Session 2 - Neuro-biology of Depression

Question 1

How do you work out DALYs? (Burden of disease)

Answer 1

DALY = YLL + YLD Disability Adjusted Life Years = Years of Life Lost + Years Lived with Disability (Burden = mortality + disability)

Question 2

Describe simply Bi-polar disorder:

Answer 2

Bi-polar disorder means that the patient will experience both manic (high) and depressive (low) mood states as a cycle.

Question 3

How big of a global burden of disease will Depression have in 2020?

Answer 3

By 2020, depression will be the 2nd most global burden of disease

Question 4

What is the largest costing factor of mood disorders? Is it direct or indirect?

Answer 4

Indirect - loss of employment

Question 5

What does DALY stand for? And what does this mean?

Answer 5

Disability Adjusted Life Years

DALY = one lost year of a healthy life

Question 6

Here is a diagram of the lobes of the brain. Can you give an overview of the functions of the following:

Answer 6

Frontal: executive descision making and movement (e.g. Playing football)

Temporal: emotion and primary auditory (listening) cortex

Parietal: sensation

Occipital: visual

Question 7

The diagram shows specific regions of the brain.

Can you identify the region that is not lablled?

And what is this areas function?

Answer 7

Broca’s area (in left hemisphere)

Oringates speech

Question 8

In the following diagram, the Parietal lobe is labelled. In what specific area is ‘understanding of language’ is its function?

Answer 8

Wernicke’s area

(found in the Parietal lobe)

Question 9

Describe the frontal lobes functions:

Answer 9

Primary motor cortex

Supplementary Motor cortex

Executive functions

Broca’s area (orginates speech)

Affect on behaviour in conjuction with the temporal lobe

Question 10

Describe the Parietal lobe functions:

Answer 10

Sensory cortex

Wernicke’s area (understanding of language)

Orientation

Recognition

Construction

Question 11

Describe the roles of the Temporal Lobe:

Why is this lobe important in understanding mood disorders generally?

Answer 11

Primary auditory cortex

Music recognition

Memory

Emotion

Behaviour

Because both emotion and behaviour are affected here

Question 12

What is the role Occipital lobe?

Answer 12

Primary and secondary visual cortex

Question 13

How can we find out which areas of the brain are involved in mood disorders?

Answer 13

Brain operations, imaging (MRI, fMRI, SPECT, PET), rabies virus affecting limbic cortex, animal testing, lesions to certain areas (amygdala) lead to a loss of spontaneous aggression

Question 14

What tests can be done to assess mood depression in mice and rats?

Answer 14

Look at appetite, weight gain, forced swimming test, and tail suspension tests.

Question 15

The following picture is of the limbic system:

Please note the key structures: Anterior nucleus of Thalamus, Hypothalamaus, Amygdala, Hippocampus, Mammillary bodies, Cingulate gyrus, Dentate gyrus, septum, olfactory bundle,

What are the 3 main functions of the limbic system?

Answer 15

Emotion, Motivation and Memory (EMM)

Question 16

The Amygdala is part of the limbic system (which controls emotion, motivation and memory).

What is the function of the Amygdala?

Answer 16

Critical for conditioning and emotional processing.

Input from a range of sensory areas

Connected to areas that control autonomic function: motor action, neuroendocrine responses

Question 17

What imaging techniques can be used to look at how mood disorders can affect the brain?

Answer 17

MRI/CT (Magnetic resonance imaging)

fMRI (functional)

SPECT (Single-photon emission computed tomography)

PET (positron emission tomography)

Question 18

An MRI scan can be used to look at the brain in someone who is depressed. Typically, white matter changes are related to depression.

How is a patients response to treatment affected with white matter changes already?

Answer 18

There is a poor response.

Question 19

What is the role of the Hippocampus ?

What happens to the size/volume of the hippocampus in a depressed state?

Answer 19

The hippocampus has a major role in memory functions.

In depression, the hippocampal volume was consistently and significantly reduced in patients with depression.

This reduction is significantly correlated with the duration of the illness

Question 20

Functional imaging looks at the activitiy of certain regions of the brain. Examples incluude fMRI, PET and SPECT (not MRI).

Explain how fMRI works?

Answer 20

fMRI focuses on blood flow.

Measures the difference between oxygen rich and oxygen poor blood flow.

As a result it measures neuronal activity in brain areas and spinal cord.

Question 21

How do the finding of an fMRI look in someone with depression before and after CBT treatment?

(Specifically looking at the Amygdala and cingulate gyrus)

Answer 21

The Amygdala and cingulate gyrus singals are abnormal before CBT treatment, but normalise after treatment.

There was also increased reactivity in these areas, which led to better outcomes post treatment.

Question 22

Briefly describe the principles of PET (positron) and SPET (single photon emission tomography).

What can PET and SPET measure?

Answer 22

Gamma emiting radio isotopes (glucose or oxygen normally)

The isotopes connect to certain structures in the brain

Cameras detect the emmiting radiation

Computer programmes quantify data.

(PET has shorter half life isotope, and more expensive)

PET and SPET can measure: blood flow, brain activity and receptors of the brain.

Question 23

Below is a SPET scan of the brain in someone who has and hasn’t got depresison. Can you describe the differences between the two images.

Answer 23

Depression: reduced blood flow, brain activity and/or receptors. This is indicated by the deeper blues seen.

Question 24

In depression, there is malfunction of the prefrontal areas. The prefrontal cortex is composed of the: VMPFC, LOPFC and DLPFC.

What do these areas stand for? And what are their functions?

Answer 24

VM - ventro-medial [aggression, sexual function, eating]

LO - lateral orbital [assesses risk, regulates affective states]

DL - dorso lateral … prefrontal cortex [executive function and attention/concentration]

Question 25

In depression, there is malfunction of the prefrontal areas in depression. Can you describe these changes that occur.

Answer 25

Hyperactivity in the VMPFC - leads to enhanced sensitivity to pain, anxiety, depressive ruminations

Hypoactivity of the DLPFC: psychomotor retardation, apathy, and deficits in attention

Disconnectivity between the prefrontal areas and the limbic system. This results in disregulation of emotional control.

Question 26

Which axis of the body has been found to be consistently high in depression?

Answer 26

Cortisol/HPA axis

[disregualation in the HPA axis appears to be related to hippocompal atropy. Cortisol is important in a stress repsonse.]

Question 27

There is evidence of over activity of cytokines in someone with depression. This is thought to be due to the increased sympathetic tone (caused by HPA axis overactivity and amygdala disregulation).

What can happen to someone who has severely raised levels of cytokines in the body?

Answer 27

Fatigue, loss of appetitie, loss of libido, hyper sensitivity to pain, disrupts blood sugar control, negative effects on neurotransmission and neuro-trophic control

Question 28

With an increased cytokine level in someone with depression. There can be negative effect on neurotransmission and neuro-trophic factors.

What is a main neuro trophic factor?

And what is its role?

What else can occur with low levels of this factor?

Answer 28

Brain derived neuro-trophic factor (BDNF)

Cell maintence and plasticity in the brain

BDNF levels have seen to be lower in someone with depression and chronic stress. The low levels of BDNF affect structures such as the limbic system negatively (which play a role in emotion, motivation and memory)

Question 29

There are neuro-endocrinal changes in someone with depression. Changes to cortisol, growth hormone and thyroid levels have all been identified.

What changes have been seen, and what are their consequences?

Answer 29

Raised cortisol levels.

Blunted response to GHRF (growth hormone releasing factor) in patients suffering from depression. This leads to reduced Growth Hormone, and may have stunted growth.

TSH reponse to TRH blunted. Reduced T3/T4. Develop possible hypothyroidism. Thyroxine is sometimes used in depression.

Question 30

Sleep has 5 stages: REM, Stages 1,2,3 and 4. An EEG (electroencephalogram) and hypnogram can be used to monitor brain activity in sleep.

What are the changes in sleep architecture seen in someone with depression?

Answer 30

Hypnogram changes in depression. The entire graph is ‘compressed’ to the left as there is Early Morning Wakening.

REM (rapid eye movement) latency is reduced in depression from 35 mins to 18 mins.

[Anti depressants can restore normal sleep architecture]