Depression Flashcards
1
Q
What are the two major forms of depression?
A
- Unipolar depression: Low level mood affecting QOL, treated with antidepressants and CBT
- Dysthymia –> low level chronic depression
- Major depressive disorder –> clinical depression and atypical depression
- Bipolar depression: Recurrent cycles of mania and depression, treated with antipsychotics
- Cyclothymia –> periods of mild elation and mild depression, low level bipolar
- Bipolar disorder
2
Q
What is the ICD 10 definition of Bipolar Disorder?
A
- Disorder characterised by 2 or more ep’s in which patient’s mood and activity levels are significantly disturbed
- Disturbance consisting of:
- Elevation of mood/ activity –> hypomania and mania
- Depression of mood/ activity –> Depression
3
Q
What are the two key symptoms of depression
A
- Persistent sadness/ low mood
- Marked loss of interest and pleasure
If one or both of these key symptoms are present look for additional symptoms, need 2/3 more for the diagnosis of clinical depression
4
Q
List:
Key symptoms of depression
Other symptoms looked for
A
- Key symptoms:
- persistent sadness/ low mood
- marked loss pleasure/ interest
- Others:
- ↓ ↑ sleep/ appetite/ weight
- fatigue/ lethargy
- inability to concentrate
- indecisiveness
- feelings of guilt or worthlessness
- suicidal ideation
- decreased movement
- agitation
5
Q
What are the 3 major grades of depression
A
- mild:
- key symptoms, and few if any more symptoms above the 5 required to make diagnosis
- mild impact on functioning
- moderate:
- inbetween mild and severe
- severe:
- most if not all symptoms of depression above that of the 5 required for diagnosis
- major impact on functioning
- can occur with psychotic symptoms
6
Q
What are the diagnostic criteria for depression?
ICD 10
DSM V
A
- ICD 10 –> 2 of the key symptoms plus 4 more
- DSM V –> at least 1 of the 2 key symptoms and at least 5 or more symptoms, occurring everyday for at least 2 weeks for diagnosis of mild depression
- or occuring for more than 2 years for chronic depression
7
Q
What is the circuitry involved in depression?
A
- balance between the postive reward pathway and the negative/stress emotions produced by the amygdala
- change in volume: ↑ amygdala volume ↓ hippocampal volume
- Postive reward p/w –> VTA –> Nucleus accumbens –> prefrontal cortex (+ve emotion)
- Negative emotions –> amygdala
- Amygdala and prefrontal cortex linked via uncinate fasciculus
8
Q
What are some of the electrophysiological changes in depression?
A
- ↓ activity in prefrontal cortex and hippocampus
- ↑ activity in amygdala and hypothalamus
- ↑ hypothalmic pituitary adrenal axis –> increased cortisol and stress response
9
Q
What are 4 theories that could help explain the pathophysiology of depression?
A
- Monoamine transmitter theory –> excess of 5HT/ NA leads to mania, defecit leads to depression
- Neurohormonal theory –> overactivity of the HPA axis, excess CRH from hypothalamus leading to excess Cortisol and stress response
- Autoimmune theory –> immune dysfunction (from stress and infections) altering the inflammatory response, alters metabolism of neurones, altering neuronal circuitry.
- Circadian theory –> changes in circadian rhythm enhancing HPA axis
10
Q
What is the monoamine theory of depression?
A
- main biochemical theory based on altered concentrations of 5HT and NA
- Depression –> defecit
- Mania –> elevation
11
Q
What is the neurohormonal theory of depression?
A
- This theory ties into the monoamine theory
- The hypothalamus is responsible for the release of CRH (Corticotropin releasing hormone) which controls the release of ACTH (adrenocorticotropic hormone) –> controls release of cortisol (stress hormone).
- Altered 5HT/ NA inputs into the hypothalamus can alter the secretion of CRH from hypothalamic parvocellular neurons
- ↑ concentrations of CRH seen in brains of depressed patients, ↑ HPA axis and stress behaviour
- Also increase R expression for CRH in amygdala
12
Q
what is the autoimmune theory of depression?
What is the link between inflammation and depression?
A
- Autoimmune theory –> the idea that changes in inflammatory response (either caused by stress or infections) leads to altered neuronal activity and pathways.
- Inflammation links to depression as there is the idea that inflammatory mediators produced in the brain itself leads to:
- microglial activation
- cell dysfunction and death
13
Q
What is the circadian theory of depression?
A
- Changes in circadian pattern feed into the HPA axis, increasing stress response
14
Q
Where is serotonin mainly produced in the brain?
What are its actions?
A
- Serotonin mainly produced in the Raphe nuclei in the brainstem
- Raphe nuclei run all the way down midline of the brainstem, 5HT is cycled up to the brain, w/in brainstem and down the spinal cord
- Serotonin also produced in the ENS
- Main actions of 5HT:
- Modulate the pain pathway
- appetite, nausea, vomiting, GI function
- mood/ agitation/ anxiety/ OCD
- sexual function and insomnia
15
Q
Where is NA produced?
Where is it circulated?
What are its main actions?
A
- NA produced in nucleus coeruleus and lateral tegmental area (LTA)
- Circulates up to cerebrum and thalamus, around brainstem, down to cerebellum and spinal cord
- Main actions:
- BP and HR
- Energy homeostasis
- Muscle action
- Attention/ agitation/ depression/ emotion
- bladder function
16
Q
What is the interaction between 5HT and NA?
How does this affect release?
A
- NA and 5HT projections from brainstem to cortex run closely alongside each other and interact strongly
- interaction dependent on the expression of adrenergic R subtypes (a1 or a2) presynaptically on dendrites and the presynaptic terminal at synapse of 5HT neuron.
- Accelerator response –> release of NA and binding to alpha 1 at dendrite increases 5HT release
- Dampening response –> release of NA and binding to alpha 2 receptor on presynaptic terminal at synapse inhibits 5HT release
18
Q
What are the changes seen at the neuronal level in depression?
A
- Normally dendrites covered in many BOUTONs which are terminal club shaped projections occuring at synapses and often are a site of NT store.
- Each dendrite often covered in multiple boutons on each branch of dendrite, therefore many connections can be made in one area
- In depression there is reduced number of bouton and reduced number of arborizations of dendrites
- ↓ connections between neurons –> leads to receptor overexpression
- Defecit in synapse number and R overexpression
- this can be reversed by GF’s (BDGF) and by antidepressants
25
Q
What is the serotonin reaction?
A
- serotonin reaction is a reaction to medications that elevate 5HT (e.g. SSRI’S, MAOI’S) and symptoms can be severe:
- hyperthermia and aggression
- tremor and rigidity
- cardiovascular collapse -> tachycardia and HTN
- diarrhoea
