Bipolar Disorder Pathophysiology Flashcards
Bipolar Disorder Heritability
0.75
Bipolar Risk Factors
Prenatal exposure to influenza (4-fold increase) BDNF Bcl-2 XBP-1 IMPase
BDNF function
Neuronal survival and neuroplasticity
Bcl-2 function
Mitochondrial anti-apoptotic protein that stimulates sprouting and regrowth
Regulates Calcium
XBP-1 functionn
Regulate ER stress
IMPase function
Inositol monophosphatase
Regenerates inositol for synthesis of lipids
Bipolar Structural abnormalities
Overall, disruption of structures of the limbic system along with ventromedial and orbital areas of PFC Reduced hippocampal volume Reduced PFC volume Reduced neuronal cell counts Decreased glutamate Excessive activation of amygdala
Why is there excessive activation of amygdala?
Lack of prefrontal cortex control leading to emotional extremes of mania and depression or mixed
Physiological Abnormalities
Elevated Ca
Mitochondrial/ER dysfunction
Too little BDNF
Abnormal Ca levels
Elevated calcium leads to:
change in gene expression and activated apoptotic pathways
Mitochondrial/ER dysfunction caused by and leads to:
Elevated Ca leads to gene expression changed which leads to oxidative stress and active apoptotic pathways
Too little BDNF can lead to
cell atropy
Synaptic pruning
Decreased/weakening synapses
Too much Ca can lead to:
Apoptotic pathway activation
No synaptic growth/synaptic plasticity
Bipolar Treatment
Antipsychotics like valproate, carbamazepine and lamotrigine which are all voltage gated Na channel blockers
Lithium MOA
Inhibit IMPase Na/K ATPase inhibition GSK3 inhibitor Potentiate AMPA currents Upregulates BDNF Stimulates hippocampal neurogenesis
