L15 - Biological basis of Anxiety and Depression Flashcards
What is the monoamine theory of depression?
Depression is caused by a reduction in monoamine function, particularly serotonin and noradrenaline, in the brain
What are monoamines?
Monoamines include catecholamines (dopamine, noradrenaline) and indoleamines (serotonin)
How does reserpine support the monoamine theory of depression?
Reserpine depletes monoamine transmitters by preventing their storage, causing depression in some patients
What role does serotonin play in depression?
Involved in pain sensitivity, emotional regulation and response to negative events.
Low levels of serotonin are associated with depression
What role does noradrenaline play in depression?
May be involved in depression, but evidence for its reduction in depressed patients is inconsistent
What are monoamine oxidase inhibitors?
Drugs that block the enzyme monoamine oxidase increasing levels of monoamines like serotonin and noradrenaline
What is the “cheese effect” associated with MAOIs?
MAOIs can cause dangerous increases in blood pressure when foods containing tyramine (e.g., cheese, wine) are consumed
How do reversible inhibitors of MAO-A ( Reversible inhibitors of MAO-A) improve safety)
Reversible inhibitors of MAO-A (RIMAs) reduce the risk of the cheese effect by allowing tyramine to compete for enzyme binding
How do tricyclic antidepressants work?
They block the reuptake of serotonin and noradrenaline, increasing the levels in the synaptic cleft
What are the common side effects of tricyclic antidepressants?
Hypotension
Dry mouth
Blurred vision
Sedation
Potentially fatal cardiac effects
How do SSRIs differ from tricyclics?
SSRIs selectively block serotonin reuptake with fewer side effects and lower overdoes risl
What are the side effects of SSRIs?
Nausea
Sexual dysfunction
Sleep disruption
Initial anxiety or panic attacks
What are SSNRIs (selective serotonergic/noradrenergic reuptake inhibitors)
Drugs that block the reuptake of both serotonin and noradrenaline –> offering dual-action treatment
What are the main limitations of current antidepressants?
Delay in clincal effect (4-6 weeks)
Side effects
Limited effectiveness in some patients
How do antidepressants compare to placebos?
Some studies show antidepressants aren’t significantly more effective than placebos in mild to moderate depression
What is a potential risk of antidepressants in some patients?
Increased rates of suicide in certain individuals
How does normal anxiety differ from anxiety disorders?
Normal anxiety - psychological response to stress
Anxiety disorders - excessive, irrational fear and disress
what are the main types of anxiety disorders?
Generalised anxiety disorder (GAD)
Panic disorder
Phobias (social, agoraphobia specific object, OCD and PTSD)
What brain regions are involved in the stress response?
The hypothalamus, pituitary gland and adrenal glands (HPA axis)
Modulated by the hippocampus (inhibitory) and amygdala (excitatory)
How is the septo-hippocampal system implicated in anxiety?
It involves high-density benzodiazepine binding and major serotonergic and noradrenergic inputs, playing in role in the regulation of anxiety
What types of antidepressants are used to treat anxiety disorders?
SSRIs and SSNRIs –> used at higher doses than for depression
How do benzodiazepines treat anxiety?
By enhancing GABAergic inhibition, reducing neural excitability and breaking the cycle of anxiety
Why are BZs less commonly used today?
Due to risks of dependence and sedation, and because antidepressants offer a more targeted treatment for anxiety disorders
How are stress and depression linked?
Through abnormal brain responses e.g., stress-diathesis model
What is the comorbitidy rate of depression and anxiety disorders?
50-60%
How does abnormal HPA axis function relate to depression and anxiety?
Dysregulation of the stress response system may underlie both conditions
What’s a major challenge for antidepressant drug development?
Creating drugs with faster onset action and fewer side effects
What’s the potential advantage of combining antidepressants with anxiolytics?
It may address both the emotional and physiological symptoms of comorbid conditions
What is the primary goal of treatment for depression and anxiety?
To restore normal neurotransmitter function while minimising side effects
Why is early intervention important for anxiety disorders?
To prevent maladaptive behaviours and improve long-term outcomes
How do MAOIs affect neurotransmitter levels?
MAOIs block monoamine oxidase, preventing the breakdown of monoamines like serotonin and noradrenaline, increasing their levels
How do tricylic antidperessants increase neurotransmitter levels
They block the reuptake of serotonin and noradrenaline –> prolonging their presence in the synaptic cleft
What is the mechanism of action of SSRIS?
SSRIS selectively block serotonin reuptake, increasing its avaliability in the synaptic cleft
How do reversible inhibitors of MAO-A (RIMAs) differ from traditional MAOIs?
RIMAs temporarily inhibit MAO-A and allow tyramine to compete for binding, reducing the risk of the “cheese effect.”
How might antidepressants increase suicide risk?
By increasing energy and motivation before mood improves, they may lead to increased impulsivity in some patients.
What is the role of the HPA axis in stress response?
The HPA axis coordinates the release of cortisol from the adrenal glands in response to stress.
How does the hippocampus and the amygdala influence the HPA axis?
The hippocampus inhibits the HPA axis to regulate stress responses.
The amygdala activates the HPA axis, increasing stress responses.
What role does the septo-hippocampal system play in anxiety?
It integrates noradrenergic and serotonergic inputs, modulating anxiety through GABAergic inhibition
How do benzodiazepines act on the septo-hippocampal system?
They enhance GABAergic inhibition, reducing anxiety.
What does the high comorbidity of depression and anxiety suggest about their treatment?
Treatments targeting both conditions, such as SSRIs, may be more effective.
Why is understanding comorbidity important for clinical management?
It helps clinicians address overlapping symptoms and choose appropriate treatment strategies.
