Neuro: Depression Flashcards
How do genetics and the environment affect behaviour?
- The brain is a product of our genetics
- The environment can interact with the genetics of our brain which can affect brain function and as a result behaviour
Depression is a type of affective disorder. What is an affective disorder?
- They are disorders of mood rather than thought or cognition
- Depression is most common affective disorder
What are the 2 main types of depression?
- Unipolar depression
- Bipolar depression
What are some of the characteristics of unipolar depression?
- Mood swings in one direction
- Most common type of depression
- Environmental factors induce this type of depression more than genetic factors
What are some of the characteristics of bipolar depression?
- Switching between depression and mania
- Mania - state of enhanced emotions. E.g. excessive self-confidence/enthusiasm as well as excesive aggression/irritability
- Less common than unipolar depression
- Much higher genetic contribution compared to bipolar depression
What is the difference between a depressive disorder and a major depressive disorder?
- A depressive disorder a low state marked by significant levels of sadness, lack of energy and self-worth
- A major depressive disorder is a severe pattern of all the characteristics of a depressive disorder and is disabling
How is depression diagnosed?
- The diagnosis for depression is based on a person having the following symptoms in the same 2 week period:
- Depressed mood - most of the day, everyday
- Greatly reduced interest/pleasure in most activities
- Signifcant weight loss (when not dieting) or weight gain
- Insomnia or hypersomnia
- Loss of energy
- Recurring thoughts of death
- One of these symptoms has to be depressed mood or loss of interest/pleasure
What are the 2 categories of symptoms of depression? For each type name a few examples
- Emotional symptoms
- Loss of motivation
- Low self esteem
- Pessimism/negativity
- Biological symptoms
- Reduced activity
- Loss of libido
- Loss of appetite
Depression is often found co-morbid (occuring with) other psychiatric and non-psychiatric disorders. Name of the disorders that often occur with depression
- Terminal illness - e.g. cancer
- Chronic pain
- Drug abuse
- Parkinson’s disease
- Anxiety
Explain the monoamine theory of depression
- Theory states that depression is caused by low levels of monoamine synaptic transmission within the brain
- Specifically low levels of Noradrenaline and Serotonin (5-HT)
What pieces of evidence are there that support the monoamine theory of depression?
- Resperine causes depletion of Noradrenaline and Sertonin stores in the brain by preventing uptake into vesicles - this eventually leds to it all leaking out into synaptic cleft
- Depression is induced in mice which are injected with reserpine
- Also, all major antidepressant drugs increase noradrenaline and/or serotonin levels in the brain
What pieces of evidence go against the monoamine theory of depression?
- Samples of Cerebrospinal fluid (CSF) and blood taken from people with depression has shown levels of NA and 5-HT to be normal - levels should be low based on monoamine theory
- Low serotonin levels more linked with increased aggression rather than depression
- Most antidepressant drugs take weeks to induce therapeutic effects - based on monoamine theory therapeutic effects should occur staright away as increase in NA and 5-HT due to antidepressants occurs straight away
Explain the neuroendocrine theory of depression
Theory states that depression is caused by hyperactivity of the HPA-axis
- Not-normally stressful stimuli will cause almost constant activation of the Noradrenergic and Serotonergic neurons in the hypothalamus
- This causes hypothalamus to release Corticotrophin-releasing hormone (CRH) into hypophyseal-portal circulation where it’ll bind to receptors on corticotroph cells on anterior pituitary
- This will cause corticotroph cells to secrete Adrenocorticotropic hormone (ACTH) into circulation
- ACTH will bind to receptors on adrenal glands leading to secretion of cortisol
- Because HPA-axis is hyperactivated cortisol levels will remain very high in the blood for an extended period of time
- This leads to symptoms of depression
What two brain areas input into the HPA-axis and what effect do they have on the HPA-axis?
- Amygdala - Activates HPA-axis
- Hippocampus - Inhibits HPA-axis
Apart from producing negative feedback on the hypothalamus and anterior pituitary, how else does cortisol prevent its own release?
- Cortisol binds to glucocorticoid receptors on hippocampus causing activation of hippocampus
- Actiavtion of hippocampus will cause the inhibition of the HPA-axis
- Inhibition of the HPA-axis will result in cortisol not being secreted
Apart from hyperactivation of the HPA-axis, how else can high cortisol levels (and therefore symptoms of depression) be induced? Explain why this is the case?
- High cortisol levels can be caused by inability of hippocampus to inhibit HPA-axis
- This can be caused by decreased glucocorticoid receptor expression on hippocampus
- Less glucocorticoid receptors mean cortisol isn’t able to bind to hippocampus and cause it to activate
- Lower activation of hippocampus means less inhibition of HPA-axis which means HPA-axis can work to produce lots of cortisol
- High cortisol levels lead to symptoms of depression
How does trauma lead to depressive symptoms/depression?
- Stress caused by a traumatic experience leads to epigenetic modulation of the gluccorticoid receptor gene
- Epigenetic modulation leads to less expression of the gene which leads to production of less glucocorticoid receptors on hippocampus
- This means cortisol less able to bind and activate hippocampus so in turn there’s less inhibition of HPA-axis
- This leads to higher cortisol levels and as a result depressive symptoms
How does tactile stimulation in a newborn lead to increased glucocorticoid receptors in hippocampus?
- Tactile stimulation leads to activation of 5-HT pathways to hippocampus
- 5-HT release in hipocampus triggers long-lasting expression of glucocorticord receptor gene
- This leads to increased production of glucocorticoid receptors in hippocampus
Explain the neuroplasticity/neurogeneis theory of depression
- States that depression is caused by the degeneration of neurons in specific regions of the brain such as the hippocampus and prefrontal cortex
What is the name of the protein that is able to induce neurogeneis (production of new neurons) in particular brain regions?
Brain-derived neurotropic factor (BDNF)
Why does exercise have a positive effect on mild depression?
- Exercise causes release of Brain-derived neuotropic factor (BDNF) which causes neurogenesis in the hippocampus
- According to theory depression caused by degeneration of neurons in hippocampus so neurogenesis of new neurons in those degenerated areas can reverse symptoms
What is it that causes the degeneration of hippocampal neurons that leads to depression?
Excessive release of glutamate which leads to excitotoxicity via excessive calcium influx into post-synaptic hippocampal neurons
Name some of the types of drugs used to treat depression
- Monoamine oxidase inhibitors
- Tricyclic antidepressants
- Selective Serotonin reuptake inhibitors (SSRIs)
- Noradrenaline reuptake inhibitors
- Mixed NA/5-HT selective reuptake inhibitors (SNRIs)
- Monoamine receptor antagonists
Explain the mechanism of how monoamine oxidase inhibitors work
- Monoamine oxidase inhibitors inhibit monoamine oxidase
- This means less Noradrenaline/serotonin is broken down when it’s taken back up into pre-synaptic neuron so there’s increased levels in the pre-synaptic neuron
- This leads to greater release of NA/5-HT into synaptic cleft which leads to more activation of post-synaptic noradrenergic and serotonergic neurons
Explain the mechanism for how tricyclic antidepressants work
- They block Noradrenaline reuptake transporter (NET) and the Serotonin reuptake transporter (SERT)
- This results in more Noradrenaline and Serotonin being in synaptic cleft so increases activation of serotonergic and noradrenergic neurons
Explain the mechanism for how selective serotonin reuptake inhibitors (SSRIs) work
- They inhibit the Serotonin reuptake transporter (SERT) which leads to more Serotonin in the synaptic cleft as it can’t be transported back into pre-synaptic neuron
- This leads to increased activation of serotonergic neurons
- They also inhibit 5-HT1A and 5-HT1D receptors which are autoreceptors for serotonin
- This leads to increased Sertonin release into synaptic cleft via exocytosis
What are some side effects of SSRIs?
- Insomnia, sexual dysfunction - via increased 5-HT2A activation
- Nausea, headache - via Increased 5-HT3 activation
What drug/substance can be used to treat bipolar depression?
Lithium
