Exam 1 (CHAPTERS 1-4) 3 Flashcards
What is the annual rate of depression?
10%
What is the lifetime rate of depression?
17%
Is depression higher or lower in women vs men?
Twice as high in women
When does depression commonly begin?
In late adolescence/early adult hood (late being 18/19)
What is the Diagnostic Criteria for Depression?
SIGECAPS
1) Sleep - too much or little
2) Interests
3) Guilt
4) Energy - too much or little
5) Concentration
6) Appetite - too much or little
7) Psychomotor - too much or too little
8) Sex or suicide
What are six ways you can treat depression?
1) More medication
2) Increase activity level
3) Therapy/counseling (journaling)
4) Transcranial Magnetic Stimulation
5) Electroconvulsive Shock Therapy (for resistant depression)
6) Deep Brain Stimulation (DBS)
What three catecholamines are related to depression? DEN
1) Dopamine
2) Serotonin
3) Norepinephrine
What is the Hippocampus related to?
Learning and memory
What is the initial evidence for the monoamine hypothesis?
Effective drugs increased these levels and drugs that depleted SE and NE caused depression symptoms
What is an example the initial evidence for the monoamine hypothesis?
Reserpine for HTN blocks monoamine transport into vesicles leaving them vulnerable for degradation leading to side effect of depression
Where are monoamines prevalent?
The limbic system and frontal cortex
What does a deficiency in monoamine neurotransmitters “cause”?
Depression
Why was a revision of the monoamine hypothesis needed?
Because of the lag time between neurotransmitter changes and change in mood
What is the revised monoamine hypothesis?
Monoamine neurons do not produce enough trophic or growth factors which leads to neural degeneration in hippocampus and frontal cortex.
What is the key protein in the revised monoamine hypothesis?
Brain-derived neurotropic factor (BDNF) (miracle grow for the brain)
Who’s research is fundamental to the idea of BDNF being a factor in depression?
Ronald Duman of yale
What is BDNF?
Growth factor for neuron survival, receptor growth, and growth of new neurons
What is the mechanism of the revised Monoamine hypothesis?
The Downregulation of monoamine neurons and BDNF
What are 8 ways to increase BDNF?
1) Green tea
2) Exercise
3) Fasting
4) Less refined sugar/fat
5) Resveratrol
6) Vitamin D
7) Social enrichment
8) Psychotherapy
CREB has to do with what?
Generating proteins
What is the monoamine hypothesis complicated by?
Chronic Stress
What does stress lead to and what does that lead to?
Stress leads to increased cortisol (stress hormone) which leads to BDNF downregulation through an increase of autoreceptor activity
What do antidepressants do to BDNF levels?
They downregulate autoreceptors and activate production of BDNF
What drug makes you eat alot?
Remeron
When were tricyclics accidentally discovered and what was their original use.
1950s and purpose was schizophrenia
What is the mechanisms of tricyclics?
Bind to reuptake transporter for NE and SE which increases duration in synaptic gap immediately. Eventually, presynaptic autoreceptor downregulation and BDNF synthesis upregulation
Imipramine significantly increased what in where?
Significantly increased BDNF synthesis in all hippocampai areas examined
What are dirty drugs?
Tricyclics, overdose/toxicity is easy to achieve
What are side effects of Tricyclics?
Block histamine receptors
block acetylcholine receptors
Overdose potential is high (toxic at 10x)
What happens when histamine receptors are blocked?
Drowsiness/fatigue
What happens when acetylcholine receptors are blocked?
Anticholinergic effects: dry mouth, dizziness, hypotension, constipation, blurred vision, difficulty concentrating and forming memories.
What were Monoamine Oxidase Inhibitors originally used for and when was the accidental discovery?
Found in 1950s used for tuberculosis
What is the mechanisms of Monoamine Oxidase Inhibitors?
1) 2 types of enzymes that degradate monoamines (MAO-A & MAO-B)
2) Original MAOIs inhibited both but newer MAOIs are more selective.
What are side effects of MAOIs?
1) Sedation/ fatigue, dizziness, movement disorders, blurred vision, decreased libido, dry mouth, weight gain.
2) Serious interaction with foods that contain tyramine
What happens when MAOIs interact with tyramine?
1) MAOIs keep liver from metabolizing tyramine
2) Severe headaches, hypertensive crisis, stroke
What foods contain tyramine?
Cheese, yogurt, aged meats, some bread, wine, beer, some fruits
SSRIs
Selective Serotonin Reuptake Inhibitors
What is another name for Serotonin?
5-hydroxytryptophan (5HT)
What is the 1988 SSRIS?
fluoxetine (Prozac)
What is primary mood-altering effects of drugs linked to 5-HT and attempts to minimize side effects?
Serotonin
What is the mechanisms of SSRIs?
1) To inhibit serotonin reuptake by binding to transporter which then increases duration of 5-HT in synaptic gap.
2) Not specific for receptor subtypes
What is the primary therapeutic mechanism of SSRIs?
Downregulation of 5-HT1a autoreceptors
What are side effects of SSRIs?
1) Sexual dysfunction in males, decreased libido, GI problems, decreased appetite, insomnia, and agitation (5-HT2receptors)
2) Serotonin Syndrome
3) Suicide ideation/attempts in kids through age 24
What is serotonin Syndrome?
Toxic reaction from to much serotonin
What are signs of serotonin syndrome?
Disorientation, confusion, agitation, mania, hyperthermia, diarrhea, coma, death
What do we know about suicide ideation/attempts related to SSRIs?
1) Recent analyses found no difference in adolescents taking antidepressants vs. placebo
2) Also prescription rates have decreased and suicide rates have increased
What are SNRIs?
Serotonin-Norepinephrine Reuptake inhibitors
What do SSRIs target?
Target serotonin to elevate depressed mood…but what about depressed behavior (fatigue, sleepiness, sleeping too much)
What does SNRIs target?
NE which promotes arousal
What are mechanisms of SNRIs?
1) They block 5-HT and NE reuptake transporters along with DA
2) Similar to SSRIs
SNRIs are —- to get on and —- to get off of
Easy to get on, hard to get off of
What do we know about mirtazapine (Remeron) and nefazadone (Serzone)?
They are more selective and minimize sexual side effects
What does bupropion (Wellbutrin/Zyban) not target?
It does not target 5-HT which minimizes side effects and may actually enhance sexual functioning
What are side effects of Wellbutrin?
Restlessness, agitation, motor tics, decreased appetite, weight loss, abdominal discomfort, and seizures
What is St. John’s Wort?
Natural remedy
What does St. John’s Wort effective for?
Mild depression but research comparing it to antidepressants and placebos is inconsistent.
What has a Meta-analysis found on St. John’s Wort?
It is effective for short term treatment of mild depression
What are mechanisms of St. John’s Wort?
1) Increases 5-HT and NE by inhibiting reuptake and storage of monoamine but not by binding to transporters
2) May be through increasing intracellular sodium
What are side effects of St. John’s Wort?
1)Less than antidepressants
2) GI upsets, sedation, restlessness, sexual dysfunction, and headaches
What is a caution about St. John’s Wort?
Serotonin Syndrome
What is an interaction of St. John’s Wort
It enhances synthesis of a liver enzyme which metabolizes most drugs, decreasing the duration of action and effectiveness of other drugs.
What is the rate of bipolar disorder in men and women?
It is equal
When does bipolar disorder typically onset?
Late adolescence/early adulthood
What is the annual prevalence rate?
6 million (2.5%)
hat is the lifetime percentage?
4.4%
Is it a simple or complex Diagnosing system?
Complex
What are Criteria for bipolar disorder (MANIA)?
1) Disproportionate/abnormally ELEVATED, EXPANSIVE, or IRRITABLE mood at least one week
2) Must have at least 3 of the items from FIGIPC
3) Causes marked impairment in occupation or social functioning
What does ketamine do?
puts people into dissociative states
What are the criteria for a hypomanic episode
1) must have symptoms for 4 days instead of week
2) May not severely impair functioning; no psychotic symptoms
Criteria of mixed episode
Meet criteria for both manic episode and major depressive episode if symptoms occur nearly every day for 1 week
Bipolar 1
Manic episode or mixed episodes; major depressive disorder episode not required
Bipolar 2
1 depressive episode and 1 or more HYPOMANIC episodes
Rapid cycling
4 or more episodes of mania or depression within 1 year
Cyclothmia
Hypomanic episodes with symptoms of depression that to not meet diagnosis for major depressive disorder for at least 2 years
What is the pathology for bipolar?
1) largely unknown
Is there a genetic component to bipolar?
Yes, there is a large genetic component
What is the large genetic component
70% monozygatic to 12% dizygotic
What genes has bipolar been identified with?
5HT transporter and BDNF
Are there structural abnormalities that come with bipolar?
Yes, there is a neural degeneration which leads to loss of neural tissue which leads to ventricle enlargement to fill up space
Where are the structural abnormalities that come with bipolar?
Prefrontal cortex, amgydala and striatum (caudate nucleus and putamen in basal ganglia_
What is the fist treatment for bipolar?
Lithium in 1948
Lithium and bipolar
1) used as salt substitute but was toxic
2) meant to treat mania but was not approved by FDA until 1970
Pharmacokinetics of lithium
1) easily absorbed, crosses BBB slowly and is excreted intact from kidneys
2) Therapeutic dose has narrow window and is toxic above levels
3) Blood testing to check for lithium toxicity
What are side effects (long term) of lithium?
Weight gain, thyroid disease, skin rash, kidney dysfunction, compromised immune functioning
What happens when you suddenly decrease lithium use?
16-fold increase in suicidality
Lithium pharmacodynamics
1) Also treats depression and suicide ideation effectively
2) Hypothesized relationship to BDNFactivity
3) Increases 5HT activity in cortex and hippocampus by agonizing autoreceptors and heteroreceptors on dopamine neurons
Heteroreceptors
Function similar to autoreceptors but activated by a neurotransmitter released by a different neuron
How does lithium pharmacodynamics have an antimanic effect?
mostly by stabilizing dopamine neurons and modest effects on 5-HT neurons
Valproic acid treatment for bipolar/mania
1) stimulates BDNF synthesis
2) affects GABA and dopamine
- inhibits GABA reuptake increases inhibition
- increases DA release in prefrontal cortex
3) Inhibits glutamate activity which may underlie mania and seizures
4) less side effects
What are side effects of Valproic Acid?
Sedation, tremor, ataxia, nausea, and weight gain
What is an example of Valproic acid?
Depecote
What is ataxia?
Poor movement (same as lithium toxicity)
Gabapentin treatment for bipolar/mania
1) approved for seizures but also used for mania and neuropathic pain
2) Designed to mimic GABA (increases GABA)
3) Side effects similar to valproic acid
How does Gabapentin mimic GABA?
It decreases Calcium influx which decreases glutamate activity in the cortex
What is an example of Gabapentin?
Neurotin
Example of neuropathic pain
Diabetic neuropathy such as feet pain
