Exam 2: Affective Disorders Flashcards
lecture 7-14
what are symptom of major depressive disorder (MDD)?
decreased interest in pleasurable activities, sleep difficulties, fatigue or loss of energy, feelings of worthlessness or excessive guilt
what is the monoamine hypothesis of depression?
the monoamine systems of serotonin, noradrenaline, and dopamine are involved, low activity of at least one of these neurotransmitters is responsible for depression
what are the major pathways of the dopaminergic system?
mesolimbic: VTA to nucleus accumbens
nigrostriatal: substantia nigra to dorsal striatum/basal ganglia
mesocortical: VTA to PFC
how does alterting the serotoninergic system cause depression?
reserpine was developed to treat hypertension, one of the side effects of reserpine was depression, this is because reserpine blocks VMAT (vesicular monoamine transporter) which blocks the reuptake of 5HT, DA, and NE into presynaptic vesicles, this allows MAO (monoamine oxidase) to break down the NT in the synapse
what do serotonin levels look like in those with depression and what symptoms do they cause?
low or abnormal serotonin activity is associated with anxiety, obsession, compulsions, and low mood, increasing serotonin can decrease dopamine and noradrenaline activity, high serotonin levels can lead to fatigue, loss of interest, insomnia and sexual dysfunction
where do serotonin neurons project and what behaviors do they regulate?
5HT neurons are in the raphe nucleus and project to the basal ganglia to control movement, obsessions, and compulsions while projections to the limbic area are involved in regulating anxiety and panic and projections to the hypothalamus regulate appetite and eating behavior
where do norepinephrine neurons project and what behaviors do they regulate?
NE cell bodies are located in the locus coeruleus, in patients with depression low noradrenaline activity is associated with decreased alertness, low energy,
inattention, loss of interest, concentration difficulties, and cognitive deficits
what do norepinephrine levels look like in those with depression and what symptoms do they cause?
low NE activity is associated with decreased alertness, low energy, inattention, loss of interest, concentration difficulties, and cognitive deficits
what do dopamine levels look like in those with depression and what symptoms do they cause?
low or abnormal dopamine activity is implicated in some aspects of cognitive dysfunction, loss of motivation, loss of interest, and inability to experience pleasure, too much dopamine can lead to nausea, activation, and hyperkinetic movements such as tics and dyskinesias, drugs with dopamine component may have a greater liability for abuse
how do monoamine oxidase inhibitors work?
MAOI bind to and inhibit MAOA in synapses from degrading 5HT and NE
MAOI bind to and inhibit MAOB in synapses from degrading dopamine
what are the 5 actions of tricyclic antidepressants (TCAs)?
- SRI: block the reuptake of 5HT by blocking SERT
- NRI: block the reuptake of NE by blocking NET
- alpha: block a1 adrenergic receptors
- H1: block histamine receptors
- M1: block muscarinic cholinergic receptors
what are the side effects of H1, M1 and alpha types of TCA?
H1: blocking histamine receptors causes weight gain and drowsiness
M1: blocking in acetylcholine receptors causes constipation, blurred vision, dry mouth, and drowsiness
a1: blocking in adrenergic receptors causes dizziness, decreased blood pressure, and drowsiness
how do selective serotonin reuptake inhibitors (SSRIs) work?
blocks SERT so that it cannot reuptake serotonin from the synapse, selective because they only block reuptake pumps for serotonin
how do norepinephrine and dopamine reuptake blockers (NDRIs) work?
blocks DAT or NET so that dopamine and NE are stuck in the synapse
how do noradrenergic and specific serotonergic antidepressants (NaSSAs) work?
acts as an antagonists to the alpha 2 receptors as well as blocking three kinds of serotonin receptors and histamine receptors, prevents the negative feedback effect of synaptic NE on 5HT (alpha receptors are autoreceptors on the presynaptic cell, by blocking NE from binding to the alpha receptors it stops them from inhibiting the release of 5HT and NE from the presynapse)
what effect does ketamine have on those with major depressive disorder?
a small dose of ketamine administered over 40 minutes increased mood in MDD patients, works in ~50% of patients with treatment resistant depression, approved by FDA for use in patients with TRD or MDD with suicidal ideation
how does ketamine effect NMDAR?
ketamine blocks NMDA channels on GABAR which blocks its inhibitory effect on glutamate synapses, this allows glutamate to stimulate BDNF to bind to its receptor which allows more spines to form, increasing synaptic plasticity
what is the learned helplessness (LH) paradigm?
a way to observe hopelessness, rats are given an electric shock with the chance to escape, rodents who have not previously experienced the inescapable shock are able to escape from the shock quickly, but animals who have previously undergone the learned helplessness paradigm struggle to learn how to avoid the shock
what does inescapable shock do to the brain?
inescapable shock induces a strong activation of the DR serotonin neurons which leads to an acute release of 5HT in the amygdala, dorsal PAG, and nucleus accumbens, also induces a long-lasting desensitization of 5HT autoreceptors in the DR
what happens to rats that experience maternal separation?
long maternal separation in rodents mimic early life neglect or loss of parents in humans, rats deprived of maternal care showed depressive-like behavior in the forced swimming test, increased levels of glucocorticoids, and a decrease in neurotrophins like BDNF and neurotrophin-3
how do we study antidepressant efficacy?
sucrose preference task: rats can choose between water and sucrose, depressed animals will not choose the sucrose as much as normal animals, anti-depressent drugs can reverse the anhedonia in the sucrose preference test
forced swim test/tail suspension test: rodents are put in an uncomfortable situation that they cannot escape from, during this they start to exhibit bouts of immobility that gradually increases, immobility then is referred to as despair and indicates depression-like states
what is stress?
any type of change that causes physical, emotional, or psychological strain, not all people perceive the same stressor equally, individual differences play a role in how stress is experienced and processed
what did Walter Cannon observe when animals were stressed?
when animals were frightened or disturbed peristatic waves in the stomach sometimes ceased abruptly, from this he described the combination of the sympathetic nervous system and adrenal systems response to stress, which induces violent displays of energy, he coined the term “fight or flight” response and homeostasis
what happens physiologically during a fight or flight response?
its energetically expensive for the body and involves large reallocation of resources like increased blood sugar levels and redistribution of blood flow
what is general adaptation syndrome (GAS)?
a foundational theory that describes how the body responds to prolonged exposure to stressors, contains an alarm stage, resistance stage, and exhaustion stage, where the bodies ability to withstand the effects of stress increase during alarm, are maintained throughout resistance, and then decreased throughout exhaustion
what is the alarm stage of GAS?
where stress resistance is temporarily lowered as the body mobilizes energy to face the threat, stress resistance then increases sharply
what is the resistance stage of GAS?
the body enters this stage to adapt and cope with stress, resources are deployed to maintain heightened level of resistance to the stressor
what is the exhaustion stage of GAS?
after prolonged exposure to stress the bodys ability to resist stress diminishes and stress resistance drops sharply
what is the allostatic load model?
allostasis is the process of achieving stability through change and allosteric load is the wear and tear on the body that accumulates when the allostasis response is activated too often or inefficiently managed, repeated stressful stimulus cause the allosteric load to build which raises the homeostatic set point (where the body returns to following stress)
what did the John W. Mason study conclude?
demonstrates the impact of psychological factors on the physiological stress response, monkeys that watched others eat while they were food deprived were more stressed than monkeys who were food deprived in isolation, concluded that stress isnt just about physical conditions but also about how we perceive and interpret our situation relative to others
what is Richard Lazarus’ Cognitive Appraisal Theory?
this theory emphasizes the role of individual perception and interpretation in the stress response, our cognitive appraisal of a situation determines its stress impact, Lazarus proposed that it’s not the objective properties of a stressor that determine its impact, but rather how we interpret and evaluate it
what is the transactional model?
this model has a dynamic nature that views stress as an ongoing, bidirectional interaction rather than a simple stimulus-response mechanism, includes:
1. primary appraisal: evaluation of the situtations relevance to ones well-being
2. secondary appraisal: assessment of available coping resources and options
these appraisals determine whether a situation is viewed as irrelevant, benign-positive, or stressful
(categorized as harm/loss, threat, or challenge)
what are the coping mechanisms of the transactional model?
after assessment individuals will reappraise the situation which helps them improve coping in the future
problem-focused coping: aimed at altering the stressful situation
emotion-focused coping: focused on regulating emotional responses
how does the hypothalamus-pituitary-adrenal (HPA) axis play a role in stress?
HPA axis is fundamental to energy homeostasis, pituitary gland and hypothalamus work together to control hormone release in the body
