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NEURAL CORRELATES OF VERBAL WORKING MEMORY DYSFUNCTION IN EARLY-ONSET SCHIZOPHRENIA: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY
438
Abstracts
Background: Long-term memory impairments are extensively documented in schizophrenia. Despite general acceptance of the idea that memory is not localized to one neural structure, there is overwhelming evidence that the hippocampus plays a central role in memory formation. Brain imaging studies of adult schizophrenia patients have found smaller hippocampal volumes, while in early onset schizophrenia patients (EOS, onset between 12-18 years of age), differences have not reached statistical significance, but bilateral reductions of about 8-9% has been reported. In healthy individuals volume–memory correlations change from generally negative to extremely variable as the age of the sample increases. No other study has looked into correlations between hippocampal volumes and memory functions in EOS. Methods: 25 adolescents with a schizophrenia spectrum diagnosis were included in the study. Mean age was 15.9 (SD = 1.9) years. The average age of onset of psychosis was 14.4 (SD = 2.1) years. 33 healthy controls screened for mental problems were included in the study. Mean age for the controls was 15.8 (SD = 1.8) years. Intelligence quotient (IQ) was above 70 for all subjects in the study. Verbal learning and memory was assessed using the Hopkins Verbal Learning Test (HVLT). The test is composed of 12 items, organized into three semantic categories, and presented over three consecutive learning trials. After 20 minutes, a delayed recall of the list is recorded. All participants were scanned using a 1.5 T Siemens Trio system (Siemens Medical Systems, Erlangen, Germany). Segmentation of the hippocampal formation was performed using Freesurfer v. 4.0.4 software. Results: The groups did not differ in age or handedness. The patients had a significantly lower IQ score (97.2 (SD = 16.1) IQ points vs 107.3 (SD = 14.8), df = 56, t = -2.478, p = 0.016). The groups did not differ in hippocampal volumes. The patient group performed significantly poorer on all the HVLT subscales: Total learning and delayed recall, both p < 0.01, and percent retained and recognition p < 0.05. There were no significant correlations between any of the HVLT subscales with the hippocampal volumes in the control group. There were significant correlations between left hippocampal volume and delayed recall (correlation = -0.451, p = 0.031) and left hippocampal volume and percent retained (correlation = -0.412, p = 0.051) in the patient group. There was no significant correlation with the other two subscales and the left hippocampus volume, and, finally, no significant correlations between any memory measure and the right hippocampal volume in the patient group. Discussion: There is a significant and moderate negative correlation between left hippocampal volume and performance on both delayed recall and percent retained on HVLT in the EOS group. Why there was no significant relationships in the control group is not clear. Part of the explanation may be that they performed relatively well on the HVLT, and thus had a tighter range of results and standarddeviations compared to the patients. This study indicates that there is noteworthy relations between left hippocampal volume and verbal memory performance in an EOS group. This is of importance as schizophrenia in many aspects is considered a neurodegenerative disorder, where one of the most affected structures in adolescent patient populations is the hippocampus. Treatment efforts to preserve the hippocampal structure, can possibly preserve memory functions in this patient group.
doi:10.1016/j.schres.2010.02.809
Poster 49 NEURAL CORRELATES OF VERBAL WORKING MEMORY DYSFUNCTION IN EARLY-ONSET SCHIZOPHRENIA: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY Marinos Kyriakopoulos, Danai Dima, Matthew Kempton, Sophia Frangou
Section of Neurobiology of Psychosis, NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London London, United Kingdom Background: Working memory (WM) deficits are among the core cognitive abnormalities in schizophrenia. WM is subserved by widely distributed fronto-parietal networks and is undergoing robust development during adolescence. Studying the neural correlates of WM dysfunction in early-onset schizophrenia (EOS) will advance our understanding of aberrant neurodevelopmental processes in the disorder. Methods: Nineteen patients with EOS aged 13-19 and 20 matched healthy participants underwent functional Magnetic Resonance Imaging (fMRI) as they performed a N-back verbal WM task with 3 levels of difficulty (1-back, 2-back, 3-back). Following matching for task performance, 14 patients were compared to 20 controls, using non-parametric whole brain and region of interest (ROI) approaches followed by psycho-physiological interaction analysis (PPI) with seed voxel from the left parietal cluster. Results: Regions within the left prefrontal cortex, the left insula and bilateral anterior cingulate cortex showed reduced activation in EOS patients compared to healthy participants at the 2-back condition. In addition, ROI analysis at the same condition revealed hypoactivation in the EOS group with large effect sizes for left prefrontal and parietal regions. The PPI results revealed negative functional connectivity in the healthy participants' group but not in EOS between left parietal and right parietal and bilateral frontal regions. Discussion: Our results support compromised function within the left prefrontal-cingulate network and left insula during the N-Back verbal WM task in patients with EOS compared to healthy participants. They also indicate the possibility of more widespread fronto-parietal network dysfunction, most noted in the left hemisphere in the disorder.
doi:10.1016/j.schres.2010.02.810
Poster 50 EVIDENCE MAPPING FOR EARLY PSYCHOTIC DISORDERS IN YOUNG PEOPLE Ping Liu, Alexandra Parker, Sarah Hetrick, Rosemary Purcell ORYGEN Youth Health Research Centre University of Melbourne Melbourne, Victoria, Australia Background: The onset of psychotic disorders peaks in young people aged 12-30 years. Given the traditionally poor prognosis associated with chronic schizophrenia, a clinical research agenda has emerged in the last 2 decades focusing on interventions during the early phases of psychosis, where opportunities for clinical and functional recovery are greater. As a large volume of such research now exists, there is a need to summarise the extent and distribution of this research to ascertain what is known, and not yet known, about the evidence for preventing and treating early psychotic disorders. Methods: Using an evidence mapping methodology, we conducted a comprehensive search of high-level evidence (RCTs, CCTs and systematic reviews) since 1980 using the Cochrane Central Register of Controlled Trials, PSYCHINFO, MEDLINE and EMBASE. Detailed inclusion and exclusion criteria were defined. Studies were screened according to these criteria and mapped according to predefined study characteristics, including the type of intervention (e.g. psychological, biological, integrated) and
Abstracts
Background: Long-term memory impairments are extensively documented in schizophrenia. Despite general acceptance of the idea that memory is not localized to one neural structure, there is overwhelming evidence that the hippocampus plays a central role in memory formation. Brain imaging studies of adult schizophrenia patients have found smaller hippocampal volumes, while in early onset schizophrenia patients (EOS, onset between 12-18 years of age), differences have not reached statistical significance, but bilateral reductions of about 8-9% has been reported. In healthy individuals volume–memory correlations change from generally negative to extremely variable as the age of the sample increases. No other study has looked into correlations between hippocampal volumes and memory functions in EOS. Methods: 25 adolescents with a schizophrenia spectrum diagnosis were included in the study. Mean age was 15.9 (SD = 1.9) years. The average age of onset of psychosis was 14.4 (SD = 2.1) years. 33 healthy controls screened for mental problems were included in the study. Mean age for the controls was 15.8 (SD = 1.8) years. Intelligence quotient (IQ) was above 70 for all subjects in the study. Verbal learning and memory was assessed using the Hopkins Verbal Learning Test (HVLT). The test is composed of 12 items, organized into three semantic categories, and presented over three consecutive learning trials. After 20 minutes, a delayed recall of the list is recorded. All participants were scanned using a 1.5 T Siemens Trio system (Siemens Medical Systems, Erlangen, Germany). Segmentation of the hippocampal formation was performed using Freesurfer v. 4.0.4 software. Results: The groups did not differ in age or handedness. The patients had a significantly lower IQ score (97.2 (SD = 16.1) IQ points vs 107.3 (SD = 14.8), df = 56, t = -2.478, p = 0.016). The groups did not differ in hippocampal volumes. The patient group performed significantly poorer on all the HVLT subscales: Total learning and delayed recall, both p < 0.01, and percent retained and recognition p < 0.05. There were no significant correlations between any of the HVLT subscales with the hippocampal volumes in the control group. There were significant correlations between left hippocampal volume and delayed recall (correlation = -0.451, p = 0.031) and left hippocampal volume and percent retained (correlation = -0.412, p = 0.051) in the patient group. There was no significant correlation with the other two subscales and the left hippocampus volume, and, finally, no significant correlations between any memory measure and the right hippocampal volume in the patient group. Discussion: There is a significant and moderate negative correlation between left hippocampal volume and performance on both delayed recall and percent retained on HVLT in the EOS group. Why there was no significant relationships in the control group is not clear. Part of the explanation may be that they performed relatively well on the HVLT, and thus had a tighter range of results and standarddeviations compared to the patients. This study indicates that there is noteworthy relations between left hippocampal volume and verbal memory performance in an EOS group. This is of importance as schizophrenia in many aspects is considered a neurodegenerative disorder, where one of the most affected structures in adolescent patient populations is the hippocampus. Treatment efforts to preserve the hippocampal structure, can possibly preserve memory functions in this patient group.
doi:10.1016/j.schres.2010.02.809
Poster 49 NEURAL CORRELATES OF VERBAL WORKING MEMORY DYSFUNCTION IN EARLY-ONSET SCHIZOPHRENIA: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY Marinos Kyriakopoulos, Danai Dima, Matthew Kempton, Sophia Frangou
Section of Neurobiology of Psychosis, NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London London, United Kingdom Background: Working memory (WM) deficits are among the core cognitive abnormalities in schizophrenia. WM is subserved by widely distributed fronto-parietal networks and is undergoing robust development during adolescence. Studying the neural correlates of WM dysfunction in early-onset schizophrenia (EOS) will advance our understanding of aberrant neurodevelopmental processes in the disorder. Methods: Nineteen patients with EOS aged 13-19 and 20 matched healthy participants underwent functional Magnetic Resonance Imaging (fMRI) as they performed a N-back verbal WM task with 3 levels of difficulty (1-back, 2-back, 3-back). Following matching for task performance, 14 patients were compared to 20 controls, using non-parametric whole brain and region of interest (ROI) approaches followed by psycho-physiological interaction analysis (PPI) with seed voxel from the left parietal cluster. Results: Regions within the left prefrontal cortex, the left insula and bilateral anterior cingulate cortex showed reduced activation in EOS patients compared to healthy participants at the 2-back condition. In addition, ROI analysis at the same condition revealed hypoactivation in the EOS group with large effect sizes for left prefrontal and parietal regions. The PPI results revealed negative functional connectivity in the healthy participants' group but not in EOS between left parietal and right parietal and bilateral frontal regions. Discussion: Our results support compromised function within the left prefrontal-cingulate network and left insula during the N-Back verbal WM task in patients with EOS compared to healthy participants. They also indicate the possibility of more widespread fronto-parietal network dysfunction, most noted in the left hemisphere in the disorder.
doi:10.1016/j.schres.2010.02.810
Poster 50 EVIDENCE MAPPING FOR EARLY PSYCHOTIC DISORDERS IN YOUNG PEOPLE Ping Liu, Alexandra Parker, Sarah Hetrick, Rosemary Purcell ORYGEN Youth Health Research Centre University of Melbourne Melbourne, Victoria, Australia Background: The onset of psychotic disorders peaks in young people aged 12-30 years. Given the traditionally poor prognosis associated with chronic schizophrenia, a clinical research agenda has emerged in the last 2 decades focusing on interventions during the early phases of psychosis, where opportunities for clinical and functional recovery are greater. As a large volume of such research now exists, there is a need to summarise the extent and distribution of this research to ascertain what is known, and not yet known, about the evidence for preventing and treating early psychotic disorders. Methods: Using an evidence mapping methodology, we conducted a comprehensive search of high-level evidence (RCTs, CCTs and systematic reviews) since 1980 using the Cochrane Central Register of Controlled Trials, PSYCHINFO, MEDLINE and EMBASE. Detailed inclusion and exclusion criteria were defined. Studies were screened according to these criteria and mapped according to predefined study characteristics, including the type of intervention (e.g. psychological, biological, integrated) and