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144 Cards in this Set

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  • Back

What is major depression?

recurring episodes of dysphoria and negative thinking

What is bipoalr disorder?

Moods swing from depression to mania over time

T or F: There are subtypes of major depression and bipolar disorder

True

What does pathological depression resemble?

An emotional state we have all experienced but differs significantly in intensity and duration (most important)

What does pathological depression cause?

loss of interest in almost everything and inability to experience pleasure

What is the loss of interest in almost everything and the inability to experience pleasure called?

Anhedonia

What do most patients with anhedonia mean?

Hopelessness, sadness, worthlessness, guilt and desperation

T or F: Mania often occurs alone

F, rarely occurs alone

What most often accompanies mania?

It alternates with periods of depression to form bipolar disorder

How often does mania often last?

Days not hours

What is the primary symptom of mania?

Elation

What are some of the other symptoms besides elation of mania?

1. little sleep need


2. unlimited confidence in themselves


3. impulsive decisions



What is the overall prevalence of major depressive episode among US adults?

6.7 (about 7/100)



What age group has the highest prevalence of 12-month major depressive disorder?

18-25 (10.3%)

What age group has the second highest prevalence of 12-month major depressive disorder?

26-49 (7.5%)

What age group has the lowest prevalence of 12-month major depressive disorder?

50+ (4.8%)

What race has the highest prevalence of 12-month major depressive episode?

Mixed race (12.2%)

What race has the lowest prevalence of 12-month major depressive episode?

Asian

What is the prevalence of 12-month major depressive episode in females?

8.5%

What is the percentage of males that have had a major depressive disorder of 12-month prevalence?

4.7%

Which gender gets more episodes of major depressive disorder?

Female

Why is it thought that females have a higher prevalence of depressive disorder?

1. guys dont talk about it


2. guys more likely to commit suicide


3. guys drink more because it is more acceptable for them to deal negative behavior

What is the lifetime prevalence of major depressive disorder?

17% major depression for a long time

What percent of the US population has a lifetime prevalence of depression?

3.9%

What percent of the US population has a 12-month prevalence of depression?

2.6%

What percent of US population has a 12-month prevalence classified as severe?

2.2%

Severity: 82.9% of these cases (2.2% of US adult population are classified as what?

severe

What is the average age of onset for major depressive episode?

25 year old

T or F: thoughts of suicide are uncommon with affective disorders

False, very common

What percentage of depressed individuals attempt suicide?

7-15%

What percent of the overall population attempts suicide?

1-1.5%

What percent of people with bipolar disorder have attempted suicide?

25-50% (most studies 40-50%)

Describe bipolar disorder #1

1. manic depression


2. periods of fluctuating mania and a swing to depression


3. Primary driver of effective drug treatment is different than bipolar 2

Describe bipolar disorder #2

Characterized by predominantly depressive that fluctuates with a milder form of mania called hypomania

In bipolar two, which symptom do you treat and how?

depression; respond better to anti-depressants

What are the monoamines?

Dopamine, catecholamine, serotonin

How did the monoamine hypothesis originate?

With the observation that reserpine induces depression as a side effect

What is reserpine primarily used for?

The treatment of high blood pressure

How does reserpine cause depression?

Prevents packaging or neurotransmitters into vesicles, leaving them in the cytoplasm where monoamine oxidases degrades them

What does reserpine do?

inhibits vesicular uptake and storage, cannot be released, MAO degrades them

What is the fate of monoamines when it comes to reserpine like meds?

stay in the cytosol resulting in less in the cells

Bottom line: why is reserpine making people derpessed?

Took away amines

What is the normal function of MAO?

Function of MAO is to metabolize monoamine transmitters in the presynaptic terminal.

What does MAO inhibition do?

Increases the amount of neurotransmitter available for release

What is a big problem with MAO?

Significant risk of liver toxci

Are MAOs widely prescribed for for depression?

No, used infrequently, only when someone doesn't response to other classes

What are Tricyclic antidepresseeants named for?

Their three ring structure

Are TCAs widely used?

Not

How do tricyclic antideprssants act?

by binding to the presynaptic transporter proteins and inhibiting reuptake of monamines

TCAs have the same effects as what drug?

cocaine

What are the monoamines?

NE, DA, 5-HT

TCAs basic structure

All look like 3 benzene rings

What are the side effects of TCAs?

1. sedation and fatigue


2. small therapeutic


3. potentially dangerous cardiovascular effects



What are the potentially dangerous cardiovascular side effects of TCAs?

1. hypotension (orthstatic, drop in systolic)


2. tachycardia (elevated HR)


3. arrhytmias

Can you overdose on TCAs?

Yes, and commit suicide

What are second-generation antidepressants designed for?

to be more selective and have fewer side-effects

How do SSRIs work?

by blocking the presynaptic re-uptake transporter for 5-HT

What was Prozac originally developed for?

High BP

Who makes prozac and what is the story of its approval?

Eli Lily, tested for high bp but did not work and Eli realized they had increased mood

On what do SSRIs have significant influence on?

1. sensitivity to pain


2. emotionality


3. response to negative consequence or reward

What are rats with depleted 5-HT like?

1. Irritable


2. aggressive


3. overly sensitive to pain


4. altered patterns of eating and satiety



What are the antidepressant action of SSRIs related to?

Increased 5-HT function at some serotonergic receptors

What are the side effects of SSRIs?

1. anxiety


2. restlessness


3. movement disorders


4. muscle rigidity


5. nausea


6. headache


7. insomnia


8. sexual dysfunction


9. motor function


10. Sleep

where has low 5-HIAA ben found postmortem?

In both the brains of suicide victims and in the CSF of depressed patients

What is the 5-HT precursor?

Tryptophan

What is 5-HIAA?

The main metabolite of serotonin

T or F: Tryptophan can be used to measure low serotonergic function

True, it is the precursor

T or F: Trytophan is usually high in depressed patients

False, low

Can SSRIs cause physical dependence?

YES

How long do withdrawal symptoms last?

Several week

What are the alleles of the serotonin reuptake transporter?

two alleles-long and short

What does SERT mean?

serotonin reuptake transporter

What percent of people have the short allele?

10-15%

What is the short allele of SERT associated with?

reduced level and function of the transporter

Having the short allele of SERT is a what for depression?

Risk factor

How is the short allele significant in medication?

Those with it respond better to SSRIs than those who do not have it

How do antidepressants increase 5-HT?

1. by blocking the re-uptake


2. inhibiting MAO

What happens at first with anti-depressants?

the increase in synaptic 5-HT activates autoreceptors to slow firing and reduce synaptic 5-HT

An increase in the synaptic cleft translates into what?

Increase in auto receptors

Antidepressants typically take how long?

2-4 weeks

What is the bottom line about the time it takes for for antidepressants to work?

down regulates the autoreceptor

What does long-term administration of antidepressant result in?

Down-regulation of the autoreceptors and synaptic 5-HT gradually increases

Go through the steps of antidepressants on serotenergic cells

1. Released


2. Binds to autoreceptor


3. shuts down release


4. downregulation


5. now leftover serotonin can activate the postsynaptic cells

Where are autoreceptors located?

Presynaptic terminal

Where are serotonin receptors located?

Post-synaptic membrane

What is the basis of serotonin syndrome?

SSRIs have potentially life threatening effects when combined with other serotenergic agonists or drugs that interfere with metabolism of the SSRIs

What are the side-effects of serotonin syndrome?

1. severe agitation


2. disorientation


3. ataxia


4. muscle spasms


5. fever


6. shivering


7. chills


8. diarrhea


9. elevated BP


10. increased HR

What is the serotinin-ne hypothesis of depression?

There are anatomical and functional interactions between NE neurons originatin in the locus coeruleus and the 5-HT neurons in the raphe nuclei

T or F: serotonin and NE systems are capable of modulating the other

True

What does current thinking suggest of therapies for affective disorders?

Enhancing both NE and 5-HT function is more beneficial than enhancing only one

What are examples of dual NE/5-HT modulators?

Effexor and Cymbalta

Even though Cymbalta does affect mood, what do most people report?

Less aches and pains

What is the goal of third-generation antidepressants?

Speed onset of effectiveness and reduce side effects

What stage are third-generation antidepressants currently in?

Development and testing stages

What are the two new approaches to therapies for affective disorders?

1. CRF receptor antagonism


2. enhancement of cAMP second-messenger system

CRF_____ can be used to help treat depression.

inhibition

What does the glucocorticoid hypothesis focus on?

The stress-related neuro-endocrine abnormalities of depression

What do depressed patients have an abnormally high secretion of?

CRF

The hypothalamic CRF neurons are normally controlled by what other areas?

the amygdala stimulates and the hippocampus has inhibitory control

What does an overactive amygdala mean?

Too much stress

What are the stress hormones pathway?

Hypothalamus, pituatary, ACH, Adrenal

What happens to glucocticoid levels when stress is prolonged and intense?

It remains high, hippocampal neurons are damaged and no longer respond

What does damage to the hippocampus include?

Decreased dendritic branches and spines in the PFC and hippocampus. Formation of new hippocampal cells is inhibited

What happens when the hippcampus shrinks?

Cant stop hypothalamus from releasing CRF

What does cell loss in the hippocampus mean?

Reduced response to cortisol levels and loss of feedback inhibition of the HPA axis

What do antidepressant drugs do to CRF levels?

Reduce them and revers loss of hippocampal dendrites in animal studies

What did CRF receptors antagonists that were developed show early promise of?

antidepressants with minimal sideffects

What happened to the CRF receptor antagonists as antidepressants?

Frequent elevation in liver enzymes and further development was halted

Depressed patients have high levels of what?

CRF

What do early life traumas alter?

the set point for the HPA axis

What does the alteration of the set point for the HPA axis do?

Make it permanently over-responsive and increasing risk for later depression, anxiety, disorders, alchol abuse

What do rats subjected to early-life trauma show?

high stress-induced ACTH and cortisol, increased CRF in brain, permanent increase in CRF gene expression as adults

What did antidepressant drug treatment prevent in adult rats?

CRF increase, and also it reduced fearful behaviors

What happened do CRF increase and reduction in fearful behavior in adult rats after they ceased treatment?

Termination caused the abnormalities to return

What does the prevented CRF increase by new antidepressant drugs in adult rats show?

new direction for antidepressant drug development and that treatment may have to be continued indefinitely

What is the neurotrophic hypothesis?

Low BDNF may be responsible for the loss of dendritic branches and spines in the hippocampus and PFC and for reduced neurogenesis in the hippocampus

What is BDNF?

Brain developed neurotrophic factos

What may antidepressants do to BDNF?

May prevent decrease of BDNF

What is the supporting evidence for the neurotrophic hypothesis?

1. Chronic Stress reduces BDNF in the hippocampus in rats.


2. Chronic but not acute antidepressant treatment increases BDNF in animals and humans


3. Antidepressants prevent stress-induced reduction in BDNF and neuronal atrophy

Stress, increase glucocorticoids and decreased BDNF cause what?

Atrophy and decreased survival and increased vulnerability of hippocampal cells

What do antidepressants, increase in NE and 5-HT and BDNF cause?

Increased survival and growth of hippocampal cells

What is the evidence for BDNF in the etiology of depression?

BDNF is low in the hippocamppus and PFC of depressed patients postmortem




BDNF gene polymorphism may be associated with mood disorders




Modifying gene expression in mice leads to depressive behaviors



What is the most effective medication for patients with bipolar disorder?

Litium carbonate

Does lithium have an effect on healthy individuals

No

What does lithium carbonate do for those with bipolar disorder?

eliminates or reduces manic episodes without causing depression or producing sensation

How effective is lithium carbonate in reducing suicide in bipolar individuals?

VERY effective

Lithium Bromide dramatically does what?

Increases the time between both depressive epidsodes and manic episodes (particularly manic ones)

What action does lithium enhance?

5-HT actions

How does lithium enhance 5-HT actions?

By elevating brain tryptophan, 5-HT and 5-HIAA and increasing 5-HT release

What does lithium do to catecholamine activity?

Reduces catecholamine activity by enhancing reuptake and reducing release

Given that lithium flattens the extremes of emotion in both directions, what is it likely that is modifies?

Synaptic transmission at points beyond the neurotransmitter receptors, for instance, in second-messenger function

What are the side effects of lithium?

generally mild but may include


1. Increased thirst and urination


2. Impaired concentration and memory


3. Fatigue


4. Tremor


5. Weight gain

Is the therapeutic index high or low for lithium?

Very low; blood levels of lithium must be monitored on a regular basis

What are some alternatives to lithium?

Valproate


Carbamazepine

What is valproate also called?

Depakote

How does Valproate work?

An anticonvulsant drug approved for treating acute mania

How does Valproate work?

Enhancing GABA and blocking Na+ channels

What is the effectiveness of Valproate similar to?

Lithium but different side effects

T or F: Valporate is safe for women of childbearing age

False, not good it its limited in this population and is teratogenic

What is carbamazepines also called?

Tegretol

What is Carbamazepine primarily?

Anticonvulsant

How does caramazepine work?

Blocks Na+ channels,


Agonists at GABA-A receptors


Releases serotonin

What seems to work better at first, Carbamazepine or lithium?

Carbamazepine

By what time period does the carbamazepine and lithium seem to balance out?

14-21 day of treatment