PBL 6 - Depression Flashcards
What are the Depression related changes in sleep?
What are the Depression related changes in sleep?
What is part of the limbic system?
- limbic lobe
- Hippocampus
- Dendate gyrus
- Amygdaloid
- Hypothalamus
- Anterior thalamus
What happens in the stress response?
• fear/anxiety
• Vigilance, avoidance behaviour
• HPA axis activation
Pro-inflammatory response
What is the Hippocampal formation ?
c shaped
• Retention of short term memory and conversion to long term declarative memory
• Long term potentiation
• Memories are believed to be located in parietal,occipital, temporal and frontal love cortex. Corpus striatum, thalamus and cerebellum
What is the amygdaloid body?
• Several nuclei situated between the anterior end of the temporal horn of the lateral ventricle and ventral surface of the lentiform nucleus
• Has a core function in the fear response and learned fear response
• Electrical stimulation causes vigilance or attention
• Ablation reduces fear and effects aggression and memory
• Sends information to:
○ Hypothalamus to produce an autonomic response
○ Periaqueductal gray matter in the brain stem for a behavioural reaction
○ Cerebral cortex for the emotional experience
What is a synapse?
• A chemical junction between two neurons
• Can be inhibitory or excitatory depending on:
○ The nature of the neurotransmitter
○ The type of post synaptic receptors
What are the steps of synaptic transmission?
• Synthesis of a neurotransmitter
○ In the synaptic terminal for small molecules- amino acid and amines
○ In the neuronal body for large molecules like neuropeptide hormones
• Release of a neurotransmitter
○ Action potential triggers calcium entry
○ Synaptic vessels merge with membrane and are expelled via exocytosis
• Interaction of a neurotransmitter with a specific receptor
• Inactivation of a neurotransmitter
○ Can be degraded in the synaptic cleft by ACE
○ Can be actively taken up by the presynaptic terminal and degraded by monoamine oxidase (MAO)
○ Inactivation prevents over excitation
What are the differences between type 1, 2 ,3 and 4 receptors?
What binds to them?
Type 1 : Ionotropic receptor
• Neurotransmitters bind to them
• Binding of an agonist causes na/ca and K to be pumped out/into the cell and change the polarisation of the cell
Type 2 : Metabotropic receptor (GPCR)
• Neurotransmitters bind to them
• Binding of an agonist causes activation of G Protein
• This causes generation of a second messenger and activation of cell signalling
Type 3:
• Binding of an agonist causes phosphorylation of tyrosines on key signalling molecules
• Causes activation of cell signalling
• Hormones bind to these
Type 4:
• Agonist enters cell via passive diffusion
• Transported to an intracellular nuclear receptor
• Activation of transcription and translation
• Used by Hormones
What does MAO do?
It degrades the Neurotransmitter inside the nerve terminal once it has be re uptaken
• It therefore determines the availability of a transmitter in a synaptic terminal
What does a reuptake transporter do? Why is it important?
- It takes up the neurotransmitter from the synapse
- It determines the time of availability of a transmitter in the synapse
- If it is blocked the neurotransmitter will be there for longer
What are the inconsistencies with the old theory of depression?
• The long onset of antidepressant effects
Some drugs with enhance monoamine neurotransmission but do not have an antidepressant action
What is the reward/Pleasure pathway?
• Dopamine is sourced from neurons located in the Ventral tegmental area
• The axons of these then release the dopamine in the nucleus accumbens in the Basal forebrain
• This is associated with pleasure and reward
• The dopaminergic neurons are under the control of Serotoninergic neurons in the midbrain raphe
• Effect of serotonin
○ Activates the VTA dopaminergic neurons
○ Enhances release of dopamine in the nucleus accumbens
○ Auto-inhibits the midbrain 5HT neurons
§ Current theory of depression and lag of antidepressant action
What is the current theory of depression?
In the normal situation:
• The serotonergic neuron is spontaneously active
• This activity is inhibited by 5HT1A auto receptors
• This is to prevent excessive firing of the neuron
In depression:
• These receptors are hypersensitive and totally inhibit the neuronal activity
• No 5HT release in VTA and N.Accumbens
After treatment:
• SSRI treatment leads to an increase in extracellular 5HT
• Leads to desensitisation of the inhibitory auto-receptors
• Leads to restoration of neuronal activity and 5HT release in VTA and N.Acc
Why is it difficult to study psychoactive drugs?
The synaptic mechanisms are complex
○ There are several co-transmitters in the same neuron
○ Complex post-synaptic and pre-synaptic interactions between transmitters
○ There are multiple receptor subtypes for a given neurotransmitter
• Multiple sites of action in the brain
Lack of adequate animal models- subjective experience is difficult to measure without communication
What neuropeptides do we know are involved in mood control?
- TRH
- Met-ENKEPHALIN
- Leu-ENKEPHALIN
- Arginine Vasopressin
- B-Endorphin
What is the evidence that 5HT1A receptors are involved in depression
Evidence
• There is an efficacy of selective 5HT1A receptor agonists (Buspirone) as an antidepressants
• Brain imaging studies show reduced density of 5HT1A receptors in the brain of depressed patients
○ Also reduced in primates
What is the theory of Inflammation in depression?
• Infection causes activation of immune cells
• Release of pro-inflammatory cytokines (IL-1b, IL-6, TNF-a)
• Sickness behaviour by the brain
○ ? If it is a direct effect
○ ? Via the vagus
○ ? Via receptors in the brain vessels
• Current suspicion of microglial cells
• Usual role of microglial cells:
○ Reuptake of neurotransmitters (especially glutamate)
○ Synaptic plasticity (memory/adaption)
○ Control of the chemical environment (including blood brain barrier)
○ Phagocytosis
○ Release of cytokines
• During chronic stress
○ Activation of microglia
• Effect of antidepressants on microglial cells
○ Suppress the cytokine effect of microglia
Possible that the true effect of antidepressants is to reduce neuroinflammation by inhibiting microglial release of cytokines
What is the effect of Depression on Cardiac health?
- Increase risk of chronic heart disease 3-4.5 fold
- Cardiac risk of major depression is comparable to smoking or lack of exercise
Why:
• reason poorly known
• Related to deficiency of 5HT1a receptors
• Effect of 5HT1a receptors in the forebrain
○ When stimulated = anxiolytic
○ When there is a deficiency = causes anxiety
• Effect of 5HT1a receptors in the medullary Raphe
○ When stimulated Inhibits cardiac sympathetic activity
○ When there is a deficiency = tachycardia/cardiac arrhythmias and hypertension
What are the physiological changes associated with sleep?
Effects of sleep:
• Reduction in sympathetic activity and increase in vagal activity
• Decrease/slowing of vital functions- metabolism, respiratory rate, heart rate, AP, body temperature
• Suppression of voluntary movements
• Changes in EEG: SWS and REM sleep
How long is approximately 1 sleep cycle?:
What is it made up of?
• ~ 90 minutes
• 80% is Slow wave sleep
20% is REM
Which brain structure is involved with turning on/off sleep?
• Interconnected groups of neurons with various specialised funcitons
• Suprachiasmatic nucleus of the hypothalamus
○ The brains biological clock
○ Can be modulated by ight via the retino-hypothalamuc tracts
○ Its output controls sleep onset and duration as well as associated bodily changes
• Pineal gland
○ Secretes melatonin
○ Suppressed by light
• Hypothalamus
○ Secretes Orexins
○ Controls arousal and apetite in the dorsal hypothalamus
Characteristics of CBT:
• Teaches clients to identify, evaluate and respond to dysfunctional thoughts and beliefs • Emphasises collaboration and active participation • Is goal oriented and problem focussed • Teaches clients to be their own therapist and aims at relapse prevention • Time limited • Sessions are structured ○ Update and check on mood ○ Bridge from previous session ○ Setting of agenda ○ Review of the homework ○ Discussion of issues , new homework ○ Final summary ○ Feedback from client • Involves homework ○ Increasing pleasure and mastery ○ Scheduling/structuring activities ○ Self-monitoring of feelingsand events ○ Manipulating behaviour via cues or consequences ○ Practising alternative behaviours ○ Increasing information ○ Will be progressive ○ Given with a rational • requires a sound therapeutic alliance ○ Bond between therapist and patient ○ Patnership ○ Confidence and trust
What are the components of the MSE?
• Appearance ○ Distinctive features ○ Clothing ○ Grooming ○ hygiene • Behaviour ○ Facial expression ○ Body language ○ Eye contact ○ Posture ○ Response to the assessment itself ○ Level of arousal ○ Rapport and social engagement ○ Ancxious or aggressive behaviour ○ Psychomotor activity and movement ○ Unusual features • Speech ○ Rate ○ Volume ○ Tonality ○ Quantity • Mood and Affect ○ Patients own words ○ Observed expression of emotion ○ Range - flat -expansive ○ Appropriateness ○ Stability or labile • Thought content ○ Delusions ○ Overvalued ideas ○ Preoccupations ○ Depressive thoughts/ruminations ○ Self harm, suicidal, aggressive or homicidal ideation ○ Obsessions ○ Anxiety- general or specific • Thought form ○ Formation and coherance of thoughts ○ Highly irrelevant comments ○ Frequent changes in topic ○ Excessive vagueness ○ Nonsense words ○ Pressured or halted speech ○ Poverty of thought or content • Perception ○ Hallucinations ○ Illusions ○ Dissociative symptoms ○ Derealisation ○ depersonalisation • Cognition ○ Level of consciousness (alert, drowsy, intoxicated) ○ Orientation to reality ○ Memory functioning ○ Literacy and arithmetic skills ○ Visuospatial processing (copying a diagram) ○ Attention and concentration ○ General knowledge ○ Language (naming objects) ○ Ability to deal with abstract concepts • Insight ○ Awareness of abnormal symptoms ○ Awareness that this is due to MH ○ Need for treatment ○ Awareness of contributing factors ie drugs • Judgement ○ Refers to problem solving ability ○ Give them a practical dilemma to see what the outcome is.
What are the typical symptoms of depression?
Mood: • low mood • Tearfulness • Irritability • Feelings of hopelessness • Helplessness
Thoughts/Cognition • Worthlessness/guilt • Burden to others • Suicidal thoughts • Indecision • Poor concentration • Complaints of memory loss
Behaviour • Withdrawal and avoidance of others • Marked loss of interest, motivation • Dispropotionate diability • Disproportionate physical symptoms • Signs of depression: appearance and reactions
Biological symptoms • Weight change • Appetite change • Sleep patterns • Fatigue • Physical complaints- pain
