MOOD DISORDERS

Uyen Ngoc Phuong Le, MD

Department of Psychiatry
Pham Ngoc Thach University of Medicine
OBJECTIVES

*After this lesson, students are expected to:

1. Have an awareness of mental health
2. Recognize clinical manifestations of depressive and bipolar disorders
(mania/hypomnia/depression)
3. Describe the diagnostic criteria of major depressive disorder (MDD), bipolar
disorder I (BD I) and bipolar disorder II (BD II)
4. Make a diagnosis of some depressive and bipolar disorders
5. Name groups of medication in treatment of depressive and bipolar disorders
What is Mood Disorders?

🠶 A GROUP OF MENTAL DISORDERS:

❖ RELATED TO MOOD
❖ INCLUDE: BIPOLAR DISORDERS AND DEPRESSIVE DISORDERS
❖ TEND TO CAUSE DISTRESS OR/AND SIGNIFICANT IMPAIRMENT IN ONE’S LIFE
FUNCTION

🠶 OLD NAME FROM DSM-IV-TR.

❖ PHENOMENOLOGICAL AND GENETIC OVERLAP BETWEEN SCHIZOPHRENIA AND
BIPOLAR DISORDER.
What is Mood?

🠶 A STATE OF EMOTION:
❖ LASTING, PERSISTENT
❖ PERVASIVE
❖ HAVE SIGNIFICANT INFLUENCE ON ONE’S PERCEPTION AND BEHAVIOUR

🠶 MEANWHILE, EMOTION:
❖ USUALLY TEMPORARY
❖ RESPOND TO INTERNAL/EXTERNAL EXPERIENCES (THOUGHTS, GRADUATION DAY,
PROMOTION DAY, FUNERAL…)
WEATHER AND SEASON
Ex: Depressed mood

🠶 DURING THE TIME,

❖ EMOTION (SAD, HOPELESS, EMPTY,…) IS DOMINANT AND PERSIST FOR DAYS OR
MONTHS.
❖ AT SOMEPOINT, IN THE CONTEXT OF A CERTAIN EVENT OR SITUATION, THEY MIGHT
HAVE A DIFFERENT EMOTION (TO HIDE THE DEPRESSION, TO BE ACCEPTABLE,…)
❖ In a restaurant, a waiter spilled out the wine and splashed your shirt. How did you feel?
Emotions

“Emotions are a process, a particular kind of automatic appraisal

influenced by our evolutionary and personal past, in which we sense
that something important to our welfare is occurring, and a set of
psychological changes and emotional behaviors begins to deal with
the situation.”

Paul Ekman
 Basic/Universal Emotions

SURPRISE

CONTEMPT

https://www.paulekman.com/universal-emotions/
 TERMINOLOGY

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
TERMINOLOGY

🠶 Mood Disorders
❖ Bipolar Disorders = Bipolar and Related Disorders
❖ Depressive Disorders

🠶 Mood Episodes
❖ Major Depressive Episode
❖ Manic Episode
❖ Hypomanic Episode

🠶 Mood Symptoms
TERMINOLOGY

🠶 BIPOLAR AND RELATED DISORDERS

❖ BIPOLAR I DISORDER (BD I)
❖ BIPOLAR II DISORDER (BD II)
❖ CYCLOTHYMIC DISORDER
❖ SUBSTANCE/MEDICATION – INDUCED BIPOLAR AND RELATED DISORDER
❖ BIPOLAR AND RELATED DISORDER DUE TO ANOTHER MEDICAL CONDITION
❖ OTHER SPECIFIED BIPOLAR AND RELATED DISORDER
❖ UNSPECIFIED BIPOLAR AND RELATED DISORDER
TERMINOLOGY

🠶 DEPRESSIVE DISORDERS
❖ DISRUPTIVE MOOD DYSREGULATION DISORDER
❖ MAJOR DEPRESSIVE DISORDER (MDD)
❖ PERSISTENT DEPRESSIVE DISORDER (DYSTHYMIA)
❖ PREMENSTRUAL DYSPHORIC DISORDER
❖ SUBSTANCE/MEDICATION – INDUCED DEPRESSIVE DISORDER
❖ DEPRESSIVE DISORDER DUE TO ANOTHER MEDICAL CONDITION
❖ OTHER SPECIFIED DEPRESSIVE DISORDER
❖ UNSPECIFIED DEPRESSIVE DISORDER
 MDD - EPIDEMIOLOGY

Kessler RC, Bromet EJ. The epidemiology of depression across cultures, 2013.
 GLOBAL PREVALENCE IN 2015 IS ESTIMATED TO BE 4.4%.

World Health Organization. Depression and Common Mental Disorders – Global Health Estimates , 2015.
World Health Organization. Depression and Common Mental Disorders – Global Health Estimates , 2015.
 DEPRESSION OCCURS AT ANY AGE.

WOMEN IS MORE LIKELY TO SUFFER FROM DEPRESSION THAN MEN.

World Health Organization. Depression and Common Mental Disorders – Global Health Estimates , 2015.
 MDD – ETIOLOGICAL FACTORS/
PATHOPHYSIOLOGY

Otte C, Gold SM, Penninx BW, et al: Major depressive disorder. Nat Rev Dis Primers 2:16065, 2016.
🠶 GENETICS:
❖ GWAS (Genome-wide Association Study) show inconsistence profiles of related gene loci.
❖ First-degree relatives of patients with MDD are three times more likely to have MDD and heritability
for the disorder is roughly estimated 35%. [1]

🠶 ENVIROMENT
❖ Childhood adverse events (abuse, neglect, separation from parents,…)
❖ Adulthood life stress (unemployment, financial status, health problems, bereavement…)
❖ Early life: in utero [2]

🠶 EPIGENETICS
❖ Individuals with related-gene have an increased risk in the presence of stressors and other adverse
environmental circumstances.
❖ Gene expression
🠶 NEUROENDOCRINOLOGY
❖ HPA axis: one of the most researched biological system in MDD [3]
• HPA Activation, Cortisol level in Blood, CRH level in cerespinal fluid, Glucocorticoid receptor resistance
• Intervention potential is lacking data.

❖ Thyroid Hormone and reproductive hormores

🠶 NEUROINFLAMMATION
❖ Increased cytokines level in MDD [4]
❖ The neuroinflammation and microglial activation in CNS [5]

🠶 NEUROPLASTICITY – NEUROGENESIS
🠶 NEUROTRANSMITTERS
❖ Monoamines: Seretonin, Norepinephrine, Dopamine [6]
❖ Others: Glutamate , GABA, Opioid
🠶 STRUCTURAL BRAIN ALTERATIONS
❖ Smaller volume in brain regions: hippocampus, basal ganglia, thalamus, frontal regions. [7]
❖ Hippocampus might be specifically affected in MDD compared to other psychiatric disorders.

🠶 FUNCTIONAL BRAIN CIRCUITS: Activation or Connectivity

❖ Affective–salience circuit
❖ Default mode network
❖ The frontoparietal cognitive control circuit
 MDD – SYMPTOMS AND DIAGNOSIS

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
🠶 SIGECAPS
❖ (S) : inSomnia/hypersomnia
❖ (I):reduced Interest/pleasure
❖ (G): excessive Guilt or feelings of worthlessness
❖ (E): reduced Energy or fatigue
❖ (C): diminished ability to Concentrate or make decisions
❖ (A): loss or increase of Appetite/weight
❖ (P): Psychomotor agitation/retardation
❖ (S): thoughts of Suicide/death or an actual suicide attempt/plan

🠶 Major Depressive Episode (MDE): meet A, B and C.

🠶 Major Depressive Disorder (MDD): meet A, B, C and D, E.
🠶 Classified into:
❖ Emotion: depressed mood, loss of interest, anxiety, angry outbursts…
❖ Thought: Thoughts of dying, negative thinking (self, world,future),
rumination…
❖ Behaviour: Commiting suicide, crying, lying, avoiding…
❖ Cognitive Function: Impaired Concentration, impaired memory…
❖ Somatic Symptoms: Appetite, Fatigue, Sleep Problem, Gastrointestinal
Symptoms, Headache…
MDD - Specifiers

MDD WITH:
🠶 Anxious Distress
🠶 Mixed features
🠶 Melancholic features
🠶 Atypical features
🠶 Psychotic features
🠶 Catatonia
🠶 Peri-partum onset
🠶 Seasonal pattern
DIFFERENTIAL DIAGNOSIS

🠶 MDE in Bipolar disorders

🠶 Schizoaffective disorder
🠶 Schizophrenia, especially with dominant negative symptoms
🠶 Personality disorders
🠶 Stress-related disorders (adjustment disorder,…)
🠶 Sadness
MDD - TREATMENT

🠶 Pharmacotherapy
🠶 Psychotherapy
🠶 Somatic Therapy: ECT (Electroconvulsive Therapy), rTMS (repetitive Transcranial
Magnetic Stimulation), DBS,…

*For more in-depth knowledge:

Canadian Network for Mood and Anxiety Treatment (CANMAT) Depression Guideline 2016.
https://www.canmat.org/resources/

🠶 Base on patient’s preference and severity.

Pharmacotherapy

🠶 Monoamine-based Antidepressants: SSRIs, SNRIs, TCAs, MAOIs, bupropion,

mirtazapine, trazodone,…
🠶 Augmentation/Combination Medications: Antipsychotics, Triiodothyronine, Lithium,
modafinil,…
🠶 Promising and future agents: neurokinin 1 antagonists, glutamatergic system
modulators, anti-inflammatory agents, opioid tone modulators and
opioid-κ antagonists, hippocampal neurogenesis-stimulating treatments and
anti-glucocorticoid therapies.
🠶 Pharmacogenomics testing: [8] https://www.cdc.gov/genomics/disease/pharma.htm
Otte C, Gold SM, Penninx BW, et al: Major depressive disorder. Nat Rev Dis Primers 2:16065, 2016.
Psychotherapy

🠶 Cognitive Behavioural Therapy (CBT): Aaron T. Beck, Beck Institute

🠶 MBCT (Mindfulness-based Cognitive Therapy),
ACT (Acceptance Commitment Therapy), DBT (Dialectical Behavioural Therapy)
🠶 Interpersonal Therapy (IPT)
*Measurable 🡪 Several research and studies

-Psychoanalytic Therapy, Psychodynamic Therapy, Client-Centered Therapy,

Existential Therapy, Family Therapy, Group Therapy,…: how to measure the
outcomes?
MDD - CONSEQUENCES

🠶 Quality of life
🠶 Suicide
🠶 Substance abuse
🠶 Increased risk of other medical illnesses
Otte C, Gold SM, Penninx BW, et al: Major depressive disorder. Nat Rev Dis Primers 2:16065, 2016.
MDD has the heterogeneity and complexity in:
⮚ MANIFESTATION
⮚ SUBTYPE
⮚ ETIOLOGY / PATHOPHYSIOLOGY
⮚ TREATMENT MODALITY / OUTCOME

🡪 How to approach patients with clinical depression?

while waiting for more concrete and clinically significant evidence
A NEW MODEL IN PSYCHIATRY

🠶 In 1948, WHO definition of Heath: “Health is a state of complete physical, mental

and social well-being and not merely the absence of disease or infirmity”.
🠶 In 1977, Dr. George Engel proposed “a biopsychosocial model” for a holistic
approach to patients.
🠶 In 1998, Paul R. McHugh and Phillip R. Slavney published “The Perspectives of
Psychiatry” with a systematic consideration of patient’s psychiatric condition from 4
perspectives: diseases, dimensions of personality, goal-directed behaviour and life
stories.

🡪 BEYOND THE BIOLOGICAL HUMAN

 The Perspective of Psychiatry

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357579/figure/fig1/
DEPRESSION REFERENCE:
[1]. Geschwind, D. H. & Flint, J. Genetics and genomics of psychiatric disease. Science 349,
1489–1494 (2015).
[2]. Entringer S, Buss C, Wadhwa PD. Prenatal stress, development, health and disease risk: a
psychobiological perspective—2015 Curt Richter Award Paper. Psychoneuroendocrinology.
2015;62: 366-375.
[3]. Holsboer, F. & Ising, M. Stress hormone regulation: biological role and translation into therapy.
Annu. Rev. Psychol. 61, 81–109 (2010).
[4]. Dowlati, Y. et al. A meta-analysis of cytokines in major depression. Biol. Psychiatry 67, 446–
457 (2010).
[5]. Setiawan, E. et al. Role of translocator protein density, a marker of neuroinflammation, in the
brain during major depressive episodes. JAMA Psychiatry 72, 268–275 (2015).
[6]. Wong, M. L. & Licinio, J. Research and treatment approaches to depression. Nat. Rev.
Neurosci. 2, 343–351 (2001).
[7]. Kempton, M. J. et al. Structural neuroimaging studies in major depressive disorder. Meta-
analysis and comparison with bipolar disorder. Arch. Gen. Psychiatry 68, 675–690 (2011).
[8]. Greden JF: Combinatorial pharmacogenomics significantly improves response and remission for major
depressive disorder: a double-blind, randomized control trial (2019).
BPD – EPIDEMIOLOGY

🠶 Lifetime prevalence for BD I and BD II are 1% and 1.1%, respectively. [1]

🠶 Comparable rates between male and female patients across bipolar subtypes. [1]
 85
75

45

Merikangas KR, Jin R, He JP, et al: Prevalence and correlates of bipolar spectrum disorder in the world mental health
survey initiative. Arch Gen Psychiatry 68(3):241–251, 2011.
Bipolar or Unipolar ?

🠶 Bobo proposed 4 risk factors for BIPOLAR: [2]

❖ A first-degree family history of bipolar disorder
❖ The early onset of first depressive episode prior to age 25 years
❖ Lifetime number of depressive episodes >=5
❖ A history of psychotic features during depressive episodes
BPD – ETIOLOGICAL FACTORS/
PATHOPHYSIOLOGY
🠶 GENETICS
❖ First-degree relatives of patients with BPD are ten times more likely to have BPD and
heritability for the disorder is roughly estimated 79%-93%. [3]
❖ GWAS showed that BPD is a polygenic illness, with multiple small-effect genes.
❖ Genetic heterogeneity between bipolar I and bipolar II disorder and genetic overlap with
schizophrenia that appears greater for bipolar I disorder the for bipolar II disorder. [4]
🠶 ENVIROMENT
❖ A number of environmental factors have been described, including pregnancy and
obstetrical complications, season of birth (winter or spring birth, perhaps indicating
maternal exposure to infection), stressful life events, traumatic brain injuries, and
multiple sclerosis. [5]
🠶 HYPOTHESIS ???
⮚ Pathway in cell signaling: Wnt/GSK3 pathway
⮚ Circadian rhythm disruption: CLOCK gene, in rodent model.
⮚ Neurotransmitters: Seretonin, Norepinephrine, Dopamine, GABA and Glutamate
⮚ Structural imaging studies: decreased gray matter volumes in prefrontal and subcortical regions.
⮚ Functional imaging studies: Abnormalities in neural circuits of emotional processing, emotional
regulation and reward processing.
 BPD – SYMPTOMS AND DIAGNOSIS

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
 🠶 Manic Episode (Mania): meet A, B, C and D.

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
 🠶 Hypomanic Episode (Hypomania): meet A -> F

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
 🠶 Bipolar Disorder I: meet A and B

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
 🠶 Bipolar Disorder II (BD II): meet A, B, C and D.

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 5ed (DSM-5),
BPD – DIFFERENTIAL DIAGNOSIS

🠶 Schizoaffective disorder -Schizophrenia

🠶 Borderline personality disorder
🠶 MDD
🠶 Substance use disorders

🠶 ADHD, Oppositional Defiant Disorder

BPD - Specifiers

BPD WITH:
🠶 Anxious Distress
🠶 Mixed features
🠶 Rapid cycling
🠶 Melancholic features
🠶 Atypical features
🠶 Catatonia
🠶 Peri-partum onset
🠶 Seasonal pattern
Massachusetts General Hospital Comprehensive Clinical Psychiatry, second edition, 2015.
BPD - TREATMENT

🠶 Pharmacotherapy
🠶 Psychotherapy

**For more in-depth knowledge:

Canadian Network for Mood and Anxiety Treatment (CANMAT) and ISBD Bipolar
Disorders Guideline 2018.
https://www.canmat.org/resources/
FDA approved list of medication in BPD Treatment
Pharmacotherapy

🠶 Challenge for treatment, especially in depressive phase both in BPD I and II

🠶 BPD II has less clinical trials compared to BPD I
🠶 Acute (Mania and Bipolar Depression) and Maintenance Phase
🠶 Medications
❖ MOOD STABILIZERS: Lithium, Valproate, Carbamazepine, Lamotrigine
❖ ANTIPSYCHOTICS: Risperidone, Olanzapine, Quetiapine, Aripiprazole,…
❖ FLUOXETINE-OLANZAPINE
❖ ANTIDEPRESSANTS: Not used as monotherapy, risk of mood switching?
Psychotherapy

🠶 Psychoeducation
🠶 Family-focused therapy
🠶 CBT
🠶 Interpersonal and social rhythm therapy
BIPOLAR DISORDER REFERENCE:
[1]. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12–month prevalence of
bipolar spectrum disorder in the National Comorbidity Survey Replication. Arch Gen
Psychiatry 64(5):543–552, 2007.
[2]. Bobo WV: The diagnosis and management of bipolar I and II disorders: clinical practice
update. Mayo Clin Proc 92(10):1532–1551, 2017.
[3]. Barnett JH, Smoller JVV. The genetics of bipolar disorder. Neuroscience.
2009;164(1):331-343.
[4]. Charney AW, Ruderfer DM, Stahl EA, et al: Evidence for genetic heterogeneity
between clinical subtypes of bipolar disorder. Transl Psychiatry 7(1):e993, 2017
[5]. Tsuchiya KJ, Byrne M, Mortensen PB. Risk factors in relation to an emergence of
bipolar disorder: a systematic review. Bipolar Disord 5(4):231–242, 2003.
*BOOKS REFERENCE:
1. Massachusetts General Hospital Comprehensive Clinical Psychiatry,
second edition, 2015.
2. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5),
American Psychiatric Association, 2013.
3. The American Psychiatric Publishing Textbook of Psychiatry, seventh edition, 2019.
4. The Maudsley Prescribing Guidelines in Psychiatry, thirteenth edition, 2018.