Depression & its treatment Flashcards
What are neurotransmitters:
Neurotransmitters are released from the nerve ending by a nerve impulse. They diffuse across the synapse (junction) and by interacting with post-synaptic receptors, effects the transfer of the impulse from one neuron to another
Noradrenaline
Serotonin
Basic Processes involved in neurotransmission:
- Synthesis
- Storage
- Release
- Inactivation/Reuptake
Noradrenaline Synapse:
Tyrosine (tyrosine hydroxylasae) Dopa (Aromatic amino acid decarboxylase) Dopamine (Dopamine B hydroxylase) Stored in vesicles
How can we increase noradrenaline?
We can block the reuptake
We can inhibit ezymes, meaning
We can inhibit breakdown
We can inhibit receptors also
Noradrenaline - Pathways:
Locus coeruleus noradrenergic projections
- Alertness
- Arousal
- Sensory perception
- Motor tone
Serotonin synapse:
-Tryptophan (tryptophan hydroxylase) - 5 hydroxy tryptophan (aromatic amino acid decarboxylase) - 5 hydroxy tryptamine - Vesicular monoamine transporter - Exocytosis into cleft
Serotonin pathway:
Serotonin pathways have a regulatory function in certain things:
- Sleep
- Food intake
- Thermoregulation
- Sexual behaviour
- Pain
- Motor tone
Raphe serotoninergic projections - projects throughout the CNS
Types of depression:
Unipolar:
- Major Depressive Disorder
- Dysthymia
- Seasonal Affective Disorder
- Postnatal Depression
Bipolar:
- Alternating periods of depression and mania
Characterised by duration – i.e. long term anxiety (everyone gets anxiety at some point)
Difference between mild and major depression:
In its mildest form, depression can mean being in low spirits. It doesn’t stop you leading your normal life, but makes everything harder to do and seem less worthwhile
At its most severe, major depression (clinical depression) can be life-threatening, because it can make you feel suicidal or simply give up the will to live
Brief overview of depression treatment;
CBT
Antidepressants
Exercise
ECT
Depression - Causes:
- Life Events
- Childhood Experience
- Genetics
- Chemical Imbalance
Relationship between neurotransmitter and symptoms of depression:
Emotional–>
- Loss of pleasure, interestest and motivation:
Dorso-lateral: PFC, DA
Sadness and suicide:
Ventro medial: PFC, 5HT, NE and DA
Somatic–>
- Fatigue, loss of energy:
DA, NE, 5HT
- Sleep, appetite, libido etc:
Nuceleus accumbens and hypothalamus: 5HT, NE, DA
Cognitive–>
- Attention, concentration, problem solving:
Dorso lateral: PFC, DA (D1), Ach, 5HT, NE , GABA, Histamine.
Antidepressant Drugs:
TCAs SSRIs NaRIs SNRIs MAOIs Atypical Ketamine
Psychotherapy includes:
- Talking therapy
- Cognitive Behavioural Therapy
- Counselling
Physical Interventions:
- ElectroconvulsiveTreatment
- Electromagnetic Therapy
- Deep Brain Stimulation
- Vagal Stimulation
Main problem with MAOI drugs ?
interactions with foods (and other drugs), which can be very severe
“Cheese reaction”
Dietary tyramine (found in particularly high levels in cheese and marmite) is absorbed as normal, but it is precursor for monoamine synthesis
As the MAO enzyme is inhibited —- huge rises in transmitter levels can occur when these foods are eaten
Large hypertensive response, often enough to cause haemorrhages, occurs. Very dangerous, and difficult to control patients’ protein intake levels/tyramine levels, so a major problem
Main reason MAOIs rarely used
Depression treatment time scales:
Antidepressant Drugs: 2-4 weeks
Psychotherapy- weeks, months, years
Physical Interventions: immediately
What is the mono amine hypothesis?
Depressive disorders are due to a depletion and mania to an excess provision of monoamine neurotransmitters at one or more CNS sites
Antidepressants correct this depletion by increasing the availability of monoamines at post-synaptic receptors
BUT
Effects on transmitters are immediate & antidepressant effects take several weeks to arise
Important to consider what secondary changes the altered monoamine levels have in the brain; these secondary changes may explain “antidepressant drugs” effects
Stress, Neurogenesis and Antidepressants:
Stress can reduce neurogenesis
Good evidence that AD’s can increase neurogenesis but obviously takes time to make the new neurons and to migrate to a particular part of the brain
You can label markers and track them .
SSRI’s physiology:
Serotinin acutely blocks the reuptake
Activation of receptors
Reduced serotnieric release
When you consistently block the reuptake you get a down regulation of all the receptors .
Ultimately you get restored release
