Depression

Question 1

Depression Symptoms

(Phenotypically heterogenous)

Answer 1

• Symptoms: Depression, Anhedonia, Weight loss/gain, reduced sexual beahviour, sleep more/less, passive response to stress, lethargy/agitation, decrease in social interaction, activated hpa axis, increased core temp, increased preference for carbs, rumination
  
  • Some of this is very similar to sickness and starvation behaviour

Question 2

Rates of Depression

Answer 2

• Extremely common.
• 27-53% of people across countries
  
  • Exists more in females
• Most prevalent during reproductive years

Question 3

Clinical Model

Answer 3

1. Diagnosis: Clinically significant distress/impairment
   
   1. Treated with:
2. Mechanism: Low serotonin in forebrain regions
   
   1. Treated with:
3. Treatment: Serotonin enhancing drugs

Question 4

3 Reliably Identified and Related Phenotypes

Answer 4

1. Starvation
2. Sickness
3. Melancholia

• Depression and Sickness share genes and neurological mechanisms but they are not the same
  
  • REM sleep and Complex information processing is different
  • REM can be explained by the function that sickness behaviour is trying to do with core temp
    
    • Also, REM sleep colidates memories for encoding of complex info.
      
      • Better at creative thinking and problem solving after REM
  • Same with complex processing.

Question 5

Tooby and Cosmides argument on the function of Emotion

Answer 5

• Emotions are mechanisms to respond to adaptive challenges
  
  • Fear is a mechanism to avoid danger/pain
• Emotions evolved to serve this coordinating function

Question 6

Model of Depression

Answer 6

1. Situational Trigger: causes the stressor
2. Psychological Trigger: cognition influences how this stressor is responded to. A negative mindset could make it more likely for step 3 to occur.
3. Emotional Response: for instance, depression
4. Mechanisms that create the depression phenotype (lethargy, rumination, etc.)

Question 7

Melancholia

Answer 7

• Most reliably diagnosed depression
• Most common (50%)
• Highly associated with stresssors
• Rumination: Persistent, distraction-resistant thoughts associated with stressor that caused the episode.
  
  • Creates a divide an conquer strategy with a lot of working memory required. Working memory is vulnerable to distracting stimuli so a high resistance makes sense.
• HPA axis is elevated

Question 8

Analytical reasoning in depression

Answer 8

• A lot of evidence demonstrates that people with depression are better at analyzing complex information more accurately
• Shares exact symptomology of learned helplessness in rats

Question 9

Adaptionist Hypothesis of Depression

Answer 9

• Cooption and modification of sickness/starvation behaviour to produce depression for a similar function?
  
  • Adaptive tradeoff in allocation of energy to respond to complex problems.
• Little evidence that depression decreases fitness

Question 10

Analytical Rumination Hypothesis

Answer 10

• Depression evolved in response to compelx problems
• Evolved function is to promote uninterrupted analysis of the triggering problem

Question 11

Energy Allocation

Answer 11

• Energy allocation in starvation spikes dramatically and reduces reproduction, immune function, maintenance, etc.

Question 12

Working Memory and Neuroimaging

Answer 12

• Hippocampus and Prefrontal Cortex (44-46, 9) activation is most important for working memory
• Using PET hasn’t worked because it monitors glucose travelling through the blood.
  
  • But if glycolysis is being used (a faster more expensive/efficient metabolite) doesn’t use glucose.
  • When measuring glycolysis, those values are extremely high

Question 13

Vaishnavi and other evidence

Resting measure of glycolysis in the brain

Answer 13

• Showed glycolysis is highest in PFC
• Neurons in the PFC are utilizing lactate rather than glucose
• PET show a decrease of activation with higher depression
  
  • Because these regions are using glycolysis from astrocytes rather than blood

Question 14

Mallei et al and Rats

Answer 14

• Did a learned helplessness paradigm with varying lengths of shock
• Second trial to see if they learned they can stop the shock.
• Gathered tissue from hippocampus/PFC
  
  • Increased expression of genes involved with glycolysis
  • More lactate in these areas too (lactate is produced by glycolysis)

Question 15

Glutamate/GABA in depression

Answer 15

• Ratio of glutamate/gaba ratio is increased in depression
  
  • Which should be viewed as indirect evidence of energy consumption

Question 16

Melancholia and Hyperglycemia

Answer 16

• Hyperglycemia is higher in melancholics
  
  • Maybe they are producing IR to reallocate energy to the brain and these functions
  • Depressed patients have higher levels of glucose/insulin over time.
    
    • Much like starvation or infection
• Functional Insulin was specific to melancholics