1. Introduction

Mood disorders involve disturbances in emotional regulation that significantly impair functioning.
The two broad categories are:

• Depressive disorders (Major Depressive Disorder, Persistent Depressive Disorder)
• Bipolar and related disorders (Bipolar I, Bipolar II, Cyclothymia)

These conditions differ in symptom patterns, biological mechanisms, course, and treatment requirements, and understanding their distinctions is essential in clinical work.

2. Depressive Disorders

A. Major Depressive Disorder (MDD)

Core Features

A minimum of two weeks of:

• depressed mood

• anhedonia

• appetite/weight changes

• insomnia or hypersomnia

• fatigue

• guilt or worthlessness

• concentration difficulties

• psychomotor changes

• suicidal thoughts/behaviour

Must cause clinically significant impairment.

Etiology

• reduced monoamine activity (serotonin, norepinephrine, dopamine)

• increased inflammatory markers (IL-6, CRP)

• HPA axis overactivation: chronic cortisol elevation

• cognitive distortions (Beck’s cognitive triad)

• early trauma or attachment disruption

• genetic vulnerability (moderate heritability)

Treatment

• SSRIs/SNRIs

• CBT (cognitive restructuring + behavioural activation)

• IPT

• exercise & sleep stabilization

• treatment-resistant depression options: ketamine, TMS, ECT

B. Persistent Depressive Disorder (Dysthymia)

Core Features

• depressed mood for 2+ years

• fewer severe symptoms, but much longer duration

• “low-grade depression” with chronic functional impairment

Etiology

• long-term stress

• early adversity

• personality traits (high neuroticism)

• serotonin imbalance

Treatment

• CBT + antidepressants

• lifestyle and relational interventions

• focus on long-term patterns rather than acute episodes

3. Bipolar and Related Disorders

A. Bipolar I Disorder

Requires at least one manic episode.

Manic Symptoms

• elevated or irritable mood

• decreased need for sleep

• increased energy

• pressured speech

• grandiosity

• racing thoughts

• risky behaviour

Episodes are severely impairing and often require hospitalization.

Etiology

• highly heritable (60–85%)

• circadian rhythm dysregulation

• dopamine hypersensitivity

• reduced prefrontal regulation

• life events can trigger episodes

Treatment

• Lithium (gold standard)

• Valproate, Lamotrigine

• Atypical antipsychotics

• psychotherapy focusing on rhythm, stress, sleep

B. Bipolar II Disorder

Involves:

• hypomanic episodes

• major depressive episodes

Hypomania is less impairing but still features elevated energy and reduced need for sleep.

Treatment

• Lamotrigine for depression prevention

• mood stabilizers

• psychotherapy

• antidepressants used with caution (risk of inducing hypomania)

C. Cyclothymic Disorder

Chronic fluctuations between subthreshold depressive and hypomanic symptoms, lasting 2+ years.

4. Scientific Expansions: Neurobiology of Mood Disorders

Prefrontal–Limbic Imbalance

• Reduced PFC activity → poor emotional regulation

• Overactive amygdala → exaggerated threat and sadness

Dopamine Pathways

• blunted reward response → depression

• dopamine surges → mania

Glutamate Dysregulation

Linked to treatment-resistant depression and rapid-cycling bipolar disorder.

Neuroplasticity

• chronic stress reduces hippocampal volume

• antidepressants increase BDNF → improved plasticity

Circadian Rhythm Disruption (Bipolar)

• unstable sleep-wake cycles

• sensitivity to light and daily routine

• mania triggered by sleep loss

5. Differential Diagnosis Logic

Major Depression vs Bipolar Depression

Bipolar depression often features:

• hypersomnia

• psychomotor retardation

• mood lability

• early onset

• family history of bipolar illness
  Misdiagnosis → antidepressant-induced mania.

Bipolar Mania vs ADHD

Mania: episodic, severe, with decreased sleep + grandiosity
ADHD: chronic, without mood elevation or psychosis

Hypomania vs Personality Disorders

Hypomania is episodic, PD traits are stable across years.

Persistent Depression vs Cyclothymia

Cyclothymia includes periods of elevated energy, dysthymia does not.

6. Treatment Mechanisms (Why They Work)

Lithium

• stabilizes intracellular signalling

• reduces dopamine hypersensitivity

• prevents relapse and suicide

Antidepressants

• increase monoamine availability

• restore prefrontal control

• increase neuroplasticity via BDNF

CBT

• strengthens PFC regulation

• reduces limbic overactivation

• restores behavioural activation cycle

Sleep Stabilization

• prevents manic switches

• regulates circadian rhythm genes

7. Case Studies for Clinical Reasoning

Case Study 1 — Bipolar I vs Bipolar II

A 28-year-old reports a week of no sleep, increased productivity, and grandiose business plans.
Two years earlier she had severe depression.

Questions:

1. Is this mania or hypomania?

2. Does this pattern fit Bipolar I or II?

3. Why wouldn’t this be explained by ADHD or anxiety?

4. What would be first-line treatment?

Case Study 2 — MDD vs Bipolar Depression

A 22-year-old presents with depression but mentions past episodes of feeling “invincible” for 3–4 days.

Questions:

1. Why is this important diagnostically?

2. What risks come with prescribing SSRIs?

3. What additional history should be explored?

Case Study 3 — Cyclothymic Disorder

A 30-year-old has lifelong mood swings but never meets full criteria for mania or MDD.

Questions:

1. Why is Cyclothymia a better fit than Bipolar II?

2. Why is long-term monitoring important?

8. Key Academic Vocabulary

anhedonia
psychomotor retardation
hypomania
mixed features
rapid cycling
mood stabilizers
circadian rhythm
neuroplasticity
HPA axis
treatment-resistant depression
behavioural activation

9. Discussion Questions

How do depressive and bipolar disorders differ biologically?
Why is lithium still considered the best long-term stabilizer?
How can sleep disruption trigger mania?
Why is CBT effective for depression?
What factors predict antidepressant non-response?