PSYCHIATRY Flashcards
how is depression diagnosed?
patient health questionnaire 9 based on DSM IV criteria for MDD
5 positive responses = diagnosis of MDD
a positive response to which question on the PHQ-9 triggers an automatic diagnosis of MDD?
suicidal ideation
according to the PHQ-9, which two symptoms have to be present (out of 5 in total) to diagnose MDD?
anhedonia
depressed mood
what things should be ruled out before reaching an MDD diagnosis?
no psychosis (hence bipolar)
not due to a physiological effects of a substance
not accounted for by bereavement
what are the most severe symptoms of depression?
psychosis (guilt)
loss of colour vision
catatonic retardation (inability to move)
suicide
are men or women more likely to get depression?
women are twice as likely to be depressed than men
from what molecule are catecholamines such as dopamine and noradrenaline synthesised from?
tyrosine
from what molecule are indolamines such as serotonin synthesised from?
tryphophan
in which region of the brain is noradrenaline synthesised in?
locus cerulus of the pons
which region of the brain is serotonin synthesised in?
raphe nuclei (brainstem)
which enzyme catalyses the conversion of tyrosine to l-dopa?
tyrosine hydroxylase
which enzyme catalyses the conversion of tryptophan to 5-hydroxytryptophan?
tryptophan hydroxylase
which enzyme catalyses the conversion of l-dopa and 5-hydroxytryphan to dopamine and 5-hydroxytryptamine (5-HT) respectively?
l-aromatic amino acid decarboxylase
what enzymes cause reuptake and degradation of serotonin at the synapse? (2)
SERT
MAO-A
what enzymes cause reuptake and degradation of noradrenaline at the synapse? (3)
NET
MAO-A
COMT
COMT functions to promote reuptake of which neurotransmitter?
noradrenaline
what is the precise function of MAO-A?
degrades noradrenaline and serotonin after reuptake in synaptic terminal
n.b. some degradation occurs in synapse
what is the precise function of the NET/SERT proteins?
reuptake of noradrenaline and serotonin for recycling/degradation
which subtype of noradrenergic receptor is of most clinical importance in psychiatry? Why?
a2 adrenoreceptor
acts through inhibitory G proteins to supress noradrenaline release via negative feedback loop
which antidepressant drug is a a2 adrenoreceptor antagonist?
mirtazapine
what is the relationship between synaptic noradrenaline release and synaptic 5-HT release?
noradrenaline release causes more 5-HT release
what effect on 5-HT does a1 adrenoreceptor activation have?
INCREASES 5-HT
what are the effects of a2 autoreceptor activation on naradrenaline?
DECREASES NORADRENALINE
what are the effects of a2 heteroreceptor activation on 5-HT release?
DECREASES 5-HT
what are MOA-A inhibitors used to treat?
MDD
MAO-A degrades 5HT and NA
what are MOA-B inhibitors used to treat?
Parkinsons
MOA-B degrades DOPAMINE
name 1 REVERSIBLE MAO-A inhibitors…
Moclobomide
name 2 IRREVERSIBLE MAO-A inhibitors…
Phenelzine
Tranylcypromine
name one specific side effect of MAO-A inhibitors
Hypertension
patients can’t metabolise monoamines, can lead to hypertensive crisis
How does antidepressant doseage effect drug efficiacy?
the higher the dose, the greater the affinity of binding to ALL receptors at the synapse
what is the kindling hypothesis?
depressive episodes become more easily triggered over time.
At first, huge stresses will trigger a depressive episode. With time, this stimuli will be need to be smaller in order to trigger
what is considered to be the gold standard of MDD management?
effective, individualised ADx treatment
talking therapies/CBT
what is negative cognitive bias?
processing of sensory stimuli which negatively impacts sense of self, world view and emotions (aka clinical pessimism)
which neural system is underactive in MDD?
DORSAL neural system
which neural system is overactive in MDD?
VENTRAL neural system
which region of the brain is responsible for the recognition of facial expression?
Amygdala
in depression, the amygdala is ………… and the hippocampus is ………….
LARGE
SMALL
low levels of what factor is thought to be responsible for the decrease in hippocampal size in depression?
BDNF
according to DSM5 diagnostic criteria, what are the criteria that differentiate BP1 and BP2?
psychosis
7 or more days
severely effects work/life
requires hospitilisation
what is the 12 month prevalence of BP1?
0.5-1%
what is the 12 month prevalence of MDD?
4-5%
what is the mean age of first mood onset for BP1 and BP2?
18
mid 20’s
what is the mean age of first mood onset for MDD?
late 20’s
by how many years is life expectancy reduced in BP?
9-20 years (mental!!!)
lifetime suicide risk of bipolar is 15 times that of general population
what comorbid conditions are common in BP?
anxiety
ADHD
impulse control
drug or alcohol abuse
which 3 psychiatric disorders have the highest degree of heritability?
bipolar
schizophrenia
autism
what would you expect to see after giving MAO-A inhibitors / TCA to a patient with undiagnosed bipolar disorder?
precipitation of a manic episode
BP1 is genetically linked with which other psychiatric disorder?
Schizophrenia
BP2 is genetically linked with which of psychiatric disorder?
MDD
what type of drug should be prescribed is if a patient is experiencing psychotic symptoms associated with a manic bipolar episode?
Dopamine D2 receptor antagonists
antipsychotics
in terms of dopamine levels in the striatum, what is the difference between bipolar psychosis and SCZ psychosis?
BP - Da elevated throughout the striatum
SCZ - Da elevated ONLY in associative striatum
What is the role of dopamine dysfunction in psychosis?
Da dysfunction is apparent in all forms of psychosis within different disorders
what are the three phases of bipolar disorder?
mania/hypomania
depression
maintenence (between the two)
which drug is effective at treating all three phases of bipolar disorder?
Lithium
which drugs are effective at treating manic bipolar episodes?
lithium
valproate
carbemazepine
which drugs should be used to treat depression associated with bipolar disorder?
LOW DOSE quetiapine
lithium
lamatrogine
which drug is the gold standard for treatment of the maintenance phase of BP?
LITHIUM
what are the three mechanisms by which valproate is teratogenic?
Potent inhibitor of histone deacetylase
Induces oxidative stress
Interference with folate metabolism
excluding valproate, which other antipsychotic is unsafe for use in pregnancy?
carbemazepine
Increases risk of NTD but DOESN’T increase risk of developmental delay
what is the shape of the graph that relates anxiety and arousal?
Yerkes-Dodson law
Bell shaped curv
what are the 5 symptoms that make up the anxiety diagnostic criteria?
poor concentration insomnia muscle tension fatigue restlessness
have to have 3 of them for GAD diagnosis
what is the diiference between generalised and specific anxiety disorders?
generalised anxiety has no environmental cues
the symptoms of anxiety are as a result of overstimulation in which endocrine system?
autonomic
excessive sympathetic arousal
what is the lifetime risk of one suffering from GAD?
1 in 20
tension headaches are a cardinal sign of GAD. In which muscle is the tension coming from?
Frontalis portion of occiptiofrontalis
how is GABA synthesised?
decarboxylation of glutamic acid
catalysed by glutamic acid decarboxylase
what is the mechanism of action of baclofen?
GABA B agonist
Used clinically as a muscle relaxant
how many GABA molecules bind each GABA receptor? Where do they bind?
between alpha and beta subunits
2
which is the only 5HT receptor that is not metabotrophic?
5-HT3
the most common form of the GABA A receptor has how many subunits?
2 x alpha
2 x beta
1 x gamma
how many transmembrane domains does each of the GABA A receptor subunits have?
4 TM domains per subunit
in order for the GABA receptor to be BDZ sensitive, what combination of GABA subunit isoforms is needed?
alpha 1-3
any form of beta
gamma 2-3
what is the function of GABA a receptors with alpha 1 subunits?
found in brain regions that regulate sleep
what is the function of GABA a receptors with alpha 2-3 subunits?
found in brain regions that regulate anxiety
what is meant by the following description ‘BDZ’s are PAM’s of the GABA a receptor’
benzos are positive allosteric modulators of GABA receptor.
In the presence of GABA their binding keeps the chloride channel open for longer and at increased frequencies
between which two subunits on the BDZ insensitive GABA A receptor does alcohol bind?
alpha 4-6
DELTA
where do barbiturates bind the GABA-A receptor?
multiple sites across the receptor- very potent
what is alogia?
inability to speak due to mental illness
what delusions are most common in Scz?
delusion of reference
delusion of persecution, control, impossibility
what delusions are most common in bipolar?
delusion of grandiosity
what delusions are most common in depression?
somatic
nihilistic
guilt
what criteria is used to diagnose Scz?
ICD10
what is catatonic behaviour?
psycho-motor inability to move
name the 4 main dopamine pathways in the brain
associative + sensorimotor = nigrostriatal pathway
tuberoinfundibular
mesolimbic
mesocortical
where is the nucleus accumbens found?
ventral striatum of basal ganglia
where are the ventral tegmental area and substantia niagra located?
midbrain
which dopamine receptors are found in the entirety of the striatum?
D1 and D2(l+s)
which dopamine receptors are in the D1 family?
D1 and D5
which dopamine receptors are in the D2 family?
D2(l+s), D3, D4
what is the correlation between dopamine levels in the striatum and risk of Scz?
direct correlation- the higher the Da, the higher the risk
what is the minimum receptor occupancy needed for D2 antagonists?
65%
what D2 receptor occupancy produces hyperprolactinaemia?
72%
what D2 receptor occupancy produces parkinsonian symptoms?
80%
what is the only true D2 antagonist used to treat scz?
Amisulpride
which 2 antipsychotics don’t tend to produce EPSE at high doses?
Clozapine
Olanzapine
both bind M1 muscarinic Ach receptor, balancing GABA input to the thalamus
what is the prevelence of scz?
0.4%
what is the lifetime risk of Scz?
1%
what are the chances of monozygotic twins developing Scz?
45%
what are the chances of developing Scz if both parents have Scz?
50%
what is the median age of onset for males and females in Scz?
26 and 29
by how much does Scz risk increase if a first degree relative suffers from it?
7%
what drugs should be used to treat depressive episodes inbetween psychotic episodes of schizophrenia?
Antidepressants e.g. citalopram
what is akathisia?
feeling of inner restlessness and inability to remain still
antipsychotic side effect
how long after taking an antipsychotic would you expect the symptoms to alleviate?
2 weeks
agranulocytosis is a side effect associated with which antipsychotic?
clozapine
what percentage of scz patients relapse after their first episode of psychosis?
80%
what are the three stages of psychosis?
prodromal
acute
recovery
