NEURO 2 - mental health Flashcards
Types of depression
Unipolar
Bipolar
Bipolar depression
Oscillation between depression and mania
Type I = increase mania episodes with/without depression
Type II = Hypomania – episodes of major depression
Strong hereditary tendency
Mania
Excessive exuberance, enthusiasm, self-confidence, impulsive actions, aggression
Unipolar depression
Mood swings in 1 direction
Most common depressive illness
75% cases reactive – induced by environment
25% endogenous – genetic
Emotional symptoms of depression
Apathy, pessimism, negativity
low self-esteem, feeling guilty
low motivation
Indecisiveness
Biological symptoms of depression
decreased activity
decreased libido
Sleep disturbance
decreased appetite
Monoamine theory
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
Neuroendocrine theory
If HP axis sensitive - in depressed people
Noradrenergic & 5HT neurones input to hypothalamus = release CRH to pituitary = release ACTH - cortisol released from adrenal cortex
Evidence for neurorendocrine theory
CRH mimics depression symptoms
Increased [cortisol] in plasma and saliva and increase [CRH] in CSH
Neuroplasticity and neurogenesis theory
Neuronal loss of hippocampus and pre-frontal cortex (decision making)
Antidepressents and ECT promote neurogenesis in regions
5HT promote neurogenesis during development.
Increased glutamate and neurogenesis
Lead to neuronal loss and depressison
Lots bind to NMDA = excitoxicity
Prevent with ketamine
Psychological treatments
Cognitive behavioural therapy
Interpersonal therapy
Cognitive behavioural therapy
helping depressed individuals recognise and change their negative cognitive processes and improve their mood and their counterproductive behaviours
Interpersonal therapy
assumes depression is multi-factorial but that interpersonal difficulties play a central role in maintain depressive symptoms
MAOIs - monoamine inhibitors mechanism
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
Early drug examples of MAOIs
Phenelzine and isocarboxazid
Irreversible and non-selective inhibitors of MAO - down regulate post synaptic and pre-synaptic receptors
Problems with MAOI
Food and drug interactions
Tyramine in cheese and wine - indirect sympathomimentic - increase NA release - excess NA destroyed by MAO - if blocked NA accumulate
What happens if there is an accumulation of NA
Headache, intercranial haemorrhage leading to elevation in BP leading to severe hypertension
Reversible MAOI
counter the cheese and wine effect
Moclobemide
Accumulation of NA displaced RIMA allowing degradation of excess NA
RIMA safer and selective RIMA better tolerated
Tricyclic antidepressants TCAs examples
AMITRIPTYLLINE
IMIPRAMINE
IOFEBRAMINE
TCA therapeutic effects
NA and 5HT reuptake inhibitor - increase [NA] and [5HT] in synaptic cleft
SSRI examples
FLUOXETINE
PAROXETINE
CITALOPRAM
ESCITALOPRAM
SSRI therapeutic effects
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
Side effects of SSRI
5HT2 - insomnia, sexual dysfunction
5HT3 - Nausea, GI distress, headache, diarrhoea
May be associated with increase violence - 5HT3
Could overdose - serotonin syndrome
Serotonin syndrome
Surge in serotonin
Seizures, tremors, hyperthermia, CV collapse
Bipolar depression treatment
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
Ion channel blockers for bipolar disorders
Valproate and gabapentin
Valproate can lead to liver damage
Physiological symptoms of anxiety
Tachycardia, shortness of breath, excessive sweating, headache and dizziness, nausea, fatigue
Alcohol and drugs effect on anxiety
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
Amygdala and anxiety
Role in emotion and fear response
Stimulate HPA - promote cortisol release
Hyperactivity linked to anxiety disorder
Hippocampus and anxiety
Role in learning and memory
Suppress HPA
Underactivity = anxiety
Specific phobias
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
Social phobias
significant anxiety provoked by exposure to certain types of social or performance situations – Social situations provoke immediate fear/anxiety
Panic disorder
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
Obsessive compulsive disorder
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
PTSD
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
Benzodiazepines
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
Tolerance to benzodiazepines
Additional glutamate receptors to cell membrane - restore initial imbalance
Need higher dose
Withdrawal to benozodiazepines
Sudden decrease in inhibitor GABA neurotransmission and increase excitatory glutamate neurotransmission
Lead to increase anziety and other side effects
Busprione - 5HT1A receptor aganoist
Activates 5HT1A autoreceptors - inhibit 5HT release and activation of noradrenergic neurons - decrease arousal reactions
Busprione mechanism
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
beta noradrenergic receptor antagonist - propranolol
Non-selective between beta 1 and 2 noradrenergic receptors - decrease some of peripheral manifestations of anxiety
tachycardia, sweating, tremor, GI problems
Positive symptoms of SCZ
Hallucinations
Delusions
Disorganised thought/speeech
Movement disorders
Negative symptoms of SCZ
Social withdrawal Anhedonia Lack motivation Poverty of speech Emotional flatness
Cognitive symptoms of SCZ
Impaired working memory
Impaired attention
Impaired comprehension
Hallucinations
Perceptions experienced without stimulus - commonly auditory
Delusions
Fixed/unshakeable belief
Not consistent with social norms. Often paranoid or persecutory
Motor, volitional, and behavioural disorders
Peculiar forms of motility, stupor, mutism, stereotypy
Stereotypies - repetitive acts - tics
Bizzare postures - strange mannerisms - altered facial expression
Bouts of hyperactivity - destructiveness
Formal thought disorder
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
Phases of SCZ
- Prodrome - late teens/early 20s - can be triggered by stress
- Active/acute phase - onset of + symptoms - difficulty differentiating real and fake
- Remission - treatment to normal
- Relapse
Nigrostriatal pathway - Dopaminergic neurons project from:
Dopaminergic neurons from:
Substantia nigra to the striatum - movement
Mesolimbic pathway -
Dopaminergic neurons project from:
VTA to nucleus accumbens and to the amygdala and hippocampus - reward
Mesocortical pathway -
Dopaminergic neurons project from:
VTA to frontal cortex - cognition and motivation
Hypophyseal pathway - Dopaminergic neuron project from:
Dopamine to hypothalamus to anterior pituitary and on D2 receptors = release prolactin
Dopamine hypothesis
Hyperactivity mesolimbic pathway - + symptoms - hallucinations and illusions
Mesocortical pathway - VTA to frontal cortex - hypoactivity associated with decrease cognitive symptom - loss memory
Evidence for dopamine hypothesis
Amphetamine increase dopamine in mesolimbic pathway - psychotic episodes.
Dopamine activate D2 receptors - block D2 = antipsychotic effect
Reserpine deplete monoamine - antipsychotic effect
Brain structure differences in SCZ
Brain slightly smaller - decrease grey matter
Enlarged lateral ventricles - smaller hippocampus
Hypofrontality SCZ
Decrease blood flow to frontal cortex - decrease activity in frontal cortex - affect decision making
NMDA receptor hypofunction
Antagonists
Decrease [glutamate] and glutamate receptors in prefrontal cortex - stereotyped behaviour and decrease social interaction
Serotonin evidence of SCZ
LSD partial agonist 5HT receptors
Overstimulation of mesolimbic D2 receptors - hypoactivity of frontal cortical D1 receptors - decrease prefrontal glutaminergic activity
Treatment for SCZ
Suppress hyperactivity of DA neurons - block D2 receptors - but D2 in striatum = decrease movement - side effects like parkinson’s
Typical antipsychotics
1st generation
Antagonise D2
Motor impairment
Atypical antipsychotics
2nd generation
Antagonise D2 and 5HT2A receptors
Limit side effects from typical antipsychotics
Anticholinergic effects of antipsychotics
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
