Lecture 9: Mood & Anxiety Disorders Pt 1 Flashcards
(103 cards)
1
Q
criteria for diagnosing depression
A
must have 5/9 symptoms of:
- sad mood
- insomnia
- feelings of guilt
- decreased energy levels
- decreased concentration
- decreased appetite
- decrease in pleasurable activities (anhedonia)
- increased or decreased psychomotor activity
- recurrent suicidal ideation/acts of self harm/suicide attempt existing over a period of 2 weeks
2
Q
diagnostic criteria for generalized anxiety disorder
A
excessive anxiety & worry occuring more days than not for 6+ months, about a number of events or activities
3
Q
what symptoms must someone have 3/6 of to be diagnosed with anxiety
A
- restlessness or feeling keyed up or on edge
- being easily fatigued
- difficulty concentrating or mind going blank
- irritability
- muscle tension
- sleep disturbance
4
Q
overlapped brain regions between mood & anxiety disorders
A
amygdala, hippocampus, nucleus accumbens, prefrontal cortex
5
Q
causes of anxiety disorders?
A
- genetic prediposition
- environmental factors (& interactions w/ genetic factors)
- sociological factors, physiological/psychological factors
- personality traits
6
Q
what are the predominantly central processes that contribute to neurobiological mechanisms of MDD
A
- neurotransmitter system
- neuroplasticity
- brain structure & function
7
Q
what parts of the NT system are involved in MDD
A
5-HT, NA, DA modulation
8
Q
what changes in neuroplasticity occur during MDD
A
decreased brain-derived neurotrophic factor expression & signaling in medial prefrontal cortex & hippocampus
9
Q
what changes in brain structure & function occur during MDD
A
- hippocampal atrophy
- thinner cortical grey matter in the orbitofrontal cortex, anterior & posterior cingulate, & insula
- overactivation of amygdala under emotion exposure
10
Q
what are the central and peripheral neurobiological mechanisms involved in MDD?
A
- immune & inflammatory systems
- gut microbiota-brain axis
- hypothalamus-pituitary-adrenal axis
- epigenetics
11
Q
symptoms of MDD
A
- emotional (such as anhedonia & depressed mood)
- neurovegetative (such as fatigue, & sleep & weight disturbances)
- neurocognitive (such as agitation & cognitive impairment)
12
Q
where are the major sites of serotonin cell bodies
A
dorsal & median raphe nuclei
13
Q
important serotonin projections
A
- raphe nucleus –> amygdala
- raphe nucleus –> hippocampus
- raphe nucleus –> nucleus accumbens
- raphe nucleus –> medial prefrontal cortex
- also projects to spinal cord
14
Q
what is the raphe nucleus –> medial prefrontal cortex important for
A
impulsivity & behavioral adaptation
15
Q
what is the raphe nucleus –> nucleus accumbens important for
A
social behaviors
16
Q
what is the nucleus accumbens –> amygdala important for
A
aversive memory acquisition
17
Q
what is the raphe nucleus –> hippocampus important for
A
learning & memory
18
Q
what is the raphe nucleus –> BNST important for
A
avoidance behaviors
19
Q
what is the raphe nucleus –> habenula important for
A
anxiety-related behaviors
20
Q
what is the raphe nucleus –> ventral tegmental area important for
A
reward
21
Q
what is the raphe nucleus –> periaqueductal gray important for
A
inhibition of panic behaviors
22
Q
5HT 1A characteristics
A
- autoreceptor (regulates presynaptic neuron)
- heteroreceptor (found on postsynaptic neurons)
23
Q
5HT - 1A receptor function
A
inhibitory - 5-HT binding to 5HT-1A will reduce neuronal activity
24
Q
what are the major sites of norepinephrine cell bodies
A
locus coeruleus & nucleus of the solitary tract
25
what is the LC --> amygdala projection important for
fear and anxiety
26
what is the LC --> hippocampus important for
dopamine release
27
what is the LC --> NAc important for
reward behaviors
28
what is the LC --> mPFC important for
arousal, cognition, attention
29
what are the major sites of dopamine cell bodies
VTA & SN
30
mesocortical pathway function
regulation of executive function
31
mesolimbic pathway function
reward processing & motivation
32
nigrostriatal pathway function
voluntary movement & balance
33
tuberoinfundibular pathway function
hypothalamic projections; inhibits prolactin release
34
where is dopamine produced outside of the brain
gastrointestinal tract
35
where is serotonin mostly synthesized
in the gastrointestinal tract by enterochromaffin cells
- only 5-10% is synthesized in the raphe nucleus of the brain
36
adrenal medulla function
synthesizes both epinephrine and norepinephrine
37
what is epinephrine
active metabolite and hormone
38
what is norepinephrine crucial for
fight-or-flight response triggered by the sympathetic nervous system
39
can circulating monoamines in the blood cross the BBB?
no, but their precursors can
40
what is the rate limiting step for the synthesis of monoamines?
the conversion of tryptophan --> 5HTP (by tryptophan hydroxylase) & tyrosine --> L-DOPA (by tyrosine hydroxylase)
41
what is L-tryptophan
essential amino acid, precursor for serotonin synthesis
42
what is L-tyrosine
nonessential amino acid, precursor for dopamine & norepinephrine synthesis
43
what drug class is fluoxetine
SSRI
44
what was the first SSRI marketed
fluoxetine
45
what drug class is imipramine
TCA
46
what was the first TCA marketed
imipramine
47
what drug class is iproniazid
MAOI
48
what was the first MAOI marketed
iproniazid
49
which drug targets MAOs
iproniazid (MAOI)
50
which drugs target reuptake channels
imipramine (TCA), fluoxetine (SSRI), venlafaxine (SNSRI), reboxetine (SNRI)
51
which drugs target postsynaptic monoaminergic metabotropic receptors
nefazodone (SRA), mirtazapine (NRA)
52
how did MAOIs contribute to medical knowledge
contributed to the scientific understanding of monoamine systems & their role in depression & parkinson's disease
53
MAOI function
can reversibly or irreversibly inhibit MOAs & are selective or nonselective for specific monoamines, thus affecting monoamine transmission & signaling
54
what are MOAs
enzymes that metabolize the monoamines
55
when are MAOIs prescribed
for treatment-resistant depression
56
how are MAOIs almost always administered
orally
57
MAOI dosage
4x/day to reach target dose & to reduce side effects of large dose at once
58
PK half life of MAOI
fast (eliminated 1.5-4 hours after administration)
59
PD half life of MAOI
longer (2 weeks)
60
why is PD half life of MAOI so long
they can irreversibly inhibit MAOIs
61
monoamine theory of depression
increased levels of MOAs results in reduced monoamines (serotonin, norepinephrine, dopamine), & causes MDD
62
why is the monoamine theory of depressino flawed
may be one mechanism for MDD, but not sufficient to understand full etiology
- monoamine depletion does not worsen depression symptoms, or cause depression in patients who do not have MDD
63
why are MAOIs rarely used
adverse side effects (hypertensive crisis, overdose), & drug-drug interactions w/ other substances
64
tyramine
false neurotransmitter, found in foods such as aged cheese & pickled or fermented foods
65
tyramine function
displaces vesicle stores of NA in the periphery (cannot cross BBB when orally consumed)
66
what does excessive tyramine in the blood cause
hypertensive crisis, by increasing NE (which causes blood vessel constriction)
67
what does MAO inhibition lead to
lack of metabolism of NE, so it builds up in the blood
68
why should MAOIs not be used with SSRIs
excessive serotonin in the CNS can lead to serotonin syndrome
69
what is the classic triad of clinical features of serotonin syndrome
neuromuscular excitation, ANS excitation, and altered mental state
70
symptoms of neuromuscular excitation
clonus, hyperreflexia, myoclonus, rigidity
71
symptoms of ANS excitation
hyperthermia, tachycardia
72
what does severe serotonin toxicity manifest as
coma, rigidity, tonic-clonic seizures, and hyperthermia
73
what is the main function of TCAs
reuptake inhibitors at SERTs and NETs primarily, with weak affinity for DAT
74
what receptors do TCAs act as antagonists at
- serotonin receptors
- histamine & muscarinic acetylcholine receptors
- NMDARs
- alpha 1 norepinephrine GPCRs
75
what channels do TCAs inhibit
sodium channels and L-type Ca2+ channels
76
what drugs should not be taken with TCAs
SSRIs or MAOIs
77
why should TCAs not be prescribed to patients with hepatic impairments
TCAs are metabolized by CYP450 family
78
what is the TCA therapeutic index
very narrow - monitoring for toxicity is crucial & they have a higher risk of overdose than many other antidepressants
79
what are risks of TCAs due to their cholinergic & adrenergic effects
cardiovascular complications & increased risk of seizures
80
TCA side effects
- tachycardia
- cardia effects
- anticholinergic effects
- sexual dysfunction/sedation
81
signs of tachycardia
rapid heart rate
82
signs of cardiac effects
low blood pressure, prolonged QT interval, can lead to arrhythmias
83
signs of anticholinergic effects from TCAs
inhibit muscarinic acetylcholine receptors, which can lead to dry mouth, constipation, blurred vision, confusion
84
why is sexual dysfunction/sedation seen with use of TCAs
due to histamine & acetylcholine receptor inhib
85
what transporters do SSRIs act at
high affinity for SERT & low affinity for other targets
86
what is the therapeutic index of SSRIs
large - very safe
87
how do side effects of SSRIs compare to MAOIs and TCAs
milder
88
half life of SSRIs
long half life - they (& active metabolites) can inhibit the CYP enzymes involved in metabolism
89
what is the first line of treatment for MDD & anxiety
SSRIs
90
what is the 2nd line of treatment for MDD
TCAs
91
how long does it take for SSRIs to take action
over 2 weeks
92
SNRI function
inhibit SERT (serotonin reuptake) and inhibit NET (norepinephrine reuptake)
93
what is the difference between TCAs and SNRIs pharmacological action
SNRIs have minimal or no pharmacological action at adrenergic, histamine, muscarinic, dopamine, or postsynaptic serotonin receptors
94
what is bupropion's function
reuptake inhibitor at DAT & NET
- also approved as a smoking cessation agent
95
advantage of bupropion over other antidepressants
lowest risk of sexual dysfunction
96
Q: do SSRIs block the reuptake of serotonin and norepinephrine?
no, just serotonin
97
Q: do TCAs and MAOIs both inhibit enzymes necessary for monoamine degradation?
no, TCAs inhibit receptors and channels, and MAOIs inhibit MOAs
98
Q: can SNRIs be prescribed for MDD and chronic pain?
yes
99
Q: does wellbutrin (bupropion) affect dopamine transmission?
no
100
Q: is depression caused by low serotonin levels?
no
101
possible mechanisms for efficacy of antidepressants
- neuroplasticity
- structural changes in synapses
- increased neurogenesis & BDNF in the hippocampus
- reduced 5-HT 1A autoreceptors --> reduced feedback inhibition
102
what is the use of ketamine for treating depression
used as a dissociative anesthetic & induces trance-like states
103
ketamine mechanism of action
noncompetitive antagonist at NMDA glutamatergic receptors (blocks the channel pore from opening)
- not fully understood
