Mood Disorders I Flashcards
(90 cards)
1
Q
Physiological correlates of fear (feelings)
A
Heart and respiratory rate Cortisol and adrenaline Blood flow Analgesia Facial muscles Attention focused on perceived threat Emotions
2
Q
Feelings are…
A
mental experiences that accompany a change in body state
3
Q
Feelings allows…
A
a glimpse into ongoing homeostatic regulation
4
Q
Feelings directly portray…
A
the advantageous or disadvantageous nature of a psychological situation, and facilitate learning of the conditions causing the imbalance and respective corrections
5
Q
Emotions
A
An action programme triggered by external stimuli
6
Q
Example of emotions
A
joy, fear, etc.
7
Q
Drive
A
action programme to satisfy an instinctual physiological need
8
Q
Drive examples
A
hunger or thirst
ex. high osmolarity –> dry mouth –> thirst
9
Q
2 action programs
A
drive and emotion
10
Q
Interoception
A
notice change in internal enviro
11
Q
Exteroception
A
notice change in external enviro
e. by 5 senses
12
Q
Nuclei involved in generating feelings
A
internal mileu –> lamina 1 pathway to homeostatic centres (NTS, PBN, PAG) –> thalamus –> cortex (esp. insula)
Viscera –> Vagus nerve –> NTS –> PBN, PAG, hypothalamus –> insula
13
Q
Pathway for feelings–from viscera
A
Viscera –> Vagus nerve –> NTS –> PBN, PAG, hypothalamus –> insula
14
Q
Pathway for feelings–for internal stimuli
A
internal mileu –> lamina 1 pathway to homeostatic centres (NTS, PBN, PAG) –> thalamus –> cortex (esp. insula)
15
Q
Mood
A
stable and constant, not linked to speicific circumstances
16
Q
Feelings
A
Reactive, breif, intense and circumscribed to a specific environmental event
17
Q
Difference b/t feelings and mood
A
feeling = short term, event-related mood= long term, un-related to events
18
Q
Dysregualtion of feeligs leads to
A
emotional arousal and exaggerated effects
ex. fear becomes anxiety (disregulated fear)
19
Q
Dyregulation of mood leads to
A
chornic, sustained negative mood
pervasive sadness and anhedonia
20
Q
Depression (defintion)
A
Unpleasant or dysphoric mood present most of the day, most days
- anhedonia
- more prevalent in women
- in response to life events but also has genetic and other factors
21
Q
Depression is a mood disorder comprised of….
A
• Sadness • Loss of interest • Anhedonia • Lack of appetite • Feelings of guilt • Low self-esteem • Sleep disturbances • Feelings of tiredness • Poor concentration Transient and mild conditions of low mood to severe psychiatric disorder
22
Q
DSM criteria for depression
A
Both of: • Depressed mood • Loss of interest Plus 4 of the following: - Altered Appetite - Altered Weight - Altered Sleep - Altered Psychomotor activity - Decreased energy - feeling Worthlessness - feeling Guilty - Difficulty Thinking - Difficulty Concentrating - Difficulty Making decisiones - Recurrent thoughts of death - Suicidal ideation
23
Q
Etiology of depression
A
- Biogenic amine hypothesis
- Endocrine factors
- Environmental factor
- Immunologic factors
- Genetic factors
- Neurogenesis
24
Q
What started the biogenic amine hypothesis
A
in 50s Noted that:
Drugs that depleted catecholamines –> depression like effects (reserpine)
Drugs that inhibited MAO and therefore increase catecholamines –> increased mood
25
NE (receptor numbers and types)
9 receptors
2 classes: alpha and beta
Coupled to G protein
26
NE roles
* Modulates PFC function
* Working memory processing
* Behaviour and attention
* Acquisition of emotionallyarousing memories
27
NE cell bodies and projection
cell bodies in LC or lateral trigeminal area
| Project to : thalamus, hypothalamus, and cortex
28
5HT (receptors numbers and types)
14 5-HT receptors
classified in 7 types
mostly coupled to G-proteins
29
Altered binding potentional of ____ and distrubition of ___ in _________ in depression
5HT1a; 5HT1b; in cingulate, PFC, hippocampus
30
5HT involved in
stress repsonse
| involved in everything but responsible for nothing
31
5HT cell bodies and projection locations
Bodies in rostral raphe nuclei or caudal raphe nuceli
| project to amygdala, hippocampus, NAc, etc.
32
DA receptor numbers and classes
5 DA receptors
classified in 2 types
mostly coupled to G-proteins
33
DA has roles in
* Reward and motivation
* Working memory
* Attention
34
DA cell bodies in the
VTA and substantia nigra
35
Substantia nigra and DA
degeneration of substantia nigra --> PD
| important for voluntary action
36
VTA and DA
axons to NAc and PFC
| reward, motication, working memory and attention
37
Monoamines in depression
want to increase MAs in depression b/c there is increased MAO activity in depression
therefore there is low bioavailability of biogenic amines and therefore low NTs
38
Transporters in depression
Transporter-reuptake of NTS to allow for continued neurotransmission but that decreases the amount of NT in the synaptic vessicles
in depression transporeters may be upregulated causing even less NT to be in the synapse
39
Receptors in depression
Altered levels of 5HT receptors in depressed patients (altered number and affinity)
40
CRF roles
CRF has a regualtory role and will cause an increase in ACTH (from ant pit) --> increased cort release
CRF is also found in extrahypothalamic brain regions where it acts as a NT--coordinating behaviour, autonomic, endocrine , and immune response to stress
41
HPA axis and depression
some depressive symptoms (ex. altered sleep, sex, eating; excessive guilt; altered psychomotor activity) are all linked to HPA activity
42
When animal models are given CRF
they show depressive symptoms
43
Depressed patients have ___ CRF and cortosol
increased; related to severity
44
Altered HPA axis in depression
Increased CRF and cortisol
dysfunctional glucocorticoid feedback
impaired corticoidsteroid signalling
45
___ cort in depression, ___ cort with SSRIs or ECT
increased with depression; decreased with therapies
46
Contradictory info on depression
HPA axis activity is hypoactive in depression BUT also depressive patients show increased CRF and cortisol
47
Thyroid hormone and depression
T3 and T4 associated with depression
T3/4 regaulte overall metabolism of body therefore weight loss, psychomotor dysfunction and altered sleep seen in depression may be due to altered throid hormone
48
T3 supplementation
helpful adjunct therapy
T3/4 may act as co-transporter to NE
t3/4 increase cortical 5HT secretion
49
Enviromental factors
Adverse life events can increase the probability of depression relapse
Environment can be + or -
Stress and depression share mediators and circuitries
Studies of monozygotic twins have shown role of environment
i.e. Depression isn't solely genetic
50
Immunological factors in depression
chronic stress is associated with altered immune function
| "sickness behaviour"
51
Anti-inflammatory drugs in depression
ineffective
52
cytokines involved in depression include:
IL-1B, IL-2, IL-4, IL-8, IL-10
Interferon gamma (IFN-γ)
TNF
53
Cytokine effects on monoamine metabolism (pathway)
Pro-inflam syotkines produced by microglia and macrophages (incl. IFNs, IL-beta and TNF) --> decrease MA availability by activating MAPK --> increase SERT, DAT, NET
AND decreasing cofactors necessary for MA synthesis
54
Cyotkine effects on glutamate metabolism
cytokines (IFNs, IL-beta, TNF) --> increase IDO --> brekadown of trypotphan (5HT precursor)
cytokines also reduce Glu rei[tkae by astrocutes --> increased glu --> NMDA activation --> decreased BDNF secretion --> decreased neurogeneis and neuronal integrity
55
Sickness behaviour: definition and why
in infections pro-inflammatory cytokines released cause hypothermia, nausea, loss of appetite
advantage: social withdrawal (prevent spread), tired (energy used to cope with infection)
56
Sickness behaviour in depression
sickness behaviour may be enoigh to confer depressive behaviour
in animals: cytokine admin --> depressive symptoms BUT anti-inflam are ineffective for depression
57
Genetic factors--sex differences
Higher prevalence in women
| Higher heritability in women
58
Genetic factors: polymorphisms
```
Only a few genetic polymorphisms associated to MDD:
APOE
SLC6A3
SLC6A4
DRD4
```
59
APOEε2 vs. 4
```
APOEε4 = significant association with reduced brain anatomical structure and decreased function in depressed patients
APOEε2 = protective against depression
```
60
DRD4
increased in individuals with major depressive disorders
61
Carriers of SLC6A4
increased amygdala activity and higher repsonsivity to social, emotional stress (compared to non-carriers)
62
Neurogenesis in depression
Reduced neurogenesis capacity causes depression but… no conclusive evidence
63
Antidepressants and neurogenesis
Antidepressants decrease ceramides, which in turn increases neurogenesis
b/c ceramides block cell growth
64
Animal neurogensis--> structural differnces
Studies in animals suggest that neurogenesis can restore structuralchanges in hippocampus
new hippocampal connections --> associated with memory formation
NOT necessarily follow by depressive symptoms
65
MAO role
MAO catalyze the oxidative deamination of MAs--produces peroxide,, aldehyde and ammonia
66
3 treatment modalities for depression
1. Antidepressant drugs
2. Cognitive-behavioural therapy
3. Electroconvulsive therapy
67
2 types of MAO
A and B
differniated by their affinity for 5HT
note: type A is found in liver and gut
68
Role of MAOI
protect neurons from exogenous amines
terminate actions of amine NTs
regulate actions of intracellular amine stores
69
In neurons and glia differential MAOA and MAOB concentrations
low MAOA --> glia cells have role in gradient of 5HT (used to breakdown 5HT)
MAOB --> main role to minimize foreign amines (limit their access to vesicles)
70
MAOIs
Inhibit MAO --> less degradation of MAs --> more MA in cleft
71
MAOA inhibitors and non-selctive A/B inhibits are good for
```
phobic anxiety
atypical depressions:
• hysterical traits hypersomnia
• bulimia
• tiredness
• impression of rejection
MAOIs are better than uptake inhibitors (SSRIs, SNRIs, TCAs) for these
```
72
Phenelzine show to ___ corticosteroin levels
increase
| the HPA axis is hypoactive in depresiion, this may help give it a boost
73
Orginial MAOIs
Iproniazis and phenelzine--original and irreversible
side effects: liver toxicity, hemorrage, hypotensive crisis, death
withdrawn from use
74
MAOA also found in ____ where they catalyze ____. Inhibition causes the _____
gut and liver; catalyze bioactive amines from food
| cheese effect
75
Cheese effect
When MAOA in gut/liver is inibited allows tyramine to enter blood and be taken up by sympathetic nerves --> displaced endogenous MA --> massive release of EPI and NE --> increased BP
76
Reversible MAOIs
lozabemide and moclobemide
| Block MAOA sufficiently in brain while gut can displace it --> less cheese effect
77
Selegiline
selective for MAOB BUT at proper doses for AD loses this selectivity
78
TCAs
ex. amitryptyline (1st), imipramine (2nd)
| inhibit wither NET or SERT or both (both by newer drugs)
79
chlorpromazine
first widely used psychiatric drug (also an antipsychotic)
80
Downsides of TCAs
DIRTY drug
also block mACHRs, H1, α1 receptor
ANti-cholinergic side effects = dry mouth, urinary retention, hypertension
Drowsiness
81
Clomipramine
TCA with high addintity for SERT
| effective for OCD
82
Iproniazid
Irreversible inhibitor of MAO A and B
83
Lazabemide
Reversible MAOB inhibitor
84
Moclobemide
Reversible MAOA inhib
85
Phenelzine
Irreversible MAOA and MAOB inhibitor
86
Tranylcypromine
Irreversible MAOA and MAOB inhib
87
MAOA breaks down
DA, NE, 5HT
88
MAOB breaks down
Mainly DA
89
Irreversible MAOA inhibition causes
the cheese effect through increased serum tyramine levels --> hypertensive symptoms
Occurs with irreversible MAOA/B combined inhibitors
90
TCA examples
Amitriptyline (1st), Imipramine (2nd), Clomipramine
