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Poster #44 ASSOCIATION BETWEEN REDUCED THALAMO-PREFRONTAL INTEGRITY AND CORTICAL THICKNESS REDUCTION IN SCHIZOPHRENIA
S296
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
suggest that patients with schizophrenia have excessive gray matter loss over time in the fronto-temporal regions compared to healthy individuals during the early phase of illness.
Poster #42 PREFRONTAL CORTEX AND HIPPOCAMPAL VOLUMES IN AGGRESSIVE AND NON-AGGRESSIVE PATIENTS WITH A PSYCHOTIC DISORDER Laura Koenders 1 , Marise W.J. Machielsen 1 , Jet D. Heering 1 , Claudia Vingerhoets 1 , Dick J. Veltman 2 , Lieuwe de Haan 1 1 Academic Medical Centre, Amsterdam, Netherlands; 2 Vrije Universiteit Medical Centre, Amsterdam, Netherlands Background: There appears to be a relationship between psychosis and aggressive or violent behavior. Previous research found reduced prefrontal cortex (PFC) and hippocampal volumes in patients with schizophrenia who displayed aggressive behavior, compared to healthy control subjects. Present study examines whether patients with a psychotic disorder who displayed aggressive behavior have smaller prefrontal cortex and hippocampal volumes compared to patients with a psychotic disorder who did not display aggressive behavior. Methods: For this study, a large sample (n=202) of patients with recent onset schizophrenia or related disorders were offered a structural MRI scan. A comparison of brain volumes was made between patients who displayed aggression and patients who did not display aggression. Aggression was assessed using the Staff Observation Aggression Scale. The results will also be compared to a sample of healthy controls in the near future. Results: Reductions were expected in both hippocampal and PFC volumes in the group with aggressive patients. The results showed that aggressive patients had significantly smaller grey matter hippocampal volumes compared to the non-aggressive patients (FWE peakvalue-corrected p<0.05). However PFC volumes did not differ significantly between the two groups. Discussion: Our results indicate that aggressive patients have smaller hippocampal volumes compared to non-aggressive patients. Since larger hippocampal volumes are associated with greater levels of inhibition, aggression in psychotic patients may be the re result of a limited ability to inhibit aggressive behavior.
Poster #43 WHITE MATTER ABNORMALITIES IN MIDDLE-AGED SUBJECTS WITH SCHIZOPHRENIA - THE NORTHERN FINLAND 1966 BIRTH COHORT Jenni S. Koivukangas 1,2 , Juha Veijola 1,3 , Osmo Tervonen 2 , Marianne Haapea 1,2 , Jouko Miettunen 1,3,4 , Matti Isohanni 1,3 , Vesa Kiviniemi 2 , Erika Jääskeläinen 1,3 , Peter B. Jones 5,6 , Anna Barnes 5,6 , Juha Nikkinen 2 1 Dept. of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; 2 Dept. of Diagnostic Radiology, Oulu, Finland; 3 Dept. of Psychiatry, Oulu University Hospital, Oulu, Finland; 4 Institute of Health Sciences, University of Oulu, Oulu, Finland; 5 Dept. of Psychiatry, University of Cambridge, Cambridge, United Kingdom; 6 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom Background: Structural magnetic resonance imaging studies of schizophrenia have revealed disturbed communication within and between brain regions. In order to determine at which extend white matter (WM) abnormalities are present in middle-aged subjects with schizophrenia or other psychoses we used diffusion tensor imaging. Methods: All subjects with psychotic disorder within the Northern Finland 1966 Birth Cohort (NFBC 1966) were invited to participate in a field study conducted in 2008-2011 when the subjects were 42-44 years. A random sample of non-psychotic members of the NFBC 1966 were invited to participate as control subjects. All participants underwent psychiatric interviews, cognitive tests and diffusion tensor imaging (DTI) brain scanning. Voxelwise approach of WM fractional anisotropy (FA) and tract-based spatial statistic (TBSS) were used to compare 169 (87 females) control subjects, 37 (13) subjects with schizophrenia and 34 (20) subjects with other psychotic disorder (schizophrenia spectrum, N=7; psychotic depression, N=14; bipolar disorder, N=4; brief psychotic disorder or unspecified psychosis not due to a substance or known physiological condition, N=9).
Results: When compared to controls, subjects with schizophrenia showed widespread areas of reduced FA, increased mean diffusivity (MD) and radial and axial diffusion in the majority of the WM fiber bundles. Compared to controls, decreased FA, increased MD and radial diffusivity were detected in subjects with other psychosis as well. Despite the fact that compared to subjects with other psychosis, subjects in schizophrenia group had lower educational level, longer duration of illness, lower SOFAS (Social and Occupational Functioning Assessment Scale) scores, higher PANSS (Positive and Negative Syndrome Scale) scores, and less of them were on remission, there were no differences in FA between those groups. In both psychotic groups mean FA value correlated negatively with PANSS - emotional and disorganized symptoms scores and positively with SOFAS scores. In addittion correlation between poor performance on grooved pegboard and low mean FA was found. Results remained significant in both groups when adjusted with sex and antipsychotic medication load. In other psychosis group statistical significances dissapeared after adjusting for sex and high alcohol use. Discussion: White matter abnormalities are extensive in middle-aged subjects with schizophrenia, but appeared to be extensive also in subjects with other psychosis. These findings imply an overlap in white matter pathology, possibly relating to risk factors common to different psychotic disorders.
Poster #44 ASSOCIATION BETWEEN REDUCED THALAMO-PREFRONTAL INTEGRITY AND CORTICAL THICKNESS REDUCTION IN SCHIZOPHRENIA Manabu Kubota 1 , Jun Miyata 1 , Akihiko Sasamoto 1 , Hidefumi Yoshida 2 , Ryosaku Kawada 1 , Shinsuke Fujimoto 1 , Yusuke Tanaka 1 , Nobukatsu Sawamoto 2 , Hidenao Fukuyama 2 , Hidehiko Takahashi 1 , Toshiya Murai 1 1 Department of Neuropsychiatry, 2 Human Brain Research Center, Graduate School of Medicine, Kyoto University Kyoto Japan Background: Dysfunction of the thalamo-prefrontal pathway is thought to account for the fundamental cognitive deficit and form the neural basis of schizophrenia. Although the mechanisms involved remain unclear, previous studies suggest an alteration of fibrous projections from the mediodorsal thalamic nucleus to layers of the prefrontal cortex. This study aimed to investigate integrity of thalamo-prefrontal pathways in schizophrenia and examine its possible association with cortical thickness. Methods: Thirty-seven patients with schizophrenia and 36 age-, genderand education-matched healthy controls underwent diffusion weighted imaging and T1-weighted 3D magnetic resonance imaging acquisition. Prefrontal regions were divided into lateral, medial, and orbitofrontal areas for each hemisphere separately. Probabilistic tractography was performed from the thalamus to the each cortical area described to investigate thalamoprefrontal pathways, and group differences of mean fractional anisotropy (FA) were examined. Surface-based analysis was applied to investigate cortical thickness, and the intercorrelation between FA values and cortical thickness was examined. Results: The patient group exhibited reduced FA for the right thalamoorbitofrontal pathway (p<0.00833, Bonferroni correction). In the patients only, the mean FA for this pathway was positively correlated with cortical thickness of the right frontal polar and right lateral orbitofrontal regions (p<0.05, clusterwise correction), but not with cortical thickness of the entire right hemisphere.Moreover, cortical thickness in these regions was reduced in the patient group. Discussion: Our results suggest that, in schizophrenia, regional thalamoprefrontal white matter pathology is specifically associated with cortical pathology where the fibers connect.
Poster #45 DIFFERENCES IN STRUCTURAL BRAIN VOLUMES BETWEEN PATIENTS WITH AN EARLY PSYCHOTIC DISORDER WITH AND WITHOUT COMORBID CANNABIS USE DISORDERS Marise Machielsen 1 , Floor van der Meer 1 , Angelique van Gasselt 1 , Jet Heering 1 , Dick Veltman 2 , Lieuwe de Haan 1 1 Early Psychosis Department, 2 AIAR, AMC, Amsterdam, Netherlands Background: Comorbidity of psychotic disorders and cannabis use disor-
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
suggest that patients with schizophrenia have excessive gray matter loss over time in the fronto-temporal regions compared to healthy individuals during the early phase of illness.
Poster #42 PREFRONTAL CORTEX AND HIPPOCAMPAL VOLUMES IN AGGRESSIVE AND NON-AGGRESSIVE PATIENTS WITH A PSYCHOTIC DISORDER Laura Koenders 1 , Marise W.J. Machielsen 1 , Jet D. Heering 1 , Claudia Vingerhoets 1 , Dick J. Veltman 2 , Lieuwe de Haan 1 1 Academic Medical Centre, Amsterdam, Netherlands; 2 Vrije Universiteit Medical Centre, Amsterdam, Netherlands Background: There appears to be a relationship between psychosis and aggressive or violent behavior. Previous research found reduced prefrontal cortex (PFC) and hippocampal volumes in patients with schizophrenia who displayed aggressive behavior, compared to healthy control subjects. Present study examines whether patients with a psychotic disorder who displayed aggressive behavior have smaller prefrontal cortex and hippocampal volumes compared to patients with a psychotic disorder who did not display aggressive behavior. Methods: For this study, a large sample (n=202) of patients with recent onset schizophrenia or related disorders were offered a structural MRI scan. A comparison of brain volumes was made between patients who displayed aggression and patients who did not display aggression. Aggression was assessed using the Staff Observation Aggression Scale. The results will also be compared to a sample of healthy controls in the near future. Results: Reductions were expected in both hippocampal and PFC volumes in the group with aggressive patients. The results showed that aggressive patients had significantly smaller grey matter hippocampal volumes compared to the non-aggressive patients (FWE peakvalue-corrected p<0.05). However PFC volumes did not differ significantly between the two groups. Discussion: Our results indicate that aggressive patients have smaller hippocampal volumes compared to non-aggressive patients. Since larger hippocampal volumes are associated with greater levels of inhibition, aggression in psychotic patients may be the re result of a limited ability to inhibit aggressive behavior.
Poster #43 WHITE MATTER ABNORMALITIES IN MIDDLE-AGED SUBJECTS WITH SCHIZOPHRENIA - THE NORTHERN FINLAND 1966 BIRTH COHORT Jenni S. Koivukangas 1,2 , Juha Veijola 1,3 , Osmo Tervonen 2 , Marianne Haapea 1,2 , Jouko Miettunen 1,3,4 , Matti Isohanni 1,3 , Vesa Kiviniemi 2 , Erika Jääskeläinen 1,3 , Peter B. Jones 5,6 , Anna Barnes 5,6 , Juha Nikkinen 2 1 Dept. of Psychiatry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; 2 Dept. of Diagnostic Radiology, Oulu, Finland; 3 Dept. of Psychiatry, Oulu University Hospital, Oulu, Finland; 4 Institute of Health Sciences, University of Oulu, Oulu, Finland; 5 Dept. of Psychiatry, University of Cambridge, Cambridge, United Kingdom; 6 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom Background: Structural magnetic resonance imaging studies of schizophrenia have revealed disturbed communication within and between brain regions. In order to determine at which extend white matter (WM) abnormalities are present in middle-aged subjects with schizophrenia or other psychoses we used diffusion tensor imaging. Methods: All subjects with psychotic disorder within the Northern Finland 1966 Birth Cohort (NFBC 1966) were invited to participate in a field study conducted in 2008-2011 when the subjects were 42-44 years. A random sample of non-psychotic members of the NFBC 1966 were invited to participate as control subjects. All participants underwent psychiatric interviews, cognitive tests and diffusion tensor imaging (DTI) brain scanning. Voxelwise approach of WM fractional anisotropy (FA) and tract-based spatial statistic (TBSS) were used to compare 169 (87 females) control subjects, 37 (13) subjects with schizophrenia and 34 (20) subjects with other psychotic disorder (schizophrenia spectrum, N=7; psychotic depression, N=14; bipolar disorder, N=4; brief psychotic disorder or unspecified psychosis not due to a substance or known physiological condition, N=9).
Results: When compared to controls, subjects with schizophrenia showed widespread areas of reduced FA, increased mean diffusivity (MD) and radial and axial diffusion in the majority of the WM fiber bundles. Compared to controls, decreased FA, increased MD and radial diffusivity were detected in subjects with other psychosis as well. Despite the fact that compared to subjects with other psychosis, subjects in schizophrenia group had lower educational level, longer duration of illness, lower SOFAS (Social and Occupational Functioning Assessment Scale) scores, higher PANSS (Positive and Negative Syndrome Scale) scores, and less of them were on remission, there were no differences in FA between those groups. In both psychotic groups mean FA value correlated negatively with PANSS - emotional and disorganized symptoms scores and positively with SOFAS scores. In addittion correlation between poor performance on grooved pegboard and low mean FA was found. Results remained significant in both groups when adjusted with sex and antipsychotic medication load. In other psychosis group statistical significances dissapeared after adjusting for sex and high alcohol use. Discussion: White matter abnormalities are extensive in middle-aged subjects with schizophrenia, but appeared to be extensive also in subjects with other psychosis. These findings imply an overlap in white matter pathology, possibly relating to risk factors common to different psychotic disorders.
Poster #44 ASSOCIATION BETWEEN REDUCED THALAMO-PREFRONTAL INTEGRITY AND CORTICAL THICKNESS REDUCTION IN SCHIZOPHRENIA Manabu Kubota 1 , Jun Miyata 1 , Akihiko Sasamoto 1 , Hidefumi Yoshida 2 , Ryosaku Kawada 1 , Shinsuke Fujimoto 1 , Yusuke Tanaka 1 , Nobukatsu Sawamoto 2 , Hidenao Fukuyama 2 , Hidehiko Takahashi 1 , Toshiya Murai 1 1 Department of Neuropsychiatry, 2 Human Brain Research Center, Graduate School of Medicine, Kyoto University Kyoto Japan Background: Dysfunction of the thalamo-prefrontal pathway is thought to account for the fundamental cognitive deficit and form the neural basis of schizophrenia. Although the mechanisms involved remain unclear, previous studies suggest an alteration of fibrous projections from the mediodorsal thalamic nucleus to layers of the prefrontal cortex. This study aimed to investigate integrity of thalamo-prefrontal pathways in schizophrenia and examine its possible association with cortical thickness. Methods: Thirty-seven patients with schizophrenia and 36 age-, genderand education-matched healthy controls underwent diffusion weighted imaging and T1-weighted 3D magnetic resonance imaging acquisition. Prefrontal regions were divided into lateral, medial, and orbitofrontal areas for each hemisphere separately. Probabilistic tractography was performed from the thalamus to the each cortical area described to investigate thalamoprefrontal pathways, and group differences of mean fractional anisotropy (FA) were examined. Surface-based analysis was applied to investigate cortical thickness, and the intercorrelation between FA values and cortical thickness was examined. Results: The patient group exhibited reduced FA for the right thalamoorbitofrontal pathway (p<0.00833, Bonferroni correction). In the patients only, the mean FA for this pathway was positively correlated with cortical thickness of the right frontal polar and right lateral orbitofrontal regions (p<0.05, clusterwise correction), but not with cortical thickness of the entire right hemisphere.Moreover, cortical thickness in these regions was reduced in the patient group. Discussion: Our results suggest that, in schizophrenia, regional thalamoprefrontal white matter pathology is specifically associated with cortical pathology where the fibers connect.
Poster #45 DIFFERENCES IN STRUCTURAL BRAIN VOLUMES BETWEEN PATIENTS WITH AN EARLY PSYCHOTIC DISORDER WITH AND WITHOUT COMORBID CANNABIS USE DISORDERS Marise Machielsen 1 , Floor van der Meer 1 , Angelique van Gasselt 1 , Jet Heering 1 , Dick Veltman 2 , Lieuwe de Haan 1 1 Early Psychosis Department, 2 AIAR, AMC, Amsterdam, Netherlands Background: Comorbidity of psychotic disorders and cannabis use disor-