Mood Disorders + Antidepressant Drugs

Question 1

DSM-IV

Answer 1

Major depression

Bipolar

Question 2

DSM-V

Answer 2

Major depressive disorder

Disruptive mood dysregulation disorder

Question 3

Depression Signs and Symptoms

Answer 3

Psychomotor retardation
Fatigue/loss of energy
Diminished ability to concentrate
Diminished social activity interest
Insomnia
Guilt + worthlessness
Weight loss + decreased appetite

Question 4

Bipolar chance

Answer 4

Increased if related to patient with bipolar

Question 5

Depression chance

Answer 5

Increases if related to patient with bipolar

Increases even more if related to patient with major depression

Question 6

Genes linked to depression

Answer 6

GRIK4
CRHR1
SLC6A4
MAOA

Question 7

Pathophysiology of depression

Answer 7

Dysfunction of noradrenergic and serotonergic pathways

Key players, but not only players

Question 8

Brain regions associated with depression

Answer 8

Amygdala- fear and anxiety
Ventrolateral prefrontal cortex
Dorsolateral prefrontal cortex
Medial prefrontal cortex
Striatal regions (ventral striatum)
Hippocampus

Question 9

Raphe

Answer 9

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

Question 10

Subgenual prefrontal cortex abnormalities- PET scan

Answer 10

Decreased metabolism- significant reduction in glucose consumption

Question 11

Subgenual prefrontal cortex abnormalities- MRI scan

Answer 11

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

Question 12

Cortical Thickness

Answer 12

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

Question 13

Default mode network

Answer 13

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

Question 14

Gene-environment interactions

Answer 14

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

Question 15

Genetic variations + CNS connectivity

Answer 15

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

Question 16

Amygdala-prefrontal cortex

Answer 16

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

Question 17

MAOA gene genetic variation

Answer 17

Encodes enzyme which controls monoaminergic signalling

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

Question 18

Higher active MAOA

Answer 18

Disrupts cortico-limbic connectivity

Question 19

Rumination

Answer 19

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

Question 20

TCAs MOA

Answer 20

Inhibit reuptake of amines

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

Question 21

TCA examples

Answer 21

Clomipramine
Imipramine
Amitriptyline

Question 22

TCA Side effects

Answer 22

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

Question 23

TCA overdose

Answer 23

Dangerous

Cardiotoxicity

Question 24

Monoamine oxidase inhibitors MOA

Answer 24

Irreversible inhibition of enzyme

Non-selective MAOa vs MAOb

Question 25

MAOIs examples

Answer 25

Phelzine Iproniazid Tranylcypromine

Question 26

MAOI - tyramine

Answer 26

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.

Question 27

MAOI side effect

Answer 27

Hepatotoxicity | Massive hypotensive activities

Question 28

MAO enzymes

Answer 28

Breakdown of noradrenaline, dopamine and serotonin

Question 29

SSRI MOA

Answer 29

Increased selectivity for serotonin reuptake | --> leave serotonin in synapse

Question 30

SSRI examples

Answer 30

Citalopram- most effective Fluoxetine Paroxetine

Question 31

SSRI side effects

Answer 31

``` Nausea Headaches GI problems Increased aggression Insomnia Anxiety Sexual dysfunction ```

Question 32

S-isomer of citalopram

Answer 32

Escitalopram

Question 33

Reversible MAOIs

Answer 33

Moclobemide Increased selectivity for MAOa Safer than irreversible MAOIs Adverse effects- nausea, agitation, confusion

Question 34

Venlafaxine

Answer 34

Serotonin noradrenaline reuptake inhibitors (SNRIs)

Question 35

Reboxetine

Answer 35

Noradrenaline reuptake inhibitors (NARIs)

Question 36

Mirtazapine

Answer 36

Noradrenergic and specific serotonergic antidepressants (NaSSAs) Antagonism at 5HT2 and alpha-2 adrenergic receptors

Question 37

Trazodone

Answer 37

Serotonin antagonist and reuptake inhibitor (SARI) | Mainly antagonist at 5HT2 receptors + serotonin reuptake inhibition

Question 38

Agomelatine

Answer 38

Agonist at melatonin MT1 + 2 receptors and antagonist at 5HT2c receptors Noradrenaline/dopamine disinhibitor

Question 39

Antidepressant drug Discontinuation Syndrome

Answer 39

Can occur after decrease in dose of drug taken, after interruption of treatment, or abrupt cessation of treatment Dependant on medication

Question 40

Discontinuation syndrome symptoms

Answer 40

``` Insomnia Anxiety Nausea Headaches Electric shock sensations Agitations ```

Question 41

Delay of action of antidepressant drugs

Answer 41

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

Question 42

Bipolar- Lithium

Answer 42

Narrow therapeutic margin Renal + thyroid function must me checked Adverse effects- thirst, nausea, fine tremor, polyuria, weight gain, oedema, acne

Question 43

Bipolar- carbamazepine, sodium valproate

Answer 43

Mood stabilisers

Question 44

Risk order for mania switch

Answer 44

TCAs> SNRIs> MAOIs> SSRIs

Question 45

Principals Depression management

Answer 45

``` 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 ```

Question 46

Phases of treatment

Answer 46

Acute Continuation Maintenance

Question 47

Acute treatment

Answer 47

First 6-12 weeks | Aims at remission (control of symptoms)

Question 48

Continuation treatments

Answer 48

For 6 months after full symptom control Maintain remission status Prevent relapse

Question 49

Maintenance treatment

Answer 49

Prevention of recurrence of further episode

Question 50

Non-pharmacological approaches

Answer 50

Electroconvulsive therapy- treatment for refractory depression with suicide risk, treatment-resistant depression CBT Vagal nerve stimulation DBS- subcallosal cingulate white mater, subgenual cingulate cortex

Question 51

Hippocampus

Answer 51

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