A Functional Imaging Study of Episodic Memory in the At Risk Mental State
Lead Research Organisation:
King's College London
Department Name: Institute of Psychiatry
Abstract
Psychotic illnesses like schizophrenia are devastating illnesses which cause enormous suffering. What triggers these conditions in early adulthood is unknown, but recent evidence suggests that poor memory may be an early sign that psychosis will develop within a year or so. We may be able to understand why impaired memory is linked to the onset of illness by studying how memory is processed in the brain, using brain scanning techniques. Brain scanning may also help to identify which individuals are most likely to become psychotic at a later date. I plan to investigate these issues by using brain scanning to study people who are at high risk of becoming psychotic. After scanning, I will keep in contact with the subjects and see which of them will go on to develop the illness. I will then compare the scans from those who became psychotic with scans from those that did not.
Technical Summary
Background:
People with an At Risk Mental State have a very high risk of developing psychosis but it is difficult to predict which individuals will become psychotic on clinical grounds. However episodic memory performance appears to be significantly more impaired in those at risk who later become psychotic than in those who do not. Functional neuroimaging provides a means of identifying the brain areas involved in the encoding and retrieval of memory in the At Risk Mental State, and determining whether they are differentially active in subjects who later develop psychosis.
Objective: to examine whether functional abnormalities associated with episodic memory processing in people at high risk of psychosis predict the subsequent onset of illness.
Design and Method: cross sectional comparison of functional MRI data from subjects with an At Risk Mental State and controls, followed by a prospective clinical evaluation of the at risk group. Functional MRI will be used to study activation during a task that engages the encoding and retrieval of verbal material. The at risk participants will be followed up For 12 months to determine which subjects psychosis subsequent to scanning.
Hypotheses:
1) ARMS subjects will show attenuated activation in the prefrontal and anterior cingulate cortex during the encoding and retrieval phases of a verbal episodic memory task compared to the healthy controls.
2) Within the ARMS sample, the subgroup of subjects who later develop psychosis will show a reduction of activation in the medial temporal cortex during successful verbal retrieval.
Implications: This study will determine whether the neural substrate of episodic memory is abnormal in the ARMS and whether this is a related to encoding and/or retrieval. It will also reveal whether the severity of these functional abnormalities predicts which individuals at high risk will later develop psychosis. These data will improve our understanding of the neurocognitive basis of psychosis. They may also lead to investigations that help predict which high risk subjects are most likely to become psychotic, facilitating the targeting of treatment to those at highest risk.
People with an At Risk Mental State have a very high risk of developing psychosis but it is difficult to predict which individuals will become psychotic on clinical grounds. However episodic memory performance appears to be significantly more impaired in those at risk who later become psychotic than in those who do not. Functional neuroimaging provides a means of identifying the brain areas involved in the encoding and retrieval of memory in the At Risk Mental State, and determining whether they are differentially active in subjects who later develop psychosis.
Objective: to examine whether functional abnormalities associated with episodic memory processing in people at high risk of psychosis predict the subsequent onset of illness.
Design and Method: cross sectional comparison of functional MRI data from subjects with an At Risk Mental State and controls, followed by a prospective clinical evaluation of the at risk group. Functional MRI will be used to study activation during a task that engages the encoding and retrieval of verbal material. The at risk participants will be followed up For 12 months to determine which subjects psychosis subsequent to scanning.
Hypotheses:
1) ARMS subjects will show attenuated activation in the prefrontal and anterior cingulate cortex during the encoding and retrieval phases of a verbal episodic memory task compared to the healthy controls.
2) Within the ARMS sample, the subgroup of subjects who later develop psychosis will show a reduction of activation in the medial temporal cortex during successful verbal retrieval.
Implications: This study will determine whether the neural substrate of episodic memory is abnormal in the ARMS and whether this is a related to encoding and/or retrieval. It will also reveal whether the severity of these functional abnormalities predicts which individuals at high risk will later develop psychosis. These data will improve our understanding of the neurocognitive basis of psychosis. They may also lead to investigations that help predict which high risk subjects are most likely to become psychotic, facilitating the targeting of treatment to those at highest risk.
