The Role of Synaptic Dysfunction in Schizophrenia

“Schizophrenia is an often misunderstood chronic mental illness that causes psychosis,” wrote Anna Guildford in a recent article for Medical News Today

It is a “debilitating, complicated mental disorder that affects 20 million people globally.

In his book, The Environment of Schizophrenia, Colorado Recovery founder Richard Warner also described psychosis as a primary feature of schizophrenia, calling it “a severe mental disorder in which the person’s emotions, thinking, judgment, and grasp of reality are so disturbed that his or her functioning is seriously impaired.”

“People with schizophrenia have a unique combination of symptoms or experiences,” explained Guildford. They may include feeling disconnected, hallucinations, hearing voices, delusions, and confused thinking or speech.

“There is no single organic defect or infectious agent which causes schizophrenia,” wrote Dr. Warner and it remains unclear what biological mechanisms are involved. Researchers have long suspected differences in brain chemistry to be the cause of schizophrenia. People with the condition typically have differences in their neurotransmitters, i.e. chemicals that control communication within the brain.

“Growing evidence implicates synaptic proteins in the pathogenesis of neuropsychiatric disorders such as autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia,” wrote Caldeira, Peça, and Carvalho in their 2019 study on synaptic dysfunction in neuropsychiatric disorders.

According to a new study by Adams, Pinotsis, Tsirlis,, the imbalance of nerve cell activity responsible for the condition and its associated symptoms may result from the body trying to rebalance excitatory and inhibitory functions. Dr. Rick Adams, a Research Fellow at the Centre for Medical Image Computing at University College London, UK, explained to Medical News Today that “there is an enormous amount of indirect evidence that synaptic gain decreases in schizophrenia. This means that excitatory neurons have a reduced ability to stimulate one another.”

Dr. Adams and his colleagues used computational modeling of electroencephalography (EEG) to record brain activity and measure overall synaptic gain. They collected EEG data from 272 participants, which comprised 107 with diagnosed schizophrenia, 57 of their relatives, and 108 control participants. Each participant underwent three EEGs and a resting functional magnetic resonance imaging (fMRI).

Dynamic causal modeling of the EEG experiments and fMRI data showed changes in the group of people who had received a diagnosis of schizophrenia. “The altered brain waves in those with diagnosed schizophrenia occurred due to a loss of synaptic gain, or excitability,” reported Guildford. “The hallucinations and other symptoms of schizophrenia were, however, associated with loss of neural inhibition.”

“This might mean that the loss of excitation comes first, then the brain tries to compensate for this by reducing inhibition, but then this leads to hallucinations,” Adams told Medical News Today.

Despite a great deal of pharmaceutical investment, there is still not a targeted drug to treat schizophrenia by understanding the biology of the disease and identifying the receptors and processes involved. Adams believes “if future studies can establish this, it means we should be able to give treatments that change excitatory or inhibitory function at the right time and to the right people.”

Such a targeted drug to treat schizophrenia is not yet available, though, and pharmacological approaches can only be a partial solution.

“Medications are an important part of treatment but they are only part of the answer,” wrote the late Colorado Recovery founder Richard Warner, MD, in The Environment of Schizophrenia (2000). “They can reduce or eliminate positive symptoms but they have a negligible effect on negative symptoms.”

The empowerment of patients and vocational rehabilitation are equally important elements in the treatment approach at Colorado Recovery. Our program approaches mental healthcare with a focus on self-reliance through developed practiced skills. Our non-institutionalized philosophy offers comprehensive levels of care supported by an expert medical and clinical team, engaging patients in increasing community participation.

Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.