Major Depression

and Bipolar Disorder

By: Aileen Concepcion M. Agustin

MMSU-COM Clinical Clerk Batch 2019
Introduction

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 Mood

▪ Pervasive and sustained emotion that influences a

person’s behavior and perception of the world
▪ Subjective sensation experienced internally
▪ Depressed, sad, empty, melancholic, distressed, irritable,
disconsolate, elated, euphoric, manic, gleeful
▪ Labile, fluctuating or alternating rapidly between
extremes

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 Mood Disorders

▪ Also called Affective Disorders

▪ Depression and mania are often seen as opposite ends
of an affective or mood spectrum
▪ Signs and symptoms: changes in activity level, cognitive
abilities, speech, vegetative functions (sleep, appetite,
sexual activity, and other biological rhythms)
▪ Impaired interpersonal, social, occupational functioning

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 Most Common Kinds

▪ Only major depressive episodes (MDE)  major depressive

disorder (MDD) or unipolar depression
▪ Both manic and depressive episodes or manic episodes alone
 bipolar disorder
▪ "Unipolar mania" and "pure mania«  bipolar, no depressive
episodes
▪ Hypomania  episode of manic symptoms that does not meet
the criteria for manic episode
▪ Cyclothymia  less severe form of bipolar disorder
▪ Dysthymia  less severe form of major depression
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 Depression

▪ Major depressive disorder (MDD)

▫ W/o a history of a manic, mixed, or hypomanic
episode
▫ Must last at least 2 weeks and at least 4 symptoms:
▫ changes in appetite and weight
▫ changes in sleep and activity
▫ lack of energy
▫ feelings of guilt
▫ problems thinking and making decisions
▫ recurring thoughts of death or suicide
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 Depression

MNEMONICS
▪ D – depressed
▪ E – energy
▪ P – lack of pleasure or interest (anhedonia)
▪ R – retardation or restlessness
▪ E – eating – hyperphagia (increased) or anorexia (decreased)
▪ S – sleep (increased or decreased)
▪ S – self blame (guilt, worthlessness); “low self-esteem”
▪ E – memory (decreased ability to concentrate and focus)
▪ D – death (suicidal thought)
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Normal Depression
• Normal reaction to life
events (death of loved one,
major changes)
• Mood described as “blue”
• Few symptoms
• Short duration (<2 weeks)
• Little impairment in
functioning
Differences between Normal and Clinical Depression
Clinical Depression
• Mood described as “black”
• Many symptoms
• Longer duration (>2 weeks to months)
• Significant impairment in
functioning (can be debilitating)
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 Mania

▪ Manic episode  abnormally and persistently elevated,

expansive, or irritable mood, at least 1 week or less if a
patient must be hospitalized
▪ Hypomanic episode  lasts at least 4 days, similar to a
manic episode except no impairment in social or
occupational functioning, no psychotic features
▪ Bipolar I disorder  clinical course of 1 or more manic
episodes and major depressive episodes
▪ Bipolar II disorder  episodes of major depression and
hypomania 9
 Mania

▪ Distractibility
▪ Indiscretion (“excessive involvement in pleasurable
activities”)
▪ Grandiosity
▪ Flight of Ideas
▪ Activity increase
▪ Sleep deficit (decreased need)
▪ Talkativeness (pressured speech)
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 Dysthymia and Cyclothymia

▪ Dysthymic disorder
▫ at least 2 years of depressed mood that is not
sufficiently severe to fit the diagnosis of MDE.
▪ Cyclothymic disorder
▫ at least 2 years of frequently occurring hypomanic
symptoms that cannot fit the diagnosis of manic
episode and of depressive symptoms that cannot fit
the diagnosis of MDE.

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Range of Mood
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Range of Mood
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 RAPID CYCLING
• At least 4 switches into
mania, hypomania,
depression, or mixed
episodes within a 12-month
period

Range of Mood
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Epidemiology

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 Incidence and Prevalence

▪ MDD  highest lifetime prevalence (17%) of

any psychiatric disorder
▪ Lifetime prevalence rate for major depression
 5 to 17%

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 Sex

▪ 2x greater prevalence of MDD in females

▫ hormonal differences, effects of childbirth, differing
psychosocial stressors for women and for men,
behavioral models of learned helplessness
▪ Bipolar I disorder  F = M
▪ Manic episodes  M > F
▫ Females  more likely to present a mixed picture
(mania and depression); rapid cyclers (4 or more
manic episodes in a 1 -year period)
▪ Depressive episodes  F > M 17
 Age

▪ Bipolar I disorder
▫ Age of onset: childhood (5 or 6 years) to 50 years or
even older
▫ Mean age of 30 years
▪ Major depressive disorder
▫ Age of onset: between 20 to 50 years (50% of all
patients), also childhood and old age
▫ Mean age of 40 years
▫ Increasing incidence in <20 y/o d/t increased use of
alcohol and drugs of abuse
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 Marital Status

▪ Major depressive disorder

▫ Persons w/o close interpersonal
relationships, divorced or separated
▪ Bipolar I disorder
▫ More common in divorced and single
persons

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 Socioeconomic and Cultural Factors

▪ Major depressive disorder  no correlation

▪ Bipolar I disorder
▫ Upper socioeconomic groups
▫ Persons who did not graduate from college
▪ Depression  more common in rural areas
▪ Prevalence of mood disorder does not differ
among races.
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Comorbidity

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 Comorbidity

▪ Increased risk of additional comorbid disorders

▪ Most frequent disorders
▫ Alcohol abuse or dependence, panic disorder, OCD,
and social anxiety disorder
▪ Unipolar and bipolar disorder
▫ Male  substance use disorders
▫ Female  anxiety and eating disorders
▪ Comorbidities worsen prognosis of the illness and
markedly increase the risk of suicide
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Etiology

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 Biological Factors

▪ Biogenic Amines:
▫ Norepinephrine
▫ downregulation or decreased sensitivity of beta-
adrenergic receptors and clinical antidepressant
responses in depression
▫ presynaptic beta2-receptors
▫ activation results in a decrease amount of
norepinephrine release

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 Biological Factors

▪ Biogenic Amines:
▫ Serotonin
▫ Biogenic amine neurotransmitter most commonly
associated with depression
▫ Depletion may precipitate depression
▫ Some patients with suicidal impulses have low
CSF concentrations of serotonin metabolites and
low concentrations of serotonin uptake sites on
platelets

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 Biological Factors

▪ Biogenic Amines:
▫ Dopamine
▫ Reduced in depression and increased in mania
▫ Reduced dopamine concentrations in drugs
(reserpine) and diseases (Parkinson's disease)
 depressive symptoms
▫ Increase dopamine concentrations w/ tyrosine,
amphetamine, and bupropion
▫ Dysfunctional mesolimbic dopamine pathway and
hypoactive dopamine D1 receptor
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 Biological Factors

▪ Other Neurotransmitter Disturbances

▫ Acetylcholine (Ach)
▫ Abnormal levels of choline in some depressed
patients, abnormalities in cell phospholipid
composition
▫ Agonists  lethargy, anergia, psychomotor
retardation in healthy subjects, exacerbate
symptoms in depression, reduce symptoms in
mania

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 Biological Factors

▪ Other Neurotransmitter Disturbances

▫ Gamma Aminobutyric Acid (GABA)
▫ Inhibitory effect on ascending monoamine
pathways (mesocortical and mesolimbic system)
▫ Decreased in depression
▫ GABA receptors are upregulated by
antidepressants

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 Biological Factors

▪ Other Neurotransmitter Disturbances

▫ Glutamate and glycine
▫ Major excitatory and inhibitory NT in the CNS
▫ Bind to sites associated with N-methyl-o-
aspartate (NMDA) receptor
▫ Drugs that antagonize NMDA receptors have
antidepressant effects.

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 Biological Factors

▪ Second Messengers and Intracellular Cascades

▫ Guanine nucleotide-binding proteins (G proteins)
▫ Connect to various intracellular enzymes that
regulate utilization of energy and formation of
second messengers
▫ Mood-stabilizing drugs act on G proteins or other
second messenger

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 Biological Factors

▪ Alterations of Hormonal Regulation

▫ Depressed humans  history of early trauma is
associated with increased HPA activity accompanied
by structural changes (atrophy or decreased volume)
in the cerebral cortex.
▫ Elevated HPA activity is a hallmark of mammalian
stress responses and one of the clearest links
between depression and biology of chronic stress

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 Biological Factors

▪ Alterations of Sleep Neurophysiology

▫ Depression  premature loss of deep (slow-wave)
sleep and increase in nocturnal arousal
▫ (1) increase in nocturnal awakenings
▫ (2) reduction in total sleep time
▫ (3) increased phasic REM sleep
▫ (4) increased core body temperature
▫ Abnormal sleep profile  less responsive to
psychotherapy, greater risk of relapse or recurrence

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 Biological Factors

▪ Immunological Disturbance
▫ Depressive disorders  several immunological
abnormalities (decreased lymphocyte proliferation in
response to mitogens and forms of impaired cellular
immunity)

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 Biological Factors

▪ Structural and Functional Brain Imaging

▪ CT scan and MRI
▫ most consistent abnormality  increased frequency
of abnormal hyperintensities in subcortical regions,
such as periventricular regions, basal ganglia, and
thalamus
▫ Diffuse and focal areas of atrophy  increased
illness severity, bipolarity, increased cortisol levels
▪ PET scan
▫ Decreased (left) anterior brain metabolism
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 Biological Factors

▪ Neuroanatomical Considerations
▫ 4 brain regions in the regulation of normal emotions:
▫ Prefrontal cortex (PFC), representations of goals
and appropriate responses
▫ Anterior cingulate cortex (ACC), point of
integration of attentional and emotional inputs
▫ Hippocampus, learning and memory, fear
conditioning, inhibitory regulation of HPA axis
▫ Amygdala, heart of the limbic system

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 Genetic Factors

▪ Family Studies
▫ 1 parent has a mood disorder: child’s risk 10 to 25%
▫ Both parents: risk roughly doubles
▫ More members affected, greater the risk, greater if
first-degree relative
▫ Unipolar disorder  most common form of mood
disorder in families of bipolar probands

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 Genetic Factors

▪ Adoption Studies
▫ approach to separating genetic and environmental
factors in familial transmission
▫ 3x increase in rate of bipolar disorder and a 2x
increase in unipolar disorder in biological relatives of
bipolar probands

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 Genetic Factors

▪ Twin Studies
▫ Most powerful approach to separating genetic from
environmental factors, or "nature" from "nurture."
▫ Genes explain only 50 to 70% of the etiology of mood
disorders
▫ Predisposition or susceptibility to disease that is
inherited

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 Genetic Factors

▪ Linkage Studies
▫ Genetically linked  a DNA marker is identified with
disease in families
▫ Bipolar disorder  Chromosomes 18q and 22q

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 Psychosocial Factors

▪ Life Events and Environmental Stress

▫ Life events play the primary role in depression
▫ most often associated with development of
depression is losing a parent before 11 y/o
▫ Environmental stressor most often associated with
onset of an episode of depression is loss of a spouse
▫ Another risk factor is unemployment
▫ 3x more likely to report symptoms of an episode
of major depression. Guilt may also play a role

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 Psychosocial Factors

▪ Personality Factors
▫ No single personality trait or type uniquely
predisposes a person to depression
▫ All humans, of whatever personality pattern, can and
do become depressed under appropriate
circumstances.
▫ OCD, histrionic, and borderline  greater risk
▫ Dysthymic and cyclothymic disorder  risk of later
developing major depression or bipolar I disorder

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 Psychosocial Factors

▪ Personality Factors
▫ Recent stressful events are the most powerful
predictors of the onset of a depressive episode
▫ Stressors the patient experiences as reflecting
negatively on his or her self esteem  more likely to
produce depression
▫ What may seem to be a relatively mild stressor to
outsiders may be devastating to patient because of
particular idiosyncratic meanings attached to event

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 Psychosocial Factors

▪ Psychodynamic Factors in Depression

▫ Classic view of depression (Freud and Abraham)
▫ (1) disturbances in infant-mother relationship during oral
phase (first 10 to 18 months of life) predispose to
subsequent vulnerability to depression
▫ (2) depression can be linked to real or imagined object loss
▫ (3) introjection of departed objects is a defense mechanism
invoked to deal with distress connected with object's loss
▫ ( 4) because lost object is regarded with a mixture of love
and hate, feelings of anger are directed inward at the self.

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 Psychosocial Factors

▪ Psychodynamic Factors in Mania

▫ Manic episodes may reflect an inability to tolerate a
developmental tragedy (loss of a parent) (Abraham)
▫ tyrannical superego  intolerable self-criticism that is
then replaced by euphoric self-satisfaction
▫ Defensive reaction to depression, using manic
defenses such as omnipotence, develops delusions
of grandeur (Klein)

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Other Formulations of Depression

Other Formulations of Depression: Cognitive Theory

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 Other Formulations of Depression

▪ Learned Helplessness
▫ Connects depressive phenomena to experience of
uncontrollable events
▫ Internal causal explanations are thought to produce a
loss of self-esteem after adverse external events
▫ Improvement of depression is contingent on the
patient's learning a sense of control and mastery of
the environment

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Diagnosis

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DSM-5 Criteria for Major Depressive Disorder
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 Major Depressive Disorder, Single VS Recurrent Episode

▪ Problem with diagnosing recurrent episodes of MDD is

the criteria to designate resolution of each period
▫ degree of resolution of the symptoms
▫ length of the resolution
▪ DSM-5 requires that distinct episodes of depression be
separated by at least 2 months during which a patient
has no significant symptoms of depression.

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 Bipolar Disorders

▪ Bipolar I
▫ one or more manic episodes and sometimes major
depressive episodes
▪ Mixed Episode
▫ period of at least 1 week in which both a manic
episode and a major depressive episode occur
almost daily
▪ Bipolar II
▫ Episodes of major depression and hypomania rather
than mania
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 Bipolar Disorders

Bipolar I Disorder
▪ Distinct period of abnormal mood lasting at least 1 week
and includes separate bipolar I disorder diagnoses for a
single manic episode and a recurrent episode
▫ Manic episodes  distinct when they are separated
by at least 2 months w/o significant symptoms of
mania or hypomania
▪ NOT, if clearly precipitated by antidepressant treatment

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Thank you for your kind attention.

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