Neurophysiology

Question 1

What electrical values describe:
- Resting potential
- Threshold value for Na+ channels to open (Na+ influx) to initiate action potential
- Threshold value for K+ channels to open (K+ outflow) to signal end of action potential

Answer 1

• resting potential -70mV
• when the synaptic signals received by the dendrites and soma of the axon hillock reach -55mV Na+ channels open and Na+ ions enter the axon - “depolarisation”
• When the membrane potential is reversed to +40mV the Na+ channels close and the voltage gated ion channels open causing K+ to move out - “repolarisation”

Question 2

Describe three types of synapses

Answer 2

a) Chemical - neurotransmitters/chemical molecules released from presynaptic neuron induces changes on the post synaptic neuron

b) Electrical - there is purely electrical communication between the presynaptic and post-synaptic neuron

c) Conjoint - mixture of both electrical and chemical stimulation

Question 3

What is meant by the following terms in the context of communication between synapses:

a) Facilitation
b) Spatial summation
c) Temporal stimulation

Answer 3

a) Facilitation refers to a presynaptic neuron inducing changes in the post-synaptic neuron which means an action potential is more likely. While some pre-synaptic neurons may directly induce an action potential in the post-synaptic neuron others will cause either slight depolarisation (excitatory neurotransmitters) or hyperpolarisation (inhibitory neurotransmitters) which serve to make an action potential respectively more or less likely

b) Spatial summation indicates that a post-synaptic neuron may be connected to several nearby pre-synaptic neurons. These pre-synaptic neurons may work together to increase/decrease the likelihood of an action potential

c) Temporal summation refers to when one post-synaptic neuron is stimulated several times by the same pre-synaptic neuron the summation of these effects increases/decreases the likelihoog of an action potential.

Question 4

What are the satiety and feeding centres

Answer 4

• Ventromedial hypothalamus is the feeding centre
• Lateral hypothalamus is the satiety centre

Question 5

Describe mediators of appetite (oxigenic) and satiety (anorexigenic)

Answer 5

Oxigenic:
-Ghrelin (only oxigenic mediator produced in the CNS)
- Neuropeptide Y

Anorexigenic:
- Leptin (produced by adipose tissue)
- Cholecystokinin
- Serotonin

Food and food cues increase dopaminergic activity in nucleus accumbens - destruction of dopamine pathways reduces eating behaviour

In obesity D2 receptors are reduced in the striatum

Question 6

What are the hypothermia and hyperthermia centres

Answer 6

• Preoptic anterior hypothalamus - hypothermia centre. Stimulation here causes sweating and vasodilation from parasympathetic drive
• Posterior hypothalamus - hyperthermia centre. Stimulation here causes shivering and vasoconstriction leading to hyperthermia.

Question 7

A lesion in BLANK would affect diurnal body temperature

Answer 7

Median eminence

Question 8

How does malignant hyperthermia arise?

Answer 8

Through abnormal excitation-contraction coupling in skeletal muscles

Question 9

Can levodopa withdrawal cause NMS

Answer 9

Yes - NMS causes hyperthermia

Question 10

What fibres carry pain sensation to the dorsal horn of the spinal cord?

Answer 10

• C fibres (unmyelinated)
• A-delta fibres (sparsely myelinated)

Question 11

Which routes are responsible for fast and slow transmission of pain

Answer 11

Fast transmission of pain occurs through lateral spinothalamic tract - this aids localisation of pain

Slow transmission of pain occurs through recticulothalamic tract (this aids subjective sensation)

Question 12

Name some neurochemical inputs that can modulate pain perception

Answer 12

• Opiod receptors in the dorsal horn and periaquetal grey matter (brain stem) modulate pain intensity
• Serotonergic raphne nuclei provide descending fibres that may affect how pain is perceived - explains the role of TCAs in pain

Question 13

What is thalamic pain syndrome?

Answer 13

Stroke affecting thalamoperforating branches of posterior cerebral artery - here light cutaneous stimulation may cause contralateral loss of sensation with burning or aching pain

Question 14

What areas of the brain play a role in the regulation of thirst

Answer 14

Subfornical organ
Organum vasculosum
Lamina terminalis

Question 15

Name some inputs that may increase thirst

Answer 15

• Angiotensin II –> neurotransmitter that increases thirst
• Baroreceptors in aorta and carotid

Question 16

How does ADH maintain a normal body fluid balance

Answer 16

Increases water reabsorption at renal tubules and maintains normal body fluid balance

Syndrome of inappropriate ADH secretion:
- Damage to paraventricular and supraoptic hypothalamic nuclei
- Carbamazepine or chlorpromazine
- Neoplastic syndromes
–> findings are low sodium, reduced osmolarity, normal renal excretion of sodium and high urine osmolality

Question 17

How do the following disorders have abnormalities of physiological drives?

a) Kluver Bucy Syndrome
b) Laurence Moon-Biedl Syndrome
c) Prader-Wili Syndrome
d) Kleine-Levin Syndrome
e) Psychogenic polydipsia

Answer 17

a) Bilateral lesions of amygdala and hypothalamus. Reduced aggressive behaviour, examine objects with mouth, hypermetamorphosis, prominent oral exploratory behaviour and hypersexuality

b) Autosomal recessive genetic locus 11q13. Hypogonadism, obesity, low IQ, retinitis pigmentosa (no hypothalamic lesion)

c) Paternal deletion 15q11-q13. Reduced oxytocin neurons and satiety neurons. Poor control of body temperature and daytime hypersomnolence - related to hypothalamic disturbance. Obesity, short stature, hyperphagia, hypogenitalism, impaired glucose tolerance, hypotonia.

d) Kleine-Levin Syndrome - viral illness, resolves by 3rd decade of life. Compulsive eating, hyperphagia, hypersomnolence, hyperactivity, hypersexuality, exhibitionism - hypothalamic abnormality

e) Increase water intake not related to hypovolaemia or hypernatraemia

Question 18

In fetal life where does neurogenesis occur?

Answer 18

Subventricular zone (surrounds the ventricles of the neural tube)

After neurons are produced in the subventricular zone they migrate outwards towards the cortical plate.
Thalamic axons that project to the cortical plate first synapse onto a transient layer of neurons called subplate neurons.
In normal development these axons detach from the subplate neurons and proceed to synapse to true cortical cells. This may not occur as readily in Schizophrenia

Question 19

What is heterotopia?

Answer 19

Abnormalities of neural migration and neurons staying in ectopic positions

Question 20

When does neuronal migration take place?

Answer 20

First 6 months of gestation

Question 21

What is radial migration?

Answer 21

The process that excitatory neurons reach the cortex. Here radial glial cells form scaffolding that helps guide migrating neuronal cells - the cells accumulate in an inside out pattern (newest on outside) to form Rakic’s cortical columns

Question 22

How does neuronal migration differ for inhibitory interneurons?

Answer 22

In external and internal granular layers - these cells tangentially migrate

Question 23

Describe the time points that myelination occurs?

Answer 23

Starts around 4th gestational month

Largely completed by year 2

In association cortix may reach full extent by third decade of life

Question 24

Which disease are associated with excessive vs. reduced synaptic pruning?

Answer 24

Schizophrenia - excessive
ASD - reduced

Synaptogenesis occurs between 2nd trimester - 10 years (peaks period < 2 years). By mid-childhood more neurons and cellular processes are established than needed for adult brain therefore pruning occurs into teenage years

Question 25

What does cerebral plasticity refer to?

Answer 25

Ability of the capability of the brain to be moulded throughout life. Cortical sensory maps can be reorganised - i.e. with practice for jugglers, musicians etc. Phantom limb pain - amputated limb may show reorganisation so that area is on cortical face area

Question 26

What hormones are released from the following areas? a) Anterior pituitary b) Posterior pituitary c) Hypothalamus

Answer 26

Anterior pituitary: - Growth Hormone - Luetenizing hormone (gonadotrophin) - Follicular stimulating hormone (gonadotrophin) - Adrenocorticotrophic hormone (corticotrophin) - Thyroid stimulating hormone (thyrotropin) - Prolactin Posterior pituitary: - Vasopressin (ADH - antidiuretic hormone) - Oxytocin Hypothalamus: - Corticotrophin releasing hormone - Growth hormone releasing hormone - Gonadotrophin releasing hormone - Thyrotrophin releasing hormone (increases prolactin release) - Somatostatin (inhibits GH) - Prolactin inhibitory factor (dopamine)

Question 27

Name some factors that affect the release of vasopressin?

Answer 27

Pain, stress , exercise, morphine, nicotine and barbituates increase release Alcohol decreases release Vasopressin is structurally very similar to Oxyctocin. Vasopressin is involved in attention, memory and learning

Question 28

What behaviours is Oxytocin involved in?

Answer 28

Bonding - initiation and maintenance of maternal behaviour, social bonding and sexual receptivity

Question 29

Describe the pathway of thryoid hormone release?

Answer 29

TRH from hypothalamus --> TSH from anterior pituitary --> Thyroxine (T4) and Triidothyronine (T3, more potent. T4 is converted to T3 at target organs) Patients with depression, mania, alcohol withdrawal and anorexia may show a blunted TSH response to exogenous administration of TRH T3 activates nerve growth factor genes in early development but not in the adults brain Hypothyroidism implicated in change to rapid cycling bipolar from previously stable. GAD associated with hyperthyroidism Lithium may predisopose to hypothroidism in middle aged women who carry antithyroid autoantibodies

Question 30

What is the pathway for cortisol release?

Answer 30

CRH (hypothalamus) --> ACTH (anterior pituitary) --> cortisol (adrenal glands)

Question 31

How does chronic stress cause atrophy in the hippocampus

Answer 31

- Decreased neurogenesis in the hippocampus and atrophy of dendrites - Atrophy of the hippocampus can cause impaired memory performance - additional as they may be aborisation of the dendrites in the basolateral amygdala there can be a memory bias towards negative events

Question 32

When do cortisol levels peak?

Answer 32

6-7am and there is diurnal variation

Question 33

Outline how cortisol levels have been found to vary in a) Depression, Mania, (psychotic), OCD and Schizoaffective Disorder b) PTSD

Answer 33

a) Hypercortisolemia - there may be loss of diurnal variation --> seen especially in melancholic depression b) PTSD - due to increased glucocorticoid receptors in the pituitary there may be hypocortisolemia (? genetic vulnerability causing)

Question 34

Outline how failure to suppress ACTH/CRH and cortisol production is shown with the dexamethasone suppression test:

Answer 34

At 11pm 1mg dexamethasone is administered with baseline cortisol measurement The next day at 8am, 4pm and 11pm - serum cortisol is measured again If any samples have > 5mcg/L this indicates non-suppression

Question 35

DST non suppression is shown in.... DST suppression is shown in...

Answer 35

Non-suppression: - Depression (especially if psychotic features/melancholic -sensitivity increases from 50% to 60-70%), mania, schizoaffective disorder - Cushing's, alcohol use disorder, extreme weight loss pregnany - Use of other drugs that reduces dexamethasone availability - barbituates, anticonvulsants Suppression: - Hypopituitarism - Steroids - High-dose benzodiazepine - Addisons

Question 36

How does DST affect prognosis in depression:

Answer 36

- If non-suppression despite recovery from symptoms evidence suggests may be more likely to relapse, poor prognosis and possible later suicidality

Question 37

Where are pinealocytes found and what do they secrete?

Answer 37

Pinealocytes are found in the pineal gland (epiphysis) and secrete serotonin and melatonin

Question 38

What is corpora arenacea or brain sand?

Answer 38

Corpora Arenacea/Brain sand are calcium deposits that are found in the pineal gland that become more prominent with age

Question 39

How is melatonin synthesised in the pineal gland?

Answer 39

Through the action of 2 enzymes: - Serotonin-N-acetlyase - 5-hydroxyindole-O-methylytansferase

Question 40

Apart from the light-dark cycle what else regulates the pineal gland activity?

Answer 40

Beta-adrenergic system - Beta-adrenergic antagonists (Propanolol) can decrease melatonin production

Question 41

State some hormonal changes that occur at the following time points during sleep: - Start - Slow waves sleep - REM sleep - Early morning sleep

Answer 41

- Start of sleep increased testosterone - Slow wave sleep: increased GH and SST with reduced cortisol - REM sleep: reduced melatonin - Early morning sleep: increased prolactin

Question 42

What circadian rhythm properties does melatonin have?

Answer 42

- Synchronising - Phase-shifting properties Circadian rhythm day to day regulation of biological processes By.1 month of age - 24-hr core body temperature rhythm By 2 months - nocturnal sleeping pattern By 3 months - melatonin and cortisol rhythms are established

Question 43

Outline some ways that the physiology of sleep is measured?

Answer 43

Actigraphy: - Assess sleep-wake patterns and movement disorders during sleep Polysomnography: - Includes electromyogram, electrooculogram, ECG, pulse oximeter and respiratory monitor - Assesses and diagnoses sleep disorders such as narcolepsy, sleep apnoea, REM behavioural disorder and restless legs

Question 44

Define the following terms: - Sleep latency - REM latency - Non-REM latency - Sleep efficiency - Multiple sleep latency test

Answer 44

- Time from bed to sleep onset - Time from sleep onset to first REM - Time from sleep onset to first Non-REM episode - (Time in asleep/Time in bed) x 100 - Helps assess daytime somonlence and daytime REM onset in narcolepsy

Question 45

How much sleep is NREM vs REM?

Answer 45

NREM sleep makes up 75% of sleep REM sleep makes up 25% of sleep

Question 46

Outline stages 1-4 of NREM

Answer 46

Stage 1 - 5% of sleep - Low voltage theta activity and sharp V waves - Drowsy - deny being asleep if awoken Stage 2 - 45% of sleep - Sleep spindles and K complexes Stage 3 - 12% of sleep - < 50% of delta waves Stage 4 - 13% of sleep - > 50% of delta waves Through stages 1-4 of NREM amplitude of EEG increases but frequency decreases Stages 3&4 together make up slow wave sleep - dominates initial part of sleep

Question 47

How does the physiology of NREM sleep and REM sleep compare to physiology of wakefulness

Answer 47

NREM sleep (reduced activity to wakefulness): - Increased parasympathetic activity (decreased HR, BP, cerebral blood flow) - Absent tendon reflexes - Upward ocular gaze with no/or less movements - Unable to recall dreams - night terrors is a NREM disorder - children can't recall the terror REM sleep (similar activity to wakefulness): - Increased sympathetic activity (increased HR, BP, cerebral blood flow) - Blood flow to genitals increased (active autonomic functions) - penile erections, vaginal blood flow - Increased protein synthesis - Can recall vivid dreams - nightmares occur in REM sleep - Muscle tone lost most however with some myoclonic jerks

Question 48

Describe EEG of REM sleep?

Answer 48

- Mixed frequency (slow alpha and theta) with mixed voltage - Brain activity and physiology similar to wakefulness

Question 49

When do the following EEG waves occur: a) Sleep spindles b) K complexes c) V waves

Answer 49

a) Stage 2 sleep. Symmetric runs of upper alpha/low beta frequency. Parasagittal region b) K complexes - occur when aroused from sleep. Large amplitude delta frequency waves (although sometimes generalised theta waves can follow K complex pattern - arousal burst). Throughout brain but bilateral in frontal areas mostly. Mediated by thalamocortical circuits c) V waves. Bilateral in vertex of brain. Occur in stage 1 and 2 predominantly. Occur after sleep disturbances (sometimes when semiaroused like K complexes)

Question 50

Where is the SCN located?

Answer 50

Anterior hypothalamus

Question 51

Which inputs reset the SCN?

Answer 51

- The SCN is controlled by light input - receives via melanopsin-containing retinal ganglion cells project via retinohypothalamic tract - Melatonin from pineal gland - during darkness and if delayed sleep onset or jet lag

Question 52

In addition to the SCN what other brain area is important for promoting sleep onset?

Answer 52

Ventrolateral preoptic nucleus - this inhibits ascending arousal system thus preventing arousal nuclei VLPO nucleus is inhibited by -ve feedback from monoaminergic system to allow people to wake up (i.e. ascending arousal pathways are active) Orexin neurons in the hypothalamus reinforce the arousal system

Question 53

What is the ascending reticular activating system?

Answer 53

A set of interconnected nuclei responsible for regulating wakefulness and sleep wake transitions

Question 54

Outline some neurotransmitters involved in ARAS, where they are produced and their function

Answer 54

Acetyl choline - midbrain pons nuclei - REM on neurons - i.e. induces REM sleep Noradrenaline - locus coerlus - REM off neurons - i.e. switches off/reduces REM sleep Dopamine - periaqeuductal gray matter - enhances REM sleep Serotonin - raphne nuclei - maintains arousal Histamine - tuberomammilary nucleus - maintains arousal

Question 55

Name some activation procedures used in EEG to bring up abnormal discharges?

Answer 55

- Hyperventilation - Photic stimulation (stobe) - Sleep deprivation (paroxysmal EEG discharges)

Question 56

What is EEG used for?

Answer 56

Exclude neuropsych conditions e.g. epilepsy, metabolic encephalopathy, CJD Monitoring of sleep in polysomnography

Question 57

Outline the following EEG with regards to their frequency, region predominately expressed and when may be observed: a) Delta (slow) b) Theta (slow) c) Alpha (fast) d) Sigma e) Beta (fast) f) Gamma g) Mu h) Lambda

Answer 57

a) 1-4Hx - frontal in adults/posterior in children - SWS (stages III and IV), if found when awake strongly suggests pathology b) 4-8Hz - generalised - stage I sleep (drowsy/sleeping), small amounts when awake in frontotemporal region but if a lot it strongly indicates pathology c) 8-13Hz - posterior (occipitoparietal areas) - when eyes closed and relaxing i.e meditation. Not present if anxiety or eyes open. With age its dominance over other waves down d) 12-14Hz - frontal and central - is sleep spindles occurs in stage 2 sleep (with K complexes) e) 12-30Hz - frontal and central - when busy or concentrating (awake) f) 30-100Hz - no specific areas - only for very advanced meditators g) 7-11Hz - over motor cortex (arch like wave attenuated by movement of the contralateral limb) h) Single waves - triangular shape, produced with visual scanning when awake (reading) or in light sleep

Question 58

When does the EEG show characteristic appearance of an adult

Answer 58

12-14 years EEG essentially has appearance of adult Newborns - delta and theta predominate Infants - irregular medium to high voltage delta waves Early childhood - alpha waves begin to develop in posterior regions

Question 59

When may the following changes been seen on an EEG? - Diffuse slowing of background EEG - Focal slowing - Epileptiform discharges (interictally) - Epileptiform discharges lateralised and periodic

Answer 59

- Diffuse slowing of background EEG is seen in encephalopathy - Focal slowing - a local mass lesion - oedema, haematoma or focal seizure - Epileptiform discharges inter-ictally indicate a seizure disorder (however these are rare) - in outpatient setting EEG detects 30-50% - Epileptiform discharges (lateralised and periodic) indicate acute destructive brain lesion

Question 60

What are the EEG findings in the following seizure disorders: a) Typical absence b) Atypical absence c) Focal d) Myoclonic e) Generalised tonic-clonic f) Atonic

Answer 60

a) Generalised 3Hz spike and wave b) Slow (< 2.5Hz) spike and wave c) Focal spikes d) Generalied 3-6Hz polyspike and discharge e) Fast rhythmic spikes in tonic stage vs. bursts of spikes and after slow-coming in clonic stage. Post ictal there is irregular slow activity f) Generalised spike and wave with atonia at time of slow wave

Question 61

How does EEG affect the following drugs? a) Antipsychotics b) Antidepressants c) Lithium d) Anticonvulsants

Answer 61

a) Slowing of beta, increase alpha, theta and delta b) Slowing of beta, increase alpha, theta and delta c) Slowing of alpha or paroxysmal activity d) No effect on awake EEG

Question 62

What has better spatial resolution - EEG or MEG?

Answer 62

MEG - magnetic field less obscured by scalp/skull and can detect activity to specific gyri and sulci

Question 63

What is an ERP

Answer 63

Event related potential - how change in activity links to a time-locked event (can happen after a stimulus or due to the absence of one)

Question 64

Compare and contrast early, mid and late latency ERPs

Answer 64

Early ERPs: - Evoked or brain stem evoked responses - Refer to early response to sensory info e.g. sounds, flashes, or electrical stimulation (somatosensory EP) Mid latency ERPs: - N100, P50, P200 - Occur after BAER - Habituation reduces amplitudes (habituation response or sensory gating) Late ERPs: - Cognitive pathways studied here with EEGs reflecting neuropsychological functions e.g, attention, memory - P300 and MMNs are late ERPs

Question 65

What are P300, MMN and CNV

Answer 65

Specific ERPs: - P300 is a positive late ERP that occurs when a rare target stimulus occurs with more frequent stimuli auditory "oddball" protocol - trait marker of schizophrenia. P300 is related to ongoing function of working memory - Mismatch negative (MMN) --> negative ERP between 100-200ms that occurs when an unexpected sound occurs following previous standard ones, with the ppts not actively attending to deviant stimuli - decrease in MMN amplitude is seen in Schizophrenia - Contigent negative variation - is a slow negative shift in the interval between two paired stimuli presented one after the other i.e. cue then an another stimulus that one should respond. In Schizohrenia there is a reduction in CNV in central electrodes

Question 66

Describe the role of neurotransmitters during sleep:

Answer 66

As light fades noradrenaline and sertonin are released (from locus coerlus and rapnhe nucleus) into the lateral hypothalamus - this prevents orexin release and wakefulness is not stabilised Ventrolateral preoptic nuclei and GABA then take charge and suppress all arousal neurotransmitters Melatonin is secreted at night in dark Acetylcholine - REM activating, lowest in phase 4 Dopamine, histamine, serotonin, noradrenaline - most active in phase 2 and lowest in REM

Question 67

How do stimulants affect sleep?

Answer 67

Reduce both REM and SWS (phases 3 and 4): - On cessation of stimulants (exlucding modafinil) REM rebound occurs - true for methylphenidate

Question 68

How do benzodiazepines affect sleep?

Answer 68

Reduced sleep latency Increased sleep time Reduced phase 1 Increased phase 2 sleep Reduced phase 3-4 sleep Reduced REM sleep REM rebound on cessation

Question 69

Is rTMS an emerging treatment for dystonia?

Answer 69

Yes

Question 70

What clinical neurotransmitter receptor finding has been replicated after a course ECT for depression?

Answer 70

Reduced post-synaptic beta-adrenergic receptors - Effects of ECT on serotonin are controversial

Question 71

What is Angelman's syndrome and how does the EEG alter?

Answer 71

- Severe development disorder - movement abnormalities (ataxia, temor), odd behaviour (frequent laughter), speech delays - Seizures begin 1-3 years - EEG shows by age 2 - prolonged runs of high amplitude 2-3Hz frontal activity with superimposed interictal epileptiform discharges AND occipital high amplitude 3-6Hz rhythmic activity faciliated by eye closure

Question 72

For depression where is the coil in rTMS?

Answer 72

- Left PFC (left DLPFC) - affects activity in other regions

Question 73

In a patient with a healthy sleep pattern what is the REM latency (sleep onset to first REM episode)?

Answer 73

90 minutes 4-5 sequential cycles of sleep each lasting between 90-110 minutes. As night goes on REM sleep increases and time in delta sleep decreases.

Question 74

What do benzodiazepine and barbituates do to beta activity?

Answer 74

Both benzodiazapines and barbituates show a significant increase in beta activity

Question 75

When do growth hormones levels peak during sleep?

Answer 75

Slow wave sleep - stage III and IV

Question 76

What is Kleine Levin Syndrome?

Answer 76

- Periodic attacks of hyperphagia, hypersomnia that has a predominance in males

Question 77

In neonates which phase of sleep predominates?

Answer 77

REM sleep - most neonates spend 50% of sleep time her (sleep for 16-20hrs)

Question 78

Where are CB1 and CB2 receptors located?

Answer 78

CB1 - primarily CNS CB2 - lower levels in CNS - in vascular areas and microglia Anandamide is a partial agonist - low affinity for CB1 and v low for CB2 2-AG has a high affinity for both

Question 79

Do cortical lewy bodies have a halo?

Answer 79

No - subcortical lewy bodies have a halo

Question 80

The posterior cranial fossa contains?

Answer 80

The foramen magnum, the occipital lobes, the cerebellum, the medulla and occipital bones Anterior cranial fossa - frontal lobes, lesser wing of sphenoid bone, ethmoid bone Middle cranial fossa - temporal lobes, greater wing of the sphenoid bone

Question 81

Differentiate UMN and LMN signs

Answer 81

UMN - Weakness - Upgoing plantars - Increased tone (spasticity) - Increased reflexes - Mild atrophy - Clonus LMN: - Weakness - Decreased tone - Decreased reflexes - Fasiculations - Atrophy

Question 82

Can serotonin cross the BBB

Answer 82

No! - L-tryptophan can but serotonin cannot

Question 83

Where is somatostatin produced and what does it do?

Answer 83

Hypothalamus - inhibits TSH and GH release Pancreas alongside Insulin, Glucagon, Pancreatic polypeptide Other actions: - Inhibit release of gastrin (stomach) secretin & CCK (duodenum), glucagon (pancreas)

Question 84

Cholecytokinin, Leptin and Serotonin

Answer 84

inhibit appetite Ghrelin (produced in stomach) and Neuropeptide Y stimulate appetite

Question 85

What is the central sulcus also known as?

Answer 85

Fissure of rolando

Question 86

Outline the four types of gene studies

Answer 86

Basic genetic epidemiology - estimates how much familial aggregation and heritability estimates Advanced genetic epidemiology - explores the mechanism of action of genetic risk factors Gene finding - locates the genomic location and finds the genes Molecular genetics - identifies the biological pathway from DNA Gene mapping refers to any methodology used to identify the location of a gene

Question 87

How does pairwise concordance and proband concordance vary?

Answer 87

Pairwise concordace: - Number of affected twins both with disorder / total pairs Proband concordance: - Number of affected co-twins in previously identified index cases

Question 88

How does the family study method differ to the family history method?

Answer 88

Family history method only interviews the index person - often many false negatives Family study method interviews all - more expensive but more reliable

Question 89

How does complete case ascertainment differ to multiple incomplete ascertainment?

Answer 89

Both methods of identifying cases from family studies - Complete case ascertainment identifies all cases that have occurred - Multiple incomplete ascertainment looks at consecutive referrals - some individuals may not have reached target age to develop - important to apply age correction (Weinberg short equation)

Question 90

What is recombination?

Answer 90

The process of generating new genetic codes through crossing over or synapsis of loci Crossing over is more likely to occur if loci are further apart (but on same chromosome) Loci close together are less likely to cross over The recombination frequency assess the distance between two loci by estimating the rate that crossing over occurs (0% - no crossing over i.e. vary close vs. 50% crossing over). Measured in centiMorgans

Question 91

What is a LOD score?

Answer 91

A way of assessing linkage between genes LOD = log10 (probability the recombination frequency is the observed value) > 3 high evidence of linkage < -2 no linkage

Question 92

What is linkage disequilibrium?

Answer 92

When different combinations of alleles at the loci are seen on chromosomes more often than chance Alleles close together are unlikely to cross over - therefore certain combinations without cross-over is likely - exhibit linkage disequilibrium

Question 93

What is positional cloning?

Answer 93

Studying genes due to their position on the genome rather than function

Question 94

Outline some problems with association studies?

Answer 94

Candidate genes are chosen - biased There may be association despite irrelevant genes if cases and controls are not ethnically well matched

Question 95

Outline the criteria that endophenotypes need to fulfill?

Answer 95

1. Must be associated with candidate gene or region 2. Must be present with high risk relative cosegragating with actual illness 3. Must be a parameter associated with biological plausibility 4. Must be independently assessed in a clinical state (must not be a state but trait marker) 5. Must be heritable 6. Must be present in relatives more often than the general population

Question 96

Who termed the coin epigenetics?

Answer 96

Waddington

Question 97

Do psychiatric conditions follow non-contingent gene-disorder relationships?

Answer 97

No - the majority follow contingent gene-disorder relationships i.e the relationship between gene and disorder depends on multiple other factors

Question 98

What two models exist regarding causal modelling of genetic in psychiatry

Answer 98

common disease - rare variant model: - There are various but rare mutations that cause the disease and at risk families may inherit one of them. When these variant occurs the disease occurs. Each variant is sufficient but not necessary to cause the disease common disease - common variants: - Diseases may arise from the action of many co-occurring polymorphisms. These are common but alone not sufficient to cause the disease but when together susceptibility of disorder increases - this is the philosophical underpinning of current linkage and association studies.