NEURO 2 - mental health

Question 1

Types of depression

Answer 1

Unipolar

Bipolar

Question 2

Bipolar depression

Answer 2

Oscillation between depression and mania
Type I = increase mania episodes with/without depression
Type II = Hypomania – episodes of major depression
Strong hereditary tendency

Question 3

Mania

Answer 3

Excessive exuberance, enthusiasm, self-confidence, impulsive actions, aggression

Question 4

Unipolar depression

Answer 4

Mood swings in 1 direction
Most common depressive illness
75% cases reactive – induced by environment
25% endogenous – genetic

Question 5

Emotional symptoms of depression

Answer 5

Apathy, pessimism, negativity
low self-esteem, feeling guilty
low motivation
Indecisiveness

Question 6

Biological symptoms of depression

Answer 6

decreased activity
decreased libido
Sleep disturbance
decreased appetite

Question 7

Monoamine theory

Answer 7

Decrease activity of NA/5HT systems
Reserpine deplete NA and 5HT from brain
Decrease monoamines = decrease activity of noradrenergic system = increase post synaptic receptors - block reuptake = [NA+] plasme increase in depressed patients = increase anxiety and sympathetic activity

Question 8

Neuroendocrine theory

Answer 8

If HP axis sensitive - in depressed people
Noradrenergic & 5HT neurones input to hypothalamus = release CRH to pituitary = release ACTH - cortisol released from adrenal cortex

Question 9

Evidence for neurorendocrine theory

Answer 9

CRH mimics depression symptoms

Increased [cortisol] in plasma and saliva and increase [CRH] in CSH

Question 10

Neuroplasticity and neurogenesis theory

Answer 10

Neuronal loss of hippocampus and pre-frontal cortex (decision making)
Antidepressents and ECT promote neurogenesis in regions
5HT promote neurogenesis during development.

Question 11

Increased glutamate and neurogenesis

Answer 11

Lead to neuronal loss and depressison
Lots bind to NMDA = excitoxicity
Prevent with ketamine

Question 12

Psychological treatments

Answer 12

Cognitive behavioural therapy

Interpersonal therapy

Question 13

Cognitive behavioural therapy

Answer 13

helping depressed individuals recognise and change their negative cognitive processes and improve their mood and their counterproductive behaviours

Question 14

Interpersonal therapy

Answer 14

assumes depression is multi-factorial but that interpersonal difficulties play a central role in maintain depressive symptoms

Question 15

MAOIs - monoamine inhibitors mechanism

Answer 15

Increase [NA/5HT] cytoplasm - Increase [NA/5HT] cytoplasm leakage of amine - increase [NA/5HT] in synaptic cleft
MAOA break down 5HT more than NA
MAOI = Increase 5HT >NA > DA
Increase NA = Increase euphoria = increase motor activity
Inhibition of MAO A correlate with AD activity

Question 16

Early drug examples of MAOIs

Answer 16

Phenelzine and isocarboxazid

Irreversible and non-selective inhibitors of MAO - down regulate post synaptic and pre-synaptic receptors

Question 17

Problems with MAOI

Food and drug interactions

Answer 17

Tyramine in cheese and wine - indirect sympathomimentic - increase NA release - excess NA destroyed by MAO - if blocked NA accumulate

Question 18

What happens if there is an accumulation of NA

Answer 18

Headache, intercranial haemorrhage leading to elevation in BP leading to severe hypertension

Question 19

Reversible MAOI

counter the cheese and wine effect

Answer 19

Moclobemide
Accumulation of NA displaced RIMA allowing degradation of excess NA
RIMA safer and selective RIMA better tolerated

Question 20

Tricyclic antidepressants TCAs examples

Answer 20

AMITRIPTYLLINE
IMIPRAMINE
IOFEBRAMINE

Question 21

TCA therapeutic effects

Answer 21

NA and 5HT reuptake inhibitor - increase [NA] and [5HT] in synaptic cleft

Question 22

SSRI examples

Answer 22

FLUOXETINE
PAROXETINE
CITALOPRAM
ESCITALOPRAM

Question 23

SSRI therapeutic effects

Answer 23

5HT reuptake inhibitor
Increase [5HT] down regulation of 5HT1A/D autoreceptors, disinhibit 5HT neuron, increase 5HT release
Increase 5HT release = down regulate post synaptic 5HT receptors

Question 24

Side effects of SSRI

Answer 24

5HT2 - insomnia, sexual dysfunction
5HT3 - Nausea, GI distress, headache, diarrhoea
May be associated with increase violence - 5HT3
Could overdose - serotonin syndrome

Question 25

Serotonin syndrome

Answer 25

Surge in serotonin | Seizures, tremors, hyperthermia, CV collapse

Question 26

Bipolar depression treatment

Answer 26

Lithium - mood stabiliser Li+ in neuron depolarises - and inhibit enzymes invovled in signal transduction Narrow therapeutic window - too little = no effect. Too high = toxicity Side effects = drowsiness, confusion, seizures, coma, hypothyroidism

Question 27

Ion channel blockers for bipolar disorders

Answer 27

Valproate and gabapentin | Valproate can lead to liver damage

Question 28

Physiological symptoms of anxiety

Answer 28

Tachycardia, shortness of breath, excessive sweating, headache and dizziness, nausea, fatigue

Question 29

Alcohol and drugs effect on anxiety

Answer 29

Increase GABAergic neurotransmission - block glutamatergic neurotransmission Balance between GABA and glutamate crucial for optimal brain function - alcohol disrupts balance Brain adapts - counter imbalance - decrease levels of GABA and increase glutamate - trigger anxiety

Question 30

Amygdala and anxiety

Answer 30

Role in emotion and fear response Stimulate HPA - promote cortisol release Hyperactivity linked to anxiety disorder

Question 31

Hippocampus and anxiety

Answer 31

Role in learning and memory Suppress HPA Underactivity = anxiety

Question 32

Specific phobias

Answer 32

extreme fears/anxieties provoked by exposure to a particular situation or object – often lead to avoidance behaviour – Phobia object or situation provokes immediate fear or anxiety

Question 33

Social phobias

Answer 33

significant anxiety provoked by exposure to certain types of social or performance situations – Social situations provoke immediate fear/anxiety

Question 34

Panic disorder

Answer 34

recurring panic attacks without seemingly clear cause or trigger An abrupt surge of intense fear/discomfort – peak within minutes Includes increased HR, sweating, trembling, shortness of breath and fear of dying

Question 35

Obsessive compulsive disorder

Answer 35

characterised by compulsive ritualistic behaviour driven by irrational anxiety – time consuming Obsessions – recurrent intrusive thoughts, images, ideas, or impulses Compulsions – repetitive behaviours or mental acts performed to decrease anxiety associated with obsession

Question 36

PTSD

Answer 36

Distress triggered by the recall of past traumatic experiences Include recurrent intrusive memories, nightmares, dissociative reactions, and psychological and physiological distress at exposure to cues

Question 37

Benzodiazepines

Answer 37

Bind to distinct regulatory site on GABAA receptors – stabilise the GABAA receptor binding site for GABA – Positive allosteric modulators Increase GABA affinity for its binding site and produce a general enhancement of its neuroinhibitory actions Suppress symtoms of anxiety

Question 38

Tolerance to benzodiazepines

Answer 38

Additional glutamate receptors to cell membrane - restore initial imbalance Need higher dose

Question 39

Withdrawal to benozodiazepines

Answer 39

Sudden decrease in inhibitor GABA neurotransmission and increase excitatory glutamate neurotransmission Lead to increase anziety and other side effects

Question 40

Busprione - 5HT1A receptor aganoist

Answer 40

Activates 5HT1A autoreceptors - inhibit 5HT release and activation of noradrenergic neurons - decrease arousal reactions

Question 41

Busprione mechanism

Answer 41

Induce desensitisation of auto inhibitory 5HT1A receptors - lead to down regulate 5HT1A receptors Desensitisation lead to heightened excitation of serotonergic neurons and increase 5HT release Suppress symptom of anxiety in GAD

Question 42

beta noradrenergic receptor antagonist - propranolol

Answer 42

Non-selective between beta 1 and 2 noradrenergic receptors - decrease some of peripheral manifestations of anxiety tachycardia, sweating, tremor, GI problems

Question 43

Positive symptoms of SCZ

Answer 43

Hallucinations Delusions Disorganised thought/speeech Movement disorders

Question 44

Negative symptoms of SCZ

Answer 44

``` Social withdrawal Anhedonia Lack motivation Poverty of speech Emotional flatness ```

Question 45

Cognitive symptoms of SCZ

Answer 45

Impaired working memory Impaired attention Impaired comprehension

Question 46

Hallucinations

Answer 46

Perceptions experienced without stimulus - commonly auditory

Question 47

Delusions

Answer 47

Fixed/unshakeable belief | Not consistent with social norms. Often paranoid or persecutory

Question 48

Motor, volitional, and behavioural disorders

Answer 48

Peculiar forms of motility, stupor, mutism, stereotypy Stereotypies - repetitive acts - tics Bizzare postures - strange mannerisms - altered facial expression Bouts of hyperactivity - destructiveness

Question 49

Formal thought disorder

Answer 49

Conceptual thinking reflected in speech that is difficult to understand - rapid shift in topics Disturbance in thinking - derailment of speech. Fail to follow through to conclusions

Question 50

Phases of SCZ

Answer 50

1. Prodrome - late teens/early 20s - can be triggered by stress 2. Active/acute phase - onset of + symptoms - difficulty differentiating real and fake 3. Remission - treatment to normal 4. Relapse

Question 51

Nigrostriatal pathway - Dopaminergic neurons project from:

Answer 51

Dopaminergic neurons from: | Substantia nigra to the striatum - movement

Question 52

Mesolimbic pathway - | Dopaminergic neurons project from:

Answer 52

VTA to nucleus accumbens and to the amygdala and hippocampus - reward

Question 53

Mesocortical pathway - | Dopaminergic neurons project from:

Answer 53

VTA to frontal cortex - cognition and motivation

Question 54

Hypophyseal pathway - Dopaminergic neuron project from:

Answer 54

Dopamine to hypothalamus to anterior pituitary and on D2 receptors = release prolactin

Question 55

Dopamine hypothesis

Answer 55

Hyperactivity mesolimbic pathway - + symptoms - hallucinations and illusions Mesocortical pathway - VTA to frontal cortex - hypoactivity associated with decrease cognitive symptom - loss memory

Question 56

Evidence for dopamine hypothesis

Answer 56

Amphetamine increase dopamine in mesolimbic pathway - psychotic episodes. Dopamine activate D2 receptors - block D2 = antipsychotic effect Reserpine deplete monoamine - antipsychotic effect

Question 57

Brain structure differences in SCZ

Answer 57

Brain slightly smaller - decrease grey matter | Enlarged lateral ventricles - smaller hippocampus

Question 58

Hypofrontality SCZ

Answer 58

Decrease blood flow to frontal cortex - decrease activity in frontal cortex - affect decision making

Question 59

NMDA receptor hypofunction

Answer 59

Antagonists Decrease [glutamate] and glutamate receptors in prefrontal cortex - stereotyped behaviour and decrease social interaction

Question 60

Serotonin evidence of SCZ

Answer 60

LSD partial agonist 5HT receptors Overstimulation of mesolimbic D2 receptors - hypoactivity of frontal cortical D1 receptors - decrease prefrontal glutaminergic activity

Question 61

Treatment for SCZ

Answer 61

Suppress hyperactivity of DA neurons - block D2 receptors - but D2 in striatum = decrease movement - side effects like parkinson's

Question 62

Typical antipsychotics

Answer 62

1st generation Antagonise D2 Motor impairment

Question 63

Atypical antipsychotics

Answer 63

2nd generation Antagonise D2 and 5HT2A receptors Limit side effects from typical antipsychotics

Question 64

Anticholinergic effects of antipsychotics

Answer 64

Antagonise mAChR Blockade of mAChRs at NMJ - alleviate EPSE - but thought to impact cognition Unblocked = parasympathetic reactions. Blocked = sympathetic reactions Salivary secretion - dry mouth Pupillary muscles - blurred vision Smooth muscle contraction - constipation and urinary retention