Mood disorders 1 Flashcards
1
Q
what are the two main types of diagnositic criteria for depression ?
A
- DMS-IV (APA)
- ICD-II (WHO)
2
Q
what are the two main categories for mood disorders ?
A
- low mood (MDD, dysthymia)
- elevated mood & low mood (Bipolar)
3
Q
MDD diagnostic criteria
A
- *depressed mood (for children this can be irritable mood) (dysphoria)
- *anhedonia (loss of pleasure in activities)
- weight/appetite changes
- sleep disturbances (insomnia or hypersomnia)
- psychomotor agitation or retardation
- fatigure or loss of energy
- feelings of worthlessness
- diminished ability to concentrate
- recurrent thoughts of death, suicide
in a 2 week period must have 5 of the criteria (inc. at least one of the first two). Must cause distress or impairment and do not have other causes e.g. drug abuse
4
Q
what is done to make diagnosis more precise ?
A
diagnostic specifiers
5
Q
what are examples of a diagnostic specifier ?
A
- MDD with anxious distress
- MDD with psychotic features
- post partum MDD
- MDD with atypical features
- MDD with psychosis
- mild/moderate/severe
- in partial or full remission
- single/recurrent episode
can have combined e.g. MDD with anxious distress and atypical features
6
Q
what are some characteristics of MDD with melancholic features ?
A
- common
- insomnia
- diurnal mood variations (worse in morning)
- anorexia
- psychomotor retardation or agitation
- lack of joy
- feelings of guilt
7
Q
what are some characteristics of MDD with atypical features ?
A
- weight gain
- worse in evening
- increased sleep
- sensitivity to rejection
- anxiety
- feeling of heaviness, leaden paralysis
- maintained ability to experience joy (can still respond positively to certain situations but go back to depressed after)
8
Q
what is the NICE diagnostic criteria ?
A
stratifies depression
- less severe (PHQ-9 < 16
- more severe (PHQ-9 > 16)
maximum score of 27/ score affects treatment pathway
9
Q
what ethnicities are more likely to be diagnosed with depression ?
A
- white americans
- native americans
- mixed race
10
Q
which gender is more likely to be diagnosed with depression ?
A
females
bipolar shows no difference in gender for diagnosis
11
Q
what does bipolar disorder consist of ?
A
depressive episodes + manic episodes
12
Q
what is significant about the diagnosit cirtieria for depressive episodes in bipolar ?
A
they are they same as MDD
13
Q
what is the percentage of people with bipolar that attempt suicide ?
A
35%
14
Q
what are the manic episodes in bipolar disorder characterised by ?
A
- abnormally elevated, expansive or irritable mood and persistently increased activity or energy, present most of the time for at least a week plus three of the following (4 if irritable mood):
- inflated self esteem/ grandiosity
- decreased need for sleep
- more talkative than usual
- flights of ideas, racing thoughts
- distractability
- increase in goal directed activity or psychomotor agitation
- excessive involvement in damaging activites: hypersexuality, gambling, spending, foolish business ventures
MUST: - cause marked impairment to functioning
OR - have psychotic features
15
Q
what are the subtypes of mania ?
why are these important ?
A
- hypomania
- mixed episode
help define subtypes of bipolar itself
16
Q
what is hypomania ?
A
- mildly elevated mood and energy levels
- must produce a definite change in functioning that is noticeable by others
- impairement not so great: individuals can be highly productive whilst hypomanic
- often seen as a ‘personality trait’ (tends to be underdiagnosed)
impairement isn’t as great as full blown mania
17
Q
what is a mixed episode of mania ?
A
- patient has elevated energy levels, psychosis etc but is simultaneously depressed
- higher risk of suicide
18
Q
what are the subtypes of bipolar disorder ?
A
- BP1
- BP2
- Cyclothymia
(-others)
19
Q
what is BP1 ?
A
- involves full blown mania and periods of MDD
- ‘classic manic depression’
20
Q
what is BP2 ?
A
depressive episodes + hypomania
21
Q
what is cyclothymia ?
A
mild depression + hypomania > 2 years
fluctuations between
22
Q
what can you also classify BP1 and BP2 as ?
A
rapid cycling
- when you have more than 4 episodes in one year
23
Q
what is bipolar disorder often linked to ?
A
creativity
- often in hypomania or when stable
24
Q
what are the main 4 brain regions that are affected in MDD and what happens to them?
A
- anterior cingulate cortex
- hippocampus
- amygdala
- prefrontal cortex
these normally atropy
25
what are links between hippocampus atrophy and depression ?
volume of hippocampus decreases the longer depression is left untreated
26
what can we use to track brain activity in MDD and what does this mean for MDD?
- PET scan to track glucose metabolism
- reduction of activity in PFC may be as a result of reduced cortical volume/ atrophy
27
what is the link between reduced activity in the PFC and hippocampus in MDD?
- PFC exerts inhibitory control of hippocampus
- if activity is reduce, hypothalamus activity increases
- this can cause an increase in cortisol which may be one of the root causes of depression
28
what is a key area of the brain involved in Bipolar disorder and how does this change ?
- PFC activity is decreased during depressive phase and increased during manic episodes
## Footnote
these changes are not diagnostic/ many other brain regions change as well
29
a case study on the amelioration of depression
- woman shot herself in the head in suicide attempt
- reduced depression
- brain area with most significant damage was ** ventral PFC**
## Footnote
ventral PFC important in regulating emotion
30
what is the role of the amygdala ?
emotional regulation
31
what is the link between MDD and the amygdala ?
amygdala volume is reduce in MDD
32
what are the two theories for the mechanisms of MDD ?
- The Monoamine hypothesis
- HPA axis dysfunction
33
what is the monoamine hypothesis ?
dysfunction of serotonergic and noradrenergic transmission is the root cause of depression
34
what is the HPA axis dysfunction theory ?
chronic stress leads to dysfunction of HPA axis, PFC and hippocampus
35
what evidence has iproniazid given for the role of monoamines in depression?
- origionally given to treat tuberculosis
- patients seemed 'inappropriatley happy'
- approved as an AD
- irreversible MAO inhibitor
36
what is the role of MAO ?
breaks down monoamines
37
what evidence has resperpine given for the role of monoamines in depression ?
- origionally an antihypertensive/antipsychotic
- blocks VMAT which depletes monoamines
- suggested to cause depression
38
what are two drugs that suppor the role of monoamines in depression ?
- iproniazid
- reserpine
39
what are two piece of evidence that support the monoamine hypothesis for depression ?
- serotonin levels lowered in depressed patients
- tryptophan depletion lowers mood, induces relapse
- almost all ADs act by alterning serotonergic and noradrenergic transmission
40
what are probelms or evidence against the monoamine hypothesis ?
- effects of ADs on transmission is very fast (hours to minutes) but takes 2-4 weeks to see clinical improvement in symptoms
- newer ADs don't work via monoaminese.g psilocybin, melatonin and are faster to work
41
how does the monoamine hyopthesis explain the delay in AD effects ?
due to changes in receptor expression/ desensitization
42
what is the HPA axis ?
## Footnote
learn and remember diagram
hypothalamic pituitart adrenal axis
- hypothalamus produces CRF
- this stimulates pituitary gland to produce ACTH
- this stimulates adrenal cortex to produce cortisol which goes into the blood stream
- negative feedback loop from cortisol acting on glucocorticoid receptors in pituitary gland and hypothalamus to reduce production
43
what is cortisol ?
a physiological regulator for the immune system and metabolism
44
what is the link between depressed patients and the HPA axis ?
- 50% of depressed patients have hyperactivity of HPA axis
- 80% in severley depressed px
- reflected in increased cortisol levels in blood plasma
## Footnote
indicates its more important in certain types of depression than others
45
what can be used to test HPA axis mechanisms such as the cortisol negative feedback loop ?
dexamethasone suppression test
46
what is the dexamethasone suppression test ?
- dexamethasone acts on glucocorticoid receptors in anterior pituitary and hypothalamus
- decreases CRF and ACTH and therefore cortisol
47
what does the dexamethasone suppression test show in control vs depressed individuals and what does this mean ?
- reduces cortisol by 85% in control, only 45% in depressed
- indicates negative feedback loop in HPA axis is not working properly
48
what is a potential cause of comprimised negative feedback loop in HPA axis for depression ?
chronic stress, high cortisol levels over a long period of time
(potentially receptors become less sensitive to cortisol)
49
how is cortisol increased in the HPA axis of depressed individuals ?
- chronic stress increases cortisol levels
- reduction in negative feedback increases cortisol and CRF
50
what does increased cortisol/CRF do to the brain ?
it increases apoptosis and decreases neurogenesis in hippocampus and PFC
- change in brain structure may be underlying cause of depression
51
what are two piece of evidence support how dysfunction of the HPA axis leading to an increase in cortisol can cause depression ?
- affects of cortisol/CRF on the brain
- cushing's syndrome
52
what is the link between cushings syndrome and depression ?
- increased cortisol due to a tumor or long term treatment with glucocorticoid
- frequently see depression
53
how does dysfunction of the HPA axis link to areas of the brain affected by depression ?
- hypothalamus is regulated by brain regions such as PFC, hippocampus and amygdala
- their dysfunction reduces regulation of hypothalamus
54
evidence for HPA axis dysfunction and depression
- loss of regulatory input into hypothalamus
- loss of negative feedback loop
55
what are the potential origins of the HPA axis dysfunction(hyperactivity) ?
- genetics (polymorphisms)
- epigenetic factors (childhood trauma, deprivation)
56
what are potential mechanisms of ADs ?
- to increase rate of neurogeneis and decrease apoptosis via monoamine transmission to restore structures of brain regions involved in MDD
- this would explain the delay we see in observing clinical symptom improvement
- by restoring these brain regions way be be able to get HPA axis under control, which would decrease levels or cortisol and CRF, which would also help decrease apoptosis and icnrease neurogenesis
57
what is dexamethasone ?
a synthetic glucocorticoid
58
in terms of genetics, what are mood disorders classed as ?
heterogeonus
59
what are the two main approaches used to study the genetics of mood disorder ?
- identical twin studies
- genome wide association studies
60
What does the term 'concordance' refer to in twin studies?
The percentage chance that one twin will develop a disorder if the other twin already has it
## Footnote
A concordance of 100% indicates strong genetic involvement.
61
What does a concordance of less than 100% but greater than the general population prevalence suggest?
There may be genetic factors at play
## Footnote
This indicates that genetics may influence the likelihood of developing the disorder.
62
What is a confounding factor in twin studies?
Similar environments experienced by identical twins
## Footnote
Identical twins often share similar life experiences, which can affect study outcomes.
63
How can childhood trauma affect the likelihood of developing a mood disorder?
It can produce epigenetic changes
## Footnote
Such changes may increase the risk of mood disorders in individuals.
64
What is one technique used to gather information about genetic influences on mood disorders?
Genome Wide Association Studies
## Footnote
This technique allows for the analysis of a larger study population.
65
What is a limitation of Genome Wide Association Studies?
Confounding factors that complicate data interpretation
## Footnote
These factors can hinder the clarity of results and conclusions.
66
What percentage of the risk of major depressive disorder is estimated to be genetic?
Around 40%
## Footnote
This statistic highlights the significant role of genetics in mood disorders.
67
68
What is the consensus about the existence of a single 'depression gene'?
There is no single 'depression gene', but rather many genetic differences that contribute to the risk of developing major depressive disorder.
69
How much do polymorphisms in the serotonin transporter (SERT) increase the risk of depression?
## Footnote
genes linked to monoamine transmission
About 20%.
70
What have studies found about the association of dopamine transporter (DAT) and dopamine D4 receptor with depression?
Stronger associations compared to genes relating to serotonin receptor and in metabolic enzymes like monoamine oxidase
71
what does the strong association between depression and polymorphisms in the dopamine transporter (DAT) and dopamine D4 receptor suggest ?
dopaminergic mechanisms could be a line of research and development for antidepressants
72
What is suggested about sertraline's action at high doses?
It may inhibit the dopamine transporter (DAT).
73
what is important about setraline as an antidepressant ?
- inhibit dopaminergic mechanisms at high doses
- only DAT active drug
- others have been withdrawn from the market due to side effects
74
What are some genes linked to HPA axis dysfunction associated with depression?
* Mineralocorticoid receptor
* Corticotrophin releasing hormone receptor
* FKBP5
75
what is the gene relating to FKBP5 ?
a protein that modulates the sensitivity of the glucocorticoid receptors
76
What role do epigenetic changes play in relation to HPA axis genes?
There is strong evidence for their role in depression.
77
What are some other polymorphisms (mutations) that have been linked to depression ?
- Polymorphisms in the G protein subunit beta 3 (mechanism unclear)
- methylenetrahydrofolate reductase (and linked to other psychiatric problems) (unclear mechanism)
78
what may a polymorphism in methylenetetrahydrofolate reductase have an impact on ?
the ability to metabolise folate and might compund environmetal factors such as childhood neglects
79
What mutations have been linked to depression and other psychiatric problems?
Methylenetetrahydrofolate reductase mutations.
80
What is the heritability estimate for bipolar disorder based on twin studies?
As high as 80%.
81
how is bipolar similar to depression in terms of the genetic basis of each disorder ?
- not one single gene
- as a result of contribution from a large number of risk factors that each produce only a small increase in the likelihood of developing this disorder
82
What three genes have been flagged by GWAS in relation to bipolar disorder?
* ANK3
* CACNA1C
* TRANK1
83
What does ANK3 code for and what is its role?
Codes for ankyrin B, involved in neuronal myelination.
84
What does CACNA1C code for?
A voltage sensitive calcium channel expressed in the brain and may have roles in development and signalling
85
What is known about the gene TRANK1?
Its expression is increased by mood stabilizers like sodium valproate.
86
Fill in the blank: The gene _______ is associated with schizophrenia and bipolar disorder.
TRANK1
87
What is the common perception of depression?
Depression is shockingly common and often debilitating.
88
What environmental challenges did early humans face and how is this linked to depression?
- Food shortages, limited access to medicine, and stresses of a hierarchical society
- why evolution has not got rid of depression
- depression may have beneficial effects under such conditions such as conserving energy
89
What is the concept of 'behavioural shutdown' in relation to depression?
It suggests that withdrawing from activities or when it is not possible to overcome a stressor it is better to conserve energy for survival.
90
What is 'sickness behaviour'?
Behaviour patterns in people with depression that resemble those of physical illness.
91
How does anxiety relate to depression from an evolutionary perspective?
Anxiety is a state of hypervigilance that offers an evolutionary advantage when sick or sheltering from danger
92
What does the animal model of learned helplessness demonstrate?
It shows that conserving energy may be a survival strategy under stress.
93
In the context of depression, what is the significance of accepting a subservient position?
It may be a survival strategy in hierarchical structures, as seen in animal models.
## Footnote
shown by placing young rats in a cage with dominant adult male rats
94
What is psychic pain in relation to depression?
It may serve a purpose similar to physical pain, prompting withdrawal from stressors.
## Footnote
tells us to stop doing something that is damaging to us or proving stressful
95
What is rumination in the context of depression?
by shutting down other behavious, it may help individuals focus on solving specific types of problems.
96
What advantage might depressed individuals have in problem-solving?
They may be better at solving certain kinds of problems than non-depressed individuals.
97
What is one social dilemma that depression might help address?
Deciding whether to stay in a relationship.
98
Fill in the blank: Depression may lead to _______ from activities that are proving stressful.
withdrawal
99
True or False: Depression is always a maladaptive response.
False
100
what may rumination be important in for depression ?
solving social dilemmas
101
what are the two sets of diagnostic criteria used to measure depression ?
ICD-11
DSM-5
102
What are questionnaire-based depression rating scales used for ?
allow doctors to get a fuller picture of the severity of patient's condition
103
what is a commonly used questionnaire to measure depression in the UK and what is it?
- Patient Health Questionnaire 9(PHQ-9)
- a version of DSM-5 which breaks down each symptom into how frequently the patient experiences it
## Footnote
uses 9 symptoms from DSM-V
104
what depression questionnaire has NICE recently published guideliness on ?
Hamilton Depression Rating Scale - HDRS or HAM-D
## Footnote
has more questions that PHQ-9
105
what is the extended version of the Hamilton scale used for ?
major depression with atypical features
