Case 12 Flashcards
1
Q
What does GABA stand for?
A
Gamma-aminobutyric acid
2
Q
What is H0?
A
The null hypothesis
3
Q
What is H1?
A
The alternative hypothesis
4
Q
What does p>0.05 show?
A
Observed difference is due to chance
Accept null
5
Q
The smaller the p value the…
A
Stronger the evidence against null
6
Q
What if the confidence interval does not contain 0?
A
0 is the value of no difference
So there is a difference
7
Q
What is CI does contain 0?
A
There’s not a difference
8
Q
Which stats test is appropriate for unpaired data (2 distinct, independent samples)?
A
Student’s t test
9
Q
Which stats test is appropriate for comparing 2 scores on the same set of people?
A
Paired t test
10
Q
What’s phenomenology?
A
Psychiatric symptoms e.g. Hallucinations
Delusions
11
Q
What’s psychopathology?
A
Study of abnormal states of mind
12
Q
What’s the format of the mental state exam?
A
As mat pc I
Appearance and behaviour Speech Mood Affect Thoughts Perceptions Cognition Insight
13
Q
What’s akathisia?
A
Subjective feeling if restlessness
14
Q
What’s alogia?
A
Poverty of speech
15
Q
What’s the difference between mood and affect?
A
Mood -subjective
Affect - objective
16
Q
What’s a mood-congruent memory?
A
A memory consistent with the patient’s mood
17
Q
What is labile mood?
A
Marked fluctuation of mood
E.g. Anger to crying to laughter within few minutes
18
Q
What’s a blunted affect?
A
Reduction in intensity of emotional response
19
Q
What is flattened affect?
A
Show no emotion
Negative symptom of schizophrenia
20
Q
What are the schneiderian first rank symptoms?
A
Thought alienation: insertion, withdrawal, broadcast
Delusional perception
Auditory hallucination
21
Q
What is circumstantial thinking?
A
Over-inclusive
But reaches the point eventually
- learning difficulty/ obsessional personality?
22
Q
What are examples of loosened association?
A
Knights move thinking/ derailment - no/ little association between one part of sentence and the next
Word salad - senseless repetition of sounds/ phrases
Neologism - new/ made up word
- suggestive of psychosis?
23
Q
What are schneiderian first rank symptoms highly suggestive of?
A
Schizophrenia
24
Q
What is perseveration?
A
Repetition of a particular response even in the absence/ cessation of a stimulus
- usually organic symptom of dementia
25
What's the difference between primary and secondary delusions?
Primary - bizarre
| Secondary - understood in the context of prevailing emotional state
26
What types of delusions are there?
Persecution
Grandiosity
Guilt
Nihilism - nonexistence of self/ parts of self/ others/ world
27
What feeling is important in assessing risk of suicide?
Hopelessness
28
What is the difference between an illusion and a hallucination?
Illusion - real stimulus, misinterpretation of actual stimulus
Hallucination - no stimulus, perception in absence of stimulus
29
What is the difference between true auditory hallucination and pseudohallucination?
True auditory hallucination - spoken aloud
| Pseudohallucination - heard within mind
30
What are 2nd/ 3rd person auditory hallucinations?
2nd person - voice talks directly to patient
| 3rd person - running commentary
31
What is confabulation and possible cause?
Fabricated/ distorted/ misinterpreted memories about oneself/ the world
Can be due to Wernicke-korsakoff's (brain disorder from thiamine B1 deficiency)
32
What are 4 things the patient may lack insight of?
Insight of abnormal symptoms
Insight of attribution of symptoms to mental disorder
Insight of appraisal of negative consequences of symptoms
Insight of acceptance of need for treatment
33
What is agoraphobia?
Extreme/ irrational fear of open/ public places
34
What are the positive symptoms of psychosis?
(something added to normality)
Delusion
Hallucinations
Catatonic symptoms - abnormal movements and behaviour
Formal thought disorder - abnormal thought processes
35
What are the negative symptoms of psychosis?
(something taken away from normality - the 5 A's)
Avolition - no motivation
Anhedonia - unable to feel pleasure
Affective flattening - no expression of emotion
Alogia - poverty of speech
Ascociality - social disinterest
36
What is psychosis?
Loss of contact with reality
Inability to differentiate salient information
Changes in the way someone thinks/ behaves/ perceives the world
37
What is euthymia?
Normal, non-deppressed, reasonably positive mood
38
What are the 3 core symptoms of depression?
Low mood
Anhedonia - inability to feel pleasure/ loss of interest
Anergia - loss of energy
39
How can unipolar depression be diagnosed?
Core symptoms everyday for at least 2 weeks
| Plus non-core symptoms
40
What are the non-core symptoms of depression?
```
Reduced conc
Reduced self esteem/ confidence
Guilt, worthlessness
Pessimistic outlook
Self harm/ suicidal idealisation
Disturbed sleep
Reduced appetite
```
41
How is unipolar depression ranked in severity?
Mild: 2 core, 2 associated symptoms
Moderate: 2 core, 3 associated symptoms
Severe: 3 core, 4 associated symptoms
42
Which type of bipolar disorder has worse recovery?
Type 2 as more depressed days, more suicidal act
43
What is type 1 bipolar disorder?
Mania
| Plus depression/ hypomania/ mixed affective state
44
What is type 2 bipolar disorder?
Hypomania
| Plus depression or another episode of hypomania
45
What does not occur in type 2 bipolar disorder?
Mania
| Mixed affective state
46
Example of an ultradian rhythm
Less than a day - Sleep cycle
47
Example of an infradian rhythm
More than a dat - Menstrual cycle
48
How often does a circannual cycle occur?
Yearly/ annually
49
How long is a cycle of a circadian rhythm?
Approximately a day (Diem)
| It is thought that our internal clock is a 25 hour cycle but zeitgebers reset the clock to our usual 24 hour day
50
What type of sleep is slow wave sleep (SWS) and what occurs during the stage?
Deep - stage 3 and 4
| Motor memory consolidation
51
Which stages of sleep are shallow?
1 and 2
52
What sort of consolidation occurs in REM sleep?
Emotional memory consolidation
53
As the length of sleep goes on, what happens to slow wave sleep (SWS)?
SWS becomes shorter
54
As the length of sleep goes on, what happens to REM?
REM becomes longer
55
How long does a sleep cycle last approximately?
Infant - 60mins
| Adolescent - 90mins
56
What sort of wave is seen in stage 1 of the sleep cycle?
Alpha waves - low amplitude, moderate frequency
57
What EEG features are seen in stage 2 of the sleep cycle?
K complexes
Sleep spindles
Slower frequency, higher amplitude compared to stage 1
58
What sort of wave is seen in stage 3 of the sleep cycle?
Delta waves - slowest wave, large amplitude
59
What sort of wave is seen in stage 4 of the sleep cycle?
Delta waves - slowest wave, large amplitude
60
What sort of wave is seen in REM sleep?
Alpha waves - looks similar to stage 1
61
Which stage are the vitals (breathing, heart rate, body temp) at their lowest?
Stage 4
62
What is a person like in REM sleep?
Vitals increase
Dreaming
Paralysed apart from resp. muscles and eyes
63
When would a patient not be paralysed during REM sleep?
REM sleep behavioural disorder - often precedes Parkinson's
64
How many hours a day do babies sleep?
16 hours
65
How much sleep do adults typically require?
7-8 hours
66
What underlies seasonal affective disorder (SAD)?
Darker in winter months so more melatonin secreted from pineal gland
Melatonin makes you sleep and affects your biological clock and mood
67
When would administration of melatonin be best to reduce the effects of jet lag and shift work?
Just before going to bed
68
How is sleep deprivation compensated for on subsequent nights?
Slow wave, non REM sleep is increased
| Stage 3 and 4 almost completely restores (increased)
69
What is the photopigment in retinal ganglion cells that are sensitive to light?
Melanopsin
70
What is the main pacemaker for endogenous rhythms and where's it located?
Suprachiasmatic nucleus
| Small group of cells in hypothalamus
71
How can the amount of light entering the eye re-set the rhythm?
Suprachiasmatic nucles - lies above optic chiasm
| Receives info directly from eye
72
What relevance does sleep have in regards to epilepsy?
Some seizures are exclusively from sleep or only on waking
| Sleep deprivation provokes most seizures
73
What are the symptoms of narcolepsy?
Irresistible sleep
Cataplexy
Sleep paralysis
Hypnagogic hallucinations
74
What is narcolepsy and what causes it?
Relatively rare sleep disorder
Appears to be hereditary autoimmune cause
Influenced by unknown environmental factors
Associated with HLA (human leucocyte antigen) DR2 and DQ1 genes
Low hypocretin/ orexin levels in CSF
75
What is a sleep attack?
Fall asleep usually when bored/ in relaxing surroundings
Lasts 2-5mins
Wakes feeling refreshed
76
What is Sleep paralysis?
Inability to move just before onset of sleep/ upon waking
| Can be snapped out of it by touching/ calling their name
77
What is a hypnagogic hallucination?
Dream whilst awake and paralysed
Often terrifying
Occurs in transition from awake to asleep (agos - sleep is near)
78
What is cataplexy?
Temporary involuntary muscle weakness or even paralysis (but still conscious) lasting few seconds - minutes
In response to emotions/ anticipation of emotion/ sudden physical effort
e.g. laughter, anger, effort to catch suddenly thrown object
79
How is cataplexy treated?
Sodium oxybate
Antidepressants
GHB - gamma-Hydroxybutyric acid
80
What are melatonin and tryptophan?
Weakly hypnotic
Induce natural sleep patterns
Tryptophan is a precursor of melatonin
81
What are the problems with using morphine, barbiturates and benzodiazepines to help with sleep?
They decrease REM sleep
| Increase drowsiness during waking
82
What happens in Cotard's syndrome?
Seen in psychotic depression and dementias
| Person believes that they are already dead, no blood/ insides
83
What does p
Reject null
| There's a statistically significant difference at 5% level
84
Which pathway is primarily affected in Parkinson's?
Nigrostriatal pathway (not extrapyramidal system)
85
How Parkinson's patients get bradykinesia?
Loss of dopaminergic neurons in substantia nigra
| Leads to deregulation of extrapyramidal system that regulates posture and skeletal muscle tone
86
Which disease is high dopamine seen in?
Schizophrenia
87
Which disease is low dopamine seen in?
Parkinson's
88
Which part of the brain is the limbic system?
Subcortical areas (below cortex)
89
What is the limbic system involved in?
```
Basic emotions - fear/ pleasure/ anger
Drives - hunger/ dominance/ care of offspring
Mood
Tone
Memory
```
90
What is the prefrontal cortex involved in?
Planning
| Executing actions
91
What can lesions in the PFC cause?
```
Dramatic changes in:
Personality
Inability to plan
Loss of spontaneity
Problems with initiating speech/ movement
```
92
What happens to the limbic system and PFC in depression?
Loss of connection between limbic system and PFC involving serotonin - affects normal function of PFC
93
Which areas are thought to be hypoactive in depression?
Anterior cingulate cortex (ACC)
| Dorsolateral prefrontal cortex (DLPFC)
94
Which areas of the brain are thought to be hyperactive in depression?
Amygdala
Thalamus
Subgenual cingulate
95
What are all catecholamines derived from?
Catecholamines - DA/ NA/ A
| From tyrosine
96
How is adrenaline synthesised?
```
Tyrosine
to L-DOPA (L-3,4-DehydrOxyPhenylAlanine) - rate limiting step
to dopamine
to NA
to A
```
97
What converts tyrosine to L-DOPA?
Tyrosine hydroxylase
| Fe2+, O2 and tetrahydrobiopterin also required
98
What converts L-DOPA to dopamine?
L-aromatic amino acid decarboxylase (AADC)
| Co-factor from vitamin B6 also required
99
What converts dopamine to noradrenaline?
Dopamine-beta-hydroxylase (DBH)
| Copper and vitamin C also required
100
What converts noradrenaline to adrenaline?
Phenylethanolamine-N-methyltransferase (PNMT)
101
How is melatonin synthesised?
Tryptophan
to 5-HTP (hydroxytryptophan) - rate limiting step
to serotonin (5-HT/ hydroxytryptamine)
to melatonin
102
What converts tryptophan to 5-HTP (hydroxytryptophan)?
Tryptophan hydroxylase
103
What converts 5-HTP (hydroxytryptophan) to serotonin?
L-aromatic amino acid decarboxylase (AADC)
104
Where is serotonin converted to melatonin?
Pineal gland
105
What effect does Ghrelin have?
Signals to brain that stomach is empty
106
What effect does Leptin have?
Stimulates brain to want to stop eating
107
What signs do babies with prader-willi syndrome show?
Hypotonia
| Failure to suckle
108
What is hyperphagia and when do prader-willi syndrome patients develop it?
Pathological overeating
Failed satiety response from failure in homeostatic regulation
Age 2-6
109
Which hormone level is increased in prader-willi syndrome?
Orexigenic ghrelin
110
What is the main excitatory neurotransmitter of the CNS?
Glutamate
111
What is the main inhibitory neurotransmitter of the CNS?
GABA
112
What do inhibitory neurotransmitters cause?
They cause Cl- to enter the membrane making it more negative inside
So action potential is less likely
As membrane hyperpolarised
113
What do inhibitory neurotransmitters cause?
Cause Na+ to enter the membrane making it more positive inside towards threshold
Making action potential more likely
114
What triggers vesicles to migrate to terminal?
Ca2+ influx into the membrane
115
What's required for vesicle fusion?
SNARE proteins
116
What are the monoamine neurotransmitters?
Dopamine, noradrenaline, adrenaline and serotonin
117
What does the chemical/ molecular hypothesis of depression propose?
Depression is caused by a chemical imbalance in the brain
| Antidepressants work by counteracting the molecular changes
118
What does the monoamine hypothesis of depression propose?
Depression is caused by a deficiency in serotonin or noradrenaline at functionally important receptor sites in the brain
Antidepressants work by increasing extracellular monoamine concentration
119
What does the network hypothesis of depression propose?
Depression is caused by problems in information processing within neural networks
Antidepressants work by gradually improving information precessing within these networks - enhance connectivity then activity-dependent pruning of synapses selects out and stabilises the active synapses
120
What would the most recent combination of the chemical and network hypothesis predict?
Antidepressants initiate a self repair process
Plasticity in neural networks and chemical neurotransmission indivisibly cooperate and gradually bring about mood elevation
121
What are the 2 elements of the neuroendocrine mechanism in depression?
Corticotrophin releasing hormone is elevated in brain and CSF in depression
And also
Reduced grey matter volume in PFC and hippocampus
Most of the grey matter is taken up by neuronal processes and synapses so this may mean that there's reduced neuronal complexity and connectivity in depression
122
How do antidepressants fit into/ support the neuroendocrine mechanism?
Antidepressants increase neurone production in rodent hippocampus
The delayed onset of clinical effect of antidepressants correlates with the time it takes newly generated neurone to differentiate and mature enough to participate in information processing several weeks after birth
123
What do antidepressants increase levels of?
Serotonin, NA and dopamine
124
What are the 2 principle mechanisms of antidepressants?
- Molecular transporter (re-uptake) inhibition - more monoamines remain in synapse
- Monoamine oxidase inhibition - DA, NA and adrenaline remain in synapse
125
What is the most effective treatment for depression?
Electroconvulsive shock treatment
126
How long do antidepressants take to show clinical improvement?
Several weeks
127
What is neurotransmitter is reduced in anxiety and how do anxiolytics tackle this?
Less GABA in cortex
Benzos activate GABAa receptors - positive allosteric modulators
(GABA is an inhibitory neurotransmitter so neuronal excitability is therefore decreased)
128
What are the 2 neurotransmitters thought to be involved in schizophrenia?
Glutamate
| Dopamine
129
What's the dopamine theory of psychosis and what evidence is there to support it?
Psychosis is caused by EXCESSIVE DOPAMINE
Cocaine and amphetamine increase DA and can produce psychotic symptoms
Most antipsychotic drugs act via dopamine-related mechanisms
130
What's the glutamate theory of psychosis and what evidence is there to support it?
Psychosis is caused by LOW GLUTAMATE
| Glutamate NMD receptor antagonists produce psychotic symptoms
131
What causes the positive symptoms of schizophrenia?
Overactivity of D2 receptors (positive +, overactivity +)
| Changes in mesolimbic pathway from VTA to nucleus accumbens, amygdala and hippocampus
132
What causes the negative symptoms of schizophrenia?
Under-activity of D1 receptors in mesocortical pathway (negative -, under activity -)
(Negative and one both contain letter N)
133
Is the nigrostriatal dopaminergic pathway affected in schizophrenics?
Which structures does the nigrostriatal dopaminergic pathway connect?
No
| Connects substantia nigra to dorsal striatum (caudate nucleus and putamen)
134
How does hypofunction of NMDA (type of glutamate receptor) contribute to schizophrenia?
Decreases activity of mesocortical dopaminergic neurons - negative symptoms
Increases activity of mesolimbic dopaminergic neurons - positive symptoms
135
Where do serotonin projections from the nucleus raphê magnus project to?
Cerebellum and spinal cord
136
Where do ascending serotonin projections from the raphê nuclei project to?
Thalamus, hypothalamus, striatum, amygdala, hippocampus and cerebral cortex
137
What are behavioural traits seen in depression with too little serotonin?
Trouble sleeping
Problems with anger control
Increase in appetite for starchy foods
138
Can serotonin cross the blood brain barrier?
No
139
What effect do
a) hallucinogenic drugs
b) antipsychotic drugs
have on serotonin receptors?
a) hallucinogenic drugs - many are agonists of serotonin receptors
b) antipsychotic drugs - many are antagonists of serotonin receptors
140
Which enzyme converts glutamic acid into GABA (gamma amino butyric acid)?
Glutamic acid decarboxylase (GAD)
141
What do guvacine, nipecotic acid and tiagabine do?
Inhibit GABA transport
142
What converts GABA into succinic semialdehyde and where does this reaction mainly occur?
Gamma-amino butyric acid transaminase (GABAT)
| Mainly in astrocytes
143
What type of GABA receptors are there and where're they located?
GABAa receptors: ligand-gated ion channels mainly on postsynaptic membrane
GABAb receptors: G protein-coupled on pre and postsynaptic membranes
144
What do GABAb receptors do?
Gi/Go coupled
Inhibit voltage-gated Ca2+ channels
Open K+ channels
Inhibits adenylyl cyclase
145
Which regions of the brain is GABA involved with?
Dopaminergic neurons in nigrostriatal system synapse onto GABAergic neurons
Lower concentration of GABA in grey matter
GABA abundant in nucleus accumbens
146
Where is the largest cluster of noradrenergic neurons and where else are they found?
Largest cluster - locus coeruleus in rostral pons
| Smaller clusters in medulla
147
What does alcohol and nicotine do to dopamine levels?
Increase DA levels
| If it feels good - DA neurons probably involved except enjoyment of food by endorphins
148
What can be given as Parkinson's treatment and why?
L-DOPA
Can cross blood-brain-barrier
Can be converted to dopamine
Avoids rate-limiting step of converting tyrosine to L-DOPA
149
What's the adverse drug effect of L-DOPA as Parkinson's treatment?
Hallucination
150
What does the mesocortical pathway connect?
Ventral tegumental area
| to cortical areas of frontal lobes
151
What does the mesolimbic pathway connect?
Cell bodies in midbrain ventral tegumental area
Medial forebrain bundle projects to parts of limbic system
Especially the nucleus accumbens and amygdaloid nucleus
152
Where is the VTA and what is it involved in?
Brain stem
| Involved in pleasure system/ reward circuit
153
Which pathway contains most of the dopamine?
Nigrostriatal pathway - substantia nigra to dorsal striatum (caudate nucleus and putamen)
154
What does the corpus striatum consist of?
Caudate nucleus
Lentiform nucleus: Putamen and Globus pallidus
Nucleus accumbens
155
Which areas contain a lot of dopamine?
VTA
Corpus striatum
Substantia nigra
Frontal cortex, limbic system and hypothalamus
156
What causes the adrenarche?
Activation of hypothalamic-pituitary-adrenal axis
| Causing increase in adrenal androgens
157
What does the increase in adrenal androgens during adrenarche cause?
Development of secondary sexual characteristics
| Changes in sweat glands
158
What happens in gonadarche?
Gonadotropin-releasing hormone pulsatile secretion from hypothalamus during sleep (initiated by activation of hypothalamic-pituitary-gonadal axis)
Stimulates anterior pituitary production of LH and FSH
Leading to gonadal maturational changes
Leading to secretion of gonadal steroid oestrogen and testosterone
159
When do girls/ boys have linear growth spurts and why?
Girls - 12 years
Boys - 14 years
GH secreted from anterior pituitary during sleep
Prolonged HPA axis activation thought to suppress GH secretion
160
What are the 3 main effects of sex steroids on behaviour and via which structures does it have its effect?
Facilitation of reproductive behaviours - hypothalamus
Reorganisation of sensory and association regions - visual cortex, amygdala, hippocampus
Motivation and reward-related behaviour - nucleus accumbens, dopaminergic pathways to prefrontal cortex
161
What is grey matter made of?
Neuron cell bodies, dendrites, glial cells
162
What is white matter made of?
Axons
163
What happens to the volume of grey and white matter in adolescence?
Linear increase in white matter volume
| Grey matter volume has pre-pubertal increase, post-pubertal loss
164
Why are adolescents more likely to encage in risky behaviour?
Prefrontal cognitive-control network not fully developed
Subcortical motivational drive network is being rapidly remodelled - sensitive to social and emotional stimuli
Decision to engage not influenced by cognitive processes alone - still participate when aware of risks
165
What are the risk factors for metabolic syndrome?
```
Large waistline
High triglyceride level
Low HDL level
High blood pressure
High blood sugar
```
166
What is metabolic syndrome?
A combination of diabetes, high bp and obesity
| That puts you at greater risk of heart disease, stroke and other conditions affecting blood vessels
167
Weight gain can be induced by several antipsychotic drugs, most notably...?
Olanzapine and clozapine
168
How do olanzapine and clozapine cause weight gain?
By inhibition of histamine H1 and serotonin 2c receptors
169
Name 2 adverse side effects of Clozapine apart from weight gain
Hyperlipidaemia
| Hypertension
170
What is an adverse drug effect of long term Risperidone use?
Hyperprolactinaemia
171
What is effective in reducing Clozapine-induced adverse drug effects?
Aripiprazole
172
Which type of antipsychotics pose the greatest risk of weight gain and metabolic syndrome?
2nd generation antipsychotics
173
What can be given for weight gain from antipsychotic medication?
Metformin
174
Why are psychosis patients at greater risk of metabolic syndrome?
Antipsychotic medication can cause weight gain
Negative symptoms of psychosis - abolition and anhedonia may lead to lack of exercise and poor diet
Other lifestyle factors: substance use, smoking, stress
175
What's activated in psychological stress?
Sympathetic adrenomedullary system
| Limbic-hypothalamic-pituitary-adrenal axis
176
What is the 1st line of treatment for depression?
Cognitive behavioural therapy
177
What are the disadvantages of MAOI compared to SSRIs and SNRIs?
More side effects
| Number of dietary restrictions
178
What is dysthymic disorder?
Persistent and long standing depressed mood that is not severe enough to be a depressive disorder
179
What is the average age of psychosis in men/ women?
Men: 18-25
Women: 25-35
180
How is life-expectancy affected in schizophrenia?
15-20 years less than national average
| Main causes of death: suicide and comorbid somatic conditions
181
What is the possible danger to a patient who takes a 2nd generation antipsychotic of quitting/ reducing smoking?
Clozapine and olanzapine and nicotine are metabolised by the same enzyme
Smoking cessation leads to enzyme activity reduction over several days, less medication is metabolised and plasma levels increase
Toxic levels of medication can accumulate in a matter of days
