18.2 - Depressive disorders Flashcards
1
Q
what is anhedonia
A
loss of cap to experience pleasure
2
Q
How extreme can depression be
A
can become impossible to meet requirements
- keep a job
- maintain social contacts
- to eat
- maintain acceptable levels of personal hygiene
3
Q
what are two common symptoms associated with depression
A
sleep disturbances
suicidal ideation
4
Q
how long do depressive symptoms need to persist before one cab ne diagnosed with clinical or major depression
A
2 weeks
5
Q
Explain the case of S.B
A
- initially - excessive sleep, problems with focus, suicidal ideation, delusions - believed he was stupid and disliked, felt persecuted
- became more severe: memory and attentional impairments affected ability to read/ delusional ideas and suicidal ideation constantly
6
Q
what are the two general categories of depression
A
- reactive - triggered by a negative experience
2. endogenous - depression w no apparent cause
7
Q
what is the LTP of depression
A
10%
8
Q
gender differences in depression prev?
A
women 2x more likely to be diagnose
9
Q
what is the current explanation fo why women have 2x higher prevalence of depression
A
unclear, but maybe gonadal-hormone related?
10
Q
what is the lifetime risk of completed suicide in someone diagnosed with depression
A
4-15% depending on the study
11
Q
at what age can you become depressed?
A
any, effects kids, adolescents and adults
12
Q
does depression tend to present alone?
A
no, often comorbid with anxiety and heart disorders and diabetes
13
Q
what are the two solid findings about genetic factors in depression
A
- twin studies - heritability estimate between 30 and 40%
- genome sequencing of those w recurrent major depressive disorder - identified 2 loci on chromosome 10 as contributors to the risk
14
Q
where has most of the research on the causal role of experience in depression focussed?
- what is the believed mechanim of these?
A
role of stress and trauma - epigenetic mechanism are heavy mediators of depression onset in those susceptible
15
Q
what are the two subtyp[es of MDD whose causes are more apparent?
A
- SAD - depression and lethargy recur during seasons - typically winter
- Peripartum depression - intense, sustained depression experience by some women during pregnancy or right after birth
16
Q
what are the two lines of evidence that suggest SAD is caused by a reduction in sunlight
A
- incidence is higher in Alaska (9%) than Florida (1%) (winter days are shorter and less bright up north)
- light therapy is often effective in reducing symptoms
17
Q
In what percentage of pregnancies do we see permpartum depression
A
~19%
18
Q
what are the 5 major classes of drugs used to treat depressive disorders
A
- monoamine oxidase inhibitors (MAO inhibitors)
- tricyclic antidepressants
- selective monoamine reuptake inhibitors
- atypical antidepressants
- NMDA receptor antagonists
19
Q
what was the first antidepressant, and what class was it
A
iproniazid (initially designed to treat suberculosis)
- monoamine agonist
20
Q
explain the mechanism of action of Iproniazid
A
monoamine agonist by inhibiting the activity of monoamine oxidase (MAO)
- these enzymes break down monoamine neurotransmitters in the neuronal cytoplasm
21
Q
what is the most dangerous side effect of MAO inhibits
A
the cheese effect - foods that contain the amine tyramine
- tyramine elevates blood pressure
- tyramine is typically metabolized rapidly in the liver by MAO
- with MAO inhibited, they risk a massive spike in blood pressure
22
Q
why are tricyclics named as they are
A
- antidepressant actin
2. chemical structures include three carbon rings
23
Q
what was the first tricyclic antidepressant
A
imipramine, initially thought to be antipsychotic - not the case
24
Q
what is the mechanism of tricyclics
A
block the reuptake of serotonin and norepinephrine
25
are tricyclics safer than MAO inhibitors?
YES
26
what is the mechanism of SSRIs
serotonin agonists - block the reuptake of serotonin from synapses
27
what was the first SSRI to be developed (both names)
fluoxetine (Prozac)
28
what drug is fluoxetine molecularly similar to
imipramine - fluoxetine is no more effective than tricyclics
29
why is fluoxetine and SSRIs so popular (2)
1. fewer side effects than tricyclics and MEO inhibitors
| 2. act against a wider range of psychological disorders (not just depression)
30
what did the success of SSRIs cause
the introduction of the selective norepinephrine reuptake inhibitors (SNRIS)
31
what is an example of an SNRI
reboxetine
32
how effective are SNRIs
as effect as SSRIs
33
are there any other forms of selective (x) uptake inhibitors that are effective?
- give an example
yes, those that block the uptake of more than one monoamine neurotransmitter
- venlafaxine
34
are atypical antidepressants all similar in some way?
no, catch all class for those that are not SSRIs, Mao inhibs or tricyclics
35
what are the two examples of atypical antidepressants
1. bupropion - various effects on NTs
| 2. agomelatine - melatonin receptor antagonist
36
explain the mechanisms of action of bupropion
1. dopamine reuptake inhibitor
2. Norepinephrine reuptake inhibitor
3. nicotinic-acytlcholine receptor blocker
37
what is the mechanim of NMDA receptor antagonists
block the glutamate NMDA receptor
38
what is an example of an NMDA receptor antagonist that has been shown to be very effective
Ketamine, dissociative hallucinogen
| - single, low doses of ketamine reduce depression very fast, even in those who've been experiencing it for over 1 week
39
what has the fact that ketamine has so many piss poor side effects caused
the search for more selective NMDA receptor antagonists that have fewer side effects
40
is there any large difference between the effectiveness of the different classes?
Not so much, MAO, tricyclics, SMRIs are all about even at 50% improvement rate
41
what fact reduces the positivity of antidepressant drug effects
25% of the 50% of participants who improve on the drugs can be attributed to placebo
42
what types of depression are antidepressants most effective in
severe depression - those who are mildly effected tend not to improve more than placebo, but they do in fact work in severe cases
43
what are the consistent findings from structural MRI studies of the brains of patients with depression (general finding plus 4 specific regions )
reductions in graymatter volumes in...
1. PFC
2. hippocampus
3. amygdala
4. cingulate cortex
44
do only people who have depression experience the gray matter loss associated with the disorder
No, even those who are just genetically predisposed to it
45
are gray matter reductions in the only negative outcomes of depression on brain
- in what brain area are these findings most consistent
No, also white matter reductions in several brain areas
| - PFC baby
46
where have fMRI studies found atypical activity in the brain? (6)
- are these just local, or are there other types of activity differences?
1. frontal cortex
2. cingulate cortex
3. insular cortex
4. amygdala
5 thalamus
6 striatum
7. relation among the activity of these structures is atypical during a variety of cognitive states
47
describe the monoamine theory of depression
depression is associated with the underacitvity at serotonergic and noradrenergic synapses
48
what is the monoamine theory of depression nalrgely based on
the fact that MAO inhibs, tricyclic, and SRIS, SNRIs are all agonists of serotonin, norepinephrine, or both
49
where do we get the other piece of support for the monoamine theory of depression?
what do the findings imply
1. autopsy studies - norepinephrine and serotonin receptors are found more numerous in those who had clinical depression and had not received. treatment
2. implicates a deficit in monoamine release bc when insufficient amount of a neurotransmitter is released at a synapse, there is usually a compensatory increase in the number of receptors for that NT
50
what is up-regulation
the compensatory increase in the number of receptors for a NT that has been released in insufficient quantities
51
what two lines of evidence have challenged the monoamine theory of depression
1. disc that monoamine agonists are not very effective for most depressed patients, and even when they are, they're only a little better than placebo
2. discovery that other NTs like GABA, glutamate and acetylcholine play a role in the development of depression
52
explain the theoretical justficiaiton for the neuroplasticity theory of depression
developed from the fact that monoamine agonists tend to only become effective after a few weeks after medication onset
- agonist effects at monoaminergic synapses is not the critical therapeutic mechanism - downstream increase? in neuroplasticitiy is the real mechanism
53
how does the neuroplasticity theory of depression explain its ethology
- depression results from a decrease of neuroplastic processes in brain structures that leads to neuron loss and other neural pathology
54
what two kinds oil research have provided general support for the neuroplasticity theory of depression
1. studies showing that stress and depression are assoc with the disruption of neuroplastic processes
2. studies showing antidepressants are associated with an enhancement of neuroplastic processes
55
what are the two examples of disrupted Neuroplastic processes in stress and depression
1. reduction in the synthesis of neurotrophins
| 2. decrease in adult hippocampal neurogenesis
56
what are the three examples of the increased neuroplastic processes after antidepressant treatments
1. increase in neurotrophic synth
2. increase in synaptogeneis
3. increase in adult hippocampal neurogenesis
57
which neurotrophic factor has been of particular interest to researchers, and why?
Brain derived neurotropic factor (BDNF)
| - treatments that improve depression (pharm and nonpharm) increase BDNF levels in patients who show improvements
58
what has the discovery that treatments that improve depression (pharm and nonpharm) increase BDNF levels in patients who show improvements led to (3)
1. the proposal that decreased blood levels of BDNF is a biomarker for depression
2. increased blood levels of BDNF as a biomarker for successful completion
3. antidepressants increase blood levels of BDNF which increases neuroplastic processes that lead to the alleviation of depression
59
what are the two treatments involving brain stimulation in depression
1. repetetive transcranial magnetic stimulation
| 2. deep brain stimulation
60
describe repetetive transcranial magnetic stimulation (rTMS)
form of transcranial mag stim that involves the noninvasive delivery of receptive magnetic pulses
- either high frequency, ie 5 per second (high frequency TMS) or low frequency (1/second) (low frequency)
delivered to specific cortical areas (typically PFC)
61
what do we think high frequency TMS does
stimulates activity within the brain region to which it is appleid
62
what do we think low frequency TMS does
inhibits activity within the brain regions to which it is applied
63
what have metaanaluysis about rTMS shown
reliable improvement of depressive symptoms after either high or low frequency rTMS when compared with sham rTMS
64
describe deep brain stimulation
chronic brain stimulation through an implanted electrode
| - shown to be effective on patients whose depression did not respond to other treatments
65
explain Loranzo and colleagues study of DBS
implanted the tip of a stimulation electrode into an area of white matter of the anterior cingulate gyrus in the medial PFC
- delivered continual pulses of electrical stimulation that couldn't be detected by patients
- all 20 patients selected bc they had repeatedly failed to respond to conventional treatment
- 60% SHOWEDE SUBSTANTIAL IMPROVEMENT
- 35% WERE LARGELY SYMPTOM FREE
- IMPROVEMETNS LASTER FOR AT LEAST A YEAR
- replicated in other centres
66
what do most researchers contend is the cause of our problems with treating depression
the diagnostic tools were using generate a large heterogeneous group of patients - misguiding research
- need more precise diagnostic tools
