PATHOGENESIS

PATHOGENESIS - OVERVIEW

• Genetics
• Physiological / biochemical
• Psychological
• Environmental
• .

GENETIC FACTORS

• 19% chance of developing bipolar disorder (BD) if family member has BD
• Genetic variation in IL-1-beta promoter gene
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PHYSIOLOGICAL/BIOCHEMICAL FACTORS

• Neuroendocrine function
• HPA-axis
• Inflammation
• Brain-derived neurotropic factor (BDNF)
• .

neuroendocrine function

• dopamine
• norepinephrine
• serotonin
• .

hpa-axis

• Chronic stress increases cortisol
• Excess cortisol = atrophy of hippocampus
• Activates pro-inflammatory cytokines
• .

inflammation

• Pro-inflammatory cytokines
• Markers of inflammation are high in BD
• BD = inflammatory disease
• .

brain-derived neurotrophic factor

• BDNF maintains neurons
• Connected with prefrontal cortex & hippocampus
• Low in BD individuals
• .

PSYCHOLOGICAL FACTORS

• Exposure to trauma, especially in early years
• Stress, excess glucocorticoids
• Impact of trauma/stress on HPA-axis, neurons, immune system
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ENVIRONMENTAL FACTORS

• Drug & alcohol abuse
• Diet & lifestyle
• Sleep
• .

PHYSIOLOGICAL CHANGES

• Age & the prefrontal cortex
• Immune system dysregulation
• CNS development
• Mitochondrial dysfunction
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AGE and the prefrontal cortex

• Early onset, usually during adolescence
• Prefrontal cortex reduces in size, impairs function
• .

IMMUNE SYSTEM dysregulation - inflammation

• Imbalance of inflammatory cytokines
• IL-6 and IL-8
• Tumor necrosis factor-alpha (TNF-α)
• TNF-α inhibits release of M2 receptors
• .

immune system dysregulation - inflammation

• Inflammation & the SAD diet
• Lipopolysaccharides (toxins) increase inflammation
• C-Reactive Protein (CRP)
• Obestiy & inflammation
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MITOCHONDRIAL DYSFUNCTION

• Oxidative stress, decreased production of ATP & apoptosis
• Depression = reduction in glucose utilization in brain (prefrontal cortex, anterior cingulate gyrus, caudate nucleus)
• .

Development of bd: conclusion

• Development is multifactorial & complex
• Other theories
• Do these abnormalities trigger BD or are they a result of BD?
• .