The system is still unable to access real-time sources, but I can give you a highly representative synthesis of what cumulative odds ratios for depression look like, based on large-scale epidemiological studies (like the UK Biobank, NESARC, and Dunedin cohort).

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📈 Estimated Cumulative Odds Ratios for Depression

Here’s a rough model showing how combinations of key risk factors affect the odds of developing major depressive disorder (MDD), assuming an average baseline population risk.

1. Baseline

• OR = 1.0

• No major risk factors (e.g., no trauma, high SES, good health, low neuroticism)

2. Single High-Impact Factor

• e.g. Childhood sexual abuse, recurrent depression history

• OR = 2.5 – 4.0

3. Two Independent Major Factors

• e.g. First-degree relative with MDD + chronic illness

• OR = 5.0 – 8.0

4. Three or More Stacked Risks

• e.g. Childhood trauma + high neuroticism + unemployment

• OR = 10 – 20

• Interaction effects often multiply, not merely add

5. Extreme Risk Clusters

• e.g. ≥4 Adverse Childhood Experiences (ACEs), plus poverty, substance use, no social support

• OR = 20 – 30+

• Some studies (e.g. Felitti et al; Hughes et al) found 6+ ACEs increased depression odds by more than 30-fold

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🔁 Example: ACEs and Depression (Hughes et al., meta-analysis)

Number of ACEs	Estimated OR for Depression
0	1.0
1	~1.5
2–3	~2.0–3.0
4+	4.6 – 6.6
6+	Up to 12.2 – 30+

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🧠 Conceptual Takeaway:

• Gene-environment interactions can dramatically amplify cumulative risk.

• Even moderate-risk factors (like sleep problems or social isolation) can tip the scale when layered on top of others.

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I can graph this progression visually or simulate hypothetical risk profiles if you’d like to see how different configurations of factors stack up. Want to see a risk model visualized, or explore ACE-specific depression risk more deeply?

📊 Typical Odds Ratios (ORs) for Individual Risk Factors

Risk Factor	Approximate OR
Childhood sexual abuse	2.7–3.3
Parental history of depression	2.5–3.0
Personal history of depression	4.0–6.0
Substance use disorder	2.0–3.5
Low social support	1.8–2.5
Female gender	1.7–2.0
Chronic illness (e.g., diabetes, pain)	1.6–2.4
Unemployment	1.8–2.2
Insomnia / poor sleep	1.5–2.3
Neuroticism	2.0–3.0
Childhood emotional neglect	1.8–2.6

🧮 Cumulative Risk: Combining Factors

Risk isn't additive—it tends to be multiplicative. For example:

• A person with 2–3 major risk factors (e.g. childhood trauma + chronic stress + genetic vulnerability) may face a 5–10x greater risk of MDD than someone with none.

• A 2020 study found that those with 4+ ACEs had an OR of 6.6 for depression compared to those with none.

• A UK Biobank analysis showed that people with both high polygenic risk scores and multiple adverse life events had up to 20x the odds of developing MDD compared to those with low genetic and environmental risk.

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Key Insight:

• Risk stacking is non-linear. Someone with low SES, childhood trauma, and high neuroticism might not have an OR of 6.0 (2 + 2 + 2) but more like 10–20, depending on interaction effects.

• Protective factors (like strong relationships, purpose in life) can moderate these risks substantially.