Depression Flashcards
What is reactive and endogenous depression?
Reactive depression: triggered by an obvious negative experience
Endogenous depression: no apparent cause
How does the prevalence of depression differ across sexes?
Women tend to be more at risk for clinical depression (diagnosed twice as frequently as men)
potential explanation: gonadal-hormone related mechanisms
What are some causal factors in major depression
- severe childhood abuse or trauma
- childhood emotional or physical neglect
- severe life stress
- seasonal affective disorder
- permpartum depression
what are some genetic factors in major depression?
- studies showing that MD aggregates within families
- heritability for MD to be around 40%
- more heritable in women than in men (40% vs 30%)
What are the actions of the HPA axis in response to stress and what are the organs/brain structures and hormones involved?
HPA is our central stress response system
- hypothalamus triggers the release of CRF (corticotropin-releasing factor)
- CRF binds to receptors on the anterior pituitary gland (ACTH (adrenocorticotropic hormone) is released
- ACTH i s carried by the blood to the adrenal gland, which releases stress hormones cortisol
- cortisol exerts negative feedback to stop the activation of this axis
What is the monamine hypothesis? What are some lines of evidence for and against it?
Hypothesis: depression associated with under-activity of monoamine systems (serotonin, norepinephrine)
- autopsy studies found deficit in monoamine release –> indicated by the compensatory increase in the number of receptors for that NT (up-regulation)
- although widely prescribed, monoamine agonists are not effective in the treatment of most depressed patients, and even when they are more effective, they are only slightly better than placebo
- depression/anxiety likely associated with dysregulation of monoamines, but not simply under-activity
What is neuroplasticity theory of depression? What evidence supports this theory?
Nearly all antidepressant drugs rapidly increase monoamine transmission, but the therapeutic effects take a while to manifest –> downstream changes from the synaptic changes
Hypothesis: depression results from a decrease in neuroplasticity
- depression is associated with various neuroplastic processes
- antidepressants are associated with increase in neuroplastic processes
- in BDNF in patients who have shown improvement
What does monoamine oxidase inhibitors do?
inhibit the activity of monoamine oxidase, the enzyme that breaks down NTs
(breaks down NTs)
What do Tricylic antidepressants do?
blocks reuptake of serotonin and norepinephrine
What do Selective monoamine-reuptake inhibitors do
blocks monoamine transporters
Is ketamine effective as a treatment for depression? What are some of the disadvantages?
- Ketamine is an NMDA antagonist and anesthetic
- Administration as sub-anesthetic does improve symptoms of depression in treatment refractory unipolar and bipolar depression
- effects seen within hours, and persist for approx 1 week
disadvantages
- has abuse liability even at low doses
effect is through a metabolite that doesn’t act on NMDA receptor
- HNK reduces effectiveness of ketamine
- more effective as a NMDA antagonist not an antidepressant
- more effective in females than males
What is ECS therapy?
-Some depressed patients are non-responders to multiple classes of drugs
-ECS is a noninvasive procedure in which small electric currents are passed through the brain, intentionally triggering a brief seizure
- Cause changes in brain chemistry that can quickly reverse depressive symptoms
Side effects: memory loss, confusion
What is Deep brain stimulation (DBS)?
- Chronically implanted electrodes to stimulate specific brain region (invasive)
- Effective among treatment-resistant depression patients
- This treatment is effective in treating severe parkinson’s disease but still experimental in treating depression
What is repetitive Transcranial Magnetic Stimulation?
- Noninvasive delivery of repetitive magnetic pulses at either high frequencies of low frequencies to specific cortical areas (usually PFC)
High frequency → stimulate
Low frequency → inhibit
How is Depression Induced in animals through Chronic Mild Stress (CMS)?
Rats of mice exposed twice for extended period each day to a different, randomly selected, mild stressor
- Cage tilt at 45° angle, food deprivation, white noise, strobe light, crowded housing, individual housing, continuous light, continuous dark, water deprivation, damp bedding
