuals who complete suicide did not have a known mental health condition
Suicide Continued

• In 2012, 804,000 people died by suicide worldwide, making in the 15 th leading cause of
death (WHO, 2014)
• Suicide rates have increased in every state in the U.S. between 1999 and 2016, and suicide
is the second leading cause of death for 10- to 24-year-olds in the US
• Leading methods of suicide include firearms (55% of completed suicides), suffocation
(27% of completed suicides), and poisoning (10% of completed suicides)
 Males complete suicide at nearly 4x the rate of
females, representing 78% of all completed
suicides in the US (CDC, 2015)– likely due to the
choice of more lethal means

Risk Highest rates of suicide found among American

Indian/Alaska Native adolescents and young adults
Factors
for Suicide
Risk of suicide appears to increase with age,
particularly among males, but rates for adolescents
and young adults appear to be increasing
 LGBTQ+ individuals are more likely to
attempt and complete suicide (Hottes et al.,
2016), likely due to increased social
stressors
Genetics: relatives of those who have died
Risk Factors by suicide are 2-6x as likely to complete
Continued suicide themselves (Mann et al., 2019)

Most significant risk factors for suicide

include current suicidal ideation, plan, or
intent, and prior suicide attempt(s)
Suicide Prevention
• Werther effect: suicide attempts increase following the
depiction of suicide in the media (Niderkrotenthaler et al.,
2010), particularly by celebrities
• Other prevention factors include better recognition of the
signs of suicide, greater awareness of treatment possibilities,
and improved training for healthcare professionals
National Suicide Prevention
Lifeline
800 273 8255
Mood Disorders: Causes and
Treatment
• Most theories and treatments tend to focus on depression, as it is far more common than
hypomania and mania
• Among general theoretical perspectives, behavioral/interpersonal, cognitive, and
neuroscience approaches have had the greatest influence on understanding the causes of
and generating treatments for mood disorders
 Focuses on the social context of depression; posits
that depressed individuals engage in maladaptive
interpersonal strategies in an attempt to regulate
their mood

Co-rumination: the engagement in repetitive, non-

Interpersonal productive, and emotion-focused dyadic discussion
of problems
Perspective

May appear helpful, but actually provides social

reinforcement for this response style; associated
with depression among children, adolescents, and
adults
 Excessive reassurance seeking: depressed
individuals persistently seek reassurance that
others care about them and value them

The individual is attempting to improve their

Interpersonal
depressed state, but it results in irritation in
Perspective friends/family members, leaving the
Continued individual rejected

Leads to a self-perpetuating cycle in which

the depressed individual uses this as evidence
for depressive cognitions (e.g., ”I’m
unlovable”)
Behavioral Perspective

• Extinction: builds upon principles of learning theory to suggest that once behaviors are no
longer rewarded, individuals will stop performing them
• Several studies support a negative correlation between number of pleasurable activities
engaged in and depression
• However, newer models suggest that depression may be related to reduced responses to
reinforcing stimuli, rather than extinction due to a loss of rewards
Behavioral Activation Therapy (BAT)

• Designed to increase activity, and in turn, develop more positively

reinforcing behavior patterns in depressed individuals
• Clients and therapists identify specific activities (positive reinforcers)
they can engage in based on a predetermined schedule
• Over time, clients are asked to engage in progressively more difficult
activities
BAT continued

• BAT has been found to reduce depression and prevent relapse over a two-
year follow-up (Jacobson et al., 1996)
• Most important components of BAT appear to be activity monitoring and
scheduling
• BAT can also involve social skills training, including reducing negative
interpersonal behaviors like co-rumination and excessive reassurance
seeking
Cognitive Perspective
• According to this perspective, the way people think about themselves,
the world, and the future gives rise to the other symptoms (negative
cognitive triad)
• Hopelessness theory of depression: derived from Seligman’s earlier
work on learned helplessness in dogs presented with inescapable
electric shocks; over time, they would stop attempting to escape even
when it was possible
• Theory posits that depressed individuals learn that they lack control
over the environment, and consequently give up
Cognitive Perspective
Continued
• According to this theory, greatest risk for depression occurs in those
who view negative events as due to causes that are
• Stable (permanent)
• Global (generalized over many areas of their life)
• Internal (part of their personalities rather than the environment)
• Both social learning factors and a history of maltreatment may
contribute to the development of these outlooks, such as having a
parent with a negative cognitive style
Negative Self-Schemas
• According to Beck, negative cognitive schemas predispose
individuals to depression
• Despite these negative biases, depressed individuals may actually be
somewhat more realistic about their degree of control over outcomes
compared to non-depressed individuals (Alloy & Abramson, 1988)
• Non-depressed people may actually be optimistically biased, which is
essential for psychological health
Treatments: Cognitive Behavioral
Therapy

• CBT aims to identify, challenge, and modify negative cognitive schemas

to generate less negative information processing
• Involves behavioral activation (see BAT) and the use of behavioral
’experiments’ to help depressed individuals challenge their distorted
thoughts
• Shown to be at least as effective of medication; a combination of the two
may be even more effective than either treatment alone (Cuijpers et al.,
2013)
Psychodynamic Perspective
• Loss and attachment: Freud (1917) likened the experience of depression to that of
mourning for a lost object, either real or imagined
• Bowlby (1982) proposed that the loss of an attachment figure predisposes children to
depression in adulthood
• Maternal depression is a strong predictor of childhood and adolescent depression (Raposa
et al., 2014)
Neuroscience
Perspective
• A meta-analysis found that individuals with a first-degree
relative with MDD are almost 3x more likely to develop the
disorder themselves (Sullivan et al., 2000)
• Those with a first-degree relative with BD are almost 10x
more likely to develop the disorder (Smoller & Finn, 2003)
• Genome-wide association studies have found striking
diversity in genetic profiles, suggesting that depression and
mania are the result of a complex integration of multiple
genetic variations with multiple environmental factors
Neurophysiological Research
• Depressed individuals show various sleep abnormalities, including shortened rapid eye
movement (REM) latency (Kupfer et al., 1976); this has also been observed in
schizophrenia, PD, OCD, mania, and eating disorders
• Seasonal affective disorder (SAD): some individuals experience depressive symptoms
only in the winter months
• Roughly 75% of these individuals report clinical improvements when treated with
morning exposure to bright, artificial light (Oren & Rosenthal, 1992)
Neuroimaging Research

• MRI studies report amygdala and hippocampal abnormalities in MDD and BD (Grotegerd
et al., 2013)
• Decreased gray matter volume has been found in the orbitofrontal cortex in individuals
with MDD and BD (Arnone et al., 2012)
• White matter abnormalities have also been observed in various brain regions in MDD and
BD
Hormone Imbalance and Mood Disorders

• Hypersecretion of cortisol is a consistent finding in the depression

literature, as measured by hypersecretion of corticotrophin releasing
hormone (CRH) and elevated cortisol concentrations in plasma, urine,
saliva, and cerebrospinal fluid
• Dexamethasone is glucocorticoid agonist that should inhibit cortisol
production; when administered with CRH (which should promote
cortisol production) individuals with MDD fail to inhibit their cortisol
secretion
Hormone Imbalance Continued

• Excess levels of cortisol have been shown to abate as mood symptoms

improve, persisting only in those with high risk of relapse (Daban et
al., 2005)
• Hypercortisolemia is associated with impairments in learning and
memory, hippocampal atrophy, and reductions in frontal lobe volume
(Young et al., 2004)
• Other hormones implicated in mood disorders include thyroid
hormone and gonadal/ovarian hormones
Immune System Dysregulation
• The immune system appears to play a role in both behaviors common to both depression
and sickness: e.g., fatigue, social withdrawal, anhedonia, and difficulty concentrating
• Researchers propose that a number of proteins play a role in both the immune system’s
response to pathogens, as well as directly activating the brain to produce these “sickness”
behaviors
• It remains unclear whether depression causes inflammatory activity, whether increases in
inflammatory activity cause depression, whether there is a bidirectional relationship, or
whether both are caused by a common underlying process
 Serotonin, norepinephrine, and dopamine all
appear to play a critical role in the neurobiology
of mood disorders

Serotonin, also known as 5-Hydroxytryptamine

(or 5-HT) is one of the most studied
Neurotransmitter
Dysfunction:
Serotonin Research has suggested that a reduction in 5-HT
activity is associated with major depression and
suicide (Carr & Lucki, 2011)

Altered 5-HT functioning is also present in

bipolar depression
 Dopamine (DA) is also critical in mood
disorders: reductions of dopamine in the
nucleus accumbens and the prefrontal cortex
are associated with blunted reward response,
anhedonia, decreased concentration, and
motivation difficulties
Neurotransmitters
Continued: Dopamine
In BD, dopamine appears to be elevated during
periods of mania and reduced during periods of
depression (Ashok et al., 2017)
 Norepinephrine also plays a central role in mood
disorders: experimentally increased levels of NE
produce mania, whereas decreased levels produce
depression (Schildkraut, 1965)

Many antidepressants, including buproprion and

Neurotransmitters venlafaxine, target norepinephrine reuptake
Continued:
Norepinephrine

Other effective treatments, such as electroconvulsive

therapy (ECT) may act by increasing the availability
of dopamine and norepinephrine
Psychopharmacological Interventions

• Primary classes of antidepressants include monoamine oxidase inhibitors (MAOIs),

tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin
reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs)
• MAOIs interfere with the enzyme that breaks down 5-HT, DA, and NE; tricyclics block
the reuptake of 5-HT and NE; TeCAs increase levels of NE and 5-HT, SSRIs block
reuptake of 5-HT, and SNRIs inhibit reuptake of 5-HT and NE
Psychopharmacological Interventions
Continued

• Choice of antidepressant depends on which drug provides greatest symptom relief with
fewest side effects
• MAOIs and TCAs tend to have higher levels of side effects, and are often only prescribe
when other medications prove ineffective
• SSRIs such as escitalopram, paroxetine, and sertraline show the highest response rates and
lowest dropout rates in clinical trials
• Emerging research shows that ketamine is associated with a rapid and sustained
antidepressant effect, and may reduce suicidal ideation (Grunebaum et al., 2018)
Psychopharmacological Interventions
Continued

• Mood stabilizer medications, particularly lithium, are the drug of choice for bipolar
disorder
• Long-term antidepressant use alone may be useful in preventing new onset of depressive
episodes in BD, but is associated with increased risk of switching to mania (Liu et al.,
2017)
• Other medications for BD include anticonvulsants, such as sodium valproate
• Antipsychotics may also be prescribed for patients experiencing acute manic episodes
Electroconvulsive Therapy
• Electric shocks to the brain have been shown to ameliorate symptoms of severe, refractory
depression; typically 70-130 volts administered 9 or 10 times over a period of several
weeks
• The exact mechanism of how ECT works is unclear, but it may involve downregulating 5-
HT receptors, similar to antidepressants
• Side effects include memory dysfunction
Repetitive Transcranial Magnetic
Stimulation

• rTMS involves producing a brief magnetic field which induces depolarization in neurons
(George et al., 1999)
• Allows for finely tuned stimulation than ECT, but ECT appears to be more effective than
rTMS
• Generally patients report no adverse side effects