W19 Depression (Unipolar and Bipolar) Flashcards
Classifying mood disorders
What are the Affective disorders?
What are the mood disorders?
Bipolar disorders
- Bipolar l , Bipolar ll, Cyclothymia
Unipolar disorders
- Major disorders
- Dysthymic disorder
Mood/Affective Disorders
What is the definition of mood/mood disorders?
Mood - conscious state of mind or predominant emotion
-Mood disorders - psychological - abnormal elevation or lowering of mood
* Leading cause of psychiatric disability and suicide
* Mostly disorder of emotion not cognition
* Can occur with anxiety and psychosis
* Commonly involves somatic symptoms
* Difficult to categorise, diagnose and treat
Affective disorders
* Unipolar depression most common
* Prevalence of 5%, ~1 in 38 adults in the UK
-female:male - 2.5:1
-Onset 25 – 35 years
-Suicide rate 0.04 – 0.08%.
* Recurrence in >50% of patients
* Most patients treated for 6-12 months after
acute response
Sadness v depression?
Sadness - a normal human emotion usually triggered by a difficult, hurtful, challenging, or disappointing event, experience, or situation. When our emotional hurt fades, and we’ve
adjusted to our loss or disappointment, our sadness remits
Depression - an abnormal mental condition characterised by feelings of severe despondency and dejection, with feelings of inadequacy and guilt, often accompanied by lack of energy and
disturbance of appetite and sleep. It can be progressive and unremitting
What are the 2 types of depression?
more common?
features?
Reactive depression
-75%
-non-familial
-associated with stressful event
-anxiety and agitation
-temporary
Endogenous depression
-25%
-familial
-not related to external stressors
-more likely episodic, recurrent & chronic
What are the Symptoms of Depression?
Emotional and Biological components?
Emotional components
* misery
* apathy
* pessimism
* negative thoughts
* loss of self-esteem
* feelings of guilt
* feelings of inadequacy
* indecisiveness
* lack of motivation
* anhedonia- lack of pleasure
* loss of reward
* suicidal thoughts
Biological components
* retardation of thought
* slowness of action
* loss of libido
* sleep disturbance
* loss of appetite
* weight loss
* GI disturbances
Aetiology (cause) of mood disorders:
What are some causes?
- Biological vulnerability:
- genetic factors
- gender - Psychosocial stressors:
- trauma
-illness
-bereavement - Biological dysfunction in: mood circuits, connectivity, transmitter function, regulation, control
Genetic factors - Heritability
estimates
o 93% Bipolar Disorder
o 37% Major depression
o Higher for women than men
* Neurotransmitter dysfunction
o monoamines
o neuroendocrine
o neurogenesis
o glutamate
* Psychosocial/environmental factors
o Life events e.g. marriage breakdown, loss of job
o Co-morbidity e.g. chronic pain, substance abuse
Brain areas involved in mood regulation?
HP: Hippocampus - cognitive function, memory
NAc: Nucleus Accumbens -reward and aversion
Amy: Amygdala - responses to emotional stimuli
HYP: Hypothalamus - sleep, appetite, energy, sex
Monoamine systems:
VTA: Ventral Tegmental Area -Dopamine projections to other areas
DR: Dorsal Raphe nuclei -5HT (serotonin) input to other areas
LC: Locus Coeruleus -noradrenaline input to other areas
What are the functional and structural brain changes in depression? (2)
fMRI= INC amygdala activation in depression
(amygdala-responses to emotional stimuli)
MRI= reduced FC volume in depression
PET= FC metabolism in depression
*FC=Frontal cortex
What are the theories of depression? (3)
- Monoamine hypothesis
- Neurotrophic hypothesis
- Neuroendocrine hypothesis
Monoamines:
What are examples of Amino acid precursors? (2)
- Catecholamines – catechol ring (benzene 2 hydroxyl side groups)
* Dopamine - DA
Noradrenaline - NA
Adrenaline - A - Indolamine
* indole ring (six-membered benzene ring fused to a five-membered nitrogen-containing)
* Serotonin - 5HT
Catecholamines (dopamine and noradrenaline):
Synthesis?
Inactivation?
Synthesis of catecholamines:
* tyrosine
-Hydroxylation occurs and is converted to
* L-DOPA
o Decarboxylation and converts into
-Dopamine
In noradrenergic neurones (only)
o Hydroxylation and converts into
* Noradrenaline- additional step
Inactivation of catecholamines:
* Reuptake
o NET (norepinephrine transporter)- reabsorbs noradrenaline
o DAT (dopamine transporter)- reabsorbs dopamine
* Degradation
o monoamine oxidase (MAO)- in the neuron and synaptic cleft
o catechol-o-methyltransferase (COMT) - extracellularly
5-hydroxy tryptamine - 5HT:
Steps in synthesis?
Steps in inactivation?
Synthesis
* tryptophan converted into 5-HTP then 5-HT
o Hydroxylation & Decarboxylation
* 5HT
Inactivation
* Reuptake
-SERT (seratonin transporter)
- terminates action in synaptic cleft
* Degradation
-monoamine oxidase (MAO)- serotonin broken down into metabolites and eliminated
Similar to catecholamine synapse
History of monoamine theory:
What is the monoamine theory of depression?
What are some of the observations that were used as evidence?
Monoamine theory
Joseph Schildkraut 1965
- Depression - a functional deficit of 5HT and/or noradrenaline in the brain
- Mania - functional excess
- Originally from observations that:
1. reserpine depletes NA/5HT vesicular stores –
depression-like behaviour
2. isoniazid used for TB - elevated mood - blocked MAO- which breaks down 5-HT and NA
3. ECT for psychosis elevated mood – increased amine metabolites which are breakdown of neurotransmitters
*Subsequently found
4. tryptophan increased 5HT elevated mood
5. tryptophan hydroxylase blockade depresses mood
6. inhibiting NA synthesis – depresses mood/calms mania
7. tricyclic antidepressants - developed for. psychosis – elevated mood - blocked amine re-uptake
How do we treat depression?
Monoamine oxidase inhibitors:
What do MAOA and MAOB break down?
What is the cheese reaction?
- MAO (~92%) extraneuronal
- MAO (~7-8%) intraneuronal mitochondrial bound target
for antidepressant inhibitors - Preferred substrates
o MAOA: NA and 5HT (breaks down)
o MAOB: DA - Elevates monoamines in cytoplasm not vesicles
- Spontaneous leakage (into synaptic cleft) increases receptor activation ( and inc mood)
- Cheese reaction
o Tyramine (cheese etc) normally metabolized fully in gut by MAO (but this in inhibited)
o High quantities of Tyramine…….
o can cause sympathomimetic effects
-severe hypertension
What are some classes of Conventional antidepressants? (5)
- MAO inhibitors
- TCAs
- SSRIs
- SNRIs
- Atypical
