- Email: [email protected]
Poster #M61 AUDITORY HALLUCINATIONS IN FIRST EPISODE PSYCHOSIS: A LONGITUDINAL DTI STUDY OF THE ARCUATE FASCICULUS
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
Poster #M60 MODELLING GENETIC AND ENVIRONMENTAL INFLUENCES ON BRAIN VOLUME IN TWINS WITH SCHIZOPHRENIA Marco M. Picchioni 1,2 , Timothea Toulopoulou 3 , Christopher Chaddock 4 , James Cole 4 , Ulrich Ettinger 4 , Robin M. Murray 6 , Philip McGuire 6 1 St Andrew’s Academic Centre; 2 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry; 3 University of Hong Kong, Hong Kong; 4 Institute of Psychiatry; 5 University of Bonn; 6 King’s College London Background: Whole brain and grey matter volumes are reduced in schizophrenia. How these pathological abnormalities are influenced by schizophrenia’s genetic and environmental risk remains less clear. Methods: We investigated the relationship between genetic, common and unique environmental risk on brain volumes in monozygotic and dizygotic twin pairs varying in their concordance for schizophrenia, and healthy control twins. Total brain, grey and white matter volumes were established from structural magnetic resonance images using an automated alogorithm in SPM8 from 86 twin pairs (n=168). Hippocampal volumes were measured manually in the same sample. Between group differences in brain volumes were tested before full genetic modelling in Mx. Results: We found that whole brain, grey, white and right hippocampal volumes were smaller in probands with schizophrenia compared to healthy controls. Well co-twins from DZ discordant pairs also had smaller hippocampal volumes compared to the healthy controls. Whole brain, grey and white matter volumes were heritable, while hippocampal volume was subject to significant common environmental effects. All of the brain volumes tested had a significant negative phenotypic correlation with schizophrenia. Lower birth weight and hypoxia were both associated with lower whole brain volumes, and with lower white and grey matter volumes respectively. There were no significant effects in the patients of cumulative antipsychotic exposure. Discussion: Our data suggest that total brain, grey, white matter and hippocampal volume reductions are associated with schizophrenia. Whole brain and white matter volumes were most strongly linked to genetic effects. Hippocampal volume reductions appear to be particularly sensitive to environmental effects.
Poster #M61 AUDITORY HALLUCINATIONS IN FIRST EPISODE PSYCHOSIS: A LONGITUDINAL DTI STUDY OF THE ARCUATE FASCICULUS Tiago Reis Marques 1 , Francisco Marques-Teixeira 2 , Heather Taylor 3 , Flavio Dell’Acqua 3 , Aurora Falcone 3 , Andy Simmons 3 , Marta DiForti 3 , Robin M. Murray 3 , Anthony S. David 1 , Paola Dazzan 4 1 Institute of Psychiatry, King’s College London; 2 University of Porto; 3 Institute of Psychiatry; 4 Psychological Medicine, Institute of Psychiatry, King’s College London Background: Auditory hallucinations occurs with a lifetime prevalence of 60% in patients with schizophrenia. The arcuate fasciculus, a white matter tract, has been implicated in auditory hallucinations, but DTI studies have so far showed contradictory findings, with studies showing increase in FA, an index of white matter integrity, while others reporting a decrease in FA. Furthermore, no study so far has analysed the longitudinal changes in white matter integrity and its relationship to changes in the severity of auditory hallucinations. Methods: 39 first-episode psychosis patients with auditory hallucinations, 46 without auditory hallucinations and 45 healthy controls were enrolled in this study. All subjects underwent MRI at baseline and 3 months follow-up. The presence and severity of auditory hallucinations was assessed using the PANSS Scale. Results: We found a reduction in FA in several segments of the arcuate in patients with auditory hallucinations compared to patients without auditory hallucinations and controls. This reduction was still present at 3 months follow-up. Furthermore, there was a significant correlation between changes in the severity of auditory hallucinations and changes in white matter integrity. Discussion: This is the first study to assess the arcuate white matter integrity in first episode psychosis and its relation with auditory hallucina-
S211
tions, using a longitudinal design. This study highlights the importance of the arcuate for in the etiopathogenesis of auditory hallucinations.
Poster #M62 WHITE MATTER VOLUME REDUCTIONS IN FIRST EPISODE PSYCHOSIS ARE ASSOCIATED WITH CORTISOL LEVELS Renate L. Reniers 1 , Belinda Garner 2 , Christina Phassouliotis 3 , Lisa Phillips 4 , Connie Markulev 2 , Christos Pantelis 4 , Sarah Bendall 5 , Patrick McGorry 2 , Stephen Wood 1 1 University of Birmingham; 2 Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Australia; 3 Melbourne Neuropsychiatry Centre; 4 University of Melbourne; 5 Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne Background: The hypothalamic-pituitary-adrenal (HPA) axis governs the release of glucocorticoids, such as cortisol, in response to stress. Stress and abnormal HPA-axis functioning have been implicated in the early phase of psychosis and may underlie reported changes in brain structure. This study investigated whether levels of morning cortisol were related to grey and white matter brain volume. Methods: Blood cortisol and MRI scans were obtained in 22 patients (18M:4F; mean age 20.64, SD=2.38) and 22 matched healthy controls (18M:4F; mean age 22.48, SD=1.95). 13 Patients had a diagnosis on the schizophrenia spectrum. Eight (36%) patients were neuroleptic naive at the time of assessment. The remaining patients received an average of 4.93 days (SD=2.13) of antipsychotic medication. Images were analysed using the VBM8 toolbox in SPM8. Spatial extent threshold was determined by 10,000 Monte Carlo simulations conducted using 3dClustSim (AFNI), which yielded a cluster extent of 317 voxels for grey matter and 309 voxels for white matter at a voxel-wise threshold of p<0.002. Results: There were no significant differences (p>0.05) between patients and controls on measures of cortisol, nor in grey or white matter volumes (p<0.05 FWE corrected). Higher levels of baseline cortisol were indicative of smaller white matter volumes in the cuneus (peak voxel [9 −84 8]) and anterior cingulate (peak voxel [12 37 −1]). This relationship was significantly stronger for the patients than the controls. No such relationship was observed for grey matter volumes. Discussion: These findings support the involvement of stress mechanisms in the pathophysiology of early psychosis and suggest that the first subtle brain changes can be observed in the white matter.
Poster #M63 PROGRESSIVE BRAIN STRUCTURE CHANGE PREDICTS NEGATIVE SYMPTOMS IN FIRST EPISODE PSYCHOSIS AT 3 YEAR FOLLOW-UP Cathy Scanlon 1 , Shane McInerney 1 , Stefani O’Donoghue 1 , Liam Kilmartin 1 , Heike Anderson-Schmidt 2 , John McFarland 1 , Mairead Waldron 1 , Joanne Kenney 1 , Srinath Ambati 1 , Brian Hallahan 1,3 , Dara Cannon 1 , Colm McDonald 1 1 National University of Ireland, Galway; 2 University Medical Centre Goettingen; 3 Galway University Hospital Background: First episode psychosis (FEP) is known to be associated with structural brain abnormalities and some evidence suggests that these changes may be used to predict clinical outcome. In a previous study, we identified caudate volume and shape abnormalities and right superior temporal gyrus (STG) thinning in a cross-sectional study of FEP, with no evidence of these brain changes predicting patient outcome. Recent studies however suggest that longitudinal rather than cross-sectional neuroimaging may be better predictors of patient outcome. In this study, we investigate how brain structure (volume, thickness and shape) may change over time in FEP and determine if identified changes may better predict clinical outcome at 3 year follow-up. Methods: 1.5 Tesla T1-weighted MR images were acquired for 28 patients (18 male, 10 female; mean age 29±9 years) at the time of their FEP and again 3.5 years (SD=0.9) later. Twenty-eight healthy controls (HC) were also scanned at the same time points (14 male, 14 female; mean age 33±9 years). Cerebral cortical thickness change was investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ven-
Poster #M60 MODELLING GENETIC AND ENVIRONMENTAL INFLUENCES ON BRAIN VOLUME IN TWINS WITH SCHIZOPHRENIA Marco M. Picchioni 1,2 , Timothea Toulopoulou 3 , Christopher Chaddock 4 , James Cole 4 , Ulrich Ettinger 4 , Robin M. Murray 6 , Philip McGuire 6 1 St Andrew’s Academic Centre; 2 Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry; 3 University of Hong Kong, Hong Kong; 4 Institute of Psychiatry; 5 University of Bonn; 6 King’s College London Background: Whole brain and grey matter volumes are reduced in schizophrenia. How these pathological abnormalities are influenced by schizophrenia’s genetic and environmental risk remains less clear. Methods: We investigated the relationship between genetic, common and unique environmental risk on brain volumes in monozygotic and dizygotic twin pairs varying in their concordance for schizophrenia, and healthy control twins. Total brain, grey and white matter volumes were established from structural magnetic resonance images using an automated alogorithm in SPM8 from 86 twin pairs (n=168). Hippocampal volumes were measured manually in the same sample. Between group differences in brain volumes were tested before full genetic modelling in Mx. Results: We found that whole brain, grey, white and right hippocampal volumes were smaller in probands with schizophrenia compared to healthy controls. Well co-twins from DZ discordant pairs also had smaller hippocampal volumes compared to the healthy controls. Whole brain, grey and white matter volumes were heritable, while hippocampal volume was subject to significant common environmental effects. All of the brain volumes tested had a significant negative phenotypic correlation with schizophrenia. Lower birth weight and hypoxia were both associated with lower whole brain volumes, and with lower white and grey matter volumes respectively. There were no significant effects in the patients of cumulative antipsychotic exposure. Discussion: Our data suggest that total brain, grey, white matter and hippocampal volume reductions are associated with schizophrenia. Whole brain and white matter volumes were most strongly linked to genetic effects. Hippocampal volume reductions appear to be particularly sensitive to environmental effects.
Poster #M61 AUDITORY HALLUCINATIONS IN FIRST EPISODE PSYCHOSIS: A LONGITUDINAL DTI STUDY OF THE ARCUATE FASCICULUS Tiago Reis Marques 1 , Francisco Marques-Teixeira 2 , Heather Taylor 3 , Flavio Dell’Acqua 3 , Aurora Falcone 3 , Andy Simmons 3 , Marta DiForti 3 , Robin M. Murray 3 , Anthony S. David 1 , Paola Dazzan 4 1 Institute of Psychiatry, King’s College London; 2 University of Porto; 3 Institute of Psychiatry; 4 Psychological Medicine, Institute of Psychiatry, King’s College London Background: Auditory hallucinations occurs with a lifetime prevalence of 60% in patients with schizophrenia. The arcuate fasciculus, a white matter tract, has been implicated in auditory hallucinations, but DTI studies have so far showed contradictory findings, with studies showing increase in FA, an index of white matter integrity, while others reporting a decrease in FA. Furthermore, no study so far has analysed the longitudinal changes in white matter integrity and its relationship to changes in the severity of auditory hallucinations. Methods: 39 first-episode psychosis patients with auditory hallucinations, 46 without auditory hallucinations and 45 healthy controls were enrolled in this study. All subjects underwent MRI at baseline and 3 months follow-up. The presence and severity of auditory hallucinations was assessed using the PANSS Scale. Results: We found a reduction in FA in several segments of the arcuate in patients with auditory hallucinations compared to patients without auditory hallucinations and controls. This reduction was still present at 3 months follow-up. Furthermore, there was a significant correlation between changes in the severity of auditory hallucinations and changes in white matter integrity. Discussion: This is the first study to assess the arcuate white matter integrity in first episode psychosis and its relation with auditory hallucina-
S211
tions, using a longitudinal design. This study highlights the importance of the arcuate for in the etiopathogenesis of auditory hallucinations.
Poster #M62 WHITE MATTER VOLUME REDUCTIONS IN FIRST EPISODE PSYCHOSIS ARE ASSOCIATED WITH CORTISOL LEVELS Renate L. Reniers 1 , Belinda Garner 2 , Christina Phassouliotis 3 , Lisa Phillips 4 , Connie Markulev 2 , Christos Pantelis 4 , Sarah Bendall 5 , Patrick McGorry 2 , Stephen Wood 1 1 University of Birmingham; 2 Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Australia; 3 Melbourne Neuropsychiatry Centre; 4 University of Melbourne; 5 Orygen Youth Health Research Centre and Centre for Youth Mental Health, University of Melbourne Background: The hypothalamic-pituitary-adrenal (HPA) axis governs the release of glucocorticoids, such as cortisol, in response to stress. Stress and abnormal HPA-axis functioning have been implicated in the early phase of psychosis and may underlie reported changes in brain structure. This study investigated whether levels of morning cortisol were related to grey and white matter brain volume. Methods: Blood cortisol and MRI scans were obtained in 22 patients (18M:4F; mean age 20.64, SD=2.38) and 22 matched healthy controls (18M:4F; mean age 22.48, SD=1.95). 13 Patients had a diagnosis on the schizophrenia spectrum. Eight (36%) patients were neuroleptic naive at the time of assessment. The remaining patients received an average of 4.93 days (SD=2.13) of antipsychotic medication. Images were analysed using the VBM8 toolbox in SPM8. Spatial extent threshold was determined by 10,000 Monte Carlo simulations conducted using 3dClustSim (AFNI), which yielded a cluster extent of 317 voxels for grey matter and 309 voxels for white matter at a voxel-wise threshold of p<0.002. Results: There were no significant differences (p>0.05) between patients and controls on measures of cortisol, nor in grey or white matter volumes (p<0.05 FWE corrected). Higher levels of baseline cortisol were indicative of smaller white matter volumes in the cuneus (peak voxel [9 −84 8]) and anterior cingulate (peak voxel [12 37 −1]). This relationship was significantly stronger for the patients than the controls. No such relationship was observed for grey matter volumes. Discussion: These findings support the involvement of stress mechanisms in the pathophysiology of early psychosis and suggest that the first subtle brain changes can be observed in the white matter.
Poster #M63 PROGRESSIVE BRAIN STRUCTURE CHANGE PREDICTS NEGATIVE SYMPTOMS IN FIRST EPISODE PSYCHOSIS AT 3 YEAR FOLLOW-UP Cathy Scanlon 1 , Shane McInerney 1 , Stefani O’Donoghue 1 , Liam Kilmartin 1 , Heike Anderson-Schmidt 2 , John McFarland 1 , Mairead Waldron 1 , Joanne Kenney 1 , Srinath Ambati 1 , Brian Hallahan 1,3 , Dara Cannon 1 , Colm McDonald 1 1 National University of Ireland, Galway; 2 University Medical Centre Goettingen; 3 Galway University Hospital Background: First episode psychosis (FEP) is known to be associated with structural brain abnormalities and some evidence suggests that these changes may be used to predict clinical outcome. In a previous study, we identified caudate volume and shape abnormalities and right superior temporal gyrus (STG) thinning in a cross-sectional study of FEP, with no evidence of these brain changes predicting patient outcome. Recent studies however suggest that longitudinal rather than cross-sectional neuroimaging may be better predictors of patient outcome. In this study, we investigate how brain structure (volume, thickness and shape) may change over time in FEP and determine if identified changes may better predict clinical outcome at 3 year follow-up. Methods: 1.5 Tesla T1-weighted MR images were acquired for 28 patients (18 male, 10 female; mean age 29±9 years) at the time of their FEP and again 3.5 years (SD=0.9) later. Twenty-eight healthy controls (HC) were also scanned at the same time points (14 male, 14 female; mean age 33±9 years). Cerebral cortical thickness change was investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ven-