Pathophysiology of Unipolar Depression

Question 1

Bipolar defined

Answer 1

Drastic mood swings from extreme highs to extreme lows

Question 2

Depression defined

Answer 2

Disorder of inner emotions
Affective disorder or mood disorder
Inappropriate exaggeration of mood

Question 3

Major depression occurs when:

Answer 3

Sadness, grief and other negative emotions interfere with the ability to function in everyday normal life

Question 4

S&S of Major Depression

Answer 4

Persistent sad, anxious, or empty mood
Loss of interest or pleasure in normal activities
Restlessness, excessive crying
Feelings of guilt, worhtlessness, helplessness, hopelessness
Disruptiono f sleep patterns
Changes in appetite and weight
Decreased energy, fatigue, feeling run down
Thoughts of death or suicide
Difficulty concentrating
Headache, digestive problems, chronic pain
Stop caring for themselves

Question 5

MDD involves

Answer 5

Cognitive
Behavioral
Social disruption

Question 6

Risk Factors for Depression

Answer 6

FH
Stress
Rural
Unemployment
Drug side effects
Ethnicity/Culture
Early Childhood Trauma
Alcohol
Divorced/separated/alone
Illness
Sex/gender
Age (mid-20s)

Question 7

Triggers + Depression

Answer 7

Results from underlying medical conditions, from drug treatments and from stress
Combination of genetic, psychological and environmental factors

Question 8

Comorbidities + Depression

Answer 8

Associated with others (hypothyroidism, nutritional deficiences, neurological/psychiatric disorders

Question 9

Psychotic Depression Defined

Answer 9

The condition also presents with psychotic behaviors such as hallucination and disturbed sense of reality

Question 10

Define Dysthymia depression

Answer 10

Less severe, less disabling
Shows a prolong time course
Predisposes you to MDD

Question 11

Define Seasonal Affective Disorder

Answer 11

Winter = depressed
Spring = remission
Light therapy might be an option

Question 12

Sleep + Depression

Answer 12

Sleep deprivation can result in mood elevation but the depression return after a night of recovery sleep

Question 13

Define Postpartum depression

Answer 13

Depression following delivery

Substantial hormone and physical changes + mental stress of having a baby

Question 14

Depression is what type of disorder?

Answer 14

Heterogeneous

Question 15

Risk ratio for 1st degree family members is:

Answer 15

2-3

Question 16

Monoxygotic twins vs dizygotic twins

Answer 16

54% vs 19%

Question 17

Heritability number is?

Answer 17

.35, which means 65% of the time the phenotypic effects are due to environment and random events

Question 18

Define Common Variant hypothesis

Answer 18

Polygenic disorder and the genes involved are common alleles with a low risk ration

Question 19

5HT involvement?

Answer 19

A polymorphism was IDed in the promotoer of SERT that is a 44 bp insertion/deletion –> short allele produce less SERT
S/S homozygotes are at greater risk of developing MDD
- Primarily in ppl with rough childhood

Question 20

Trp ydroxylase 2 (TPH2) involvement?

Answer 20

Hypomorphic allele in the enzyme that catalyzes the rate-limiting step in 5HT synthesis in the brain

Question 21

Brain-derived Neuronotrophic Factor (BDNF)

Answer 21

Regulates synaptic plasticity and neuronal survival/differentiation
Reduced by stress
Missense mutation affects synthesis and stability
- Typically in bipolar

Question 22

Define Monoamine Hypothesis

Answer 22

Depression is due to serotonergic and noradrenergic hypofunctions

Question 23

Monamine hypothesis explained

Answer 23

NE: attention and vigilance, hunger and satiety
5HT: eating behaviors, sleep libido, body temp, melatonin conversion (low 5HT = aggression and impulsive behaviors)

Question 24

Diffuse Neuromodulatory Systems

Answer 24

NT just send their signals down neurons

Question 25

The fact that it takes so long for antidepressant drug to work means:

Answer 25

Gene changes must be involved /changes in gene regulation alter the pattern of receptors and ion channels in the affected neurons Could also mean there is a structural change

Question 26

What regions of the brain are involved in the disruption of inner emotions?

Answer 26

Limbic system and prefrontal cortex

Question 27

Prefrontal cortex and limbic system are a part of?

Answer 27

Part of the Default Mode Network (active during times of engagement)

Question 28

Prefrontal cortex function

Answer 28

Planning, motivation and working memory "elaboration of thoughts" which includes ability to predict and plan for the future, analyze consequences of planned actions Control over steroeotyped actions

Question 29

Disfunction in the Prefrontal cortex leads to?

Answer 29

``` Inability to solve complex problems Lack of motivation Lack of focus Impulsivity Inappropriate social interactions ```

Question 30

Limbic System Function

Answer 30

Interconnected structures that function together in emotion and behavior Includes: hypothalamus, amygdala, hippocampus, accumbens, cingulate cortex

Question 31

Hypothalamus Function

Answer 31

Regulates autonomic function, endocrine function, basic behaviors (eating/sleeping) Activation of PS: pleasure/warm fuzzy Activation of S: anxiety, fear, anger Controls display of emotional behavior

Question 32

Dexamethasone Suppression Test used

Answer 32

Test hypothalamic function in MDD

Question 33

Treatment with Dexamethasone leads to

Answer 33

Reduced ACTH and cortisol levels

Question 34

50% of pts have

Answer 34

Elevated cortisol levels

Question 35

Amygdala Function

Answer 35

``` Inner emotions (joy, anger, hope, fear, anxiety) Receives input from PFC and applies emotions to cortical info ```

Question 36

Hippocampus function

Answer 36

Memory consolidation | Positional memory, timing mechanisms, inhibitiono f hypothalamic function

Question 37

Accumbens function

Answer 37

"Reward center" which is activated by DA neurons | Responds to novelty and applies positive reinforcements to thoughts and actions

Question 38

Cingulate Cortex Function

Answer 38

Emotional awareness

Question 39

How does the limbic system function together?

Answer 39

Cingulate gyrus receives sensory info from thalamus, PFC and association cortex Then sends axons to the hippocampal formation Hippocampus innervates cortical regions and hypothalamus - Link outcomes to memory, motivation and behavioral responses

Question 40

Pathology + Depression

Answer 40

Reduced volume of hippocampus and areas in PFC

Question 41

Atrophy + Depression

Answer 41

None is seen although one study shows dendritic spine reduction

Question 42

Depression + Dentate Gyrus

Answer 42

Neurogenesis occurs here and is important for hippocampal function to form new memories

Question 43

Elevated cortisol levels can cause:

Answer 43

Hippocampal atrophy (Cushing's disease) and impaired hippocampal neurogenesis

Question 44

Exercise + Antidepressant + Depression

Answer 44

Enhances neurogenesis and elevate BDNF levels (important regulator of hippocampal function)

Question 45

Ketamine + Depression

Answer 45

Antidepressant Rapid effects Dissociative analgesic and psychotomimetic action Supposed to rapidly reverese dendritic atrophy with BDNF