Psychopharmacology- Depression and bipolar Flashcards
Public perceptions of mental illness
Emotional weakness Bad parenting Victims fault Incurable Sinful behaviour Biological
Vegetative sx
Sleep
Appetite
Weight
Sex drive
Cognitive sx
attention span frustration tolerance memory negative distortions
impulse control features
suicide and homicide
behavioural and physical sx
motivation pleasure interests fatigueability headaches stomach aches muscle tension
Brief psychoed for depression
Medical illness, not character defect
Recovery is the rule
Treatments are effective, many options
Aim is complete symptom remission, not just getting better and staying wel
Risk of recurrence is 50% after 1, 70% after 2 and 90% after 3.
Should be alert to early warning signs and seek treatment.
How many % of those with affective disorder exhibit non-fatal suicidal behaviours
20-40%
Depression and the rules of 7
1/7 with recurrent depressive episode commits suicide
70% suicides have depressive illness
70% suicide see GP within 6 weeks
Suicide 7th leading cause of death
Causes of mortality in depression
suicides
fatal accidents due to poor concentration/attention
due to illness sequelae-alcohol etc
morbidity in depression
suicide attempts accidents illness job loss failed advance in school/career substances
societal costs depression
dysfunctional families absenteeism decreased productivity job related injuries quality control in workforce
how long does untreated depression last
6-24 months
3 R’s improvement in treated depression
Response- 50% reduction (Hamilton depression rating scale)
Remission
recovery- remission for 6-12 mo
(relapse and recurrence)
predicting relapse in depression
multiple severe long duration bipoolar/psychotic incomplete recovery
followup of depressed patients after 1 year clinical treatment
40% no diagnosis
40% diagnosis
20% partial
response rate to every antidepressant
67% respond
33% fail to respond
Apathetic responders (partial remission)
Reduction in depressed mood
Continuing anhedonia, lack of motivation, decreased libido, lack of interest, no zest
cognitive slowing
dec concentration
Anxious responders
Reduced depressed mood
anxiety
worry, insomnia, somatic
implications of partial response in patients who do not attain remission
milder form inadequate early treatment ?underlying PD or dysthymia increased relapse rates functional impairment increased suicide rates
Monoamine hypothesis depression
deficiency of NE and serotonin +(DA)
mechanism of TCA
inhibit reuptake pump of NE, 5HT
Amino acid precursor for NE, conversion steps
Tyrosine-> converted by tyrosine hydroxylase->DOPA-> DOPA decarboxylase-> DA-> dopamine beta-hydroxylase-> NE
NE destroyed by which enzymes
MAO in presynaptic neurons
COMT outside presynaptic terminal
Types of NE receptors
B1, B2
A1, A 2 (autoreceptors)
Location and function of most nonadrenergic neurons
Locus coerulus
determine whether attention is being focused on external environment or internal
Cognition, mood, emotions, movements, blood pressure, energy, psychomotor agitation/retardation
Dopamine receptors in pharmacology
Dopamine 1,2,3,4
NE deficiency syndrome
Impaired attention Poor concentration Deficiency in working memory Slowness of information processing Depressed mood Psychomotor retardation Fatigue
AA converted to 5HT
tryptophan-> try hydroxylase->5 hydroxytryptophan-> aromatic AA decarboxylase into 5HT
Serotonin receptor subtyeps
- presynaptic 1A- autoreceptors-> reduce
- 1D-> terminal autoreceptor- inhibit release
- a2 heteroreceptors-presynaptic, inhibit release when occupied by 5HT (cortex)
- Axodendritic interactions a1 on cell bodies, enhance serotonin release when occupied with NE (brainstem)
- 2A-> projections to basal ganglia-> movements, obsessions and compulsions. Raphe to limbic-> eating and appetite, anxiety Brainstem-> sleep
2C, 3 (CTZ vomiting), appetite GIT motility-> postsynaptic, sexual functions
Serotonin deficiency syndrom
Depressed mood Anxiety Panic Phobia Anxiety Obsessions and compulsions Food craving, bulimia
Why doesn’t the monoamine hypothesis fit
Immediate increase in MA, however delayed response
Neurotransmitter receptor hypothesis for depression
depletion of MA causes compensatory up regulation of NT receptors
?abnormality in gene expression
Monoamine hypothesis of gene expression
despite normal MA levels and receptors- deficiency in signal transduction to post-synaptic neuron
“pseudoamine deficiency”
BDNF-> normally sustains viability of neurons, when stressed, supressed-> apoptosis of vulnerable neurons in hippocampus-> depression
Neurokinin hypothesis of emotional dysfunction
antagonist to substance P may have depressant effects
Present in amygdala, may have role in regulating emotions
when is it rapid cycling
when it occurs more than 4 times/year
who described several categories along the bipolar spectrum
Hagop Akiskal
Bipolar 0.25
unstable mood, depressed with good response to antidepressant, may benefit from mood stabiliser
dichotomous view point in relation to schizphrenia and bipolar
Krapelinian dichotomy- that they are two entities. Schizo- unremitting, poorer outcome.
If you have bipolar, do you have good outcome?
If you have schizophrenia, do you have poor outcome
Continuum disease model proposes both manifestations of complex set of disorders expressed on spectrum
bipolar 0.5
schizoaffective disorder
bipolar 1.5
hypomania without depression
bipolar 2.5
cyclothymic patients who develop MDD
bipolar 3
develop manic/hypomanic disorder on antidepressants (substance induced)
bipolar 3.5
mania induced by substances
bipolar 4
association of depressive episodes with pre-existing hyperthymic temperament. may respond well to mood stabiliser
bipolar 5
depression with mixed hypomania, requires mood stabiliser.
worse outcome- more mood episodes, more work impairment, likely FHx
bipolar 6
bipolarity in setting of dementia
Is it unipolar or bipolar depression- questions to ask
“Who’s your daddy”
- fhx of mood disorder, psych hospitaliation, suicide, lithium/mood stabilisers/AP/ED, ECT
“Where’s your mumma?”
Need to get additional history
?Bipolar depression
-more time sleeping, overeating, co-morbid anxiety, motor retardation, mood lability, psychotic sx, suicidality.
Early age onset, hgih freq depressive sx, ++time spent ill, acute abatement or onset of sx
Response to AD- failure, rapid recovery, activating side effects, insomnia, agitation anxiety
What has been the paradigm shift in relation to prevalence of mood disorders
Many patients once considered to have MDD are now recognised as having bipolar illness along bipolar spectrum
Autoreceptor regulation for dopamine, serotonin and NE
Dopamine-> D2
Serotonin-> 5HT 1A, 5HT 1B/D
NE-> a2
a1 and a2 regulation of serotonin
a1= accelerator for 5HT (raphe nucleus) a2= brake for 5HT (cortical)
Major dopamine projections
VTA and SNg-> extend via hypothalamus, to PFC, basal forebrain, striatum, NAc
Movement, pleasure and reward, cognition, psychosis
May also have role in sleep via projections to thalamus
Major serotonin projections
Ascending projections originate in brainstem-> thalamus, striatum, NA, basl forebrain, PFC, hypothalamus, amygdala
Regulate mood, anxiety, sleep
Descending down spinal cord-> pain, GIT, sexual function
Major NE projections
Locus C-> thalamus, cerebellum, basal forebrain, amygdala, hypothalamus
Link between stress, BDNF and brain atrophy in depression
++stress, reduced expression of BDGF, decrease in 5HT, increase then depletion of NE and DA
possible apoptosis of vulnerable neurons
These neurons normally regulate HPA-> when ++stress, atrophy, loss of inhibitory input to hypothalamus= overactivity of HPA.
Vulnerability-stress model
Epigeneic changes
Environmental stressors creating molecular alterations in brain circuits
Vulnerable brain circuits that may break down into depression upon exposure to future stressor
explain the idea of mood-related sx of depression being characterised by their affective expression
Positive affect reduced-> depressed mood, anhedonia, x happiness, loos of energy/enthusiasm, dec alertness, dec self-confidence-> DA dysfunction, NE dysfunction
Negative affect ++-> dep mood, guilt/disgust, fear/anxiety, hostility, irritability, loneliness
Matching diagnostic sx for manic episode to hypothetically malfunctioning brain circuits
Motor agitation- striatum
dec sleep/arousal- thalamus, hypothalamus, basal forebrain
mood- amygdala
risks, grandiosity, talkative/pressured speech, racing thoughts- PFC, NA
Neuroimaging in mood disorders- response to induced sadness vs happiness
DLPC in depression associated with cognitive sx, reduced activity
AMygdala- +activity in depression , over active to induce sadness, under active to induce happiness
OFC in manic pts-> fail to appropriately activate= problems with impulsivity associated with mania. Do not activate the ‘no-go’
