New research findings, which show how overactivity in the hippocampus is linked to certain schizophrenia symptoms, may open up the possibility of new treatments

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The possibility of new treatments for schizophrenia has opened up with the findings from new research that showed how overactivity in the hippocampus is linked to certain schizophrenia symptoms.

In their study, published in eNeuro, researchers from the University of Nottingham set out to test whether hippocampal disinhibition—which, via reduced GABAergic inhibition, is a key feature of schizophrenia pathophysiology—contributes to the deficits in latent inhibition and fear conditioning reported in the condition. Previously, it remained unclear how hippocampal disinhibition might contribute to psychological deficits.

Post-doctoral researcher Stuart Williams, PhD, who led the study, said: ‘We know that people with schizophrenia have increased hippocampal activity; we wanted to explore this further and find out exactly how this manifests itself.’

The authors explained how studies in patients with schizophrenia using classical-conditioning assays have shown ‘aberrant salience allocation to stimuli that healthy participants have learnt to ignore, as well as reduced fear conditioning, which have been linked to psychosis and negative symptoms, respectively’.

They continued that since the hippocampus modulates neural substrates of salience allocation and is part of the fear-conditioning neural circuit, ‘these impairments may be related to hippocampal disinhibition’.

Hippocampal hyperactivity and neural disinhibition are key characteristics of schizophrenia pathophysiology and have been implicated in behavioural deficits characterising the disorder, they said.

Associative learning disrupted

To test their hypothesis that ventral hippocampus disinhibition might disrupt the acquisition of latent inhibition and fear conditioning, the researchers combined selective pharmacological manipulation of the hippocampus with a conditioning assay in rats.

They found that faulty inhibitory neurotransmission and abnormally increased activity in the hippocampus doesn’t disrupt the ability to filter out irrelevant information—a key process that has been shown to be deficient in patients with schizophrenia, and is thought to cause hallucinations or delusions—but does disrupt associative learning. Deficits in associative learning, such as Pavlovian fear conditioning, have been linked to the negative symptoms of the disorder, which include reduced motivation and disrupted emotional and reward processing.

Dr Williams said: ‘Through our research carried out in rats, we were able to ascertain the importance of GABAergic inhibition within the hippocampus in relation to certain symptoms associated with schizophrenia.

‘Specifically, we found no evidence that faulty inhibition within the hippocampus disrupts behaviours related to the underlying cognitive processes that are thought to contribute to the onset of hallucinations or delusions.’

However, he went on to say that they did find that it may contribute to some of the negative symptoms, disrupting associative learning in the form of conditioned fear.

Future targeted treatments

Dr Williams explained that by revealing previously unknown detail about the role of aberrant activity in the hippocampus, their research provides ‘insights into the behavioural consequences that disruption of specific neural structures, such as the hippocampus, have in schizophrenia’.

He added: ‘This could help to develop more targeted treatments that improve the management of specific aspects of schizophrenia symptomatology, such as improving negative symptoms, potentially by dampening down this overactivity in the hippocampus.’

This article originally appeared on Medscape, part of the Medscape Professional Network.

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