Causes and risk factors of Schizophrenia

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Central nervous system in pain

Biochemical alterations. Schizophrenia could be the consequence of a problem in communication between neurons. It has been observed that dopamine (present in several parts of the brain and particularly important for the body’s motor function) undergoes the greatest alteration of all the neurotransmitters (the chemicals which transmit information between neurons). Classically, the hypothesis that there is an imbalance in dopaminergic function has provided the leading neurochemical explanation for schizophrenia, suggesting that the disease, or at least the psychotic symptoms, are the result of an excess of dopaminergic activity. The main advantage of this hypothesis derives from the fact that medicines which decrease dopamine levels improve psychosis, whereas medicines or drugs which increase levels can trigger this type of symptoms or worsen the schizophrenia.

However, in recent years, the glutamate hypothesis of schizophrenia has gained strength. This proposes that dysfunction linked to glutamate (the main excitatory neurotransmitter in the brain) may play a fundamental role in explaining the causes of the disease, especially the negative symptoms and cognitive alterations. These are probably complementary and not exclusive hypotheses.

Brain with a marked area

Alterations in brain structure. Almost half of all patients with schizophrenia present alterations in brain structure. These include ventricular dilation, a decrease in the volume of certain areas of the brain (especially the temporal lobe, amygdala-hippocampal formation, thalamus, prefrontal cortex) and an overall decrease in brain size. Nevertheless, it is important to point out that these alterations are neither specific to schizophrenia nor do all patients present them.


Alterations in brain function. The majority of functional neuroimaging studies, which study not just the structure but also brain function, have observed that individuals with schizophrenia present a decrease in prefrontal cortex function – the area responsible for our ability to reason. This hypofrontality constitutes one of the most widely verified biological findings relating to schizophrenia. Hypofrontality is most apparent when performing mental tests that require prefrontal activation.

In spite of all the research and major advances achieved in the last 40 years, there are no complementary diagnostic tests available to confirm the diagnosis of the disease.

Typically, symptoms first appear in late adolescence, when the structures involved reach their functional maturity, given that the brain does not mature fully in adolescence and actually continues developing during adulthood, in a stage where some unused neurons and circuits are eliminated through complex processes such as neuronal and synaptic programmed cell death (apoptosis). We now know that certain inflammatory and immunological phenomena could also be involved in the onset and progression of schizophrenia.

Risk factors

A risk factor is a condition that does not actually cause a given disease, but it is associated with it. For example, a high cholesterol level (hypercholesterolemia) is a risk factor for suffering a heart attack. It does not necessarily mean it will cause a heart attack, as not everybody with high cholesterol will suffer one and not all heart attack victims have high cholesterol. But it does mean the likelihood of having a heart attack increases.

As such, several risk factors that increase the likelihood of developing schizophrenia have been identified, although they do not cause it directly.

Cannabis, pills and a syringe

Environmental factors, including:  obstetric complications, substance abuse, and certain viruses.

DNA molecule or helix

Genetic factors

The genetic aspect is the most significant and estimated to make an 80% contribution to determining its presence. The likelihood of a family presenting a case of schizophrenia is greater if another family member has already been diagnosed with the disease.

The amount the risk increases depends on the degree of kinship with the affected family member. Does that mean schizophrenia is a genetic disease? If using the term genetic disease to mean an illness caused by a single gene, then the answer is no. Genetics play an enormous role in this disease (around 80%), but it is not just one unique gene.

The most recent theories indicate that the presence of a number of mutated genes predisposes an individual to developing schizophrenia. In other words, as with other complex medical complaints such as diabetes, more than one gene must be mutated in order to develop the disease. This inheritance predisposes a greater vulnerability to developing schizophrenia if faced with certain environmental factors which would trigger the onset of the clinical symptoms.

Population Prevalence (%)
General population 0.7-1
Siblings, not twins 8
Child with one affected parent  12
Child with two affected parents 40
Nonidentical twins  12
Identical twins 47

Substantiated information by:

Eduard Parellada Rodon
Miguel Bernardo Arroyo
Miquel Bioque Alcázar

Published: 20 February 2018
Updated: 30 November 2022

The donations that can be done through this webpage are exclusively for the benefit of Hospital Clínic of Barcelona through Fundació Clínic per a la Recerca Biomèdica and not for BBVA Foundation, entity that collaborates with the project of PortalClínic.


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