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Sunday, October 24, 2021

UCD researchers determine source of memory loss in psychosis

JOHN RAGLAND / COURTESY
JOHN RAGLAND / COURTESY

Researchers, counselor discuss findings and implications for schizophrenic patients

For the over three and a half million patients suffering with schizophrenia in the United States, recent groundbreaking research at UC Davis provides hope in treating the symptom of relational memory loss.

Genetics, chemistry or issues during pregnancy and birth are believed to cause schizophrenia, which typically manifests itself in patients between the ages of 16 and 30.  Schizophrenia is a psychotic disorder, which means it is characterized by delusions and hallucinations. These symptoms hamper the ability of patients to differentiate between reality and unreality.

“Psychosis involves a couple of different symptoms,” said Cameron Carter, senior author and psychiatry professor. “One is hallucination, that’s hearing things or seeing things that other people can’t hear or see. The other is delusion, [which is] extreme beliefs that become stuck. There are paranoid delusions – that some enemy is after them, or other delusions where they feel that they have special powers.”

Psychotic symptoms can be caused by an overabundance of the chemical dopamine in the brain, and treated by dopamine-blocking drugs. These drugs are effective in reducing hallucinations and delusions. However, in schizophrenia, memory loss is another significant symptom. No treatment has ever been developed for memory loss – until now.

“The reason we study memory in schizophrenia is because cognitive deficits in schizophrenia are very common,” Carter said. “When you look at what limits people in the world having this illness – it’s not whether or not they are hearing voices, or whether or not they have delusions. It’s this cognitive dysfunction that gives people much more difficulty working or living independently. Memory deficit is a very prominent path of cognitive dysfunction.”

The memory dysfunction associated with schizophrenia affects working memory. While schizophrenic patients seem to perform well with itemized memory, relational memory can pose an issue.

“If you think about going to a grocery store and making a list that you’re trying to remember, you can try to remember it by individual items [or] grouping similar items together,” said John Daniel Ragland, lead author of the study and psychiatry and behavioral sciences professor. “For example, grouping dairy products or bread products. Another way you can remember items is by thinking about their relationships. For example, I want to buy ingredients for a cake. Flour, sugar and baking powder are all related to each other and that’s why I’m going to remember them.”

The researchers’ tested their hypothesis: patients with schizophrenia have more problems with relational memory, but could actually work with itemized memory quite well. The study added to an ongoing study on how schizophrenia affects learning memory. Data was collected at UC Davis and four other campuses: University of Minnesota, Washington University, University of Maryland and Rutgers University in New Jersey.

“I do see that the cognitive deficits associated with schizophrenia are very devastating to patients and their family,” said Sarah Hahn, director of counseling services at UC Davis Student Health and Counseling Services. “This research holds great promise and I think people could potentially remain much higher functioning if we understand more about this memory deficit, and by working on early identification and prevention, keep the illness from being more profound.”

The study was completed with 52 schizophrenic patients and 57 controls. Participants were shown several items in itemized and relational conditions. For the itemized test, they were asked to recall whether one of two items was living. For the relational test, they were asked whether one item could fit inside the other. Some items were learned during both the conditions, while others were new.

“What this study added was that we found that patients of schizophrenia have much more difficulty with relational memories,” Ragland said. “The fMRI showed that this was due to two findings: use of the dorsolateral prefrontal cortex in relational memory but not in itemized memory, and activation of the hippocampus during retrieval of information, again only for relational memory.”

Researchers used functional magnetic resonance imaging (fMRI) to measure changes in blood flow in the brain. This allowed them to determine which parts of the brain were active during different conditions of the trials.

“In other parts of the body, when tissue increases its function, oxygenation goes down, but in the brain, when a part of the brain is working harder, it increases its oxygenation,” Carter said. “We used this scanning to compare people with healthy brains, and people with schizophrenia. We found that the dorsolateral prefrontal cortex, which is very involved in keeping you on task even during distraction, was not supporting memory function in schizophrenia in the way that it did in healthy control subjects.”

This finding clarifies both the specific type of memory issue as well as the target of improvement for patients with schizophrenia. Researchers can now focus on improving the function of the dorsolateral prefrontal cortex to improve relational memory.

“This tells us there is most likely a single mechanism that involves this element of cognitive circuitry in the dorsolateral prefrontal cortex related to a whole range of problems patients may have in cognition,” Carter said. “If we could find a treatment to increase the function of the dorsolateral prefrontal cortex, we would be able to improve memory in schizophrenia.”

Based on the findings of this study, schizophrenic patients now have several options. Patients can be taught to organize memories with an itemized feature to decrease daily frustration with memory loss. Alternatively, a few brain stimulation techniques could be studied and tuned to target the dorsolateral prefrontal cortex.

“We can train that part of the brain, stimulate it electrically or bring it online with drugs,” Carter said. “Most importantly, we could make a big difference to these memory deficits and that is how we can make a big difference to the quality of life of people with schizophrenia.”

As previous studies at UC Davis have shown, cognitive function can be improved by computerized cognitive training. Low-intensity electrical stimulation or specialized drugs are also points of future study. Ragland and Carter hope to further research and develop such treatment options.  

“At this point, the medications out there do not target specific parts of the brain,” said Dr. Celeste Wiser, chief of psychiatry at UC Davis. “But, if they can be developed in the future, then this research could be applied to drugs and completely change everything.”

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