neuro: depression Flashcards
what are affective disorders?
- it is more a disorder of mood rather than thought/cognition
- most common is depression
- major cause of premature death and disability
what are the types of depression?
-unipolar depression:
- mood swings in one direction
- most common depressive illness, 75% cases are environmental and 25% are genetic
Bipolar depression:
-oscillations between depression and mania
Mania : enthusiasm, self confidence, impulsivity, irratibility
Type 1: more mania episodes, with or without depression
Type 2: hypo mania and more episodes of major depression.
-strong hereditary tendency (no genes found yet)
what are the following symptoms used to diagnose depression with?
(Points with this * are must have symptoms for the diagnoses) should be present during the same 2-week period.
- depressed mood most of the day, nearly every day (in children irritable mood) *
- diminished interest in pleasure in all or almost all activities most of the day nearly everyday *
-significant weight loss when not dieting, or increased/decreased appetite nearly eberyday - fatigue/loss of energy all day nearly everyday
- feelings of worthlessness or excessive guilt nearly everyday
-diminished ability to think or concentrate nearly everyday.
-recurrent thoughts of death , recurrent suicidal ideation without a specific plan or a suicide attempt or a specific plan for committing suicide.
what are some emotional and biological symptoms of depression?
emotional:
-low self esteem, feeling guilty
- loss of motivation
-indecisiveness
-pessimism, negativity
Biological:
- reduced activity
-loss of libido
- sleep disturbance
-loss of appetite
what is co-morbidity?
- two disorders happening in the same person at the same time
what is the major theory of depression? Suggest evidence for and against.
-the monoamine theory
-evidence for:
reduced activity of the noradrenergic and serotonergic systems
-respirine depletes the brain of NA and 5-HT which then induced depression. It can be seen in a mouse which shows depression like symptoms
- the main anti depressive drugs increase amine levels in the brain, therefore telling us that depression is related to lower monoamine levels.
Evidence against:
-plasma and cerebral spinal fluid of a depressed patient was examined, and it was difficult to suggest that there was a deficit in the brain that produces 5-HT and noradrenaline
- most antidepressant drugs take several weeks to work on the patient, if it were a case of monoamines being low then it should have worked immediately
- low serotonin levels is more linked with mania and aggression in bipolar compared to depression.
- some antidepressants are weak, there is no effect on amine uptake, no increase in 5-HT and NA however they are still antidepressants
-cocaine blocks the transporters that uptake the amines, increasing the amoiunt of 5-HT and NA, however cocaine is not an antidepressant
NEuroendocrine theory of depression?
- The next is the neuroendocrine theory and this states that there is hypersensitivity of the HPA axis with stress activating production of CRH, then ACTH from the pituitary then releasing cortisol, which is the main stress hormone. Depression makes you hypersensitive to this and the HPA is activated by minor stress, which wouldn’t normally be considered stressful. This is due to increased basal levels of cortisol for a longer period of time, so you have a reset of the threshold. Plasma levels are increased and consistently high.
-NAergic & 5-HT neurons input to hypothalamus
• Hypothalamus releases corticotropin-releasing hormone (CRH)
• CH acts on pituitary - release of adrenocorticotrophic hormone (ACTH)
• Cortisol release from adrenal cortex in response to I ACTH in blood
what parts of the brain regulate the HPA axis?
-the amygdala and the hippocampus.
- amygdala stimulated, stimulates HPA axis to release more cortisol
- when the hippocampus is activated, it inhibits the release of cortisol.
- a good balance between both is needed.
how does the HPA axis regulate itself?
-release of cortisol, cortisol will then act on the glucocorticoid receptors in the hippocampus. It will then activate on the hippocampus to inhibit the HPA. It is a negative feedback regulatory response.
how do traumatic do traumatic experiences affect glucocorticoid receptors?
- stops the development of glucocorticoid receptors, therefore they do not increase in number (as receptors increase as you get older).
-if they are lower, there will be less cortisol activation of the hippocampus. Therefore the HPA axis is no longer inhibited, still releasing cortisol which can lead to depression.
-however this is re reversible, so if serotonin increases the amount of glucocorticoid receptors can grow again.
-touching and cuddling can also increase glucocorticoid receptors. Which is why it is important to touch and cuddle your child to prevent the child from feeling neglected.
explain the neuroplasticity and neurogenesis theory of depression?
- evidence of neuronal loss and decreased neuronal activity in hippocampus and prefrontal cortex (decision making centres) which is why indecisiveness is a symptom of depression.
-antidepressants and electroconvulsive therapy promote neurogenesis in these regions - 5-HT promotes neurogenesis during development. ( BDNF) brain derived neurotrophic factor (increased neurogenesis). An increase in BDNF can be used to treat depression and decrease depressive like episodes.
- an increase in glutamate can cause depression, due to it causing excitotoxicity, causing cell death and death of neurones. (Excitoxicity caused by a big release of glutamate)
what pharmacological treatments can be used to treat depression?
- tricyclic antidepressants
- monoamine oxidase inhibitors (not used as much)
- selective serotonin reuptake inhibitors. (Recommended by NICE)
-SSRIS selectively inhibit the reuptake of serotonin in the synapse - bc they are more selective in molecules to which they bind to, they do not bind to receptors on other classes of neurones (fewer side effects)
three things to rmbr Abt antidepressants?
-all antidepressants take 3-4 weeks to display any benefits, so there is a delay
-all the antidepressants increase monoamine levels (serotonin NA)
-all these drugs can downregulate receptors on either the pre or post synaptic neurone.
explain monoamine oxidase inhibitors?
monoamine oxidase inhibitors antidepressants use the logic of the monoamine theory of depression.
Monoamine oxidase breaks down the monoamines, for reuptake
Therefore if it is inhibited it does not break the monoamine down, therefore doesn’t uptake it.
This is irreversible, so an increase of noradrenaline may start to build up (especially if you eat things like cheese which is said to increase NA levels)
-NA accumulation causes : increased headaches, intracranial haemorrhage, elevation in blood pressure, severe hypertension
what are tricyclic antidepressants?
they are called tricyclic bc they have “three cyclic shapes” in the molecule
Tricyclic antidepressants are used to increase the levels of NA and 5-HT by inhibiting the reuptake for them by blocking NA and 5-HT transporters, therefore a higher concentration in the synaptic cleft.
