Week 1 Part 2 Flashcards

1
Q

What is depression?

A

Common and serious medical illness that negatively affects how you feel, the way you think and how you act

It is polymorphic

Huge impact on quality of life of patients

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2
Q

The global burden of disease study used what?

A

Disability-adjusted life years (DALY) to compare death and disability from
Various disorders in developing and developed countries

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3
Q

What is DALY?

A

One lost year of “healthy” life
Measurement of the gap between current health status and an ideal health situation where the entire population lives to an advanced age, free of disease and disability

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4
Q

What is the major issues of depression (1)

A

75% patients experience more than one episode

15-20% experience depression as a chronic condition

Many patients suffer residual symptoms between episodes

20% of patients lifetime is spent in a depressed state

With each new episode the the risk of depression increases

10-20% depressed patients commit suicide

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5
Q

What is the major issues of depression (2) ?

A

25-35% of patients do not respond to antidepressant medications

The effects of antidepressant drugs are delayed
(2-3 weeks after initiation of treatment)

Preventing relapse remains a challenge

The pathophysiology of depression is I completely understood

There are no reliable biological markers

No availability of adequate animal models

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6
Q

What is syndrome profile of major depression? According to DSM-IV?

A
  1. Psychomotor retardation
  2. Fatigue or loss of energy
  3. Diminished ability to concentrate
  4. Diminished interest in social activity
  5. Psychomotor agitation
  6. Depressed mood
  7. Feelings of guilt and worthlessness
  8. Suicidal ideation
  9. Insomnia
  10. Weight loss and decreased appetite
  11. Lack of interest and anhedonia
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7
Q

What are brain regions associated with depression?

A
Amygdala 
Ventrolateral prefrontal cortex 
Dorsolateral prefrontal cortex 
Medial prefrontal cortex 
Orbitofrontal cortex 
Anterior cingulate cortex 
Striatal regions (ventral stratium)
Hippocampus 
Hypothalamus 
Thalamus
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8
Q

How is the cognition of depressed individual affected?

A

Ability to function optimally intellectually

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9
Q

What so depressed people have deficit in?

A

Monoamine in the brain called monoamine hypothesis of depression

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10
Q

What does depression genetic hit have a link to?

A

Activities of the enzyme catechol-O-methyltransferase

This is involved in the metabolism of dopamine

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11
Q

How do drugs act in treating depression?

A

Differently on 5-HT and noradrenaline transmission

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12
Q

What are examples of drugs for treating depression?

A
  1. TCA
  2. SSRIs
  3. MAOIs
  4. RIMA
  5. SNRIs
  6. NRI
  7. Nefazodone
  8. Mirtazapine
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13
Q

What are the non-pharmacological approaches for mood disorder?

A

Electroconvulsive therapy
Cognitive behavioural therapy (CBT)
Deep brain stimulation
vagal nerve stimulation

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14
Q

What are the phases of treatment ?

A
  1. Acute treatment
  2. Continuation treatment
  3. Maintenance treatment
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15
Q

What is an example of clinical entity?

A

o A patient is treated with a variety of approaches e.g. electro-convulsive therapy

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16
Q

What is ECT?

A

treatment that involves sending an electric current through the brain to trigger an epileptic seizure to relieve the symptoms of some mental health problem

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17
Q

What is features observed of ECT?

A
  1. changes pattern of blood flow in the brain

2. Changes the way energy is used in parts of the brain that are thought to be involved in depression

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18
Q

What are adverse effects of ECT?

A
  1. Memory loss - usually short term
  2. Anxiety
  3. Short term headaches
  4. Nausea
  5. Muscle aches
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19
Q

What is Tranylcypromine?

A

Antidepressant - monoamine oxidase inhibitor

treats depression by restoring the balance of certain natural substances in the brain

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20
Q

When is Tranylcypromine used?

A

persons who have not responded to treatments with other drugs

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21
Q

What does ketamine infusion have the ability to revolutionise?

A

The way doctors treat depression

give people struggling with depression unprecedented relief from their symptoms

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22
Q

What is ketamine effective and tolerable for?

A

minority of patients

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23
Q

What does major depression have a huge impact ?

A

compared to other serious conditions

  1. trauma
  2. Ischemic heart disease
  3. stroke
24
Q

What are the leading causes of diseases predicted for 2020?

A
  1. Ischaemic heart disease
  2. Unipolar major depression
  3. Road traffic accidents
  4. Cerebrovascular disease
  5. COPD
  6. Lower respiratory infections
  7. Tuberculosis
  8. War Injuries
  9. Diarrhoeal diseases
  10. HIV
25
Q

WHAT DOESNT 1/3rd of the patient not respond to?

A

Medication

26
Q

What does placebo effect of depression show?

A

There is very little intrinsic efficacy of antidepressants used today

27
Q

what is Acute treatment?

A
  1. first 6-12 weeks of treatment

2. aims at remission (control of symptoms)

28
Q

What is inadequate early response associated with?

A

Poor prognosis

29
Q

What is continuation treatment?

A

For 6 months after full symptom control

maintain remission status

prevent relapse

30
Q

What is maintenance treatment?

A

Aims at prevention of reoccurence of further episodes of depression

31
Q

What are the important aspects in the choice of prescribed antidepressant drug and the treatment regime?

A
  1. clinical characterisation of depression
  2. Adverse effects profile
  3. Danger of suicide/overdose
  4. Response to previous treatment
  5. The issue of relapse (maintenance)
  6. possibility of considering augmentation therapy
32
Q

Why should we maintain treatment?

A

Avoid relapse

33
Q

what is an example of maintenance treatment?

A

Tianeptine

unusual antidepressant

34
Q

Why is it important to have a drug which doesnt have too many adverse side effects?

A

compatible of having a reasonable quality of life and relatively disease free state

partial alleviation of depression so that they can function

35
Q

What various angles can folic acid come in?

A
  1. Cancer Field

2. Metabolism Field

36
Q

What is Folic acid important for?

A

Normal neurodevelopment

37
Q

What is folic acid important for?

A

Synthesis of purine nucleotides

38
Q

What is Folic acid an important intermediate for?

A

Conversion of homocysteine to methionine

39
Q

What is the consequence of accumulation of homocysteine?

A

Increases the production of excitatory amino acids in the brain

40
Q

Why is methionine important?

A
  1. optimum epigenetic state - reflects the methylation of gene
41
Q

What is methylation related to?

A

How accessible the genes are for transcription

42
Q

What contributes to optimum epigenetic state in our gene?

A

Optimum level of S-adenosylmethionine level

43
Q

What does Folic Acid have a metabolic role in?

A
  1. synthesis of serine
  2. synthesis of purine nucleotide
  3. synthesis of transfer RNA
  4. conversion of homocysteine to methionine
44
Q

What are the excitatory amino acids?

A
  1. Homocysteic acid

2. Cysteine sulphic acid

45
Q

What has imaging studies clearly documented?

A

Hypofrontality

46
Q

What are the deficits in the prefrontal cortex?

A
  1. decreased blood flow

2. depressed patients take medications e.g. lithium or VPA - better in terms of signal in subgenual prefrontal cortex

47
Q

What are the accumulated evidence for the glutamatergic transmission as a target/

A
  1. NMDA glutamate receptor antagonist are active in animal models of depression
  2. chronic antidepressant treatment changes the binding characteristic of NMDA glutamate receptor
  3. stress leads to increased levels of glutamate in the cortex (PFC)
48
Q

What happens when antidepressants are given?

A

Decrease in glutamate and other excitatory amino acid aspartate decrease in release

49
Q

What is linked to excitotoxicity?

A

Calcium permeability

50
Q

What is the consequence of unresolved psychosocial conflict?

A
  1. increased cortisol levels
  2. very stressed
  3. testesterone level collapses
51
Q

What does stress decrease the expression of?

A

GluR2 receptor subunits in tree shrews

52
Q

What is an important link in depression?

A

Glutamate

53
Q

What do we see in depressive disorder?

A

more increase in GABA markers such that GABA A receptors

54
Q

What can glutamate antagonist ketamine induce?

A

fast improvement in depressive symtpoms in treatment- resistant patients

55
Q

What can ketamine through GABAergic link seem to increase?

A

aspect of glutamate signalling

release of neurotrophic factors

improve synaptogenesis

56
Q

What is ketamine?

A

NMDA receptor blocker

leads to AMPA signalling which increases the activity of neurotrophic factors such as BDNF

57
Q

What do patients with depression develop?

A

possible deficit in neurotrophic factors