Lecture 6: Depression and physical health

Question 1

What has research found about the link between CVD and depression?

Answer 1

• depression results in 80-90% increased mortality risk
• CVD comorbidity risk is higher for a clinical diagnosis of MDD than for self-reported depressive symptoms, but risk is high for self-reported too
• depression contributes to onset but also to progression and prognosis of CVD-> downward spiral in which depression and CVD reinforce each other
• depression is linked to other somatic conditions beyond CVD-> more general mechanism than organ related

Question 2

Which other psychiatric conditions are linked to higher CVD risk?

Answer 2

Panic disorder, specific phobia, PTSD, alcohol use disorder, non-specific anxiety disorder

Question 3

What are causal mediating mechanisms?

Answer 3

• unhealthy lifestyle
• pathophysiology
• residual confounding (depression part of a not discovered or not measured sub-clinical conditions)
• latrogenic effects (impact of antidepressants increases CVD)
• third underlying factors (childhood stressors, personality, genetics)

Question 4

What are sociodemographic factors implicated with depression?

Answer 4

Female gender, low SES, general lower health, worse baseline health conditions

Question 5

What was found after controlling for these confounding factors and what were the implications?

Answer 5

The cardiovascular risk in depressed people is still significantly increased. Could be that some confounding factors are hard to fully rule out as some aspects only partially cover the factor. So depression is an indicator of not yet discovered and diagnosed of sociodemographic, subclinical or medical conditions that can affect disease onset-> residual confounding hypothesis. But does not fully explain the increased CVD risk

Question 6

How does unhealthy lifestyle link depression to CVD health?

Answer 6

• depression linked to increased smoking and alcohol consumption, reduced food intake and less nutritious, less physical activity (possibly due to more negative attitudes)
• NESDA study found that all measured unhealthy lifestyle indicators were more common in current and remitted MDD patients as compared to controls
• adjusted for lifestyle factors and none made little difference-> not only due to lifestyle differences

Question 7

How does autonomic dysregulation link depression to CVD health?

Answer 7

• depression has an ANS that is a state of more sympathetic and less parasympathetic activation
• so linked to lower heart-rate variability also linked to cardiac vagal control
• autonomic dysregulation linked to somatic symptoms like: tachycardia, blood pressure liability and hypertension can predict dysregulation onset

Question 8

What is polyvagal theory?

Answer 8

Impairments of low vagal activity is linked to reduced social engagement and a less flexible behavioural response to environmental changes

Question 9

What has research found about low HRV and depression?

Answer 9

Mixed findings about the consistency of this finding

Question 10

What could be the reasons for this?

Answer 10

• can be explained by type and severity of depressed patients
• depression is a heterogeneous condition and various symptom profiles
• different trajectories of depression which differs for age, onset, duration and genetic vulnerability
• HRV differences only become apparent when exposed to stress conditions rather than resting-> results were confirmed during stress

Question 11

Why is it important to consider anti-depressants?

Answer 11

With no separation between anti-depressant users and non-users there can be inconsistent results. TCAs found to have a decreasing effect on HRV and SNRIs, (but not SSRIs or depression) had increased sympathetic cardiac control shown by a higher heart rate

Question 12

How does HPA axis dysregulation link depression to CVD?

Answer 12

• corticoid receptors can impact cortisol effects on starting and ending the stress response-> chronic activation of stress response (atrophy of hippocampus, reduced neurogenesis, synaptic cells etc)
• found higher cortisol levels for those with depression and an increased cortisol awakening response for remitted and current cases (HPA axis vulnerability factor)
• non-suppression of the HPA axis is linked to severe cases, higher cortisol more prevalent with CVD

Question 13

What is metabolic syndrome?

Answer 13

-It is a clustering of metabolic risk factors like abdominal obesity, increased blood glucose, elevate blood pressure, increased triglycerides and decreased HDL cholesterol. It reflects a pre-clinical state of risk factors for the development of CVD

Question 14

What is the link between depression and metabolic syndrome?

Answer 14

They have a dose- response association (increasing relationship). But also bidirectional as depression predicts the onset of metabolic syndrome which predicts depression onset over time. These dysregulations are found to sustain the chronicity of depression. But depression found to be more related to obesity-relate aspects than elevated blood pressure

Question 15

How did the link between depression and metabolic dysregulations arise?

Answer 15

1. white adipose tissue is an endocrine organ which produces inflammatory cytokines and hormones which results in pathogenic immune-metabolic response in CNS, brain and body
2. Cerebrovascular damage can predispose to depression in late life (vascular depression hypothesis)
3. Depression related biological dysregulations can have shared underlying pathways to metabolic changes

Question 16

How does immuno-inflammatory dysregulation link to depression?

Answer 16

Depression is linked to increased pro-inflammatory cytokines which are produced in innate immune cells in response to immunological threats. Chronic increases of these molecules increase the onset of CVD and mortality. Immunotherapy can lead to improvements in depression, cytokines can affect brain structures additionally. Depression can lead to weight gain which can promote inflammation which reinforces depression

Question 17

What are the different sub-types of depression?

Answer 17

Melancholic depression involves appetite and weight decline, insomnia, early morning awakening, linked to higher suicidality and anxiety.
Atypical depression involves appetite and weight increase, feeling of limbs being weighed down.

Question 18

What are the alternative mechanisms linking depression to CVD risk?

Answer 18

1. childhood maltreatment like emotional, physical, sexual abuse is a strong risk factor of late depression onset, also linked to CVD processes and risk
2. personality traits like neuroticism, introversion and type D personality are linked to the development of depression and CVD
3. Genetic vulnerability can make individuals vulnerable for biological dysregulations which can result in depression and CVD

Question 18

What are the iatrogenic effects linking depression to CVD risk?

Answer 18

There are increased CVD risks for those using antidepressants but not enough to be interpreted as causal evidence. Only way to do so is through a large long-term RCT. Many studies suggest that anti-depressants can increase autonomic activity and that SSRIs can reduce cytokine levels

Question 18

How do the types of depression differ in pathophysiological dysregulation?

Answer 18

Do not differ in prevalence of core symptoms, severity, duration of depression, disability or psychiatric comorbidity patterns.
-> melancholic: more often smokers, more childhood trauma and negative life events, more hyperactivity of HPA axis, higher general psychiatric vulnerability. Associated with greater cortisol-depression association
-> atypical: more often female, earlier age of onset, higher inflammatory markers, metabolic abnormalities like obesity and higher BMI, linked to genome wide BMI and triglycerides genetic risk

Question 19

What is genetic pleiotropy?

Answer 19

Shared genetic effects such as twins showing reducing exercise behaviour and mood symptoms due to shared genetic risks