Unipolar Depression and Anxiety Disorders

what is unipolar depression

Sustained period of depression from weeks to months at a time causing an interference with daily living (no mania)

what are some depression symptoms

Helplessness
Hopelessness
Gloominess
Loss of interest
Loss of energy
Loss of appetite
Difficulty concentrating
Restless agitation
Pessimism
Anhedonia (inability to experience pleasure)

what are some biological causes of depression

Genetics
Hormonal
Stress responsivity
Neurotransmitter systems
Abnormal hemispheric dominance

genetic biological mechanism of depression

Depression tends to run in families; adopted children resemble biological parents (not adoptive parents)

hormonal biological mechanism of depression

Postpartum depression and Menopause

neurotransmitter biological mechanism of depression

Altered neurotransmitter activity of Monoamines (catecholamines and serotonin), Norepinephrine (NE) and Epinephrine (E), Dopamine (DA), and Serotonin (5-HT)

what is the evidence for the neurotransmitter biological mechanism of depression

Evidence comes from effectiveness of antidepressant medications

what is the abnormal hemispheric dominance biological mechanism of depression

Low activity in left hemisphere: Left associated with positive emotions
High activity in right hemisphere: Right associated with negative emotions

what is the stress responsivity biological mechanism of depression

Problem with HPA (hypothalamo-pituitary-adrenal) axis (hormonal stress response). Depressed individuals have higher basal levels of CORT and they fail the dexamethasone suppression test showing a problem with negative feedback regulation

what is the Dexamethasone suppression test

People with clinical depression have no reduction in CORT release (showing an issue) from Dexamethasone as it does in "normal" people

explain how the dexamethasone suppression test works

dex acts like CORT and can turn off CORT release in the HPA hormonal stress response. In someone with depression, dex fails to decrease CORT and the person "fails the test" because they have higher basal levels of CORT

what does the dexamethasone suppression text measure

CORT levels

what are five kinds of antidepressant medications

MAOIs, SSRIs, SNRIs, Tricyclics, and Atypical Antidepressants

How does an MAOI work

It blocks MAO (monoamine oxidase) in the presynaptic terminal or synaptic cleft. MAO is an enzyme that breaks down monoamines (NE, E, DA, 5-HT), so MAOIs keep the monoamines in the cleft so that they can have a longer effect

what is a side effect of the MAOIs

cheese effect (hypertensive crisis)

explain the cheese effect

Tyramine broken down by MAO but with MAOI, there is a build-up of tyramine. Tyramine causes release of catecholamines (Ep, NEp) and causes a sudden activation of the sympathetic nervous system.

why is it called the cheese effect?

Tyramine is high in foods like cheese and can cause an increased risk of stroke

what are SSRIs

Selective serotonin re-uptake inhibitors; Only blocks re-uptake of 5-HT (serotonin); serotonin stays longer in synapse

what can SSRIs treat

Poor self-esteem
Fear of failure
Sensitivity to criticism
Social anxiety
Generalized anxiety
Obsessive-compulsive disorder
Panic disorders

what are tricyclics

Re-uptake inhibitors that block re-uptake of monoamines (E, NE, DA, 5-HT)

can tricyclics be abused?

No, it produces dysphoria, anxiety, restlessness, and depression in normals

what are side effects of tricyclics

Drowsiness, dry mouth, heart irregularities

what are SNRIs

Serotonin-norepinephrine re-uptake inhibitors; Act to block re-uptake of both 5HT and NE

What are atypical antidepressants

Collection of miscellaneous drugs such as Wellbutrin (bupropion) which is a selective DA re-uptake inhibitor

what is the monoamine theory of depression

All effective antidepressants act on monoamines, so Depression is caused by low levels of monoamines such as Norepinephrine, Serotonin, and/or Dopamine

what are the two main issues with the monoamine theory

1. Inconsistent time-course effects
2. Monoamine metabolites in depression do not differ from normal

explain the inconsistent time course effect issue of the monoamine theory

Drugs immediately affect NT levels but clinical effectiveness takes weeks (drugs change NT levels, but the symptoms stay)

explain the monoamine metabolite effect issue of the monoamine

there is no evidence from human patients for lower levels of serotonin in depression and no direct evidence that serotonin has effects on depression except for the medication effects

how is 5-HIAA connected to the monoamine metabolite

5-HIAA (metabolite of 5-HT) only measures amount of 5-HT broken down; much 5-HT inactivated by re-uptake

what are 5-HTT polymorphisms

5-HTT polymorphisms refer to variations in the gene that codes for the serotonin transporter protein, often abbreviated as 5-HTT (5-hydroxytryptamine transporter). Polymorphisms can affect the function and expression of the serotonin transporter, leading to differences in serotonin reuptake and availability in the brain.

where are 5-HTT polymorphisms

serotonin transporter gene

what do 5-HTT polymorphisms cause and how do you get them

Long and short alleles:
Susceptibility to depression after stress
related to which alleles you receive from parents

what does the 5-HTT gene code for

Codes for serotonin transporter (reuptake mechanisms)
2 alleles (one from each parent) - short or long

what does the 5-HTT gene have to do with depression

People with at least one short may be more susceptible to depression and it doubles risk of onset of depression following life stresses

symptoms of short 5-HTT allele carriers

More anxious
View things in more negative light
Over-react to stress
Prone to depression

where is the emotion regulation circuit

Amygdala and the Prefrontal Cortex (Area 25)

what is a normal emotional regulation circuit

two long 5-HTT alleles; amygdala activates prefrontal cortex, which dampens amygdala activity

what is the emotional regulation of a S allele carrier

amygdala fails to activate prefrontal cortex, less able to dampen prefrontal cortex activity, causing the amygdala to be overactive

what causes the short allele to be susceptible for depression

Short allele codes for less protein that makes up 5-HT transporter, so the Serotonin released is not recycled properly and it disrupts emotion regulation circuit

what is ECT

electroconvulsive shock therapy

where is ECT administered

Only administered to the Right Hemisphere

how fast is the onset of relief from ECT

Rapid onset of benefits (unlike drugs that take 3-4 weeks) and repeated treatments have long-lasting benefits (6-12 sessions over 2-3 weeks).

how does ect work

Depressed patients may show over-activity of right hemisphere (negative emotions), so ECT brings systems back into balance

what are side effects of ect

retrograde amnesia usually slight (months) but sometimes severe (years)

what is Transcranial Magnetic Stimulation

a less severe/intense form of ECT

where is TMS administered

right hemisphere

what is deep brain stimulation and how common is it?

reduces activity of Amygdala by increasing activity of Area 25; is experimental and used as a last resort (electrodes in the brain)

what do anxiolytic drugs do

Reduce anxiety and can also reduce fear at high doses

what are the two classes of anxiolytic drugs

Barbiturates
Benzodiazepines

how do barbiturates and benzodiazephines work?

Anxiety is thought to be caused by excessive amygdala activity, so these reduce activity in the cells of the amygdala by increasing GABA activity.

what kind of drugs are anxiolytic drugs

Indirect Agonist - increase GABA activity indirectly

how do anxiolytic drugs work chemically

When anxiolytic drugs bind to the receptor at specific sites, it makes it so GABA can bind for longer and has a stronger bind. There is increased GABA activity causing increased inhibition. So, the ion channel is open for longer; more negative chloride comes into the amygdala cell, which hyperpolarizes the cell and brings it back to normal activity.

what effect would anxiolytic drugs have without GABA

Without GABA, drugs would have no effect but also you would be dead from inability to breathe because you don't have GABA

what is tolerance

in order to keep the effect of the drug, you have to increase the amount of drug over time; tolerance usually happens recreationally/self-medicated

how does tolerance affect the amygdala

Anxiolytic (amygdala) - anxiety
over time, the dose you're taking becomes less effective for treating anxiety, so the dose has to be increased for the desired affect

how does tolerance affect the hindbrain

Not respiratory (hindbrain) - breathing
you do NOT see tolerance in these areas; more GABA is inhibitory, will hyperpolarize cells increasingly, and will stop the ability to breathe

what is the formula for therapeutic index

TI = LD50/ED50

do you want a therapeutic index to be low or high

Want a drug with a high TI (effective dose is much lower than lethal dose) becuase you want the numerator to be really high and the denominator to be really low (because you want the LD to be super high and you want the ED to be super low)

what is LD and ED

LD= lethal dose
ED= effective dose

what happens when the ED50 approaches the LD50 and why does it happen

Effective dose becomes higher with tolerance (approaches lethal dose). This causes death from respiratory depression
because GABA receptors are highly concentrated in respiratory regions of the hindbrain

do barbiturates have a low or high TI

overdose is very common in Barbiturates due to the low TI and addictive nature/tolerance

what is another use for benzodiazepines and how do they work/what are their symptoms

Benzodiazepines are "Date Rape" Drugs; Act at GABA receptor and cause Sedating: drowsiness, confusion, dizziness, visual disturbances

what happens when date rape drugs are combined with alcohol

Mixed with alcohol, BZ exacerbates effects and can be lethal. Huge binding to BZ and ethanol sites causes greater GABA binding and greater inhibition in the hindbrain. This causes respiratory failure

explain cross-tolerance

Barbiturates, benzodiazepines and alcohol all act at GABA receptor and all show cross tolerance. If you are tolerant to alcohol, you need more barbiturate/benzo to see positive effects. This causes a Low TI and overdose is more likely!