Depression Triggers: Genetic Vulnerability and Environmental Stressors

Depression arises from the interaction of diathesis (vulnerability) and stress (triggers).

Genetic/Biological Vulnerability

• Family history (2–3× risk with 1st-degree relative).
• Polygenic risk (serotonin transporter 5-HTTLPR, BDNF, inflammatory genes).
• Neuroendocrine: HPA axis hyperreactivity.
• Temperament: High neuroticism, low extraversion.

Environmental Triggers

• Acute stress: Bereavement, divorce, job loss, trauma, assault.
• Chronic stress: Caregiving, poverty, discrimination, work strain, relationship conflict.
• Medical illness: Cancer, CVD, stroke, chronic pain, thyroid disease, Parkinson's.
• Substance use: Alcohol, cannabis, opioids, stimulants (intoxication/withdrawal).
• Postpartum: Hormonal drop + psychosocial stress.
• Seasonal: Reduced light (SAD).

Psychological Factors

• Negative cognitive style (hopelessness, self-criticism, rumination).
• Maladaptive coping (avoidance, suppression).
• Early adversity (ACE score) → sensitized stress response.

Prevention & Early Intervention

• Stress management, CBT skills, social support, regular sleep/exercise.
• Monitor high-risk individuals (postpartum, post-cardiac event, bereaved).
• Treat subthreshold symptoms to prevent full syndrome.