Schizophrenia Mechanisms

The underlying mechanisms of schizophrenia are not entirely understood in their complexity by medical researchers at this point in time. There are several theories that can be applied to explain why the function of the brain changes to cause the characteristic symptoms of this condition such as disorganized thinking, emotions, and behavior.

These mechanisms include the function of neurotransmitters in the brain, as well as specific structural and functional characteristics of the brain. In actuality, it is likely that schizophrenia is, in fact, a group of disorders with similar characteristics and symptoms. This would explain the ununiform nature of the pathophysiology of the condition, the numerous proposed mechanisms, as well as the variable efficacy of the drugs used in the treatment of schizophrenia.

What Causes Schizophrenia? | Schizophrenia

Dopamine hypothesis

Dopamine is a neurotransmitter found in the brain that plays a role in the mesolimbic pathway and the positive symptoms of schizophrenia.

The involvement of dopamine in the mechanism of schizophrenia was first introduced due to the ability of phenothiazines, a class of dopamine antagonist drugs, to reduce psychotic symptoms. Similarly, amphetamines tend to aggravate psychotic symptoms due to their dopamine agonist effect.

Newer research also indicates that the neurotransmitter serotonin may also be involved in the mechanism, as atypical antipsychotic medications, which act primarily on serotonin, also have a similar effect on positive symptoms.

Glutamate hypothesis

Another neurotransmitter, glutamate, and the n-methyl-d-aspartic acid (NMDA) glutamate receptor have also been suggested to play a role in the pathophysiology of schizophrenia.

This hypothesis came about due to the low number of glutamate receptors observed in the brain of people who had been diagnosed with schizophrenia. The relevance of these receptors has been supported by further research, which found that drugs with a mechanism that blocked the glutamate receptors tended to precipitate symptoms of the condition.

Structural abnormalities

There is also some evidence that the structure of the brain may influence the likelihood of an individual suffering from schizophrenia. Imaging techniques such as magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and computed tomography (CT) scans have made it possible to visualize the structure of the brain and establish patterns of those who are affected.

A meta-analysis concluded that the size of the brain and hippocampal volume was reduced, whereas the ventricles appeared enlarged in people following an initial psychotic episode. It has also been observed that patients with schizophrenia have abnormal structures of the prefrontal cortex, temporal cortex, or anterior cingulate cortex.

Positive and negative symptoms are thought to be associated with specific structural areas of the brain, which also explains why many antipsychotic drugs are more effective at treating positive than negative symptoms.

Functional abnormalities                        

The functional abnormalities of the brain in the pathophysiology of schizophrenia have been observed with the use of positron emission tomography (PET) scans. This has enabled scientists to measure the cerebral blood flow and metabolic rate for glucose as indicative factors for synaptic activity in the brain.

Current research suggests that cerebral blood decreases in the left parahippocampal region of individuals with schizophrenia.


Further Reading

Last Updated: Apr 13, 2021

Susan Chow

Written by

Susan Chow

Susan holds a Ph.D in cell and molecular biology from Dartmouth College in the United States and is also a certified editor in the life sciences (ELS). She worked in a diabetes research lab for many years before becoming a medical and scientific writer. Susan loves to write about all aspects of science and medicine but is particularly passionate about sharing advances in cancer therapies. Outside of work, Susan enjoys reading, spending time at the lake, and watching her sons play sports.


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