29th January 2024

Pathophysiology

The exact pathophysiology of Schizophrenia remains unknown; however, there is significant evidence to suggest a complex interaction between genes and the environment.

Genetic Factors

Genes are believed to play a pivotal role in the development of schizophrenia. This has been evaluated through twin studies conducted on monozygotic and dizygotic twins. Studies have demonstrated that the risk of developing schizophrenia is between 10-15% in dizygotic twins and 40-50% in monozygotic twins. This is compared to the lifetime risk of 1% in the general population. Although we understand that there is a strong genetic predisposition, the exact causative genes have yet to be identified.

Biochemical factors

Ongoing research has identified a variety of chemicals and neurotransmitters that play a role in the development of schizophrenia. Dopamine is one of the main neurotransmitters that has been found in excess within mesolimbic areas of the brain, causing positive symptoms such as hallucinations. Other substances, such as opioids and amphetamines increase dopaminergic activity, thus contributing to the causation of psychosis. In addition to Dopamine, an excess of Serotonin is also recognised to likely be causative of psychosis. This pathway is targeted by Second-Generation Antipsychotics working antagonistically at Serotonin receptors(5-HT2-R).

Environmental Factors

The fact that monozygotic twins only have a 50% chance of developing schizophrenia, supports the idea that there is a complex interaction between genes and environment that influences their risk. There are a number of recognised environmental factors that are thought to predispose an individual to developing schizophrenia. This includes:

• Obstetric complications (haemorrhage, preterm labour, foetal hypoxia)
• Cannabis, amphetamine and cocaine (increase dopaminergic activity)
• Smoking
• Immigration: There is notably a higher prevalence of schizophrenia in immigrant populations. This is thought to be due to higher levels of stress activating latent genetic factors
• Neurodevelopmental abnormalities in utero
• High expression households: levels of emotion expressed in a household may be ‘high’ or ‘low.’ The emotions can be positive (reassuring, warm) or negative (hostile, critical). High levels of both positive and negative emotions can have a significant impact on the development, management and relapse of schizophrenia. For example, high levels of negative emotions are a known psychological stressor which could trigger a relapse, whereas an over-involved family impedes the development of independent coping strategies.