Case 3: Katherine Cornish - Bipolar Disorder

MDD vs Bipolar Depression

MDD: 1 major depressive episode without manic/hypomanic episodes

• Unipolar depression

Bipolar Depression: 1 major depressive episode with manic (bipolar I) or hypomanic (bipolar II) episodes

Bipolar Disorder: Description

Mood disorder with alternating manic/hypomanic and major depressive episodes

Types:

• Bipolar I

• Bipolar II

• Cyclothymic

Bipolar I

≥ 1 manic episodes ± psychosis or major depression

Bipolar II

≥ 1 major depressive episodes + ≥ 1 hypomanic episodes

• No manic episodes

Cyclothymic

Hypomania + depressive periods (rapid cycling) ≥ 2 years

Not meeting criteria for episodes

Bipolar Disorder: Epidemiology

Risk factors for rapid cycling…

• Female

• Early disease onset

Bipolar Disorder: Etiology

Genetics

• 1º relative with bipolar disorder

Increased paternal conception age = Increased sperm mutations

Environmental triggers

• Chronic stressors

• Childhood physical + sexual abuse

Bipolar Disorder: Pathophysiology

HPA axis dysfunction

1. Chronic stress = Chronic HPA axis activation = Increase cortisol production

• Mania: Highest

• Depression: Moderate

• Baseline: Elevated

2. Decreased receptor expression in hypothalamus + anterior pituitary (glucocorticoid resistance) = Impaired negative feedback from cortisol

3. Cause…

• Hippocampal damage

• Neural inflammation

Bipolar Disorder: Clinical Presentation

Alternating manic/hypomanic and major depressive episodes

Bipolar Disorder: Manic/Hypomanic Episodes

Elevated mood

DIGFAST

• D: Distractibility

• I: Irritability + irresponsibility (risk behaviour)

• G: Grandiosity

• F: Flight of ideas

• A: Activity increase

• S: Sleep deficit

• T: Talkativeness

Bipolar Disorder: Major Depressive Episodes

Depressed mood

MSIGECAPS

Bipolar Disorder: Diagnostic Criteria

DSM-5

Hypomanic episode:

• ≥ 3 of DIGFAST for ≥ 4 days

• Cause…

  • Observable differences from baseline

  • No significant professional/social dysfunction + hospitalization

• NO psychotic features

Manic episode:

• ≥ 3 of DIGFAST for ≥ 7 days

• Cause…

  • Significant professional/social dysfunction

  • Hospitalization

  • Psychotic features

Major Depressive episode:

• ≥ 5 of MSIGECAPS for ≥ 2 weeks

• Cause…

  • Significant distress

  • Impair life function

Bipolar Disorder: Screening

Manic episodes: Mood disorder questionnaire

Depressive episodes: Pt health questionnaire-9 (PHQ-9)

Bipolar Disorder: Investigations

Blood tests

• CBC

• BMP

• Creatinine + urea → Affected by treatments

• LFTs

• TFTs

Urine tests

• Urinalysis: UTIs

• Urine toxicology

• Pregnancy

ECG

• Identify prolonged QT interval → Affected by treatments

Bipolar Disorder: Treatment/Management

Nonpharmacological

Pharmacological

Bipolar Disorder Management: Nonpharmacological

Reduce external stimuli

Bipolar Disorder Management: Pharmacological

Mood stabilizers

Antipsychotics

Mood Stabilizers

Lithium

Valproic acid

Lamotrigine

Mood Stabilizer: Lithium

MOA:

• Inhibit phosphoinositol cascade = Decrease overactive receptor signalling

• Decrease excitatory NT (dopamine + glutamate) activity + increase GABA activity

Indications:

• Acute mania

  • Mild-severe

• Long-term maintenance

• Refractory + 2-gen antipsychotic

Adverse Effects:

• Motor (tremors, weakness)

• Endocrine (hypothyroidism, hyperparathyroidism)

• Renal (diabetes insipidus, interstitial nephritis)

Mood Stabilizer: Valproic Acid

MOA: Increase GABA + inhibit Na+ channels = Decrease excitatory signals

Indications: Same as lithium

Adverse Effects:

• Tremor

• Alopecia

• Teratogenic

• Thrombocytopenia

• Agranulocytosis

Mood Stabilizer: Lamotrigine

MOA: Inhibit Na+ channels = Decrease glutamate release

Indications: Long-term maintenance

Adverse Effects:

• GI sx

• Blurry vision

• Sedation

Antipsychotics

1st, 2nd, 3rd gen

Bipolar Disorder: Complications

SI

Metabolic conditions

• Obesity

• CVD

• T2DM

• Pathophysiology: HPA axis dysfunction = Chronic hypercortisolism = Increase visceral fat deposition + insulin resistance

Endocrine dysfunction

• Thyroid dysregulation

  • Pathophysiology: Thyroid hormone receptors in limbic system = Dysregulated mood = Abnormal thyroid hormone production

• Increase LH and AMH production