Schizophrenia is associated with reduced synaptic gain, explaining hallmark electroencephalography signs.
Now, a study in Biological Psychiatry, led by Rick Adams (University College London, UK), has utilized electroencephalography (EEG) to determine that schizophrenia is associated with reduced synaptic gain (a loss of neural excitation), whilst hallucinations and other symptoms are associated with a loss of neural inhibition.
“The nature of brain circuit changes in schizophrenia is unclear,” describes Adams. “Is it too much excitation or not enough, or too much inhibition or not enough, or some combination?”
Researchers have long suspected that the symptomology of schizophrenia fundamentally arises from disrupted synaptic function, or abnormalities in the way that neurons communicate with one another, perhaps leading to an imbalance between excitatory and inhibitory transmission.
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Working with colleagues from City University of London (UK), Yale University School of Medicine (CT, USA), University of Maryland School of Medicine (MD, USA), and University of Ljubljana (Slovenia), Adams used the noninvasive techniques of EEG and fMRI to measure differences in brain waves and assess local changes in excitability of people with and without schizophrenia.
Data were collected from 107 participants with a diagnosis of schizophrenia, 57 of their relatives and 108 control participants. The EEGs of people with schizophrenia displayed hallmark signs including increased theta waves.
Dynamic causal computational modeling of the EEG and fMRI data highlighted that the EEG differences seen in people diagnosed with schizophrenia resulted from reduced synaptic gain. This means that excitatory neurons had a diminished ability to stimulate one another. Symptoms of schizophrenia – including auditory hallucinations – however, were associated with a loss of neural inhibition, especially in auditory brain areas.
These findings support the hypothesis that in schizophrenia, a primary reduced synaptic gain on pyramidal cells is then compensated by interneuron downregulation. Furthermore, they suggest that psychotic symptoms, such as hallucinations, relate to this secondary downregulation.
“This might mean that the loss of excitation comes first, and the brain tries to compensate for this by reducing inhibition, but then this leads to hallucinations,” Adams said. “Imagine you are trying to listen to someone speaking on the radio, but the signal is very weak; if you turn the volume up, the speech is louder–but so is all the static and background noise–and so you may mistake some of this noise for actual speech. Something analogous might be happening in brain circuits in schizophrenia.”
By understanding synaptic dysfunction in schizophrenia, this may help guide treatments for patients both pharmacologically and by neurostimulation.