Causes of Schizophrenia: A multi-factorial disorder

Causes of Schizophrenia. We’ve already talked about schizophrenia, but until now we knew very little about its origin. This illness is so complex that we still don’t fully understand it, but a recent study may have found out what causes schizophrenia. The key may be in a genetic component Complement component 4, or C4. This may be the secret that helps us better treat this illness.

Causes of Schizophrenia
Causes of Schizophrenia

Schizophrenia may present itself in many different ways and intensities. Some patients suffer from hallucinations (paranoid schizophrenia), others make no sense when they talk, and some even fall into a catatonic state that incapacitates them. Aside from the different manifestations of schizophrenia, those who have it may have other disorders that are associated with schizophrenia, like depression and anxiety.

Due to the various problems and symptoms associated with schizophrenia, it’s difficult to fully understand it. Let’s breakdown the different causes of schizophrenia according to researchers. 

Causes of Schizophrenia


There have been twin studies that have proven the inheritability of this disorder however the exact genetic cause still remains unknown. The most popular hypothesis are the glutamate hypothesis of schizophrenia, where there would be a hypofunction of the glutamatergic signaling via the N-methly-D-aspartate receptor (NMDA), and the dopamine hypothesis where there is a disturbed and hyperactive dopamingeric signal transduction.


Researchers have established that the combinations between genetic vulnerability and environmental factors may be responsible for the development of schizophrenia. Not all causes are due to heritability, however those who are its considered to be multifactorial, where several genes interact together.

Evolutionary Hypothesis

The most popular hypothesis among this category for the causes of schizophrenia are the imprinted brain theory. This theory is based on the conflict theory of imprinting which argues that in organisms such as humans, the maternal and paternal set of genes have antagonistic reproductive interests. It is believed that a genomic imprinting with a favor in maternal genes may cause psychosis, while a favor in paternal genes may cause autism.


Since the 1970’s it’s been hypothesized that low oxygen levels in the brain (hypoxia) before, at or after birth may be one of the causes of schizophrenia. Fetal hypoxia has been related with a reduced volume of the hippocampus which is correlated with schizophrenia. There have been studies that show that neurological soft signs or obstetric complications may carry an elevated risk for schizophrenia and  other nonaffective psychosis.

Infections and Inmune System

Experts at Harvard University have discovered that schizophrenia may be related to the complement system C4, which is in charge of carrying out some immune functions that protect us from infectious elements. Throughout adolescence, the participation of this complement is vital for our mind. The C4 does a kind of “pruning” of neuronal connections, as adolescent brains have an excess. During this process, the brain strengthens the connections that are most frequently used and gets rid of the less useful ones. Here is where schizophrenia may begin, the roots of an immune system problem, like multiple sclerosis.

After analyzing a group of more than 65,000 patients over 30 years and comparing the study’s hypothesis uses 700 brain samples, experts have determined that there is a relationship between the C4 and the development of schizophrenia. This may be due to an excess of neural “pruning” during adolescence that causes this pathology.

If this hypothesis were true, a drug could be created that would regulate the excessive C4 gene and prevent the more serious symptoms. New methods for staving off the most difficult cases of schizophrenia could be researched and developed, as well.

Substance use

The relationship between schizophrenia and drug use is complicated. Even though we know that some substances induce psychosis, it’s still unclear if they lead to a schizophrenia diagnosis. In recent studies 60% of people diagnosed with schizophrenia were found to use substances and 37% were diagnosed as substance abusers.

  • Cannabis: Among drug use, this drug is considered to be a main cause of schizophrenia due to its cognitive skills impact. In recent studies it was established that cannabis doubles the risk of developing schizophrenia on an individual level and may be responsible for the 8% of the cases in the population. It is said to contribute with the hyperdopaminergic state that is common in schizophrenia.
  • Amphetamines and stimulants: Since amphetamines trigger the release of dopamine and excess of dopamine can be responsible for symptoms of schizophrenia it is believed that they worsen the symptoms. Medication for ADHD has been under doctor scrutiny due to its later symptoms of paranoia, behavioral sensitization and schizophrenia.
  • Alcohol: There is evidence that alcohol abuse with increasingly withdrawal symptoms can occasionally cause the development of an induced psychotic disorder or schizophrenia.

Life Experiences

  • Close relationships: Critical moments, hostility, authoritarian and intrusive attitudes can increase the risk of schizophrenia relapse or cause schizophrenia symptoms. Developmental issues such as very low sense of self and boundary confusion may cause schizophrenia.
  • Social Adversity: Social factors such as exclusion, socioeconomic disadvantages, etc. present in childhood may increase risk factors for developing schizophrenia. Experiences of abuse or trauma my also be risk factors for a schizophrenia diagnosis in adulthood.
  • Urbanicity: A recent study established that there is a 67-77% increased risk of diagnosed schizophrenia for people living in the most urbanized environments. There is no concrete reason why, however, people think it’s due to generic stress caused by the city.

Even though the causes of schizophrenia are not entirely clear, as we have seen there are many hypothesis. Hopefully soon, research will be able to pinpoint with more accuracy what exactly causes this disorder, until then feel free to leave a comment below discussing these.