How does schizophrenia affect the brain?

Which parts of the brain does schizophrenia affect?

The cerebral cortex is the outer layer of the brain, which is made up of mostly gray matter. Gray matter contains neurons, which process and release information.

Beneath this layer is white matter. White matter contains axons, or nerve fibers, that join neurons together, allowing communication around the brain and central nervous system ^[1].

The brain is made up of several areas, or lobes. Schizophrenia often affects the frontal lobe and the temporal lobe. People with schizophrenia are found to have a significantly reduced volume of gray matter in these areas, as well as impaired white matter integrity ^[2].

Changes in the structure and function of gray and white matter reduce the brain’s ability to send messages and information. This is believed to contribute to the development of schizophrenia symptoms ^[3].

Frontal lobe

The frontal lobe is responsible for several cognitive functions, such as ^[1]:

• Memory
• Emotional expression
• Voluntary movement
• Social interactions and behaviors
• Impulse control
• Planning, organizing, learning, and problem-solving
• Speech

When the structure and function of gray and white matter in the frontal lobe are impaired, abilities in these areas are significantly impacted. This can lead to several of the negative and cognitive symptoms often seen in patients with schizophrenia, including ^[2][5][6]:

• Disorganized thoughts and speech
• Unusual or odd movements
• Impaired memory
• Flat or blunted affect
• Social withdrawal

Temporal lobe

The temporal lobe contains areas of the brain including the hippocampus, amygdala, and thalamus, and is responsible for functions such as ^[1][4]:

• Auditory perception, such as recognizing and making sense of speech and language
• Visual perception, such as recognizing objects and understanding visual information
• Understanding and processing other types of sensory information, such as smells and pain
• Forming memories, particularly visual and auditory memories
• Recognizing faces and emotional expressions

Severe impairments in the processing of sensory information and cognitive functioning can result from reduced gray matter volume and white matter integrity in specific areas, leading to positive and cognitive symptoms. This includes ^[5][6][7]:

• Hallucinations
• Delusions
• Impaired social abilities
• Disorganized speech
• Memory loss

Neurotransmitters

A significant amount of research examines the significance of neurotransmitters, especially dopamine, in the development of schizophrenia. The dopamine hypothesis of schizophrenia suggests that positive symptoms, such as hallucinations and delusions, can be caused by an overactivity of dopamine in the brain ^[8][9].

Dopamine is involved in several functions, including reward pathways, mood, movement, and attention. Studies also suggest that reduced levels of dopamine in other areas of the brain can also impact these functions, potentially causing negative symptoms of schizophrenia ^[8][10].

As such, it is believed that dopamine dysregulation occurs in various areas of the brain, thus contributing to a mixture of schizophrenia symptoms ^[10].

Research also indicates that there may be dysregulation in other neurotransmitters in the brains of people with schizophrenia, such as serotonin, glutamate, GABA, and acetylcholine. These neurotransmitters are involved in functions relating to mood, memory, learning, and movement, so abnormalities can contribute to several schizophrenia symptoms ^[8][10].  

Brain volume

Gray matter loss in certain areas of the brain contributes to a reduction in the overall size of the brain in people with schizophrenia. Research shows that tissue loss often occurs before the onset of schizophrenia symptoms. This suggests that it may be possible to determine whether an individual is at higher risk of developing schizophrenia by looking at the size of their brain ^[2][11].

Studies also show that brain size continues to reduce over the first 2-5 years of the condition, then remains roughly the same size following this. However, significant tissue loss can continue with the use of high doses of antipsychotic medications ^[11][12][13].

Can schizophrenia be caused by brain damage?

Traumatic brain injury has been found to increase the risk of various mental health conditions, including mood disorders, cognitive impairments, and changes in personality and behavior, but it is unclear whether there is an association between head injury and schizophrenia development ^[14].

Some studies indicate that traumatic brain injury can increase the risk of schizophrenia, while others dispute this. Schizophrenia has been found to occur more often in those with traumatic brain injury than without, although it is unclear if schizophrenia is specifically caused by this type of injury ^[15].

Studies have shown that the risk of developing schizophrenia in individuals with a genetic vulnerability to the condition is doubled in those who have experienced a traumatic brain injury, compared to those who have not. This suggests that brain injury may contribute to the condition's development when combined with other factors ^[14][15].

Similarly, some studies have found that childhood traumatic brain injury significantly increases the risk of later schizophrenia, which may be related to impaired brain development, thus contributing to psychotic symptoms. However, this link has not been confirmed and may instead be related to shared risk factors for both exposure to head injury and the development schizophrenia ^[16].

So far, research indicates that it is difficult to determine a clear cause and effect between head injury and schizophrenia development, due to the uncertainty of several factors.

For example, it is unclear whether individuals in these studies would have gone on to develop schizophrenia regardless of head injury, whether the condition was also influenced by other factors such as drug use, and whether early signs and symptoms of schizophrenia, such as cognitive or mobility impairments, can increase the risk of exposure to traumatic brain injury.

As such, it is believed that traumatic brain injury is likely not a causal factor of schizophrenia, but that early symptoms of a pre-existing psychotic illness may increase the risk of head injury ^[14][15].

With many weaknesses and limitations among current studies investigating this topic, further research is required to gather more information and better understand the association between brain injury and schizophrenia.

Other causes of schizophrenia

In addition to various neurological factors, there are several other possible causes and contributing factors believed to be linked to the development of schizophrenia. It is likely that many genetic and environmental factors also impact brain development or functioning, suggesting that the cause of schizophrenia is complex and multidimensional ^[7][11].

Genetics

The likelihood of developing schizophrenia is significantly increased in people who have a family member with the condition. The specific genes involved in this hereditary factor are not known, but it is believed that several genes can influence the likelihood of developing the condition.

Individuals who have an identical twin with schizophrenia are believed to have a 1 in 2 chance of developing the condition, while people with a non-identical twin, sibling, or parent with schizophrenia are believed to have a 10% genetic risk of developing the condition, which is around 10 times higher than the general population ^[16][17].

As such, there is a clear heritability to the condition. However, this is not the only contributing factor, as demonstrated by the fact that a large proportion of individuals with schizophrenia do not have a first-degree relative with the condition ^[16].

Substance use

It is thought that substance abuse can increase the risk of developing schizophrenia. For example, research indicates that individuals who use cannabis are more likely to develop the condition than those who don’t, particularly if large quantities of cannabis are used frequently from a young age.

Cannabis use is linked to changes in neurotransmitters, such as dopamine and serotonin, which are also believed to influence the development of schizophrenia. This indicates that early cannabis use may alter brain functioning and cause abnormalities that can lead to schizophrenia ^[16][17].

Complications in pregnancy and birth

Studies show that there is a high prevalence of pregnancy and childbirth complications in individuals who develop schizophrenia. This includes exposure to infection and nutritional deficiencies during pregnancy, low weight at birth, and lack of oxygen at birth.

It is not clear how these occurrences influence the development of schizophrenia, but it is thought that they may impact brain development. This may increase the risk of neurological abnormalities that can lead to schizophrenia ^[11][16].

Childhood environment

Several factors related to childhood environment are believed to be linked to an increased risk of schizophrenia. This includes growing up in an urban area, family migration, low socioeconomic status, and difficulties within familial relationships and dynamics within the home ^[16].

What's the difference between the brain of a person with schizophrenia vs without?

The main differences between the brain of a person with schizophrenia and a person without are the size and volume of certain areas, as well as the levels and activity of certain neurotransmitters ^{[2][3][6][10][11]}:

• The total brain size of a person with schizophrenia is often smaller than that of a person without schizophrenia.
• The volume of grey matter in the brain of someone with schizophrenia is often significantly reduced compared to a healthy brain.
• Certain areas of the brain, including the amygdala, hippocampus, and thalamus, are often smaller in the brains of people with schizophrenia than those without.
• People with schizophrenia are likely to have dopamine activity and production abnormalities.
• Other neurotransmitters, including serotonin, glutamate, GABA, and acetylcholine, are also likely to be altered in the brains of people with schizophrenia compared to a healthy brain.

These differences are thought to significantly contribute to the cognitive, positive, and negative symptoms of schizophrenia. Research also indicates that the more severe these differences are, the more severe the symptoms are likely to be ^[5][6].