Mood Disorders + Antidepressant Drugs Flashcards

1
Q

DSM-IV

A

Major depression

Bipolar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

DSM-V

A

Major depressive disorder

Disruptive mood dysregulation disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Depression Signs and Symptoms

A
Psychomotor retardation
Fatigue/loss of energy
Diminished ability to concentrate
Diminished social activity interest
Insomnia
Guilt + worthlessness
Weight loss + decreased appetite
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Bipolar chance

A

Increased if related to patient with bipolar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Depression chance

A

Increases if related to patient with bipolar

Increases even more if related to patient with major depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Genes linked to depression

A

GRIK4
CRHR1
SLC6A4
MAOA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pathophysiology of depression

A

Dysfunction of noradrenergic and serotonergic pathways

Key players, but not only players

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Brain regions associated with depression

A
Amygdala- fear and anxiety
Ventrolateral prefrontal cortex
Dorsolateral prefrontal cortex
Medial prefrontal cortex
Striatal regions (ventral striatum)
Hippocampus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Raphe

A

Place of origin of most of innervation of cortical structures
Neurones in raphe have slow activity in waking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Subgenual prefrontal cortex abnormalities- PET scan

A

Decreased metabolism- significant reduction in glucose consumption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Subgenual prefrontal cortex abnormalities- MRI scan

A

Mean grey matter volume of subgenual anterior cingulate cortex is REDUCED in patients with major depressive or bipolar disorder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cortical Thickness

A

Depressed patients have significant cortical matter loss
12-15% change
–> structure abnormality/volume loss –> grey/white matter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Default mode network

A

Network of brain regions active when brain is at wakeful rest
Increased DMN connectivity in subjects with major depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Gene-environment interactions

A

5HT transporter polymorphism is associated with a higher risk of major depression
Different alleles lead to different transcription of the transporter
Short allele, more at risk of depression
Long allele, more resistant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Genetic variations + CNS connectivity

A

Correlation between decreased connectivity amygdala-prefrontal cortex, certain MAOA isoforms (affect activity of enzyme) and state of clinical depression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Amygdala-prefrontal cortex

A

Connectivity is significantly reduced in depressed patients + carries of the higher active MAOA risk alleles (MAOA-H)
Reduced coupling in this circuit –> longer + more severe course of disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

MAOA gene genetic variation

A

Encodes enzyme which controls monoaminergic signalling

May affect the course of major depression by disrupting cortico-limbic connectivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Higher active MAOA

A

Disrupts cortico-limbic connectivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Rumination

A

Regions involved in persistent recurring thoughts in depression include amygdala + hippocampus
Hyperactivation in amygdala + hippocampus –> increased activity in subgenual cingulate cortex, region that integrates limbic feedback + relays to prefrontal cortex
–> increased subgenual activity increases activity in MPFC, region associated with internal representations of oneself
Activation decreased in DLPFC and VLPFC- areas associated with cognitive control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

TCAs MOA

A

Inhibit reuptake of amines

Have affinity for H1, muscarinic, alpha-1 and alpha-2 adrenoreceptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

TCA examples

A

Clomipramine
Imipramine
Amitriptyline

22
Q

TCA Side effects

A
Muscarinic- dry mouth, blurred vision, constipation, urinary retention
Adrenoreceptors- Postural hypotension
Fatigue
Sedation
Weight gain
Dizziness 
Loss of libido
23
Q

TCA overdose

A

Dangerous

Cardiotoxicity

24
Q

Monoamine oxidase inhibitors MOA

A

Irreversible inhibition of enzyme

Non-selective MAOa vs MAOb

25
MAOIs examples
Phelzine Iproniazid Tranylcypromine
26
MAOI - tyramine
Interactions with tyramine-containing foods --> mature cheese, pickled fish + meat, red wine, beer, yeast With MAOIs, tyramine accumulates in brain --> will penetrate monoaminergic presynaptic terminals containing noradrenaline, pushing it out, leading to higher BP, headaches etc.
27
MAOI side effect
Hepatotoxicity | Massive hypotensive activities
28
MAO enzymes
Breakdown of noradrenaline, dopamine and serotonin
29
SSRI MOA
Increased selectivity for serotonin reuptake | --> leave serotonin in synapse
30
SSRI examples
Citalopram- most effective Fluoxetine Paroxetine
31
SSRI side effects
``` Nausea Headaches GI problems Increased aggression Insomnia Anxiety Sexual dysfunction ```
32
S-isomer of citalopram
Escitalopram
33
Reversible MAOIs
Moclobemide Increased selectivity for MAOa Safer than irreversible MAOIs Adverse effects- nausea, agitation, confusion
34
Venlafaxine
Serotonin noradrenaline reuptake inhibitors (SNRIs)
35
Reboxetine
Noradrenaline reuptake inhibitors (NARIs)
36
Mirtazapine
Noradrenergic and specific serotonergic antidepressants (NaSSAs) Antagonism at 5HT2 and alpha-2 adrenergic receptors
37
Trazodone
Serotonin antagonist and reuptake inhibitor (SARI) | Mainly antagonist at 5HT2 receptors + serotonin reuptake inhibition
38
Agomelatine
Agonist at melatonin MT1 + 2 receptors and antagonist at 5HT2c receptors Noradrenaline/dopamine disinhibitor
39
Antidepressant drug Discontinuation Syndrome
Can occur after decrease in dose of drug taken, after interruption of treatment, or abrupt cessation of treatment Dependant on medication
40
Discontinuation syndrome symptoms
``` Insomnia Anxiety Nausea Headaches Electric shock sensations Agitations ```
41
Delay of action of antidepressant drugs
Changes in autoreceptors (5HT1a) Autoreceptors activated due to immediate increase in synaptic amine concentration --> decrease firing of neurones They then become desensitised --> neurones back to normal firing rate --> effect no longer inhibited
42
Bipolar- Lithium
Narrow therapeutic margin Renal + thyroid function must me checked Adverse effects- thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne
43
Bipolar- carbamazepine, sodium valproate
Mood stabilisers
44
Risk order for mania switch
TCAs> SNRIs> MAOIs> SSRIs
45
Principals Depression management
``` Ensure optimum thyroid function Treat co-morbidity (substance misuse) Ensure full symptom control Monitor course of illness (mood chart) Adapt and review treatment Prevent recurrence ```
46
Phases of treatment
Acute Continuation Maintenance
47
Acute treatment
First 6-12 weeks | Aims at remission (control of symptoms)
48
Continuation treatments
For 6 months after full symptom control Maintain remission status Prevent relapse
49
Maintenance treatment
Prevention of recurrence of further episode
50
Non-pharmacological approaches
Electroconvulsive therapy- treatment for refractory depression with suicide risk, treatment-resistant depression CBT Vagal nerve stimulation DBS- subcallosal cingulate white mater, subgenual cingulate cortex
51
Hippocampus
Neuronal loss + neurogenesis in hippocampus affects whole spectrum of symptoms associated with depression Increases in cortisol + pro-inflammatory cytokines --> neuronal loss + structural changes in hippocambus