psychiatry Flashcards
what is a hallucination?
hearing/seeing something without any stimulus
i.e. if just at night, it it just an illusion
what is an adjustment reaction?
states of subjective distress and emotional disturbance, usually interferes with social functioning and performance
arises in the period of adaptation to a significant life change or a stressful life event
manifestations vary, include:
- depressed mood
- anxiety or worry (or mixture of these)
- feeling of inability to cope, plan ahead, or continue in the present situation
- some degree of disability in the performance of daily routine
what is an organic delusional disorder?
persistent or recurrent delusions dominate clinical picture
may be accompanied by hallucinations
some features suggestive of schizophrenia may be present (e.g. bizarre hallucinations or thought disorder)
organic = physical cause (e.g. start after a stroke)
what is the prevalence of post-stroke psychosis?
delusions: 4.67% (95% CI 2.30% to 7.79%)
hallucinations: 5.05% (95% CI 1.84% to 9.65%).
more common in right hemisphere strokes (5:1)
what are some common delusional themes in post-stroke psychosis?
persecutory
jealousy
environment
what is the interaction between physical and mental illness?
30% of those with long term medical conditions have a mental health problem
46% of those with mental health problems will have a long term condition
what are some some long term physical conditions associated with a definite causal link in increased risk of mental illness symptoms?
cardiovascular diseases - 3x risk of depression and anxiety
diabetes - 2x risk of depression
COPD - 10x risk of panic disorder
musculoskeletal disorders - 2x risk of depression
what are some some long term physical conditions that are associated with a discrete increased risk of mental illness symptoms (no definite causal link)?
thyrotoxicosis - anxiety, mania
thyroid deficiency - depression, dementia
Cushing’s disease - (excess cortisol) depression
- prednisolone, dexamethasone may lead to mania
infections (syphilis, HIV) - psychosis
cancer - depression
Parkinson’s disease - depression, anxiety, dementia
why may a long term physical condition cause mental illness symptoms?
increased social isolation
loss of quality of life
how may COPD increase risk of a panic disorder?
many people pant to get enough oxygen into their system
increased CO2 production - become alkalotic
this changes calcium metabolism
leads to anxiety
why may people with chronic mental illness be at greater risk of physical illness?
diet and exercise (association with poverty)
smoking, alcohol, drugs
medication side effects
generally die 20 years younger than general population
what factors may affect timely diagnosis of physical disorders in people with mental illness?
illness behaviour - help seeking (lack of recognition, more tolerance of symptoms)
diagnostic overshadowing - physical disorder is often mistaken as part of the mental illness
stigma - towards person, within health service
lack of resources - lack of funding
what is the Montreal Cognitive Assessment?
30 point assessment
visuospatial skills (drawing)
simple numerical manipulation
recognition
recall
orientation
what is delirium?
organic cerebral syndrome characterized by concurrent disturbances of:
- consciousness and attention
- perception
- thinking
- memory
- psychomotor behaviour
- emotion
- sleep-wake schedule
duration is variable
degree of severity ranges from mild to very severe
what is the prevalence of delirium?
20% acute hospital patients >65 on admission
20% more develop delirium after admission
overall prevalence 30% on wards, 80% in intensive care
50% undetected, “hypoactive”
what are the practical implications of delirium?
psychiatric manifestation of a physical illness - impairs treatment
delays discharge
increases mortality if untreated
what causes delirium?
infection (urine, pneumonia, cellulitis, wound etc.)
change in environment (ITU, HDU, ward)
medication (opiates, anticholinergics, steroids)
alcohol withdrawal
surgery
pain
liver/ renal impairment
hypoxia
hyponatraemia
stroke
encephalitis
constipation
urine retention
dehydration
what are the predisposing factors for delirium?
advanced age
dementia (often undetected)
impaired activities of daily living
immobility
sensory impairment
urinary catheterization
malnutrition
alcohol
depression
how is delirium managed?
anticipate
modify risk factors if possible
early diagnosis
treat the causes
good nursing
- single room, well lit, familiar staff/family (in an ideal world)
medication (do not give)
wait
what are some potential examples of stigma in an acute case of delirium?
delay diagnosing underlying condition (not seen on every ward round)
may be interviewed by police if aggressive (meaningless, punitive)
detainment under Mental Health Act (unnecessary - Mental Capacity Act appropriate)
reluctance of care homes to take sufferers
friction between acute hospital staff and liaison team
what is stigma?
refers to challenges faced by people with mental illness related to knowledge, attitudes, and behaviour of people they meet
poor understanding of mental health
negative attitude
social exclusion
what are the practical effects of stigma?
leads to discrimination
increases disability caused by mental illness
creates disadvantage with personal relationships, education, and work
75% people with mental illness experience stigma
what are the 3 types of stigma in mental health?
intrapersonal stigma
- direct effect on the individual
- internalised discrimination
- compounded by direct effects of illness
interpersonal stigma
- friends, family, colleagues
structural stigma
- poor resources and funding
- access to physical health care
what is psychosis?
descriptive term: difficulty perceiving and interpreting reality
can be caused by many disorders
what are some psychotic disorders?
schizoaffective disorder
depression with psychotic features
substance related
due to other medical condition
schizophrenia
delusional disorder
bipolar I
what are the two types of positive symptom of psychosis?
hallucinations - perceptions in absence of a stimulus
delusions - fixed, false beliefs, out of keeping with social/cultural background
what are the types of hallucination?
auditory
voices commenting on you, talking to each other
visual
somatic/tactile
olfactory (rare)
what are some examples of delusions?
persecutory
control
reference
mind reading
grandiosity
religious
guilt/sin
somatic
thought broadcasting
thought insertion
thought withdrawal
what are the 4 types of negative symptom of psychosis?
alogia - poverty of speech
anhedonia, asociality
avolition/apathy
affective flattening
what are the characteristics of alogia?
paucity of speech, little content
slow to respond
what are the characteristics of anhedonia/asociality?
few close friends
few hobbies/interests
impaired social functioning
what are the characteristics of avolition/apathy?
poor self-care
lack of persistence at work/education
lack of motivation
what are the characteristics of affective flattening?
unchanging facial expressions
few expressive gestures
poor eye contact
lack of vocal intonations
inappropriate affect
what are the two types of disorganisation symptom?
bizarre behaviour
thought disorder
what are the characteristics of bizarre behaviour?
bizarre social behaviour
bizarre clothing/appearance
aggression/agitation
repetitive/stereotyped behaviours
what are the characteristics of a thought disorder?
derailment
circumstantial speech
pressured speech
distractibility
incoherent/illogical speech
what is the epidemiology of psychosis in terms of onset?
can occur at any age
peak incidence in adolescence/early 20s
peak later in women
what is the epidemiology of psychosis in terms of course?
often chronic, episodic
very variable
what is the epidemiology of psychosis in terms of morbidity?
substantial, both from disorder itself and increased risk of common health problems e.g. heart disease
significant impact on education, employment and functioning
what is the epidemiology of psychosis in terms of mortality?
substantial
all-cause mortality 2.5x higher, ~15 years life expectancy lost
hgh risk of suicide in schizophrenia – 28% of excess mortality
what is important when taking a psychiatric history?
history of presenting concern
past psychiatric history
background history (family, personal, social)
past medical history and medicines
corroborative history
what is important when taking a psychiatric history of a presenting concern?
patient’s description of the presenting problem
- nature
- severity
- onset
- course
- worsening factors
- treatment received
circumstances leading to arrival to hospital
why now?
what is important when taking past psychiatric history?
any known diagnosis?
any treatment?
known to a community team?
any previous admissions to hospital?
what is important when taking past family history?
age of parents, siblings, relationship with them
atmosphere at home
mental disorder in the family, abuse, alcohol/drugs misuse, suicide
what is important when taking personal history?
mother’s pregnancy and birth
early development, separation, childhood illness
educational and occupational history
intimate relationships
what is important when taking social history?
living arrangements
financial issues
alcohol and illicit drug use
forensic history
what is important when taking past medical history and medicines?
regular medications?
compliance?
over the counter medications?
interactions?
what is important when taking corroborative history?
informants: relatives, friends, authority
confidentiality
consent
what is noted during a mental state examination?
appearance and behaviour
speech
mood
thoughts
perceptions
cognition
insight
what is noted about appearance and behaviour during a mental state examination?
general appearance
facial expression
posture
movements
social behaviour
what is noted about general appearance during a mental state examination?
neglect
- alcoholism
- drug addiction
- dementia
- depression
- schizophrenia
weight loss
- anorexia nervosa
- depression
- cancer
- hyperthyroidism
- financial issues/homelessness
bizarre or inappropriate clothing
poor personal hygiene
injuries/wounds - self inflicted? harm to self?
what is noted about facial expression during a mental state examination?
depressive, anxious
“wooden” Parkinsonian
what is noted about posture during a mental state examination?
hunched shoulders, downcast head and eyes – depressive
sitting upright, head erect, hands gripping the chair – anxious
overactive, restless – manic
inactive, slow - depressive
immobile, mute – stupor
tremors, tics, choreiform movements, dystonia, tardive dyskinesia
mannerisms, stereotypies
what is noted about social behaviour during a mental state examination?
disinhibited, overfamiliar
withdrawn, preoccupied
signs of impending violence: raised voice, clenching fists, pointed fingers, intrusion into personal space
what is noted about speech during a mental state examination?
quantity
rate
spontaneity
volume
what is noted about quantity of speech during a mental state examination?
less, more, mutism
what is noted about rate of speech during a mental state examination?
slow, fast, pressure of speech (keep talking)
what is noted about spontaneity of speech during a mental state examination?
latency
what is noted about volume of speech during a mental state examination?
quiet, loud
what are the two types of mood that are assessed during a mental state examination?
subjective
objective
- predominant mood
- constancy
- congruity
what is noted about objective constancy during a mental state examination?
emotional lability/incontinence
reduced reactivity/blunting/flattening
irritability
what is noted about objective congruity during a mental state examination?
cheerful while describing sad events etc.
what is noted about thoughts during a mental state examination?
stream
form
content
- preoccupations
- morbid thoughts, suicidality
- delusions, overvalued ideas
- obsessional symptoms
what is noted about stream of thoughts during a mental state examination?
pressure, poverty, blocking
what is noted about form of thoughts during a mental state examination?
flight of ideas, loosening of associations, perseveration
disorganised thoughts may lead to disorganised speech (spontaneous speech that slips off track, difficulty holding train of thought)
what is noted about delusions and overvalued ideas (content of thoughts) during a mental state examination?
primary – occurs suddenly
secondary – arises from previous abnormal idea/experience (hallucination/mood/delusion)
delusional mood/perception/memory
shared delusion = folie à deux
how may delusional thoughts manifest?
paranoid
of reference
grandiose/ expansive
of guilt/ worthlessness
hypochondriacal
of jealousy
sexual/ amorous
religious
of control
concerning the possession of thought (insertion, withdrawal, broadcast)
what is noted about obsessional symptoms (content of thoughts) during a mental state examination?
obsessional thoughts: dirt and contamination, aggressive actions, orderliness, disease, sex, religion
compulsions: checking, cleaning, counting, dressing rituals
what is noted about perceptions during a mental state examination?
illusions (misperception of a real external stimulus)
hallucinations (perception in the absence of external stimulus)
distortions
what kind of hallucinations may be noted during a mental state exam?
1) true perception + 2) coming from outside the head
pseudohallucination = 1) OR 2)
hypnagogic (while falling asleep), hypnopompic (while waking up)
auditory – second person, third person
visual – Charles Bonnet syndrome (visual hallucinations caused by brain’s adjustment to significant vision loss)
olfactory
gustatory
tactile, of deep sensation
what is noted about cognition during a mental state examination?
consciousness
orientation
attention and concentration
memory
language functioning
visuospatial functioning
what is noted about insight during a mental state examination?
awareness of oneself as presenting phenomena that other people consider abnormal
recognition that these phenomena are abnormal
acceptance that these abnormal phenomena are caused by mental illness
awareness that treatment is required
acceptance of the specific treatment recommendations
what is the prodromal stage of psychosis?
early stage prior to a full-blown episode of psychosis
symptoms of this phase are often subtle - develop gradually and can be mistaken as “normal” behaviour (particularly in adolescents/young adults)
can include things like sleep schedule, social isolation etc.
what is a pseudohallucination?
not originating externally
i.e. “voices in my head” as opposed to “the people I see and hear talking about me”
what are the pharmacological options for treatment of psychosis?
antipsychotic medications (often mainstay of treatment)
what are the psychological options for treatment of psychosis?
CBT for psychosis
newer therapies like avatar therapy
what are the social support options for treatment of psychosis?
supportive environments, structures and routines
housing, benefits
support with budgeting /employment
typical vs
s
what are the differentials for psychosis?
schizophrenia
(mania, depression, schizoaffective disorder, puerperal psychosis, other psychotic disorders)
personality disorders
dementia
- Alzheimer’s
- vascular
- Parkinson’s/Lewy body
- Huntington’s
encephalopathy, acquired brain injury, stroke etc.
delirium
drugs (e.g. LSD)
metabolic (calcium, magnesium, B12 disorders)
endocrine (thyroid - Cushing’s, Addison’s)
infections (encephalitis, syphilis etc.)
what neurotransmitter system is most implicated in the mechanism of antipsychotics?
dopamine
what is the usual drug action on dopamine receptors to improve psychotic symptoms?
excessive dopamine can cause hallucinations etc.
antagonists lower dopaminergic neurotransmission
what are some extrapyramidal side effects caused by antipsychotics?
tardive dyskinesia
- causes uncontrollable stiff, jerky movements of face and body
- impaired buccal/lingual movements
akinesia
- loss of ability to move muscles voluntarily
akathisia
- inner restlessness - feel compelled to move but does little to alleviate
- can lead to overt restless movement
- legs most commonly affected
dystonia
- increased motor tone leads to sustained abnormal posture
- can occur shortly after taking dopamine antagonist
- can be acute, painful, even fatal (laryngeal dystonia)
what is a typical vs. atypical antipsychotic?
typical antipsychotics commonly cause extrapyramidal side effects at therapeutic doses (not based on drug mechanism)
how are the side effects of typical antipsychotics managed?
avoid in first place (atypical antipsychotics usually first line)
change medication
anticholinergic medications can help (e.g. procyclidine)
patients should be informed about risks
what are some potential side effects of antipsychotics on the CNS?
EPSEs (extra pyramidal side effects)
sedation
what are some potential haematological side effects of antipsychotics?
agranulocytosis
neutropenia
what are some potential metabolic side effects of antipsychotics?
increased appetite
weight gain
diabetes
what are some potential gastrointestinal side effects of antipsychotics?
constipation
what are some potential pituitary side effects of antipsychotics?
increased prolactin (release is generally suppressed by dopamine)
what are some potential cardiac side effects of antipsychotics?
dysrhythmia
long QTc
what is the long term management plan for psychosis?
some people after an episode of psychosis recover completely and remain well, majority follow an episodic course with periods of wellness and relapses
community follow-up
managing antipsychotic side effects (e.g. weight, diabetes - manage comorbidities in other specialties)
health promotion: reducing risk factors e.g. smoking, diet
what is a mood or affective disorder?
fundamental disturbance is a change in affect or
mood to depression (with or without associated anxiety) or to elation
usually accompanied by a change in the
overall level of activity
what causes mood disorder episodes?
mood disorders tend to be recurrent
onset of individual episodes often related to stressful events
what is the prevalence of major depressive disorder (MDD)?
10-20%
what is the prevalence of bipolar disorder (I and II), both lifetime and 12-month?
bipolar I - 1%
bipolar II - 1.1%
how has age of onset changed in major depressive disorder (MDD)?
increasing rate of MDD with earlier age of onset
what is the gender distribution of bipolar I disorder?
equal
what is the gender distribution of bipolar II disorder?
more women than men
what is the gender distribution of major depressive disorder (MDD)?
twice as many women than men
what percentage of mental/substance abuse disorders do MDD and bipolar disorders account for?
MDD - 40%
bipolar - 7%
what percentage of disability adjusted life years (DALYs) do mental and substance abuse disorders account for?
7%
what is low mood/depression characterised by?
circles of thought
- negative automatic thinking e.g. what’s the point?
behaviour
- rumination
- isolation (passive, stay at home)
physiological symptoms
- exhaustion/low energy
feelings
- low, flat
- irritability, agitation
what are the DSM-5 criteria for depressive episodes?
sustained, severe lowering in mood for at least 2 weeks
PLUS at least 4 from:
- sleep alterations (insomnia or hypersomnia)
- appetite alterations (increased or decreased)
- diminished interest, anhedonia
- decreased concentration
- low energy/exhaustion
- guilt
- psychomotor changes (agitation or retardation)
- suicidal thoughts
what is the basis of a longitudinal diagnosis of major depressive disorder (MDD)?
diagnosis of a major depressive episode by DSM-5 criteria
no past manic or hypomanic episodes
what are the 3 DSM-5 subtypes of major depressive disorder (MDD)?
atypical features
melancholic features
psychotic features
what are the features of the atypical subtype of major depressive disorder (MDD)?
mainly increased sleep and appetite
heightened mood reactivity
what are the features of the melancholic subtype of major depressive disorder (MDD)?
no mood reactivity
marked psychomotor retardation
anhedonia
what are the features of the psychotic subtype of major depressive disorder (MDD)?
presence of delusions or hallucinations
what are the 3 triads of depression?
core symptoms
biological symptoms
psychological symptoms
what are the 3 core symptoms of depression?
low mood
anergia
anhedonia
what are the 3 biological symptoms of depression?
sleep
libido
appetite
what are the 3 psychological symptoms of depression?
the world
oneself
the future
what are the behaviours associated with a typical cycle of low mood (unipolar/bipolar depression)?
rumination
isolation (passive, stay at home)
what are the thoughts associated with a typical cycle of low mood (unipolar/bipolar depression)?
circles of thought - negative automatic thinking e.g. what’s the point?
what are the physiological symptoms associated with a typical cycle of low mood (unipolar/bipolar depression)?
exhaustion/low energy
what are the feelings associated with a typical cycle of low mood (unipolar/bipolar depression)?
low, flat
irritability, agitation
what are the behaviours associated with a typical cycle of high mood (mania)?
impulsivity
increased activity
what are the thoughts associated with a typical cycle of high mood (mania)?
grandiose, self related thinking
e.g. “I can do anything, I’m the best”
what are the physiological symptoms associated with a typical cycle of high mood (mania)?
increased energy
racing sensation (related to behaviours, thoughts)
what are the feelings associated with a typical cycle of high mood (mania)?
refreshing - euphoria, elation, excitement
tips over into more aggressive feelings - agitation, irritability, confusion
what are the DSM-5 criteria for manic episodes?
euphoric or irritable mood
PLUS 3 or more from
- decreased need for sleep with increased energy
- distractibility
- grandiosity or inflated self-esteem
- flight of ideas or racing thoughts
- increased talkativeness or pressured speech
- increased goal-directed activities or psychomotor agitation
- impulsive behaviour (sexual impulsivity, spending sprees)
what is the basis of a diagnosis of a type I bipolar disorder?
manic symptoms according to DSM-5 for at least 1 week with notable functional impairment (i.e. manic episode)
what is the basis of a diagnosis of a hypomanic episode?
manic symptoms according to DSM-5 for at least 4 days but without notable functional impairment
what is the basis of a diagnosis of a type II bipolar disorder?
manic symptoms according to DSM-5 for at least 4 days but without notable functional impairment (i.e. hypomanic episode)
no manic episodes in history (only hypomanic)
at least 1 major depressive episode
what is the basis of a diagnosis of an unspecified bipolar disorder?
manic symptoms occur for fewer than 4 days
or other specific thresholds are not met for manic or hypomanic episodes
bipolar disorder can manifest with many different patterns (different frequencies, amplitudes, distribution of manic vs. depressive episodes)
what caveats are given for a diagnosis of a hypomanic episode (i.e. manic episode is diagnosed instead)?
presence of psychotic features (e.g. hallucinations/delusions) - these features involve functional impairment by definition
hospitalisation - even if manic symptoms last fewer than 4 days
what is the most consistent clinical feature for diagnosing mood disorders?
psychomotor changes
mood can be variable in these conditions - e.g. MDD can be without sad mood and mania can be without euphoria
what is the diagnosis if manic or hypomanic episodes are caused by antidepressants?
bipolar disorder
what is cyclothymia?
significant mood swings
do not reach the extreme levels of mania or depression
how does mood in bipolar I disorder change with respect to mania and depression?
first episode is usually depressive
severe mood swings to extremes of mania and depression
how does mood in bipolar II disorder change with respect to mania and depression?
severe mood swings
does not reach extremes of mania
reaches extremes of depression
how does bipolar disorder change over time?
people largely autonomous in between episodes (50-60% relapse within 1 year after recovering from a mood episode)
long term (prospective study over 12 years)
- just over half the time symptom free
- about 1/3 of the time in depressive episodes
(varies depending on individual)
how does anxiety interact with bipolar disorder?
anxiety prevalent amongst bipolar individuals
worse prognosis and outcomes
why were bipolar and unipolar disorder defined as separate entities in DSM-III?
age of onset
- bipolar had earlier onset (19yrs vs. late 20s)
episode duration
- shorter depressive episodes in bipolar (<3 months) compared to unipolar (6-12 months)
course
- more frequent episodes in bipolar than unipolar (rapid cycling - 4 or more per year)
genetic specificity
- manic episodes found in FHx of people with manic episodes but not in FHx of people with unipolar depression
treatment
- unipolar depression - antidepressants
- mania - neuroleptics, lithium
why are bipolar and unipolar disorders more difficult to separate than they were in DSM-III?
age of onset
- MDD commonly diagnosed in children (onset below mean of late 20s)
episode duration and course
- brief depressive episodes that occur multiple times yearly are diagnosed in MDD - if MDD and bipolar disorders were further apart this would be a rare occurrence
genetic specificity
- depressive episodes (without mania) in FHx of bipolar individuals and vice versa
treatment
- overlaps (neuroleptics and lithium)effective in mania, unipolar and bipolar depression
how does heritability differ between bipolar and unipolar mood disorders?
bipolar has higher heritability
depression is about half as heritable as bipolar
how does insight differ between bipolar and unipolar mood disorders?
often preserved in depression but impaired in mania
how does insight present in bipolar mood disorders?
about half of patients with severe mania and most patients with hypomania deny having symptoms despite them being observable
insight has a U-shaped curve in relation to severity (i.e. most impaired in hypomania and severe mania, but more preserved in moderate states)
what mood disorder diagnosis can easily be missed (and what is the likely misdiagnosis)?
lack of insight in mania/hypomania may cause misreporting of bipolar disorders
patient may end up with an MDD diagnosis despite a history of mania
how can misdiagnosis of bipolar disorders as MDD due to lack of insight be avoided?
collateral history (friends, family)
what is a problematic consequence of misdiagnosing bipolar disorder as MDD?
treatment issues - i.e. choose to treat with antidepressants (standard for depressive episode without mania)
antidepressants appear to be mostly ineffective in acute bipolar depression and
prophylaxis
cause acute manic/hypomanic episodes
worsen long-term course of bipolar illness (especially those with a rapid-cycling course)
in rapid-cycling cases - appear to lead to more mood episodes, (including
depressive states) over time
what are the attention biases in depression?
biases in maintaining/shifting attention
difficulties for depressed people to disengage from negative material
one study showed prolonged maintenance of attention over negative pictures - what does this demonstrate?
reduced attention allocation to positive stimuli
long term effects - seen in individuals with high risk of depression, people with depression and remitted depressed adults
how does an fMRI work?
detects changes in blood oxygenation and flow in response to neural
activity via BOLD signals
(when an area is more active more oxygen is consumed, blood flow increases to meet increased demand)
what are the physiological changes that allow an fMRI to be taken?
neural activity systematically associated with changes in relative concentration of
oxygen in local blood supply
oxygenated blood has different magnetic susceptibility relative to
deoxygenated blood
changes in the ratio of oxygenated/de-oxygenated blood
(haemodynamic response function) can be inferred with fMRI by measuring the blood-oxygen level dependent (BOLD) response
fMRI can be used to produce activation maps showing which parts
of the brain are involved in a particular mental process
which parts of the brain display different activity in depression which can be seen using an fMRI?
sustained amygdala response to negative stimuli
prefrontal cortex:
- sustained perigenual anterior cingulate cortex (ACC) activity (BA 24, 25, and 32)
appears to mediate negative attentional biases
- increased activity in lateral inferior frontal cortex (associated with impaired ability
to divert attention from task-irrelevant negative information)
how does depression affect memory processes?
preferential recall of negative material compared to positive material
increased negative memory bias
- ability to recall memory related to negative words 10% more easily than positive words
who do memory biases present in?
individuals at risk (high on personality trait measure of neuroticism)
recovered depressed individuals
individuals with depression
what does the facial expression recognition test show in depression?
increased recognition of sad faces and/or decreased recognition of happy faces
(can be seen in healthy individuals with high levels of neuroticism)
what do the results of the facial expression recognition test demonstrate?
emotion recognition deficits in MDD
reduced recognition of all basic emotions except for sadness
what effect does incidental/passive viewing of emotional facial expressions have in depression?
enhanced amygdala response to negative faces
what is the function of the amygdala?
involved in perception and encoding of stimuli relevant to current or chronic affective goals
ranges from reward/ punishment to facial expressions of emotion to aversive/pleasant images
where is the amygdala found?
medial temporal lobe region
when does the amygdala show bias?
generally sensitive to detecting and triggering responses to arousing stimuli
shows bias towards detecting cues signalling potential threats (e.g. expressions of fear)
how does an acute single dose of noradrenergic antidepressant (e.g. reboxetine, duloxetine) affect facial expression recognition in healthy volunteer models?
better recognition of happy faces
how does an acute single dose of serotonergic antidepressant (e.g. SSRIs, mirtazapine) affect facial expression recognition in healthy volunteer models?
overall affect negative emotional face processing
mirtazapine - decreased recognition of fearful faces
SSRIs (e.g. citalopram) - mixed results, can sometimes increase fear recognition (both increased and decreased amygdala response)
how does 7 days treatment of serotonergic or noradrenergic antidepressant affect facial expression recognition in healthy volunteer models?
reduced recognition of anger and fear
reduced amygdala and medial prefrontal cortex response
how does clinical response to antidepressants change over time?
early changes in positive processing (facial expression recognition after single dose) are predicative of later response
what changes in the anterior cingulate cortex predict a positive response to treatment of depression (medication, neurostimulation, CBT)?
elevated baseline ACC activity during tasks that probe affective circuitry (also executive functions or self-referential processes such as the resting state)
where are the nuclei from where the serotonergic neurons project located?
raphe nuclei in midbrain
how many different serotonin receptors are there?
14
what is serotonin also known as?
5-hydroxytryptamine (5-HT)
where does serotonin reuptake occur?
proteins located on pre-synaptic membrane
what does the monoamine deficiency hypothesis of depression postulate?
depressive symptoms arise from insufficient levels of monoamine neurotransmitters - serotonin/5-HT - norepinephrine - dopamine
how does use of reserpine (antihypertensive) provide indirect evidence of 5-HT hypofunction in depression?
reserpine (antihypertensive) can lead to 5-HT depletion - causes depressive symptoms
how does use of clinically useful antidepressants provide indirect evidence of 5-HT hypofunction in depression?
all help with depressive symptoms through mediating increase in synaptic monoamine
(some selectively 5-HT) concentrations
how does use of PET scanning provide indirect evidence of 5-HT hypofunction in depression?
shows lower levels of 5-HT1A and 5-HT4 receptors in brains of people with depressive symptoms
how do monoamine oxidase A levels provide indirect evidence of 5-HT hypofunction in depression?
increased levels of monoamine oxidase A in MDD (more degradation of 5-HT)
how does blocking serotonin synthesis provide indirect evidence of 5-HT hypofunction in depression?
inhibition of tryptophan hydroxylase (converts tryptophan to serotonin) with p-chlorophenylalanine prevents antidepressant effects of MAOIs and TCAs
how does tryptophan depletion provide indirect evidence of 5-HT hypofunction in depression?
depletes synthesis of serotonin via tryptophan hydroxylase
can trigger relapse in MDD
how do mood changes provide indirect evidence of 5-HT hypofunction in depression?
correlation between monoamine depletion and decreased mood (i.e. the lower the serotonin levels, the lower the mood)
both in at-risk individuals and individuals with MDD in remission
how does serotonergic transmission in vulnerability marker traits provide indirect evidence of 5-HT hypofunction in depression?
traits such as pessimism, dysfunctional attitudes in people with MDD, negativism and neuroticism in healthy individuals (vulnerability markers) positively correlated with levels of 5-HT2A receptor (inversely proportional to serotonin levels)
what are the disadvantages of PET imaging in comparison to fMRI?
invasive
radioactive
expensive
less optimal temporal and spatial resolution
what are the advantages of PET imaging in comparison to fMRI?
more selective (fMRI gives no information about molecules or transmitters involved in increased or decreased brain activity)
how does PET imaging work?
injection of a radioactive
pharmaceutical tracer
tracer travels through blood across blood brain barrier
binds to specific target that it has affinity for, accumulation on target occurs
decay causes tracers to release positrons
positrons meet electrons - sets photons 180 degrees from each other
sends data into PET scanner - can determine site of decay as tracer has specific target (density will be high near target)
how can PET imaging be used practically?
measure dopamine levels and dopamine release in brain
how can PET imaging be used to compare dopamine levels and release (quantify dopamine receptors)?
take baseline PET scan
scan later in the day after you have given a pharmacological challenge (e.g. amphetamines like ritalin methylphenidate) that releases dopamine from presynaptic site
high levels of dopamine after amphetamine challenge competes with the radioactive tracer
subtract both scans, see difference in binding of tracer to the receptors - difference gives a measure of how much dopamine was released from the challenge given
why has usage of PET imaging to measure 5-HT levels by issuing a pharmacological challenge not been successful so far?
tracers used are all antagonists (i.e. not as sensitive to changes in synaptic levels of the transmitter)
how may usage of PET imaging to measure 5-HT levels by issuing a pharmacological challenge be successful in the future?
development of agonist PET tracer targeting 5-HT2A receptor
test with amphetamine as pharmacological challenger to increase serotonin levels
can see ‘real time’ release of serotonin
what has PET imaging with a pharmacological challenge shown about serotonin thus far?
patients with MDD release less serotonin in response to pharmacological challenge in comparison to healthy individuals
lower levels of serotonin associated with more depression
(aligns with serotonin hypothesis - i.e. hypofunction of serotonin system causes depressive symptoms)
what are the advantages of being able to measure serotonin levels in the brain directly (e.g. PET imaging with pharmacological challenge)?
predict treatment response
understand treatment resistance and give target medication based on this
what is important in taking a past psychiatric history in suspected depression?
previous episodes of depression?
did previous episode(s) resolve with or without treatment?
history of any other mental illness? (important to rule out manic episodes)
previous admissions? (informal versus under the mental health act)
collateral history (mainly important when risks / patient being guarded)
what is important in taking family history in suspected depression?
any mental illness?
who (e.g. first degree relative?)
what are the family relationships like?
what is important in taking medication history in suspected depression?
- antidepressants? antipsychotics? mood stabilisers?
- side effects?
- ECT?
- psychology?
substance misuse
- cannabis / alcohol / cocaine / heroin (opiates) / hallucinogens
- self medication?
details:
- when treated?
- for how long?
- what exact medication?
- what doses?
- how well tolerated?
- did it help?
what is important in taking forensic history in suspected depression?
arrests
cautions
incarcerations
forensic mental health act admissions
probation officer
what is important in taking personal history in suspected depression?
birth, early life
school, qualifications, higher/further education
employment
psychosexual history
premorbid personality
what risk assessment is taken in suspected depression?
to self:
- current suicidal ideation/plans/intent
- previous attempts (method/how many episodes/how did they feel when they survived
- self harm/cutting
- self neglect/poor care of physical illness
to others:
- more rare in depression but still ask!
- thoughts/plans to harm others?
from others:
- vulnerability to exploitation
what are the differentials in a suspected case of depression?
bipolar vs unipolar?
bipolar (and depression) vs borderline personality disorder?
bipolar vs schizophrenia?
bipolar vs attention deficit disorder?
what is cluster A of personality disorders according to DSM-5?
paranoid: pattern of irrational suspicion and mistrust of others, interpreting motivations as malevolent
schizoid: lack of interest and detachment from social relationships, apathy, and restricted emotional expression
schizotypal: extreme discomfort interacting socially, and distorted cognition and perceptions
what is cluster B of personality disorders according to DSM-5?
antisocial: pervasive pattern of disregard for and violation of the rights of others, lack of empathy, bloated self-image, manipulative and impulsive behaviour
borderline: pervasive pattern of abrupt mood swings, instability in relationships, self-image, identity, behaviour andaffect, often leading to self-harm and impulsivity
histrionic: pervasive pattern ofattention-seekingbehaviour and excessive emotions
narcissistic: pervasive pattern ofgrandiosity, need for admiration, and a perceived or real lack of empathy
what is cluster C of personality disorders according to DSM-5?
avoidant: pervasive feelings of social inhibition and inadequacy, extreme sensitivity to negative evaluation.
dependent: pervasive psychological need to be cared for by other people.
obsessive-compulsive personality disorder: rigid conformity to rules, perfectionism, and control to the point of satisfaction and exclusion of leisurely activities and friendships (distinct fromobsessive-compulsive disorder)
what are the similar traits between bipolar affective disorder and borderline personality disorder?
rapid mood swings
unstable interpersonal relationships
impulsive sexual behaviour
suicidality
how can you differentiate between bipolar affective disorder and borderline personality disorder?
BPAD:
- runs in family; heritability +++
- grandiosity
- mood states typically less affected by environment
BPD:
- poor self image
- fear of abandonment
- feelings of emptiness
what are the similar traits between bipolar affective disorder and schizophrenia?
hallucinations (present in 50% of mania & 10% of depression)
cognitive impairment
depression, negative symptoms of schizophrenia (apathy, lack of affect, low energy, and social isolation)
schizoaffective shares features of both BPAD and schizophrenia
how can you differentiate between bipolar affective disorder and schizophrenia?
BPAD:
- episodic delusions/hallucinations
schizophrenia:
- chronic delusions/hallucinations
what are the similar traits between bipolar affective disorder and attention deficit disorder?
impaired concentration
impairment of executive function
abnormal working and short term memory
how can you differentiate between bipolar affective disorder and attention deficit disorder?
family history (heritability+++)
recurrent depressive episodes
amphetamines worsen mania
what are some endocrine causes of symptoms of depression?
hyperthyroidism, hypothyroidism
hyperparathyroidism, hypoparathyroidism
hyperadrenocorticism, hypoadrenocorticism
hypoglycaemia
Cushing’s syndrome
Addison’s disease
what are some systemic conditions that may lead to symptoms of depression?
viral infections
systemic lupus erythematosus
HIV infection
pancreatic (and other) cancer
how may systemic diseases lead to causes of depression?
cytokines manifested in systemic diseases are considered to be a cause of depression
what are some deficiencies that may lead to symptoms of depression?
vitamin B12 or folic acid
what are some neurological conditions that may lead to symptoms of depression?
multiple sclerosis
Alzheimer’s
Parkinson’s
what are some medications that may lead to symptoms of depression?
beta-blockers
steroids
anti-Parkinson’s
anti-cholinergics (e.g. dicyclomine for IBS)
some antibiotics (e.g. ciprofloxacin)
statins
oestrogen
opiate pain killers
acne medications
who is vascular depression/early sub-cortical dementia common in?
later life
what is vascular depression associated with?
white matter hyperintensities
how do white matter hyperintensities increase risk of vascular depression?
impact on cognitive function
makes the individual more vulnerable to stressors
what are vascular risk factors that could increase risk of vascular depression?
diabetes
hypertension
smoking
alcohol use
what features are prominent in post-stroke depression?
retardation in thinking and behaviour
lesions in which areas of the brain can cause post-stroke depression?
left frontal lobe
basal ganglia
how does the position of a lesion affect the severity of post-stroke depression?
the more frontal the lesion, the more severe the symptom
what questions should be asked about drug abuse?
drug being abused
quantities taken? frequency taken? (some drugs can have therapeutic effects at certain doses but harmful effects at others)
over the counter? prescription? internet? illegal?
what are the 4 broad categories of drug?
depressant
stimulant
hallucinogenic
cannabinoid
why may someone take a drug recreationally?
positive reinforcement
('gain positive state' - want to gain something from the drug)
- get high
- like it
- stay awake
- escapism
negative reinforcement
('overcome adverse state' - want to overcome something unpleasant)
- boredom
- to get to sleep
- to feel better
- to reduce anxiety
other:
- why not?
- to rebel
- curiosity
- to fit in/everyone does it
how can recreational use of a drug lead to dependency?
“like” - recreational usage, people can leave at any point
shift in motivational desire to “want” - ‘necessary’ to have drug available
“need” - regular usage
spiral into dependence (for normal function) - must have the drug, dominates life
(neuroadaptations)
what proportion of people that recreationally use a drug will become dependent?
“funnel” shaped progression
people use recreationally/to alleviate negative feelings
as feelings recede (i.e. drugs take effect) drug use usually recedes
smaller number spiral into dependence
how is harmful substance use defined according to ICD-10?
pattern of substance use causing actual damage to health (mental or physical) of the user in the absence of diagnosis of dependence syndrome
adverse social consequences
includes bingeing on substances (does not include ‘hangover’ alone)
e.g. someone who has fallen, someone who has got into a fight, heavy smoker with recurrent chest infections
how is hazardous substance use defined according to ICD-10?
one step before harmful substance use
i.e. likely to become harmful if they carry on in the same manner
what are the 6 criteria that define dependence syndrome according to ICD-10?
strong desire or sense of compulsion to take the substance
difficulties in controlling substance taking behaviour in terms of its onset, termination, or levels of use (key aspect of dependence)
- who has control, you or ‘the drug/behaviour’?
- when did you last have a drink/drug?
physiological withdrawal state when substance use has stopped or been reduced
- a ‘negative’ state (from uncomfortable to intolerable) so user takes drug/alcohol to get relief from it or ‘treat’ it
evidence of tolerance: need to take more to get same effect
progressive neglect of alternative interests
persisting with substance use despite clear evidence of overtly harmful consequences
what is a ‘binge’?
may use a substance relatively rarely, but do not have control once they begin (large quantities of substance taken in short period of time)
what is necessary for a diagnosis of dependence syndrome (ICD-10)?
meet 3 ICD-10 criteria within a period of 12 months
what is the difference between addiction and dependence?
addiction
- compulsive drug use despite harmful consequences
- characterized by an inability to stop using a drug
- failure to meet work, social, or family obligations
- (depending on the drug) tolerance and withdrawal
dependence
- (biology/pharmacology) refers to a physical adaptation to a substance (neurochemistry, body adapts to presence)
- tolerance/withdrawal
- can be dependent and not addicted - no behaviours around it (no drug seeking, taking more than needed, no failure to make other commitments)
how does a drug produce psychoactive effects?
enters brain
what property of drugs affects its addictive potential?
speed of entry into brain
faster entry = more “rush”, more addiction
(difference in intake method of coca leaves vs cocaine vs crack)
what 3 things contribute to the speed of entry of a drug into the brain (and therefore higher addictive potential)?
speed of reaching the brain
speed of crossing the blood-brain barrier
lipophilicity of drug
what 3 elements are involved in substance use and addiction?
social, environmental factors (access, social norms, cost etc.)
personal factors (genetics, personality traits like impulsivity, family history)
drug factors (kinetics, formulation taken)
what factors influence pre-existing vulnerability to addiction?
family history
age
how may age influence pre-existing vulnerability to addiction?
the earlier you tend to use a drug, the more likely you are to become dependent on it
young brains not fully formed in terms of myelination (more synaptic plasticity) - therefore more vulnerable
what factors influence increased drug exposure in addiction?
compensatory
neuroadaptations
to maintain
brain function
resilience (i.e. being able to take a drug and not experience many detrimental effects)
how may acute use of alcohol help users to sleep or reduce anxiety?
alters balance between brain’s inhibitory system (GABA-A system, involves GABA-A ion channel) and excitatory system (glutamate system, involves NMDA ion channel)
alcohol boosts inhibitory system (leads to anxiolysis, sedation) - i.e. GABA
alcohol blocks excitatory system (leads to impaired memory, alcoholic blackouts)
how may chronic use of alcohol affect the GABA and glutamate systems?
neuroadaptations to allow GABA and glutamate systems to remain balanced in presence of alcohol (allows normal function)
reduced function of inhibitory system: switches subunit type within GABA-A receptor to a subtype that is less sensitive to alcohol
upregulation of excitatory system: more NDMA receptors
how may genetics affect the GABA-A receptor and therefore alcohol tolerance?
less sensitive GABA-A receptor
feel fewer adverse effects - can drink more, therefore damage is greater
in the absence of alcohol (withdrawal) after chronic use, how do the GABA and glutamate systems react?
in absence of alcohol GABA and glutamate systems are no longer in balance - reduced function in inhibitory system, upregulated excitatory system
NMDA receptor - increase in Ca2+ entering cell - toxicity leads to hyperexcitability (seizures) and cell death (atrophy)
how can withdrawal symptoms after chronic alcohol usage be treated?
benzodiazepines
boost function of GABA system
counteract glutamatergic hyperactivity, restore balance
how can magnetic resonance spectroscopy demonstrate the effects of benzodiazepines in treating alcohol withdrawal?
higher synaptic and metabolic glutamate levels in people that use alcohol
glutamate levels in anterior cingulate cortex (frontal cortex) raised one day after withdrawal
14 days on benzodiazepines - glutamate levels reduced closer to healthy controls
how does acamprosate help people to abstain from alcohol?
reduces NMDA function
reduces toxicity in brain, potentially neuroprotective (idiopathic improved cognitive function, reduced seizure risk)
why may anticonvulsants be able to treat alcohol withdrawal?
affect glutamate and GABA systems
what are the 3 models of addiction?
reward deficiency (positive reinforcement)
overcoming adverse state, negative reinforcement (e.g. withdrawal, anxiety)
impulsivity/compulsivity
how does the reward deficiency model work?
natural rewards increase dopamine levels in ventral striatum - pleasure, reward, motivation
drugs of abuse also increase dopamine levels
lack of control increases as dependence increases - less about pleasure/reward, more about motivation
therefore addiction conceptualised as “reward-deficient” state
what does the reward (dopaminergic) system look like?
dopaminergic projections in ventral tegmental area (VTA) of brain stem project into ventral striatum and frontal cortex
how does the opioid system act as a key modulator for the dopamine system?
mediates pleasurable effects (e.g. of alcohol) - produces endorphin rush that modulates dopamine system
what are some modulators of the dopamine system?
GABA-B
cannabinoids
glutamate
how does cocaine interact with the dopamine system?
block post-synaptic dopamine re-uptake channel
more dopamine in the synapse, more of a signal
how do amphetamines interact with the dopamine system?
block post-synaptic dopamine re-uptake channel - more dopamine in the synapse, more of a signal
enhances release of dopamine
why do drugs of abuse like cocaine or amphetamines (stimulants) have such a potent effect on addiction and the reward process?
directly target dopamine synapse
how do drugs of abuse like alcohol, opiates or nicotine interact with the dopamine system?
increase dopamine neuron firing in ventral tegmental area (VTA) by altering tonic inhibitory responses
(indirect effects)
how does the reward-deficient addiction model work with respect to availability of dopamine receptors?
people with higher availability of D2 receptors do not like the effect of stimulants
people with lower availability may have lower level of dopaminergic function in natural pleasure-reward system - drug-induced increase of dopamine increases feeling of pleasure
in people with higher availability increased dopamine levels could cause anxiety, paranoia etc. (important when considering psychotic states e.g. in schizophrenia)
how can reward deficiency in adolescence be linked to vulnerability to problematic drug use?
blunted brain activation in striatum when winning money aged 14 as part of IMAGEN study linked to problematic drug use at 16
reward deficient model
how does the reward system appear in abstinent addicts as compared to healthy controls?
blunted activation of reward system
how does the reward system appear in poly drug users as compared to healthy controls?
blunted activation of reward system
how does the reward system appear in relapsed addicts as compared to abstinent addicts?
substantial blunting of reward system
not in all individuals
theoretically, how could risk of relapse be mitigated when treating addiction?
medication that boosts dopamine system to counter naturally blunted reward system activation
what are the 3 stages involved in the cycle of addiction?
binge/intoxication - positive reinforcement
withdrawal (negative affect, negative reinforcement)
preoccupation/anticipation - craving
which region of the brain does withdrawal affect?
hypothalamus and brainstem effectors (autonomic, somatic, neuroendocrine)
amygdala
what effects does withdrawal produce due to its impact on the amygdala?
highly aroused, anxious state
how can the change from positive to negative reinforcement be described as dependence develops?
non-dependent: “high” produced, declines into negative (withdrawal state), returns to homeostatic set point eventually
neuroadaptations take place as drug use/ tolerance increases
dependent: smaller “high” produced, greater negative withdrawal state - returns to allostatic set point lower than homeostatic set point
what is an addict’s motivation when taking a drug after reaching a point of negative reinforcement?
need to overcome greater withdrawal state rather than achieve pleasure
fear/anxiety apparent without access to drug - cannot counter negative state
how does dysregulation of the amygdala affect the ‘reward’ system?
reduced dopamine and mu opioid function
how does dysregulation of the amygdala affect the ‘stress’ system?
increased activity
- arousal system (noradrenaline)
- CRF system (cortisol)
- kappa system (dynorphin)
decreased ‘anti-stress’ neurotransmitters (e.g. oxytocin, nociceptin)
what is the kappa opioid/dynorphin system?
opposite to mu opioid/dopamine system which produces endorphins
what kind of state is produced by stimulation of the kappa opioid/dynorphin system?
produces aversive, dysphoric state
how can dysregulation of the amygdala in addiction be demonstrated using aversive images and fMRI?
heightened brain response to aversive images in left amygdala for abstinent polydrug addicts
(but not in alcoholism)
what transition in the brain takes place during the change from voluntary drug use to compulsive drug use?
executive control moves deeper from prefrontal cortex to striatum
specifically - move from ventral (limbic/emotional) to dorsal (habitual) striatum
what does the balance between the prefrontal cortex and the striatum usually moderate?
internal drives
what disease is associated with the dorsal striatum?
Parkinson’s
which part of the brain is highly associated with craving?
hippocampus (memory)
how can neurocircuitry involved in inhibitory control be assessed?
go - no go task with fMRI
where can activity be seen in a go - no go task with fMRI?
putamen (dorsal striatum and inferior frontal gyrus)
what does a go - no go task with fMRI show in abstinent addicts?
greater activity in putamen
higher in abstinent alcoholics when compared to abstinent poly drug users and controls
what does a higher level of activity in the putamen shown in an fMRI of abstinent addicts indicate?
greater response associated with longer abstinence
i.e. greater activity during inhibitory control, facilitates staying sober
how can units of alcohol be calculated?
% strength x ml/1000
what is the excretion rate of alcohol?
1 unit per hour
what are the symptoms of opiate withdrawal?
tachycardia
sweating
restlessness
dilated pupils
bone aches
runny nose
GI upset
tremor
yawning
anxiety/irritability
gooseflesh skin
what drugs can be given to aid abstinence of alcohol?
acamprosate
disulfiram (antabuse)
naltrexone
nalmefene
how does acamprosate help alcohol abstinence?
increases GABA, NMDA antagonist
how does disulfiram (antabuse) help alcohol abstinence?
inhibits acetaldehyde dehydrogenase
therefore feel nauseous/flushes if mixed with alcohol
how does nalmefene help alcohol abstinence?
opioid antagonist
given on days at high risk of drinking, in those dependent but without withdrawal, to reduce alcohol intake
what drugs can be given to aid abstinence of opioids?
methadone
buprenorphine
what are the DSM-5 criteria for opioid/alcohol use disorder?
taken in larger amounts/over a longer period than intended
persistent desire or unsuccessful efforts to cut down
great deal of time spent obtaining, using and recovering from it
craving to use
recurrent use results in failure to fulfil major obligations (work, school, home)
continued use despite persistent social/interpersonal problems caused or exacerbated by usage
important social, occupational or recreational activities are given up due to use
recurrent use in situations where it is physically hazardous
continued use despite knowledge of having a persistent physical/psychological disorder caused or exacerbated by usage
tolerance, either:
a) need for increased amounts to achieve intoxication/desired effect
b) diminished effects with continued use of same amount of drug
withdrawal, either:
a) characteristic withdrawal syndrome
b) same/similar substance taken to avoid or relieve withdrawal
how is opioid/alcohol use disorder categorised according to DSM-5?
2 symptoms - opioid/alcohol use disorder
mild: 2-3 symptoms
moderate: 4-5 symptoms
severe: 6+ symptoms
what does a history taking look like in substance misuse?
presenting complaint (PC) – snapshot of main problem/s
history of presenting complaint (HPC) – length of current problem/s, onset, causes, signs and symptoms etc
substance misuse history (following areas should be assessed for each substance):
- length of current use and when last used
- current amount (units/grammes per day) and for how long at this level
- total length of use, max use, and any periods of abstinence
- mode/method of use
- evidence of withdrawals and severity (e.g. seizures, admissions)
- any previous treatments - medication, psychotherapy, detox, rehab
- any previous substance overdoses (accidental vs deliberate)
- assess triggers to use substances/alcohol
- assess motivation to change/engage in treatment
family history – include mental illnesses and addiction disorders, often history of trauma (neglect, abuse)
screen for developmental disorders, especially ADHD (25% of substance use disorders have comorbid ADHD), assess developmental and educational history
social/personal history
- relationships
- accommodation
- money, employment
- forensics (cautions, convictions etc.)
what are some common comorbid conditions with substance use disorders?
depression
anxiety
suicidality
personality disorder
PTSD
bipolar disorder
what are the major causes of morbidity and mortality associated with substance abuse?
trauma (e.g. fractures)
road traffic accidents
homicide
suicide
overdose (deliberate, and frequently accidental)
cirrhosis (alcohol)
endocarditis (IV)
abscesses (IV)
BBV: hepatitis B/C & HIV (IV)
(ask about vaccinations)
what is drug induced psychosis?
cluster of psychotic phenomena occurring during or immediately after substance use, especially stimulants
(e.g. crack, methamphetamine)
how may drug induced psychosis present?
vivid hallucinations, often auditory
paranoid delusions (can be severe)
how long does drug induced psychosis take to resolve?
within 1-6 months
why must diagnosis of drug induced psychosis be done carefully?
care not to diagnose something like a schizophrenic episode, which may be ‘triggered’ by substance abuse
what features of alcohol abuse should be noted during examination?
jaundice
anaemia
clubbing
cyanosis
oedema
ascites
lymphadenopathy
DVT
what investigations should be done in suspected alcohol abuse?
fibro scan /ultrasound
bloods (LFT, GGT, lipids, U&E, amylase)
breathalyser
urine drug screen
what features of opioid abuse should be noted during examination?
collapsed veins / track marks
endocarditis
skin abscesses
hepatitis / HIV
pneumonia
what investigations should be done in suspected opioid abuse?
bloods (LFT, GGT, U&E, glucose)
breathalyser
urine drug screen
sexual health screening/BBV
what is CAGE screening (alcohol assessment)?
have you ever felt you needed to CUT DOWN on your drinking?
have people ANNOYED you by criticizing your drinking?
have you ever felt GUILTY about drinking?
have you ever felt you needed a drink first thing in the morning (EYE-OPENER)?
what is an AUDIT test?
alcohol use disorders identification test - 10 questions about alcohol intake
how can AUDIT test results be categorised?
0-7 = low risk
8-15 = increasing risk (brief advice to reduce risk)
16-19 = higher risk
20+ = possible dependence (consider referral to specialist alcohol harm assessment)
what are the immediate effects of alcohol on the CNS?
impaired reaction time and motor co ordination
impaired judgement
sedation
(coma and death)
what are the immediate effects of alcohol on the senses?
less acute
what are the immediate effects of alcohol on the stomach?
nausea
inflammation
bleeding
what are the immediate effects of alcohol on the skin?
flushing
sweating
heat loss and hypothermia
formation of broken capillaries
what are the immediate effects of alcohol on sexual functioning?
reduced erection response
reduced vaginal lubrication
what are the chronic effects of alcohol on the brain?
damaged brain cells
reduced brain size
impaired memory
loss of sensation in limbs
brain atrophy
what are the chronic effects of alcohol on the cardiovascular system?
weakened cardiac muscle
elevated blood pressure
irregular heartbeat
increased stroke risk
what are the chronic effects of alcohol on the breast?
increases risk of breast cancer
what are the chronic effects of alcohol on the immune system?
lowered disease resistance
what are the chronic effects of alcohol on the digestive system?
cirrhosis
inflammation of stomach and pancreas
increased risk of lip, mouth, larynx, oesophagus, liver, rectal and stomach cancers
what are the chronic effects of alcohol on the kidney?
kidney failure associated with end stage liver disease
what are the chronic effects of alcohol on nutrition?
nutrient deficiencies
obesity
what are the chronic effects of alcohol on the reproductive system?
menstrual irregularities
increased risk of children with foetal alcohol syndrome
impotence
testicular atrophy
what are the chronic effects of alcohol on bone?
increased risk of osteoporosis
increased risk of fractures (frequent falls)
how does alcohol withdrawal present over time?
Worsening pattern of symptoms
onset usually from 6 hours
hallucinations can occur any time
delirium tremens is a late sign
what are the 2 effects of opioids?
analgesic effect
sense of euphoria
what are some examples of opioid agonists that affect mu, delta and kappa opioid receptors?
heroin, methadone, fentanyl, codeine
what are some examples of partial opioid agonists that affect mu, delta and kappa opioid receptors?
buprenorphine
what are some examples of opioid antagonists that affect mu, delta and kappa opioid receptors?
naltrexone
what is the difference between opiates and opioids?
opiates: naturalopioids (e.g. morphine,codeine, heroin to some extent)
opioids: all natural, semisynthetic (e.g. heroin, oxycodone),andsynthetic (e.g. fentanyl, methadone)opioids
what are the 4 types of treatment in psychiatry, with examples?
chemical
- drugs, medicines
electrical stimulation
- ECT for depression
- neurostimulation for pain syndromes
structural rearrangement
- psychosurgery/deep brain stimulation for severe depression
talking therapy
- CBT
- exposure therapy for phobias
what are the advantages of classifying psychiatric drugs based on chemical structure?
each drug has unique structure, easy to allocate data
what are the disadvantages of classifying psychiatric drugs based on chemical structure?
no use in clinical decision making
what are the advantages of classifying psychiatric drugs based on what illnesses they treat (antidepressant, antipsychotic etc.)?
easy for doctors to choose as they make the diagnosis
what are the disadvantages of classifying psychiatric drugs based on what illnesses they treat (antidepressant, antipsychotic etc.)?
many medicines treat several disorders (some antidepressants also treat anxiety and OCD etc.)
most disorders have multiple symptoms - a single medication may not treat them all
(e.g. depression may present with anxiety, insomnia, loss of libido - all have different neurotransmitter mechanisms)
what do psychiatric medicines target?
1 (maybe 2) of 4 different systems
- receptors
- neurotransmitter reuptake sites
- ion channels
- enzymes
how can psychiatric drugs produce unwanted side effects?
targets are in the brain but drugs can affect systems elsewhere (especially liver enzymes)
how are neurotransmitters create/inhibit an action potential in the receiving neuron?
action potential moves down axon
neurotransmitters released across synapse
activate receptors on post-synaptic membrane
how are neurotransmitters released across the synapse?
action potential arrives and depolarises the terminal region
depolarisation allows calcium to flow into terminal region
calcium activates enzymes that allows vesicles containing neurotransmitter to fuse with the cell membrane to release neurotransmitters
what happens to neurotransmitters after acting on post synaptic receptors?
most taken back up in the pre synaptic neuron through transporter/re-uptake site
which neurotransmitter is not taken back up through re-uptake proteins?
acetylcholine
how is acetylcholine broken down?
degrading enzymes outside the terminal
how are autoreceptors involved in inhibition of action potentials?
neurotransmitter attaches to autoreceptors inside first neuron and activates them
activation causes inhibition of calcium influx
causes inhibition of action potential - terminal does not fire
how do monoamine oxidase inhibitors act on enzymes to treat anxiety and depression?
block the breakdown of 5-HT and noradrenaline
how do acetylcholinesterase inhibitors act on enzymes to treat dementia?
block the breakdown of acetylcholine
deficiency of acetylcholine in dementia
how does lithium act on enzymes to treat bipolar disorder?
blocks glycogen synthase kinase
stabilises neurones to produce mood stability
how do dopamine blockers act on receptors to treat schizophrenia?
antagonists
how do serotonin receptor subtype antagonists act on receptors to treat depression?
augment effects of SSRIs
how do benzodiazepines act on receptors to promote sleep and reduce epilepsy?
agonists
enhance inhibitory transmitter GABA
how does guanfacine act on receptors to control ADHD?
enhances noradrenaline
what is the principle behind psychiatric drugs that target reuptake sites?
block them to increase neurotransmitter concentration in the synapse to enhance post-synaptic receptor activity
some switch the reuptake site direction to enhance release
what are 3 examples of drugs that target reuptake sites?
citalopram
- SSRI, enhances serotonin
- used for depression and anxiety
desipramine
- noradrenaline reuptake inhibitor, enhances noradrenaline
- used for depression
methylphenidate
- dopamine reuptake inhibitor, enhances dopamine
- used for ADHD
why is the 5-HT1A receptor targeted in treatment of depression?
increased stimulation of receptor inhibits activity in neurons with these receptors
why is the 5-HT2 receptor targeted in treatment of schizophrenia, sleep regulation and eating?
psychedelic drugs act on 5-HT2 to produce hallucinations, disturbance of consciousness
targeting this is thought to regulate receptor activity in mental disorders with similar effects
what is the principle behind psychiatric medication targeting ion channels?
block channels to reduce neuronal excitability
how do drugs like sodium valproate and carbamazepine aid treatment of epilepsy by targeting ion channels?
block sodium channels
block transmission of information down the axon
prevention of action potentials prevents process of recruiting neurones in an epileptic focus that would cause a seizure
how do drugs like sodium valproate and carbamazepine aid mood stabilisation in bipolar disorder by targeting ion channels?
block sodium channels
block transmission of information down the axon
prevention of recurrent cyclical activity between groups of neurones helps stabilise mood
how do drugs like gabapentin or pregabalin aid treatment of epilepsy and anxiety by targeting ion channels?
block calcium channels in terminal region of axons (synapse)
prevent neurotransmitter release
how can neurotransmitters be divided into 2 categories?
fast acting (on-off)
slow acting (neuromodulators)
what kind of fast acting neurotransmitter is glutamate?
excitatory
where is glutamate present?
80% of all neurons
pyramidal cells (regulation of brain function)
what kind of fast acting neurotransmitter is GABA?
inhibitory
where is GABA present?
15% of all neurons
interneurons (connect other neurons together, make up network of brain)
what is the balance between glutamate and GABA responsible for?
content of everything
e.g. memory, movement, vision
what is the role of neuromodulators?
adds emotions, drives, valence to content created by fast acting neurons
what is valence?
attractiveness/”good”-ness (positive valence) or averseness/”bad”-ness (negative valence) of an event, object, or situation
what does excess glutamate cause?
epilepsy
alcoholism
how can epilepsy caused by excess glutamate be treated?
perampanel (glutamate receptor blocker)
how can alcoholism caused by excess glutamate be treated?
acamprosate, ketamine (glutamate receptor blocker)
what does deficient GABA cause?
anxiety
how can anxiety caused by deficient GABA be treated?
benzodiazepines (GABA enhancer)
what does deficient 5-HT cause?
depression
anxiety
how can anxiety and depression caused by deficient 5-HT be treated?
SSRIs and MAOIs (serotonin enhancers)
what does excess dopamine cause?
psychosis
how can psychosis caused by excess dopamine be treated?
dopamine receptor blockers
what does excess noradrenaline cause?
nightmares (e.g. in PTSD)
how can nightmares caused by excess noradrenaline be treated?
prazosin (noradrenaline receptor blocker)
what does deficient acetylcholine cause?
impaired memory/dementia
how can impaired memory caused by deficient acetylcholine be treated?
acetylcholinesterase enzyme blockers
when can partial agonists be safer than full agonists?
improved safety in overdose
how can a partial agonist act as a modulator?
effect of partial agonist determined by level of neurotransmitter
excess neurotransmitter - blocks receptor (acts as an antagonist)
neurotransmitter deficit - acts as an agonist
why is a partial agonist’s action as a modulator better than that of a full antagonist?
blocking all effects of a neurotransmitter may have more side effects
how can a partial agonist be used in treating heroin addiction?
buprenorphine
- heroin alternative
- used to treat pain and addiction syndromes
how can a partial agonist be used in treating depression?
full antagonist (haloperidol) may produce extrapyramidal side effects
aripiprazole prevents side effects, can also allow normal motor function by acting as an agonist if dopamine is deficient
how can a partial agonist be used in treating nicotine addiction?
varenicline
- replacement therapy for tobacco
what is an inverse agonist?
opposite effect to an agonist
e.g. GABA has inhibitory effect, inverse agonist has excitatory effect
how can an inverse agonist be used to improve memory (e.g. in alcoholism)?
alpha-5IA acts as inverse agonist for GABA
acts in hippocampus, increases activity/functionality to reverse amnesiac effects
how can an inverse agonist be used to improve attention (e.g. in ADHD)?
histamine blockers cause sedation
inverse agonists have opposite effect
what is the most common GABA-A receptor sub-type?
2 alpha, 2 beta, 1 gamma proteins
what are the components of a GABA-A receptor?
5 separate proteins combined in multiple ways to form different receptor sub-types
where is the most common type of GABA-A receptor found?
cortex
how are different GABA-A receptors arranged at the synapse?
alpha-1 - synaptic
alpha-2 - proximal segment of synapse
alpha-5 - extra synaptic
how does the arrangement of alpha-1 GABA-A receptors at the synapse relate to their function?
alpha-1 - synaptic
regulates inhibition from the GABA inter-neurons onto these pyramidal cells
how does the arrangement of alpha-2 GABA-A receptors at the synapse relate to their function?
alpha-2 - proximal segment of synapse
control the output of the pyramidal cells - inhibition of proximal segment prevents firing of pyramidal cell to control overall activity
how does the arrangement of alpha-5 GABA-A receptors at the synapse relate to their function?
alpha-5 - extra synaptic
produce a tonic activity (dampen down tonic activity in the brain)
how is the GABA-A alpha-5 receptor distributed in the brain?
highly expressed in ‘emotionally rich’ areas
cingular cortex, hippocampus
why is the tonic activity of GABA-A alpha-5 in emotionally rich areas of the brain (cingular cortex, hippocampus) important with reference to conditions like addiction or anxiety?
tonic activity necessary to maintain equilibrium
lack of function may contribute to anxiety, addiction etc.
what is an orthosteric site/orthosteric receptor?
receptor/site that the original transmitter binds to
how does the binding of GABA to its receptor produce an effect?
GABA-A receptor is ion-channel linked receptor
GABA binds to GABA receptor (orthosteric site)
binding enhances chloride ion conductance, therefore inhibits neurons to calm the brain
how does the binding of benzodiazepines to the GABA-A receptor produce an effect? (also barbiturates, neurosteroids, ethanol)
bind to GABA receptor (allosteric site)
enhances action of GABA (sedation)
therefore help with sleep, anxiety reduction, anti-epilepsy
why does haloperidol cause side effects in treatment of schizophrenia with reference to its selectivity?
highly selective for D2 receptor
(minor effects of alpha-1 receptor)
adverse effects due to full dopamine receptor block
why does clozapine cause side effects like sedation and weight gain in treatment of schizophrenia with reference to its selectivity?
non-selective for D2 receptor (lower affinity than haloperidol)
has actions at histamine receptors as an antagonist (also 5-HT1A receptor as a partial agonist, alpha-2 receptors as an antagonist)
histamine blockade causes sedation, weight gain
why does clozapine cause side effects like constipation in treatment of schizophrenia with reference to its selectivity?
non-selective for D2 receptor (lower affinity than haloperidol)
has actions at cholinergic muscarinic receptors as an antagonist (also 5-HT1A receptor as a partial agonist, alpha-2 receptors as an antagonist)
causes constipation, maybe paralytic ileus (lethal)
why does amitriptyline cause side effects in treatment of depression with reference to its selectivity?
derived from tricyclic structure compounds, therefore not very selective (not specific to 5-HT and noradrenaline receptors/transporters)
also blocks histamine receptors, is a muscarinic anticholinergic blocker
adverse effects from histamine and acetylcholine receptor blockade
why may the side effects of amitriptyline cause death?
overdose may lead to cardiac and brain toxicity
why is citalopram preferred to amitriptyline with reference to its selectivity?
selective for 5-HT reuptake transporters
adverse effects solely driven by increased serotonin (therefore limited)
how can dementia be described?
degenerative disease of the brain
with cognitive and behavioural impairment
sufficiently severe to interfere significantly with social and occupational function
what are amyloid plaques?
insoluble β-amyloid peptide deposits as senile plaques or β-pleated sheets
where are amyloid plaques found?
hippocampus
amygdala
cerebral cortex
how do amyloid plaques relate to the pathophysiology of dementia?
increased density with advanced disease
what are neurofibrillary tangles (NFTs)?
consist of phosphorylated tau protein
where are neurofibrillary tangles (NFTs) found?
cortex
hippocampus
substantia nigra
how are amyloid plaques and neurofibrillary tangles (NFTs) related to the pathophysiology of dementia?
co-occurrence of amyloid plaques and NFTs now accepted as a hallmark of dementia
(NFTs are also found in normal ageing)
how are the neurons affected in the pathophysiology of dementia?
up to 50% loss of neurons and synapses in cortex and hippocampus
how is chromosome 21 implicated in development of dementia?
gene for amyloid precursor protein (APP) found on the long arm
(also implicated in Down’s syndrome)
how is chromosome 19 implicated in development of dementia?
codes for apolipoprotein E4
presence of E4 alleles increases risk of Alzheimer’s
how is chromosome 14 implicated in development of dementia?
codes for presenilin 1
implicated in B-amyloid peptide
how is chromosome 1 implicated in development of dementia?
codes for presenilin 11
implicated in B-amyloid peptide
what is the cholinergic hypothesis?
the pathological changes lead to degeneration of cholinergic nuclei in the basal forebrain (nucleus basalis of Meynert)
this results in reduced cortical acetylcholine (ACh)
how may drugs such as donepezil be used in treatment of dementia?
acetylcholinesterase inhibitor
increased levels of cortical acetylcholine
how may drugs such as memantine be used in treatment of dementia?
NMDA receptor antagonist
high levels of glutamate in Alzheimer’s causes damage to neurons due to overactivity, increased calcium
memantine prevents glutamate from binding to neurons (i.e. inhibit calcium release to prevent action potentials)
what are the early signs of dementia?
absent-mindedness
difficulty recalling names and words
difficulty learning new information
disorientation in unfamiliar surroundings
reduced social engagement
what are the signs of progressive dementia?
marked memory impairment
reduced vocabulary
loss of less complex speech patterns.
mood swings and/or apathy
decline in activities of daily living and social skills
emergence of psychotic phenomena
what are the signs of advanced dementia/Alzheimer’s?
monosyllabic speech
psychotic symptoms
behavioural disturbance
loss of bladder and bowel control
reduced mobility
what are some psychiatric symptoms of dementia?
delusions (15%) -(usually of a paranoid nature)
auditory and/or visual hallucinations (10–15%)(may be simple misidentification, and indicate rapid cognitive decline)
depression (requires treatment in up to 20% of patients)
what are some behavioural disturbances seen in dementia?
aggression
wandering
explosive temper
sexual disinhibition
incontinence
excessive eating
searching behaviour.
what are some personality changes seen in dementia?
often reflects an exaggeration of premorbid traits with coarsening of affect and egocentricity
why is differential diagnosis of Alzheimer’s difficult/inexact?
due to mixed nature of dementia pathologies
e.g. AD frequently occurs in the presence of vascular changes, indicating coexisting vascular dementia
what are the criteria for a clinical diagnosis of ‘probable Alzheimer’s disease’?
presence of dementia
insidious onset
deterioration from the individual’s baseline
not more likely to be accounted for by another cause (e.g. other types of dementia, neurological, medical or psychiatric comorbidities etc.)
how does dementia differ from delirium and depression in terms of onset?
dementia - insidious (months to years)
delirium - acute (hours to days)
depression - acute or insidious (weeks to months)
how does dementia differ from delirium and depression in terms of course?
dementia - progressive
delirium - fluctuating
depression - may be chronic
how does dementia differ from delirium and depression in terms of duration?
dementia - months to years
delirium - hours to weeks
depression - months to years
how does dementia differ from delirium and depression in terms of consciousness?
dementia - usually clear
delirium - altered
depression - clear
how does dementia differ from delirium and depression in terms of attention?
dementia - impaired
delirium - normal (except in severe dementia)
depression - may be decreased
how does dementia differ from delirium and depression in terms of psychomotor changes?
dementia - often normal
delirium - increased or decreased
depression - may be slowed in severe cases
how does dementia differ from delirium and depression in terms of reversibility?
dementia - irreversible
delirium - usually
depression - usually
why are routine dementia investigations done?
exclude reversible causes of cognitive deterioration
what blood tests are done as part of routine dementia investigations?
FBC, ESR, CRP - anaemia, vasculitis
T4 and TSH - hypothyroidism
biochemical screen - hypercalcaemia or hypocalcaemia
urea and creatinine - renal failure, dialysis dementia
glucose
B12 and folate - vitamin deficiency dementia
clotting and albumin - liver function
(midstream urine test if delirium is likely)
why is imaging a part of routine dementia investigations?
exclude other cerebral pathologies
may help to identify treatable causes (e.g. subdural haematoma, normal pressure hydrocephalus, cerebral tumours)
help establish subtype of dementia
how is an MRI useful as a part of routine dementia investigations?
assists with early diagnosis
detects subcortical vascular changes
(CT scanning could also be used)
