Causes of Bipolar Disorder

The causes of bipolar disorder likely vary between individuals and the
exact mechanism underlying the disorder remains unclear

1) Genetic factors
- Bipolar type I (BPI) disorder, has a major genetic component (ANK3,-
CACNA1C, and CLOCK genes)
- First-degree relatives of a person with bipolar disorder are
approximately 7 times more likely to develop bipolar disorder than
the rest of the population
2) Neurophysiologic factors
- Neuroimaging studies eg. meta-analysis by Houenou et al
1) Decreased activation and diminution of gray matter in a cortical-
cognitive brain network - emotional regulation
2) Increased activation in ventral limbic brain regions - mediate and
generate emotional responses
3) Biochemical factors
- Catecholamine hypothesis study:
 ↑ epinephrine and norepinephrine – mania
 ↓ epinephrine and norepinephrine – depression

- Drugs (↑ monoamine) :
 Cocaine
 L-dopa,
 Amphetamines
 Antidepressants (SSRI)

- Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal

axis
4) Environmental factors
- Stressful life events (bereavement, personal separation, etc.)
- Pregnancy
- Work

5) CNS Disorders
- Stroke
- Cerebral tumour
- Epilepsy
- Multiple Sclerosis
- AIDS
Aetiological Theories
1) Abnormal programmed cell death
- Neuroimaging studies indicate apoptosis in frontal cortex and the
hippocampus
- Mood stabilizers and antidepressants stimulate cell survival pathways
which may improve cellular resilience.

2) Kindling Hypothesis
• Genetically predisposed individual + Minor Insult (drugs of abuse,
excessive glucocorticoid stimulation, acute or chronic stress) = Mania
• After 1st episode, neuronal damage may persist
• Recurrence with or without minor environmental or behavioural stressors
resulting further injury
• Source
- https://emedicine.medscape.com/article/286342-overview#a4
- https://en.wikipedia.org/wiki/Bipolar_disorder#Mechanism
- Oxford Handbook of Psychiatry