Depression essay plan

Question 1

1. Introduction

Answer 1

Define MDD: ≥2 weeks low mood, anhedonia, cognitive/somatic symptoms

Leading cause of disability worldwide (280 million+ cases, WHO)

High suicide risk, especially in youth

Aim: discuss biological basis, current treatments, and novel strategies

Question 2

2.1 Aetiology / Risk Factors (Genetic)

Answer 2

Heritability ~35–40%

Key genes: 5-HTTLPR, BDNF, FKBP5, CRHR1

Polygenic: many small-effect variants

Question 3

2.2 Aetiology / Risk Factors (environmental)

Answer 3

Early life stress, loss, chronic illness, social isolation

Strong gene–environment interaction

Question 4

2.3 Aetiology / Risk Factors (connection to anxiety)

Answer 4

[Connection: Same key genes and ELS model as anxiety — overlap important for comorbidity.]

Question 5

3.1 Neurobiology (Monoamine Hypothesis)

Answer 5

↓ 5-HT, NA, DA → reduced mood, motivation, reward

Limitations: doesn’t explain treatment delay or partial response

Question 6

3.2 Neurobiology (Neuroplasticity Deficits)

Answer 6

↓ BDNF in hippocampus/PFC

Reduced synaptogenesis and dendritic complexity

Reversed by antidepressants & ketamine

Question 7

3.3 Neurobiology (HPA Axis Dysfunction)

Answer 7

Chronic stress → hypercortisolemia

Hippocampal atrophy and PFC dysregulation

Question 8

3.4 Neurobiology (Neuroimmune Model)

Answer 8

↑ IL-6, TNF-α → inflammation-induced anhedonia, fatigue

Question 9

3.5 Neurobiology (Neuroanatomy)

Answer 9

↓ DLPFC, hippocampus activation

↑ subgenual cingulate (Area 25)

Impaired reward processing (mesolimbic DA)

Question 10

4. Preclinical Models

Answer 10

FST (forced swim test): learned helplessness model

Sucrose preference test: anhedonia

CUMS (chronic unpredictable mild stress): widely used model of depression

Limitations: ethical and translational challenges, but useful for screening novel agents

Question 11

5.1 Treatments (Pharmacological)

Answer 11

SSRIs (fluoxetine, citalopram): ↑ 5-HT levels

SNRIs (duloxetine): target both 5-HT and NA

Atypicals: mirtazapine, bupropion

TCAs / MAOIs: rarely first-line due to side effects

30–50% do not respond → TRD = major clinical problem

Question 12

5.2 Treatments (Non-pharmacological)

Answer 12

CBT and behavioural activation

ECT (effective in severe depression)

rTMS, DBS (Area 25) for TRD

Question 13

6.1 Novel / Future Therapies

Answer 13

Ketamine: rapid-acting antidepressant (NMDA antagonist)

Psilocybin: 5-HT2A agonist; modulates network connectivity

Anti-inflammatory drugs for patients with ↑ CRP

Neurogenesis and epigenetics

Pharmacogenomics: tailoring treatment to genotype (e.g. 5-HTTLPR, CYP enzymes)

Question 14

6.2 Novel / Future Therapies (Connection to anxiety)

Answer 14

[Connection: Most of these are shared targets with anxiety — same systems, different circuit emphasis.]

Question 15

7. Conclusion

Answer 15

Depression is multifactorial, with monoamine, plasticity, and immune dysfunction

Current drugs limited in speed and efficacy

Future lies in personalised, rapid-acting, and circuit-targeted treatments