week 10 part 2 Flashcards
What does dysfunction of specific areas in the brain give rise to?
Neurobiological and behavioural changes
Definition of a mental disorder?
A psychological disorder characterised by elevation or lowering of a person’s mood
What are examples of mental disorder?
- Major depression
- Bipolar disorder
- Panic/Anxiety disorder
- Eating disorder
- Schizophrenia
According to WHO-2019, what is depression characterised for?
low mood for a constitutive period of mood more than 2 weeks
What is depression?
Leading cause of ill health and disability worldwide
What is lifetime risk for major depression?
15% of the population (varies on country)
Who suffers from depression once in your life?
1 in every 10 will suffer from depression
What is the incidence of depression?
women: 10-25% in women
Men: 5-10%
men are 3X as likely to take their own lives than wimen
what are the symptoms of major depression?-
Atleast 2 weeks if:
- Depressed mood
- Rumination
- Feelings of worthlessness
- Anhedonia - decreased ability to experience pleasure of normal activity
- Diminished ability to think or concentrate
- Weight gain or weight loss (>5% change in a month)
- Insomnia or hypersomnia
- Fatigue
- Thoughts of dead and suicide
What are examples of severe and chronic life stressors?
- Death of relative/Divorce
- Loss of social status
- Chronic illness
- Poverty
- Illness
- Hormonal upheaval
What are the leading cause of major depression?
- Severe and chronic life stressors
- Certain medications/drugs - drugs for diabetes/cancer
- Genetic vulnerability
What was the treatment for depression?
'’Shock’’ therapy
What is shock therapy?
- treatment of chronic mental conditions by electroconvulsive therapy or by inducing physiological shock
- ECT invented in italy in 1930
- ECT works by using electricity to induce seizures
What did psychiatrist discover?
Inducing seizures could relieve symptoms of mental illness
What was ECT used as?
Treatment for homosexuality
- No evidence it did alter anyone’s sexuality
What is the world’s first antidepressant?
Iproniazid
What does Iproniazid have?
Antimicrobial effects: Orginally developed for the treatment as an antimicrobial therapy for people suffering from tuberculosis
Why does Iproniazid have?
- Historic value
2. Helped establish the relationship between psychiatric disorders and the metabolism of neurotransmitters
What was Iproniazid?
Monoamine oxidase inhibitory
when did pharmacological characterisation of drugs start?
The modern era of the pharmacologic treatment of psychiatric disorders
Where did monoamine hypothesis originate from?
Early clinical observations
What was other compounds used to treat depression originally been designed to treat?
Parkinson’s or TB
for non-psychiatric conditions (Parkinson’s)
What did the compounds do?
Enhance concentration of central serotonin or norepinephrine transmission
What was the monoamine hypothesis of depression?
Depression is caused by the imbalance or deficiency of monoamine neurotransmitters”
- Dopamine
- Serotonin
- Norepinephrine
What does the imbalance of monoamine neurotransmitter explain?
Different symptoms of depression
What is the hypothesized pathophysiology appear to be supported by?
the mechanism of action of antidepressants: agents that elevate the levels of these neurotransmitters in the brain have all been shown to be effective in the alleviation of depressive symptoms
What are antidepressant responses?
Transiently reversed, with the results being dependent on the class of antidepressants
What is there a large diversity of?
Neurotransmitters in the brain
What are neurotransmitters?
Abundant and associated with many different brain areas
some are associated with specific neural networks
What does 3 neurotransmitters send projection to?
Rest of the brain - reaches cortex and limbic system and therefore explains mood changes and motivation changes seen in depression
What is Iproniazid?
An inhibitor of monoamine oxidase a and b molecules
a and b are in the presynaptic space
What is monoamine oxidase?
Enzymes involved in the breakdown of bioamines: dopamine, serotonin, norepinephrine
contributes to recycling of neurotransmitter
What does recycling of neurotransmitter contribute to?
Production of more molecules of these neurotransmissions
What does inhibition of monoamine oxidase results in?
Increased levels of bioamines and increase MOOD
What does serotonin imbalance cause?
mood differences in depression
What are the modern antidepressants?
Selective serotonin reuptake inhibitors (SSRI) - 40 years old
What is the most prescribed antidepressant, well known SSRI?
Prozac
What is the mechanism of action SSRI?
- Blocks serotonin re-uptake transporters
2. Decreased uptake of serotonin
what has antidepressant allowed?
Revolutionised mental health care
What doesn’t depression improve?
cellular and molecular characteristic of mood/health outcomes
What does SSRI allow?
Deinstitutionalisation
What has discoveries of drugs allowed patients to be?
Dehospitalised
What gives clues about cause?
- Brain imaging
2. Postmortem studies
What are the affected brain areas?
- Frontal cortex - cognition, attention procesisng
- Hippocampus - working memory, cogntive function
- Amygdala - fear, anxiety, aggression
- Hypothalamus - sleep, apetite, sexual desire
- Thalamus - processing of thoughts, movement
- Stratium - Reward
What does these affected brain areas have?
Changes in size or activity in depressed patients
How long does it take for antidepressant effect to take place?
3-4 weeks
What is the possible explanation for why there is a disconnect between onset of treatment and onset of resolution of treatment?
- • Acute increases in the amount of synaptic monoamines induced by antidepressants produce secondary neuroplasticity effects:
- • function on a longer timescale
- • involve transcriptional and translational changes -EPIGENETIC
- • SSRI mediate molecular and cellular plasticity
What do you use to study depression?
- Human genetics
- Scan of human brain
- Postmortem brain and animal model
What suggested the plasticity and neurogenesis hypothesis?
- Genetics
- Environment
- Neurotrophic processes
What are trophic factors?
• Signal molecules to allow neurons first to migrate to destiny of fate, they contribute to maintenance and survival of neuron – one neuron attaches to another neurons and exchange NTF and keep eachother healthy
What are signal factors called?
NGF
What are examples of neurotrophic factors or NTF?
- NGF
- Neurotrophins (NT-3,4,5)
- BDNF
- CNTF
- Ephrins
What is the plasticity and neurogenesis hypothesis?
- Decrease in the volume of hippocampus and other forebrain regions observed in subsets of depressed patients
- Also in post mortem theres a reduction of formation of synapse in hippocampus
What is plasticity?
Changes and formation of synapses
What is adult neurogenesis?
Proliferation
What lead to depression hypothesis?
the findings of damage to hippocampus
What is depression caused by?
Decreases in neurotrophic factors
Neurotrophic factors
neurodevelopmentally expressed growth factors that promote neuronal survival and regulate plasticity within adult brain → in hippocampus
What is hippocampus in depressed patient?
Atrophy
What does precursors in the basal subgranular zone give?
Rise to postmitotic neuroblasts
Where does neuroblasts translocate to?
Apical zones
What does neuroblasts differentiate?
Produce dendrites and axons
What is decreased in depression?
Neurogenesis
What increases adult hippocampal neurogensis?
Chronic antidepressant treatment
What is neurogenesis associated with?
Plasticity of the brain
What does reduced neurogenesis in depression involve?
Trophic factors
What does stress reduce?
BDNF signalling in the hippocampus
What is consequences of reduced BDNF signalling in the hippocampus?
Reduced proliferation and plasticity in hippocampus
Reduced hippocampal formation
What is Antidepressant therapy?
- Antidepressant increases BDNF signalling
- Neural progenitors in the hippocampus divide mitotically to form new neurons that differentiate
- Hippocampal circuitry and output increases
What does BDNF lead to?
- loss of plasticity
What is BDNF polymorphism associated with?
short-term episodic memory impairment and mood disorder and schizophrenia
What does stress reduce ?
BDNF
What is the effect of antidepressant on neurogenesis?
- Antidepressant growth factors
- Adult hippocampal neurogenesis
- Hippocampal circuitry
- Output: amygdala, stratium, prefrontal cortex
