Medical Genetics - V. M. Zaporozhan 2005

Multifactorial Diseases
Genetics of Some Common Multifactorial Diseases
Schizophrenia

It is likely a group of disorders characterized by distinct genetic defects and a common set of symptoms. Several key candidate genes have been identified.

1. The catechol-O-methyltransferase Gene (COMT, 22q11) is involved in the degradation of catecholamines, including dopamine, and serves as the primary enzyme for dopamine breakdown in the prefrontal cortex. A COMT genetic polymorphism has been described, associated with the presence of either valine or Methionine at position 108 (short COMT form) or position 158 (long COMT form). The Val-COMT allele is significantly more prevalent in patients with schizophrenia.

2. The second candidate gene is the 5-HT2A serotonin receptor gene (13q32). A link has been established between schizophrenia and the T102C gene polymorphism.

3. The third candidate gene, DISC-1 (Disrupted-in-Schizophrenia 1, 1q32), was initially discovered in a Scottish family with a high incidence of psychiatric disorders and a balanced translocation leading to the disruption of this gene. The involvement of the DISC-1 gene in the Pathogenesis of schizophrenia has also been supported by studies of Finnish families. The protein product of this gene has not yet been fully characterized, nor has the exact mechanism by which it contributes to The Development of schizophrenia.

Recent studies have shown that environmental risk factors contributing to the development of schizophrenia may include birth trauma and neonatal viral infections. For instance, according to one study, nucleotide sequences homologous to retroviral pol genes were detected in the CEREBROSPINAL FLUID of 29% of schizophrenia patients. Indirect evidence supporting The Role of viral infections is provided by the noticeably higher incidence of schizophrenia among individuals born during the winter months.