Why Schizophrenia Makes It Hard To Remember

Although medications can often treat the delusions and hallucinations that accompany schizophrenia, it’s been more challenging to address memory problems, which can make it difficult to perform daily activities. Says J. Daniel Ragland, professor of psychiatry in the UC Davis School of Medicine:

“People with schizophrenia have difficulty retrieving associations within a context, and this creates a pervasive loss of memory that makes everyday life a challenge. You can’t work if you can’t remember the next step in what your boss told you to do.”

Ragland and colleagues say the memory troubles arise from dysfunction of frontal and temporal lobe regions in the brain. Memory is most impaired when people with schizophrenia try to form relationships between items—remembering to also buy eggs, milk, and butter when buying flour to make pancakes—and that this encoding problem is accompanied by dysfunction in the dorsolateral prefrontal cortex.

People with schizophrenia also have greater difficulty retrieving this relational information even when they can remember the individual items, and this relational retrieval deficit is accompanied by functionally specific dysfunction in a brain area called the hippocampus.

“If you’re going to develop a drug or other therapy to improve memory, we found that this frontal and temporal lobe relational memory network may be a target or ‘biomarker’ for treatment development,” Ragland says.

What Brain Scans Show

For the study, researchers used fMRI to analyze the brains of 60 men and women with schizophrenia. The participants viewed a series of pictures of everyday objects, and made either an item-specific encoding decision about whether the object was living or non-living, or made a relational encoding decision about whether one of the objects could fit inside of the other during fMRI scanning.

This was followed by an item-recognition task consisting of previously studied objects presented together with never-studied objects. Participants had to assess whether or not the object was previously studied.

Participants also were tested on their associative recognition of which objects were paired together during the relational encoding task. The more severe pattern of relational memory deficits and dorsolateral prefrontal and hippocampal dysfunction was revealed by contrasting the item-specific and relational memory conditions during encoding and retrieval.

In the participants diagnosed with psychosis, the dorsolateral prefrontal cortex appeared substantially less activated than in healthy control participants—28 percent to 30 percent less activated.

Although participants with schizophrenia activated the ventrolateral prefrontal cortex during relational versus item encoding, they failed to activate the dorsolateral prefrontal cortex—a finding that is consistent with earlier fMRI studies of attention and problem–solving in individuals with schizophrenia.

In addition, the study revealed that healthy controls exhibited increased activation in the hippocampus, while activation was significantly reduced in the participants with psychosis for retrieval following relational-memory encoding, but not for retrieval following item memory encoding.

Thus, the hippocampus—which plays a unique role in creating relational memories—joins the dorsolateral prefrontal cortex in helping to explain the disproportionate relational memory deficits experienced by people with schizophrenia.

Similarity to ADHD

Senior author Cameron Carter, a psychiatry professor and director of the Imaging Research, Behavioral Health and Neuroscience centers at UC Davis, says the finding is exciting because it points the way to potential pathways to improve the lives of people with psychosis.

“This shows that the memory problems in people with schizophrenia are not the same as those of people with Alzheimer’s disease,” where the brain region is damaged and deteriorating. “It’s more like those of people with other cognitive deficits, such as ADHD.

We now know that, if we’re going to improve memory in people with psychosis we have to improve the functioning of the dorsolateral prefrontal cortex. And there are many different ways that we can do that, such as through cognitive brain training,” he adds.

Carter says that another experimental treatment, called transcranial direct current stimulation, is designed to activate and enhance the function of the brain region.

“This research is directly informing the next steps in our research. And the area that we’ll stimulate will be this one. Twenty or 30 years ago we couldn’t do any of this,” Carter says. “So this is real progress.”

Ragland J, Ranganath C, Harms MP, et al.
Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in Schizophrenia: A Functional Magnetic Resonance Imaging Study of the Relational and Item-Specific Encoding Task.
JAMA Psychiatry. 2015;72(9):909-916. doi:10.1001/jamapsychiatry.2015.0276.

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