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NEUROIMAGING
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
15:45 HEARING AND SPEECH IMPAIRMENT AT AGE 4 AND RISK OF LATER NON-AFFECTIVE PSYCHOSIS Annica Fors 1 , Kathryn M. Abel 2 , Susanne Wicks 1 , Cecilia Magnusson 1 , Christina Dalman 1 1 Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet Norrbacka, Stockholm, Sweden; 2 Centre for Women’s Mental Health, Manchester Academic Health Sciences Centre University of Manchester, Manchester, United Kingdom Background: Schizophrenia often becomes manifest in late adolescence and young adulthood, but deviations in physical and behavioral development may already be present in childhood. Studies in the elderly and in adults have reported associations between hearing impairment and non-affective psychotic disorders whereas speech impairment has been examined in children but with inconsistent results. Here we investigate the relationship between the presence of hearing (measured with audiometry) and speech impairment (broadly defined) in the same population at age 4 and adult risk of non-affective psychosis. Methods: We used a case control design where the study population consisted of all individuals born in Sweden 1975-1985. The cases were identified from the Swedish National Patient Register and the Stockholm local outpatient registers (N=785). The cases had been treated before 1st of January 2004 with a diagnosis of schizophrenia or other non-affective psychoses. Controls, matched for sex, date and place of birth, were identified in the Population Register. The controls had no history of psychiatric care. Well Baby Clinic (WBC) unit-records were collected for 105 consenting cases and 213 matched controls. Information from the WBC journals was extracted by an outcome-blind nurse. Results were adjusted for parental psychiatric history, socioeconomic status (SES) and obstetric complications (Apgar 1 & 5 min, birth weight, gestational age). Results: Speech impairment (OR 2.6 [95% CI 1.38-4.90]) and hearing impairment (OR 6.04 [95% CI 1.58-23.15]) in childhood were each associated with a significantly increased risk of subsequent onset of non-affective psychotic illness. The risk remained significant after adjustment for family SES, obstetric complications and parental psychiatric history both for speech (OR 2.54 [95% CI 1.25-5.17]) and hearing impairment (OR 6.68 [95% CI 1.32-33.83]) although the confidence intervals are wide. The results also indicated that hearing and speech impairment were independent risk factors. Discussion: This is the first study examining childhood onset hearing and speech impairment in the same study population and its association with later non-affective psychosis. The results support the hypothesis that non-affective psychoses have a developmental aspect with presentation of antecedent markers early in life, and long before the onset of the psychosis. Our findings add to the growing evidence that early hearing and speech impairment are risk indicators for later non-affective psychosis and possibly represent etiological clues and potentially modifiable risk factors. Notably, speech and language impairment are both detectable with inexpensive, easily accessible screening.
Oral Presentation NEUROIMAGING Chairpersons: Paola Dazzan and Jun Soo Kwon Tuesday, 17 April 2012 2:00 pm – 4:00 pm
14:00 REPEATED OBSERVATION OF ABNORMAL GYRIFICATION LOCALIZED TO THE FRONTOINSULAR CORTEX FROM FOUR INDEPENDENT SAMPLES WITH SCHIZOPHRENIA Lena Palaniyappan 1 , Anthony James 2 , Timothy J. Crow 3 , Peter F. Liddle 1 1 Division of Psychiatry, University of Nottingham, Nottingham, United Kingdom; 2 Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom; 3 SANE POWIC, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom Background: Distinct genetic modulators and separable developmental trajectories have been proposed for thickness, surface area and gyrification of
S87
cerebral cortex. Alterations in one or more of these properties can produce a volumetric defect in the grey matter. Despite consistent observation of structural abnormalities in schizophrenia, the origins of these abnormalities are presently unclear. Studying cortical gyrification, which is coupled to the formation of early cortical circuits, has the potential to inform the neurodevelopmental models of schizophrenia. Cortical Surface Based Analysis offers a powerful means to study the 3-dimensional property of cortical gyrification across numerous vertices throughout the cerebral surface. This technique is not restricted to preselected lobar divisions and is independent of MRI slice thickness and orientation. Methods: Regional differences in cortical gyrification patterns between patients with schizophrenia and healthy controls were investigated in structural MRI data from the entire cortical surface using Freesurfer in 3 independent samples of adults, aged 18-50, recruited from Nottingham and Oxford, UK {n [controls:patients] = 99 [41:57] for Nottingham Dataset-1, 82 [41:40] for Nottingham Dataset-2, 108 [57:51] for Oxford Dataset)} and one sample of adolescents, aged 13-19, from Oxford {n [controls:patients] = 37 [19:18]}. A follow-up scan (mean duration of follow-up = 2.18 years) was also obtained from the adolescent sample to study the longitudinal changes in gyrification. Each group comparison was controlled for intracranial volume, age and gender. Permutation tests were used to correct for multiple comparisons with a two-tailed cluster-wise probability of 0.05. Results: In each of the cross-sectional samples of adults with schizophrenia, the most significant gyrification defect was a reduction in gyrification (hypogyria) in a large cluster comprising of anterior insula and parts of inferior frontal gyrus predominantly in the left hemisphere (5-7% reduction). In contrast, in adolescents with schizophrenia this frontoinsular cluster displayed a significant hypergyria (increased gyrification). Longitudinal follow-up of these patients revealed that this hypergyric cluster showed a distinct reduction in gyrification whereas in healthy controls gyrification continued to increase. The reduction was most pronounced in male adolescents with schizophrenia. Discussion: The consistency of frontoinsular hypogyria and its evolution during adolescence suggests a prominent role for abnormal development of insula and inferior frontal cortex based cortical circuits in the pathophysiology of schizophrenia. This region is tightly linked to the language network and has also been identified as a key player in the process of stimulusresponse association (“proximal salience”). A focussed investigation of cortical networks involving insula holds substantial promise to further our understanding of the neural processes underlying schizophrenia.
14:15 DECREASED WHITE MATTER INTEGRITY IN PSYCHOTIC DISORDER: ASSOCIATION WITH CHILDHOOD TRAUMA? Machteld Marcelis 1 , Patrick Domen 1 , Stijn Michielse 1 , Ed Gronenschild 1 , Petra Habets 1 , Jim van Os 1,2 1 Department of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, Netherlands; 2 King’s College London, King’s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom Background: Evidence suggests that childhood trauma contributes to the risk for psychotic disorder, but reports on structural brain correlates of developmental trauma are scarce. A recent study showed that patients with psychotic disorder had significantly lower cortical thickness when exposed tot higher trauma levels, which was not found in controls and siblings of these patients [1]. In the same study sample, there was evidence for disease-related decreased white matter integrity, most pronounced in the corpus callosum (Domen et al, submitted). The present study examined whether the hypothesized effect of childhood trauma on structural white matter alteration is conditional on background genetic risk for psychotic disorder. Methods: As part of the first assessment in a longitudinal study, 85 patients with a psychotic disorder, 93 non-psychotic siblings of patients and 80 healthy controls underwent a Diffusion Tensor Imaging protocol. Using Tract Based Spatial Statistics, mean fractional anisotropy (FA) values of major white matter structures of the three groups were assessed and exported to a hierarchically structured STATA dataset, with 47 white matter structures (level 1), nested in subjects (level 2), who were part of the same families (level 3). Trauma levels were assessed with the Childhood Trauma
15:45 HEARING AND SPEECH IMPAIRMENT AT AGE 4 AND RISK OF LATER NON-AFFECTIVE PSYCHOSIS Annica Fors 1 , Kathryn M. Abel 2 , Susanne Wicks 1 , Cecilia Magnusson 1 , Christina Dalman 1 1 Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet Norrbacka, Stockholm, Sweden; 2 Centre for Women’s Mental Health, Manchester Academic Health Sciences Centre University of Manchester, Manchester, United Kingdom Background: Schizophrenia often becomes manifest in late adolescence and young adulthood, but deviations in physical and behavioral development may already be present in childhood. Studies in the elderly and in adults have reported associations between hearing impairment and non-affective psychotic disorders whereas speech impairment has been examined in children but with inconsistent results. Here we investigate the relationship between the presence of hearing (measured with audiometry) and speech impairment (broadly defined) in the same population at age 4 and adult risk of non-affective psychosis. Methods: We used a case control design where the study population consisted of all individuals born in Sweden 1975-1985. The cases were identified from the Swedish National Patient Register and the Stockholm local outpatient registers (N=785). The cases had been treated before 1st of January 2004 with a diagnosis of schizophrenia or other non-affective psychoses. Controls, matched for sex, date and place of birth, were identified in the Population Register. The controls had no history of psychiatric care. Well Baby Clinic (WBC) unit-records were collected for 105 consenting cases and 213 matched controls. Information from the WBC journals was extracted by an outcome-blind nurse. Results were adjusted for parental psychiatric history, socioeconomic status (SES) and obstetric complications (Apgar 1 & 5 min, birth weight, gestational age). Results: Speech impairment (OR 2.6 [95% CI 1.38-4.90]) and hearing impairment (OR 6.04 [95% CI 1.58-23.15]) in childhood were each associated with a significantly increased risk of subsequent onset of non-affective psychotic illness. The risk remained significant after adjustment for family SES, obstetric complications and parental psychiatric history both for speech (OR 2.54 [95% CI 1.25-5.17]) and hearing impairment (OR 6.68 [95% CI 1.32-33.83]) although the confidence intervals are wide. The results also indicated that hearing and speech impairment were independent risk factors. Discussion: This is the first study examining childhood onset hearing and speech impairment in the same study population and its association with later non-affective psychosis. The results support the hypothesis that non-affective psychoses have a developmental aspect with presentation of antecedent markers early in life, and long before the onset of the psychosis. Our findings add to the growing evidence that early hearing and speech impairment are risk indicators for later non-affective psychosis and possibly represent etiological clues and potentially modifiable risk factors. Notably, speech and language impairment are both detectable with inexpensive, easily accessible screening.
Oral Presentation NEUROIMAGING Chairpersons: Paola Dazzan and Jun Soo Kwon Tuesday, 17 April 2012 2:00 pm – 4:00 pm
14:00 REPEATED OBSERVATION OF ABNORMAL GYRIFICATION LOCALIZED TO THE FRONTOINSULAR CORTEX FROM FOUR INDEPENDENT SAMPLES WITH SCHIZOPHRENIA Lena Palaniyappan 1 , Anthony James 2 , Timothy J. Crow 3 , Peter F. Liddle 1 1 Division of Psychiatry, University of Nottingham, Nottingham, United Kingdom; 2 Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom; 3 SANE POWIC, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom Background: Distinct genetic modulators and separable developmental trajectories have been proposed for thickness, surface area and gyrification of
S87
cerebral cortex. Alterations in one or more of these properties can produce a volumetric defect in the grey matter. Despite consistent observation of structural abnormalities in schizophrenia, the origins of these abnormalities are presently unclear. Studying cortical gyrification, which is coupled to the formation of early cortical circuits, has the potential to inform the neurodevelopmental models of schizophrenia. Cortical Surface Based Analysis offers a powerful means to study the 3-dimensional property of cortical gyrification across numerous vertices throughout the cerebral surface. This technique is not restricted to preselected lobar divisions and is independent of MRI slice thickness and orientation. Methods: Regional differences in cortical gyrification patterns between patients with schizophrenia and healthy controls were investigated in structural MRI data from the entire cortical surface using Freesurfer in 3 independent samples of adults, aged 18-50, recruited from Nottingham and Oxford, UK {n [controls:patients] = 99 [41:57] for Nottingham Dataset-1, 82 [41:40] for Nottingham Dataset-2, 108 [57:51] for Oxford Dataset)} and one sample of adolescents, aged 13-19, from Oxford {n [controls:patients] = 37 [19:18]}. A follow-up scan (mean duration of follow-up = 2.18 years) was also obtained from the adolescent sample to study the longitudinal changes in gyrification. Each group comparison was controlled for intracranial volume, age and gender. Permutation tests were used to correct for multiple comparisons with a two-tailed cluster-wise probability of 0.05. Results: In each of the cross-sectional samples of adults with schizophrenia, the most significant gyrification defect was a reduction in gyrification (hypogyria) in a large cluster comprising of anterior insula and parts of inferior frontal gyrus predominantly in the left hemisphere (5-7% reduction). In contrast, in adolescents with schizophrenia this frontoinsular cluster displayed a significant hypergyria (increased gyrification). Longitudinal follow-up of these patients revealed that this hypergyric cluster showed a distinct reduction in gyrification whereas in healthy controls gyrification continued to increase. The reduction was most pronounced in male adolescents with schizophrenia. Discussion: The consistency of frontoinsular hypogyria and its evolution during adolescence suggests a prominent role for abnormal development of insula and inferior frontal cortex based cortical circuits in the pathophysiology of schizophrenia. This region is tightly linked to the language network and has also been identified as a key player in the process of stimulusresponse association (“proximal salience”). A focussed investigation of cortical networks involving insula holds substantial promise to further our understanding of the neural processes underlying schizophrenia.
14:15 DECREASED WHITE MATTER INTEGRITY IN PSYCHOTIC DISORDER: ASSOCIATION WITH CHILDHOOD TRAUMA? Machteld Marcelis 1 , Patrick Domen 1 , Stijn Michielse 1 , Ed Gronenschild 1 , Petra Habets 1 , Jim van Os 1,2 1 Department of Psychiatry and Psychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center, Maastricht, Netherlands; 2 King’s College London, King’s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom Background: Evidence suggests that childhood trauma contributes to the risk for psychotic disorder, but reports on structural brain correlates of developmental trauma are scarce. A recent study showed that patients with psychotic disorder had significantly lower cortical thickness when exposed tot higher trauma levels, which was not found in controls and siblings of these patients [1]. In the same study sample, there was evidence for disease-related decreased white matter integrity, most pronounced in the corpus callosum (Domen et al, submitted). The present study examined whether the hypothesized effect of childhood trauma on structural white matter alteration is conditional on background genetic risk for psychotic disorder. Methods: As part of the first assessment in a longitudinal study, 85 patients with a psychotic disorder, 93 non-psychotic siblings of patients and 80 healthy controls underwent a Diffusion Tensor Imaging protocol. Using Tract Based Spatial Statistics, mean fractional anisotropy (FA) values of major white matter structures of the three groups were assessed and exported to a hierarchically structured STATA dataset, with 47 white matter structures (level 1), nested in subjects (level 2), who were part of the same families (level 3). Trauma levels were assessed with the Childhood Trauma