12/2 Flashcards
More serotonin in the cleft for s/s
(Potential hypothesizes for why s/s inc. risk of depression)
SSRI - block reuptake
difference in transporters at early age - MAOI diff
- or COMP - less receptors produced
more serotonin - less releases of it
PTSD
one of anxiety disorders we know the most about.
Psychiatric illnesses (most people with)
have more than one disorder (ex. anxiety and depression)
Why is depression hard to treat
Feedback cycle
Feedback cycle
thoughts -> moods -> behaviors -> back to thoughts
Torpor
restlessness or agitation
Typical patient with depression sleep cycle
extended period of wakefulness
sever reduction in stage 3 sleep
REM starting earlier in the night
Increased activation in depression
Amygdala (part of limbic system, emotional processing, persists after depression has alleviated) Prefrontal cortex (executive processing and decision making)
Decreased activation in depression
parietal
temporal
cingulate cortex (part of limbic system)
Serotonin is produced in
cell bodies in restricted locations of the brain raphe nuclei some midbrain (project to forebrain inc. temporal (limbic system)), ponds, medulla
sert
serotonin reuptake transmitter
removes serotonin from cleft
Serotonin is a
monoamine
L- tryptophan to __ to __
5-HTP (Phan)
5-HT (or serotonin, amine)
Families of serotonin receptors
7
6 are G-protein coupled receptors
1 is a ligand-gated ion channel
Serotonin receptor subtypes
is 14
Drug classes to treat depression
MAOI
Tricyclics & Heterocyclics (inhibit reuptake of norepinephrine, serotonin and/or Dopamine
SSRI
Second gen & investigational (ex. NDRI, SNRI, NaSSA, SARI, opioid receptor modulator, ketamine)
NaSSA
noradrenergic and specific seratogenic antidepressant
SARI
Serotonin agonist and reuptake inhibitor
MAO
is an enzyme that breaks down 5-HT
is (mainly) inside of NA cells
SSRI & Serotonin hypothiss of depression
does not fully explain effects of depression because it take weeks to have an effect even though 5-HT ~immediately increases
Serotonin transporter gene
most studded
major interaction with childhood
s/s (short/short) increased risk for depression with maltreatment (vs l/l or long/long)
Goal of CBT
to change feedback loop
Large part of SSRI effectiveness
Placebo effect
If depression is less severe (SSRI)
are not effective
need to be severe depression (at onset)
ECT
Electroconvulsive shock therapy
causes a significant seizure
electrical current is passed through the brain
used in severe depression where there was no response to drug
Can be effective/lasing results for weeks or moths
TMS
Transcranial magnetic stimulation
is a form of ECT
DBS
Deep brain stimulation
surgically implant electrode(s) into small brain areas
effectiveness is controversial because there is no control group
Vagal never stimulation
Pace Maker stimulates it
Ketamine
often an anesthetic
mechanism of action not fully understood
PCP- like drug that relives depression almost immediately
Leptin
Hormone that controls eating behavior
being researched for depression treatment
Tourette’s
Abnormalities in dopamine receptors (high number of D2 receptors, especially in the basal ganglia)
uncontrolled, unconscious mussel movements
motor ticks vocal ticks compulsive action
Age of onset much younger
Some neuroleptics (from schizophrenia) can treat
starts with eye, face, head motor ticks
Anxiety disorders are linked to
Frontal and temporal lobe changes
often treated with benzos.
Anxiolytic
anti - anxiety
Benzodiazepines
Treat anxiety by binding to GABA-A receptors
enhances GABA’s inhibitory effects
Brain may contain some __ to interact with GABA receptor
of its own anti-anxiety substances
GABA receptors are widely distributed in
the cortex, hippocampus, and amygdala
Allopregnanolone
a neuro-steroid
natural anxiolytic produced by the brain
interacts with GABA-A receptor(s)
OCD
routine acts become compulsions (behaviors)
recurrent thoughts become obsessions (thoughts)
OCD responds to
SSRI’s
serotonin dysfunction in orbitofrontal or prefrontal cortex plays a major role
OCD surgery
lesion made in cingulate cortex on both sides may help
PTSD is anxiety related to
an inability to forget
PTSD symptoms are related to
fear conditioning and amygdala
also abnormal stress hormone systems
PTSD “Flow Chart”
Original trauma activates two systems 1) Brainstem 2) Amygdala
Brainstem - acute neurochemical responses - sensitizes person to related stimuli in the future
Amygdala - fear conditioning (potential failure in extinction response) - sensitivity to sensory and cognitive associations to original trauma
Acute neurochemical responses in PTSD
Locus coeruleus (norepinephrine)
VTA (Dopamine)
Endogenous opioids
Corticotropin- releasing hormones
Hippocampal size & PTSD
is a risk factor
small hippocampal size - if deployed/ has combat exposure - high susceptibility for PTSD
Benzodiazepines & GABA
Different site on receptor
When benzo’s bind they change the conformation that causes more Cl- to enter the cell WHEN GABA binds to the receptor
enhance ability for GABA to hyperpolarize
GABA
is agonist for own receptor
Depression
Is clinically characterized by a commination of unhappy mood, loss of interests, reduced energy, changes in apatite, sleep patterns, and loss of pleasure in most things.
Stress and Depression
Can occur without any readily apparent stress
Suicided appears to be
an impulsive act
after stopped first time only 6% went on to commit
when more planning required - large decrease
Descendants of people with severe depression
also have a thinner cortex across large swaths of the right hemisphere.
Hippocampal volume in people with depression
reduced
ECT may hemp by
inducing the release of monoamines
SSRI’s increase the rate
of the birth of new neurons
Meta - Analysis
analysis that combines the results of many previously published studies
Men vs Women Major Depression
Women more likely (hormones may play a role - postpartum depression)
Learned helplessness
in animal models, linked to a decrease in serotonin function
Rapid cycling bipolar disorder
four or more distinct cycles in a year
Bipolar disorder
also have enlarged ventricles, more manic episodes experienced, greater the ventricular enlargement.
More in common w schizophrenia than depression
Lithium
treatment of BPD, also second gen antipsychotics may help people in the manic phase
Buspirone
Buspar
agonist of 5-HT1A receptors
Children with OCD produce
antibodies to brain proteins
perhaps along with a strep antibody response
