mood disorders Flashcards
mood disorders can be split into
low mood
elevated mood & low mood
low mood disorders divided
major depressive disorder
dysthymia
elevated & low mood disorder
bipolar disorder
major depressive disorder 2 diagnostic criteria
Depressed mood: For children and adolescents, this can also be an irritable mood
Diminished interest or loss of pleasure in almost all activities (anhedonia)
must have on of these for a diagnosis
diagnostic criteria of MDD
In a two week period, must have 5 of the criteria (inc. at least one of key two).
Must cause distress or impairment and do not have another cause e.g. drug abuse.
notable diagnostic specifiers for MDD
anxious distress
atypical features
melancholic features
post partum onset
seasonal pattern
melancholic features MDD
lack of joy = required
insomnia
diurnal mood variations
anorexia
psychomotor retardation or agitation
feelings of guilt
atypical features MDD
maintained ability to experience joy=required
weight gain
worse in evening
increased sleep
sensitivity to rejection
anxiety
feeling of heaviness
what NICE diagnostic category is not seen in DSM5
subthreshold depressive symptoms (fewer than 5 symptoms)
MDD rates in females vs males
2 x in females
prevalence MDD world population
5% world population
MDD and age
peak for diagnosis in 30s and 40s
age of onset decreasing- people becoming more frequently diagnosed in teens and 20s
prevalence bipolar world population
1%
largest cost of MDD
workplace cost (loss of productivity) > direct cost of care > suicide cost
risk factors of depression
age, gender, ethnicity
bipolar consists of
depressive episodes and manic episodes
suicide risk bipolar
35% attempt suicide
manic episode bipolar
Abnormally elevated, expansive or irritable mood and persistently increase activity or energy, present most of the time for at least a week. Plus three of the following (four if irritable mood):
-inflated self esteem, grandiosity
-decreased need for sleep
-more talkative than usual
-flights of ideas, racing thoughts
-distractibility
-increase in goal directed activity or psychomotor agitation
-excessive involvement in damaging activities: hypersexuality, gambling, spending, foolish business ventures
Episode causes marked impairment to functioning or has psychotic features (delusions or hallucinations)
mania subtypes
hypomania or mixed episode
hypomania
mildly elevated mood and energy level
must produce a definite change in functioning that is noticeable by others
impairment not so great: individuals can be highly productive whilst hypomanic
Tends to be underdiagnosed as often seen as a “personality trait”
mixed episode
patient has elevated energy levels, psychosis etc but is simultaneously depressed
even higher risk of suicide
-elevated energy allows you to follow through with suicidal ideations that you may not have energy to in depressive episode
type 1 bipolar
classic manic depression
-can get rapid cycling
type 2 bipolar
depressive episodes and hypomania
-can get rapid cycling
cyclothymia
mild depression + hypomania >2 years
what is rapid cycling?
> 4 episodes in a year
what positive characteristics is bipolar suggested to be linked to
creativity and productivity
what 4 brain areas atrophy in MDD?
prefrontal cortex
hippocampus
anterior cingulate cortex
amygdala
hippocampal atrophy in depression
Negative correlation- the longer depression is untreated the smaller the total hippocampal volume
glucose metabolism in depression and its implications
lower glucose metabolism un prefrontal cortex than rest of the brain - likely as result of reduced cortical volume
PFC important in regulation of emotion and exerts inhibitory control over the hypothalamus
hypothalamus regulates amount of cortisol
cortisol may be root cause of depression
glucose metabolism in bipolar disorder
PFC activity decreased during depressive phase - lower metabolism
PFC activity/ metabolism increased during manic episodes
amelioration of depression
Attempted suicide by gunshot to head
Survived
Afterwards it was found her depression was deeply abated
The brain region that took the most damage was the ventral prefrontal cortex – shows its importance in emotion
the amygdala and major depressive disorder
thought to be very important in emotional regulation
thought its volume is reduced in major depressive disorder
amygdala activity in response to positive and negative stimuli also appears to be altered
mechanisms of depression
Monoamine hypothesis: dysfunction of serotonergic and noradrenergic transmission
Chronic stress - dysfunction of the HPA axis, prefrontal cortex and hippocampus
Iproniazid
Approved as AD in 1958
Irreversible MAO inhibitor - increases monoamine concentrations
1952) developed to treat tuberculosis
Patients seemed “inappropriately happy”
resperpine
early antihypertensive/ antipsychotic
Blocks VMAT, depletes MA from the presynaptic nerve terminal
Suggested to cause depression, seen as evidence for the monoamine hypothesis
VMAT
vesicular monoamine transporter
historical basis for role of monoamines in depression
iproniazid
resperpine
serotonin levels lowered in depressed patients
tryptophan depletion lowers mood, induces relapse in sufferers of depression
problems with the monoamine hypothesis (antidepressants)
Almost all AD drugs act by altering serotonergic or noradrenergic transmission
Effects on transmission are very quick
But!
AD effects delayed by 2-4 weeks
MA hypothesis explains this by changes in receptor expression/desensitization
what is cortisol
very strong physiological regulator. It regulates the immune system and metabolism
important to regulate this, so we have negative feedback systems
stress and cortisol
Stress can cause plasma cortisol levels to rise-
useful mechanism as cortisol will help mobilise glucose
works well in normal individual but seems to go wrong in depressed individuals
HPA activity in depressed patients
50% of depressed patients have hyperactivity of HPA axis
80% of severely depressed patients have HPA axis hyperactivity
Reflected in increased cortisol levels
what is the dexamethasone suppression test
tests whether negative feedback systems in the HPA axis are working properly
Dexamethasone is a very potent glucocorticoid and if you give someone a dose of it it will act on the glucocorticoid receptors in the anterior pituitary and the hypothalamus
Result in decreased production of CRF, ACTH and therefore cortisol
results of dexamethasone suppression test
reduces cortisol by 85% in controls; 45% in depressed
in depressed patients negative feedback loops are not working properly
negative feedback of HPA axis not working & depression
caused by chronic stress
increased amount of cortisol and over a long period of time somehow compromises the negative feedback loops
perhaps receptors become less sensitive to cortisol
dramatically increase past the point stress itself would
also see high levels of CRF
actions of CRF and cortisol on the brain
hippocampus and prefrontal cortex have receptors for cortisol and CRF
Cortisol and CSF cause increased apoptosis and decreased neurogenesis of these areas
leads to atrophy and depression
(amygdala also has receptors for these)
evidence cortisol and CSF = atrophy and depression
Cushing’s syndrome
(increased cortisol/long term treatment with GC)
frequently -> depression
genetic factors of HPA hyperactivity
Polymorphisms in genes involved in the HPA axis?
epigenetic factors of HPA hyperactivity
Childhood trauma
Deprivation
May explain while early childhood problems are risk factors for depression as an adult
what may explain time difference between antidepressant start and effects
Drugs may influence rate of neurogenesis and apoptosis
Result in restoration of structure of critical brain regions
This would take time explaining 2-4 weeks
If we can restore brain regions, may get HPA axis back under control
approaches to study mood disorders
twin studies
genome wide association studies
genetic risk of MDD
40%?
genes linked to MMD (monoamine transmission)
polymorphism SERT - increase risk 20%
strong association between polymorphisms in DAT and d4 receptor
genes linked to MMD (HPA axis dysfunction)
polymorphisms for genes involved in:
the mineralocorticoid receptor
corticotrophin releasing hormone receptor
FKBP5, which is a protein that modulates the sensitivity of the glucocorticoid receptor
strong evidence for the role of epigenetic changes
genes linked to MMD (other)
polymorphisms in the G protein subunit beta 3 - but the mechanism is unclear.
Methylenetetrahydrofolate reductase mutations
-could be that this impacts on the ability to metabolize folate and might compound environmental factors such as childhood neglect.
genetic contribution disease risk bipolar
as high as 80% reported
genes linked to bipolar
ANK3, CACNA1C and TRANK1
ANK3
codes for ankyrin B, which is a protein involved in neuronal myelination
CACNA1C
CACNA1C codes for a voltage sensitive calcium channel that is known to be expressed in the brain and which may have roles in both development and signalling
TRANK1
expression of its product is increased by mood stabilizers such as sodium valproate, perhaps offering clues as to the mechanism of action of these drugs in bipolar disorder
also associated with schizophrenia
behavioural shutdown
that when it is not possible to immediately overcome a stressor, it is better to conserve energy in order to survive
may also explain why there are high levels of anxiety seen in people with depression.
Anxiety is essentially a state of hypervigilance and that would have an evolutionary advantage if you were sick and sheltering from danger.
Acceptance of subservient position
Another animal model of depression is to place young rats in a cage with a dominant adult male rat. The best way for someone in a position like this to survive, is to be subservient and accept their position
Psychic pain
Physical pain serves a purpose: it tells us to stop doing something that is proving damaging to us. It is possible that depression may serve a similar purpose i.e. it will make us withdraw from activities that are proving stressful
Rumination
that people who are depressed are actually better at solving certain kinds of problem than non-depressed individuals. By shutting down other behaviours, depression may allow us to focus on certain types of problem and find a solution. This may be particularly important in solving social dilemmas e.g. whether to stay in a relationship.
measures of depression
Patient health questionnaire 9
Hamilton depression rating scale
