Chapter 13: Antidepressants Flashcards
anhedonia
loss of interest in normally pleasurable activities
what disorder is characterized by a mildly depressed state but does not meet the full criteria for major mood disorder?
dysthymic disorder.
gender differences in depression?
women are twice as likely to suffer from depression
T/F: compared to the general population, there is an increased overall mortality rate ofr depressed people?
true
name 5 DSM criteria of depression
1) anhedonia
2) fatigue
3) diminished brain activity
4) insomnia or hypersomnia
5) sad
people with depression have decreased activity in the ___ and increased activity in the ____
people with depression have decreased activity in the PFC and increased activity in the AMYGDALA, makes them respond negatively to stress
monoamine theory of depression?
the theory that depression stems from decreased neurotransmitter activity in the
1) NE decrease in locus coerelues
2) Serotonin in raphe system
3) dopamine in ventral tegmental area
which amino acid is associated with the formation of serotonin?
tryptophan
problems with monoamine theory of depression?
1) there is a lag time in the efficacy of anti depressants. If monoamines were solely affected, giving more monoamines should immediately reverse depression, which doesn’t happen
2) tryptophan depletion effects on mood do not occur on anyone. In people with no history of depression, tryptophan shortages do not affect serotonin levels and moods.
how does cocaine and antidepressants increase monoamine levels?
by blocking reuptake.
depression is reflected in ____ cortical function due to :
depression is reflected in DECREASED cortical function due to LACK OF MONOAMINE TRANSMISSION from the VTA, locus coereleus, and raphé
although all monoamines are related to risk of depression, what is the key neurotransmitter?
serotonin. People with depression are found to have lower levels are serotonin, and people that killed themselves are found to have below normal levels of tryptophan and serotonin metabolites like 5H1AA
how is it that there are less serotonin reuptake transporter proteins in the brainstem? isn’t this counterintuitive?
the reason why there’s less reuptake transporters are because there are less raphe serotonin neurons to begin with. This means less serotonin is being projected in the cortex, even though reuptake protein concentrations are lessened.
which chromosome is responsible for depression? how
a shortened version of chromosome 17 is responsible for decreased production of serotonergic neurons and significantly few 5HT transporter proteins.
where is the raphé serontinergic neurons normally supposed to project?
from the raphe to the medial forbrain bundle and prefrontal cortex
which serotonin receptor is problematic in individuals with depression? is this receptor inhibitory or excitatory? where are these receptors located and what is their effect?
affects the 5HT1A receptors. inhibitory receptors. In the raphe nuclei, these receptors are autoreceptors and decrease the serotonin output of the cells. In the amygdala and hypothalamus, receptors are located POSTsynaptically and stimulation of those receptors increases seotonin neurotransmission that makes amygdala hyper active.
how do antidepressants affect that 5HT1a receptors?
they are able to enhance sensitivity and functioning of 5HT1a receptors POST synaptically, reducing the amount of hyperactivity in the amygdala. They are also able to desensitize these receptors in the auto receptors, increasing the amount of monoamines released by the raphé and VTA
explain the mechanism of the hypothalamic-pituitary-adrenal axis
the stress response starts in the hypothalamus where the neurons release corticotropin releasing hormones (CRH). the CRH initiates the release of adrenocorticotropic hormone (ACTH) from the pituitary, which stimulates the secretion of CORTISOL from the adrenal glands.
in a normal person, once the stressful stimulus ends, the HPA axis is turned off
in overstressed and depressed individuals, the HPA axis is ___. Why?
overactive. because the hippocampus and PFC is depressed, and there is nothing controlling the amygdala and stress response.
what brain centers are affected once cortisol is released upon the activation of the HPA axis?
the cortisol levels inhibit proper functioning of the hippocampus and PFC, and activates the amygdala.
the effect of excess cortisol on the PFC, hippocampus and the amygdala
PFC and Hippocampus atrophy and lose volume. they do not work as well due to increased inhibition. The amgydala grows and increases in volume, It is over active. it is causing the person undue negative feelings due to cortisol levels.
how does the glucocorticoid theory of depression tie together with the monoamine theory of depression?
excess cortisol in the body may affect 5-HT neurotransmission and reduce the number and function of POST SYNAPTIC 5-HT1a receptors in the hippocampus. (less serotonin altogether in the PFC and hippocampus)
T/F Overactive HPA axis are seen in individuals with short forms of chromosome 17
true. chromosome 17 is also responsible for decreased serotonin neuron growth
How do antidepressants affect the HPA axis?
they reduce HPA activity by increasing the number of cortisol receptors to create more efficient negative-feedback loops. this also decreases the amount of 5HT1a receptor density decreases that often occur during times of elevated stress hormones.
when are inflammation factors like cytokines secreted?
in times of pain or stress
how do cytokines produce depressive-like alterations?
uncontrolled stress due to decreases in PFC and hippocampal activity triggers the release of cytokines, which decreases activity even more AND INHIBITS BDNF, producing more depressive symptoms.
What is BDNF?
brain derived neurotrophic releasing factor that stimulates neuron growth
the more atrophy in the ____ and ___ causes HYPOfrontality, which is why depression is considered to be a neurodegenerative disorder.
the more atrophy in the HIPPOCAMPUS and PFC causes HYPOfrontality, which is why depression is considered to be a neurodegenerative disorder.
