Bipolar Disorder (Manic-Depressive Illness): Causes

Pathogenesis (disease development)

The cause of bipolar disorder is thought to be multifactorial. Genetics, in particular, play a role, as do personality characteristics and environmental factors.

Herpes viruses may also play a role in the pathogenesis of bipolar disorder: patients with bipolar and major depressive disorder were found to have a high rate of infection with the human herpes virus HHV-6 in Purkinje neurons.

Risk factors for frequent recurrent episodes.

  • Female sex
  • Young age of onset
  • Serious life events
  • Mixed episodes
  • Psychotic symptoms
  • Rapid cycling (rapid alternation between depressive and manic episodes; ≥ 4 affective episodes in 12 months)
  • Insufficient response to therapy (phase prophylactic therapy).

Risk factors for a chronic course

  • Frequent episodes
  • Premorbid personality
  • Poor compliance
  • Insufficient response to therapy (acute/phase prophylactic therapy).
  • Other mental/somatic illnesses
  • Additional substance abuse

Etiology (causes)

Biographical causes

  • Genetic burden from parents, grandparents
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Genes: ANK3
        • SNP: rs4948418 in the gene ANK3
          • Allele constellation: TT (2.10-fold).
          • Allele constellation: CT (1.45-fold)
          • Allele constellation: CC (0.94-fold)
    • A genome-wide association study (GWAS) detected a total of 30 regions associated with bipolar disorder; it also genetically distinguished two subtypes of the disorder:
      • Type I, with more pronounced manic and depressive phases, appears to be more related to schizophrenia at the genetic level
      • Type II suggests a “milder” course with a relationship to depression
  • Positive family history
  • Temperament abnormalities

Behavioral causes

  • Nutrition
    • Consumption of foods cured with nitrate salts: Patients hospitalized for a manic episode were 3.5 times more likely to have ever eaten meat cured with nitrate than persons who did not have a severe psychiatric disorder (odds ratio = 3.49, 95% confidence interval 2.24-5.45, p < 8.97 × 10-8). Note: Rat experiments with nitrate-containing diets confirm the risk of mania. Note: Nitrates and nitrites are also present in vegetables and salads. Seasonal vegetables contain fewer nitrates.
  • Substance dependence, unspecified (alcohol; cannabis (hashish and marijuana)).
  • Circadian rhythm disorder (disturbance of the day-night rhythm), i.e., increased activity during nocturnal rest periods and inactivity during the day

Environmental stress – intoxications (poisonings).

  • Regions with particularly poor air quality