Anxiety essay plan

Question 1

1. Introduction

Answer 1

Define anxiety disorders: excessive fear and worry disrupting daily life (includes
GAD, panic disorder, phobias, etc.)

Affects ~301 million globally (WHO, 2021)
Enormous economic and societal burden

Often comorbid with depression → shared mechanisms

Aim: examine biological basis, current pharmacology, and emerging targets

Question 2

2.1 Aetiology / Risk Factors (Genetic)

Answer 2

Genetic
Twin studies: ~30-50% heritability

Polygenic: small-effect genes (e.g. 5-HTTLPR, CRHR1, BDNF Val66Met)

Gene-environment interaction: stress sensitivity modulated by genotype

Question 3

2.2 Aetiology / Risk Factors (environmental)

Answer 3

Early life stress (ELS): trauma, abuse → lasting sensitisation of fear circuitry

Chronic stress and poor social support

Not sufficient alone - requires interaction with genetic vulnerability

Question 4

2.3 Connection to depression

Answer 4

[Connection: These risk factors overlap with depression - especially ELS, HPA dysregulation, and BDNF pathways.]

Question 5

3.1 Neurobiology (neurotransmitters)

Answer 5

5-HT dysfunction → impaired inhibition of fear responses

GABA deficiency → reduced inhibitory tone (explains benzodiazepine efficacy)

NA: overactivity in the locus coeruleus → hyperarousal

Question 6

3.2 Neurobiology (Neural circuits)

Answer 6

Amygdala hyperactivation (threat detection)

Poor prefrontal inhibition (esp. vmPFC-amygdala axis)

Insula
hyperactivity → interoceptive awareness (panic, social anxiety)

Question 7

3.3 Neurobiology (stress systems and circadian disruption)

Answer 7

Stress Systems
HPA axis hyperresponsivity: increased CRH, cortisol

Feedback inhibition disrupted, esp. in chronic anxiety

Circadian Disruption

Insomnia → worsens anxiety → vicious cycle

Question 8

3.4 Neurobiology (connection to depression)

Answer 8

[Connection: Shared with depression — but in anxiety, overactivation of fear circuits is more prominent; in depression, hypoactivation of reward/motivation networks dominates.]

Question 9

4. Preclinical Models

Answer 9

Rodent models: Elevated plus maze, light-dark box, open field

Genetic: 5-HT1A KO mice show increased anxiety-like behaviour

Environmental: maternal separation, chronic mild stress

Important for validating drug targets and understanding circuit-level mechanisms

Question 10

5.1 Treatment (Pharmacological)

Answer 10

SSRIs/SNRIs: first-line for chronic anxiety (esp. GAD, panic disorder, PTSD)

Benzodiazepines: GABA-A agonists — rapid, effective short-term relief
Risks: sedation, tolerance, dependence

Buspirone: 5-HT1A partial agonist — non-sedating

Beta-blockers (e.g. propranolol): for somatic symptoms (e.g. performance anxiety)

Question 11

5.2 Treatment (Non-pharmacological)

Answer 11

CBT: highly effective (targets avoidance, catastrophic thinking)

Mindfulness-based therapy, biofeedback

rTMS/DBS: emerging, still experimental for anxiety

Question 12

6.1 Novel/ future therapies

Answer 12

Glutamatergic modulation (e.g. ketamine low dose)

Endocannabinoids, neuropeptides (e.g. NPY)

Anti-inflammatory agents: CRP/IL-6 elevated in anxiety

HPA axis modulators: GR antagonists

Epigenetic therapy, neurogenesis enhancers

Question 13

6.2 Novel/ future therapies (connection to depression)

Answer 13

[Connection: All these future targets overlap with depression — both share plasticity, inflammation, and HPA dysfunction as common roots.]

Question 14

7. Conclusion

Answer 14

Anxiety involves hyperactivity of fear networks and dysregulation of serotonin, GABA, and stress systems

Current drugs effective but limited by side effects and delay

Future lies in targeting neuroplasticity, inflammation, and personalising treatment