Bipolar Pathophysiology

Question 1

Bipolar Disorder is associated with

Answer 1

Depressive symptoms and abnormally elevated mood (mania)

“Manic-depression”

Question 2

Manic phase is characterized by:

Answer 2

Overly happy, excited
Extremely irritable
Racing thoughts/behaviors
Easily distracted
Restless w/o tired
Little sleep
Impulsive
Unrealistic beliefs
Aggressive/provactive
Substance abuse
Denial of symptoms

Question 3

Define Bipolar I

Answer 3

More severe disorder where the manic phase is disruptive to normal daily function

Question 4

Define Bipolar II

Answer 4

Manic phase is less severe and referred to as “hypomanic

Question 5

Uncontrolled Bipolar

Answer 5

“progressive disorder”

Untreated leads to euthmyic periods becoming shorter over time and highs may become higher with lower lows

Question 6

Rapid cycler BD

Answer 6

More than 4 mood swings in a year

Question 7

Mixed BD

Answer 7

Pts show both depressive and manic symptoms at the same time

Question 8

Cyclothymic BD

Answer 8

Both the manic and depressive phase are less severe

Question 9

Lifetime prevalence of BD and suicide risk

Answer 9

1.5%
Late adolescence to early adult (younger than MDD)
10-20% suicide and higher in BDII

Question 10

Men vs Women presentation

Answer 10

Men: first mania
Women: first depression

Question 11

Causes of BD

Answer 11

Environmental (physical, nutrition, social stressors)

Genetics

Question 12

Pregnancy + Influenza

Answer 12

Increased risk of BD by 4-folds

Question 13

First degree relatives + BD

Answer 13

5-10 fold increase risk

Question 14

Monozygotic twin + BD

Answer 14

~70% increased risk

Question 15

Dizygotic twins + BD

Answer 15

~20% increased risk

Question 16

Heritability for BD

Answer 16

0.75 (MDD was 0.35)

Question 17

BD has a shared genetic etiology with

Answer 17

Schizo and MDD

Question 18

Possible risk factors for BD

Answer 18

BNDF
Bcl-2
XBP-1
IMPase

Question 19

BNDF + BD

Answer 19

Neurotrophic factor important for neuronal survival and neuroplasticity

Question 20

Bcl-2

Answer 20

Mitochonddrial anti-apoptotic protein that stimulates dendritic sprouting and regrowth
Regulates intracellular Ca homeostasis

Question 21

XBP-1

Answer 21

Enzyme regulates the ER stress response that results form accumulation of damaged proteins

Question 22

Structural abnormalities in BD

Answer 22

Reduced hippocampal volume
Reduced PFC volume
Reduced neuronal cell counts
Decreased glutamate

Question 23

Most consistent finding with BD

Answer 23

Excessive activation of amygdala (in response to some emotional triggers) –> due to decreased inhibition from prefrontal regions that regulate limbic activity leading to dysregulation which causes emotional extremes (mania/depression)
- wiring is disrupted between emotional networks and brain regions disrupted too

Question 24

Abnormalities showing face:

Answer 24

Before first episode meaning that the development of the networks is abnormal

Question 25

Define kindling

Answer 25

Progressive nature of the disorder which is reinforced by abnormal activity through the normal mechanisms of synaptic strengthening

Question 26

Alter Ca Homeostasis in BD

Answer 26

Elevated cytoplasmic levels of Ca Second messenger involved in synaptic plasticity Changes gene expression Too much ca __> activates apoptotic pathways

Question 27

Mitochondrial/ER dysfunction + BD

Answer 27

Altered Ca leads to mitochondrial dysfunction due to gene expression changes in oxidative phosphorylation and antioxidant defenses All this leads to oxidative stress and activation of apoptotic pathways

Question 28

Neuronal atrophy/death + BD

Answer 28

Altered BDNF and Ca disrupts trophic pathways that support the survival and elaboration of neurons Too little BDNF = cell atrophy Too much Ca = activated apoptotic pathways - death

Question 29

Abnormal synaptic plasticity + BD

Answer 29

Normally BDNF enhances anabolic pathways that increase and strengthen synpases and inhibit GSK-3 which promotes pruning Ca stimulates synaptic growth

Question 30

Mood stabilizers =

Answer 30

Lithium and anticonvulsants (valproate, carbamazepine, lamotrigine)

Question 31

Use of anti-depressants in BD

Answer 31

Means it is similar to MDD

Question 32

Use of anti-psychotics in BD

Answer 32

Means mania involves dopaminergic hyperactivity involving accumbens and prefrontal cortex

Question 33

valproate, carbamazepine, lamotrigine target

Answer 33

"mood stabilizers" | Target voltage gated Na channels which shows that toning down activity in limbic circuits would reduce mood swings

Question 34

Lamotrigine also tragets

Answer 34

Ca channels and could mitigate altered Ca homeostasis

Question 35

Valproate also does what

Answer 35

Histone deacetylase activity that could normalize gene expression

Question 36

Lithium in BD

Answer 36

Citrate or carbonate salt Inhibition of IMPase which decreases PI lipids and Ca bc IP3 Na/K ATPase inhibition Inhibit GSK3 Potentiate AMPA currents Upregulates BDNF (promotes dendritic growth) Stimulates hippocampal neurogenesis