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ALTERATIONS OF HIPPOCAMPAL SHAPE IN CANNABIS USERS WITH AND WITHOUT SCHIZOPHRENIA
426
Abstracts
Poster 23 ALTERATIONS OF HIPPOCAMPAL SHAPE IN CANNABIS USERS WITH AND WITHOUT SCHIZOPHRENIA
Nadia Solowij1,2, Mark Walterfang3, Colleen Respondek1, Sarah Whittle3, Brin Grenyer1, Valentina Lorenzetti3, Alex Fornito3,4, Dan Lubman5, Dennis Velakoulis3, Christos Pantelis3, Murat Yücel3,5 1 School of Psychology, University of Wollongong, Wollongong, NSW, Australia; 2Schizophrenia Research Institute, Sydney, NSW, Australia; 3 Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, VIC, Australia; 4Department of Psychiatry, University of Cambridge, Cambridge, UK; 5Orygen Youth Health Research Centre, University of Melbourne Melbourne, VIC, Australia Background: There is a paucity of research examining the longterm impact of cannabis use on the human brain. We have previously reported significant reduction in hippocampal volume in long-term heavy cannabis users1. Hippocampal alterations are implicated in psychosis and significant numbers of patients also use cannabis. In this study we performed hippocampal shape analysis in the same cohort of healthy cannabis users and a sample of patients with schizophrenia with and without comorbid cannabis use. Methods: Participants were recruited from the general community to form the following groups for comparison: long-term heavy cannabis users (THC: n = 16, 1 female, mean age 39 yrs, 21 yrs regular use, near daily); non-user controls (CON: n = 18, 2 female, 35 yrs); cannabis users with schizophrenia (SZ + THC: n = 10, 2 female, 35 yrs, 19 yrs regular use, near daily); and nonusers with schizophrenia (SZ–THC: n = 12, 3 female, 42 yrs). Groups did not differ in age, education or IQ (p > 0.05) and THC and SZ + THC were matched on cannabis use parameters and alcohol and tobacco use. Hippocampal volumes were traced from 3T magnetic resonance images and shape analysis was undertaken using the University of North Carolina toolkit. Segmented 3D binaries underwent morphological closing and minimal smoothing, and were subjected to spherical harmonic shape description (SPHARM-PDM). All surfaces were uniformly sampled into sets of 1002 surface points each and aligned to a study-averaged template with normalization for head size. To compare structural shape between groups, we computed the local Hotelling T2 two-sample mean difference, and corrected for multiple comparisons using false discovery rate. We generated mean difference magnitude displacement maps and significance maps of the local p-values in raw format, and corrected for multiple comparisons. Results: Significant differences between groups were found bilaterally in the hippocampus as follows. Compared to CON: THC showed a significant shape change in right hippocampus (p < 0.05) but only a trend in left hippocampus (p < 0.08); SZ–THC showed a marginally significant shape change for left hippocampus (p < 0.056) but not right hippocampus (p > 0.2); SZ + THC showed a highly significant change in left hippocampus (p < 0.003) and a marginal change in right hippocampus (p < 0.058). When THC were compared to SCZ + THC, there was a significant difference on the left (p < 0.05) and a trend on the right (p = 0.077). There was no significant shape difference between THC and SCZ–THC for either left or right hippocampus (p > 0.3). Significant regional changes were not confined to a particular subregion of the hippocampus, tending to be dispersed. Relationships with various cannabis use parameters and symptom measures were also observed. Discussion: Our findings continue to challenge the widespread perception of cannabis as having limited or no neuroanatomical sequelae. We found highly significant shape changes in the left hippocampus of patients with schizophrenia and comorbid cannabis use compared to controls, and some evidence of
hippocampal shape alterations in healthy cannabis users and non-users with schizophrenia. These showed differentially lateralised effects in each group, suggesting specific effects associated with cannabis use and with schizophrenia per se, and an interaction effect evident in the cannabis-using group with schizophrenia. Shape analysis provides further information beyond simple volumetric analysis and this study is the first to report an additional adverse effect of cannabis use on brain structure in chronic schizophrenia, in this instance specific to hippocampus. 1. Yücel, M., Solowij, N., Respondek, C., et al. (2008) Arch Gen Psychiatry, 65, 694-701. doi:10.1016/j.schres.2010.02.784
Poster 24 BRIEF SCHIZOPHRENIA ADDICTION SCALE (BSAS): A PILOT STUDY Martin L. Vargas, Sonia Lopez-Lorenzo Complejo Asistencial de Zamora, Zamora, Spain Background: Addiction is a frequent comorbid diagnosis in schizophrenia, that can be either one aetiological factor or a consequence of the disease. But the systematic evaluation of the use of drugs of abuse is still not an habitual clinical practice in schizophrenia, except in the cases where one drug-induced psychosis is suspected. The lack of useful and brief scales specifically designed for the evaluation of addiction in schizophrenia could contribute to this problem. The objective is to present a new tool to briefly measure addiction in schizophrenia and to study its main psychometric characteristics. Methods: We conduct one cross-sectional study on 60 schizophrenia out-patients (43 male; average age: 38.9 years, SD 9.4). The diagnose were: paranoid schizophrenia 26.7%, schizoaffective disorder 25.0%, residual schizophrenia 21.7%, other subtypes of schizophrenia 26.6%. The BSAS reflects life use of drugs and addiction: tobacco, coffee, alcohol, cannabis, cocaine, amphetamines, hallucinogens, opiates and gambling. For every substance and gambling, one five-point scale (lower 0, higher 4) was applied regarding to five characteristics: first use, frequency, length of use, last time use and harmful consequences. PANNS, FCQ-3, CGI and GAF were applied as clinical variables. The composite score was obtained for every substance and gambling. One factor analysis using principal components (Varimax rotation) was performed to study the dimensionality of BSAS. It was also studied the correlation between the factors and the clinical variables. Results: Two factors were defined, that explains for 66.1 of the variance: 1) Illegal addiction: cocaine, opiates, cannabis, hallucinogens, cannabis, amphetamines (mean score: 16.4, SD:20.4); 2) Legal addiction: alcohol, coffee, tobacco, gambling (mean score: 41.7, SD: 19.2). The distribution of both factors do not adjust to the normal curve but they suggest three subgroups of patients: those without addiction, one second group with moderate addictive trend and a third group highly addictive. The correlation (Spearman's Rho) between both factors was r = 0.58 (p < 0.001). The legal addiction factor did not correlate with any clinical variable. The illegal addiction factor was associated only with the negative syndrome (r = -0.30, p = 0.18). Discussion: Addiction in schizophrenia has two factors (illegal and legal addiction), which are independent from symptoms and severity of the disease. The quantification of the addictive syndrome as one independent dimension from the psychotic one could contribute to a better differentiation between the different disorders that constitute the schizophrenia syndrome. We propose that
Abstracts
Poster 23 ALTERATIONS OF HIPPOCAMPAL SHAPE IN CANNABIS USERS WITH AND WITHOUT SCHIZOPHRENIA
Nadia Solowij1,2, Mark Walterfang3, Colleen Respondek1, Sarah Whittle3, Brin Grenyer1, Valentina Lorenzetti3, Alex Fornito3,4, Dan Lubman5, Dennis Velakoulis3, Christos Pantelis3, Murat Yücel3,5 1 School of Psychology, University of Wollongong, Wollongong, NSW, Australia; 2Schizophrenia Research Institute, Sydney, NSW, Australia; 3 Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, VIC, Australia; 4Department of Psychiatry, University of Cambridge, Cambridge, UK; 5Orygen Youth Health Research Centre, University of Melbourne Melbourne, VIC, Australia Background: There is a paucity of research examining the longterm impact of cannabis use on the human brain. We have previously reported significant reduction in hippocampal volume in long-term heavy cannabis users1. Hippocampal alterations are implicated in psychosis and significant numbers of patients also use cannabis. In this study we performed hippocampal shape analysis in the same cohort of healthy cannabis users and a sample of patients with schizophrenia with and without comorbid cannabis use. Methods: Participants were recruited from the general community to form the following groups for comparison: long-term heavy cannabis users (THC: n = 16, 1 female, mean age 39 yrs, 21 yrs regular use, near daily); non-user controls (CON: n = 18, 2 female, 35 yrs); cannabis users with schizophrenia (SZ + THC: n = 10, 2 female, 35 yrs, 19 yrs regular use, near daily); and nonusers with schizophrenia (SZ–THC: n = 12, 3 female, 42 yrs). Groups did not differ in age, education or IQ (p > 0.05) and THC and SZ + THC were matched on cannabis use parameters and alcohol and tobacco use. Hippocampal volumes were traced from 3T magnetic resonance images and shape analysis was undertaken using the University of North Carolina toolkit. Segmented 3D binaries underwent morphological closing and minimal smoothing, and were subjected to spherical harmonic shape description (SPHARM-PDM). All surfaces were uniformly sampled into sets of 1002 surface points each and aligned to a study-averaged template with normalization for head size. To compare structural shape between groups, we computed the local Hotelling T2 two-sample mean difference, and corrected for multiple comparisons using false discovery rate. We generated mean difference magnitude displacement maps and significance maps of the local p-values in raw format, and corrected for multiple comparisons. Results: Significant differences between groups were found bilaterally in the hippocampus as follows. Compared to CON: THC showed a significant shape change in right hippocampus (p < 0.05) but only a trend in left hippocampus (p < 0.08); SZ–THC showed a marginally significant shape change for left hippocampus (p < 0.056) but not right hippocampus (p > 0.2); SZ + THC showed a highly significant change in left hippocampus (p < 0.003) and a marginal change in right hippocampus (p < 0.058). When THC were compared to SCZ + THC, there was a significant difference on the left (p < 0.05) and a trend on the right (p = 0.077). There was no significant shape difference between THC and SCZ–THC for either left or right hippocampus (p > 0.3). Significant regional changes were not confined to a particular subregion of the hippocampus, tending to be dispersed. Relationships with various cannabis use parameters and symptom measures were also observed. Discussion: Our findings continue to challenge the widespread perception of cannabis as having limited or no neuroanatomical sequelae. We found highly significant shape changes in the left hippocampus of patients with schizophrenia and comorbid cannabis use compared to controls, and some evidence of
hippocampal shape alterations in healthy cannabis users and non-users with schizophrenia. These showed differentially lateralised effects in each group, suggesting specific effects associated with cannabis use and with schizophrenia per se, and an interaction effect evident in the cannabis-using group with schizophrenia. Shape analysis provides further information beyond simple volumetric analysis and this study is the first to report an additional adverse effect of cannabis use on brain structure in chronic schizophrenia, in this instance specific to hippocampus. 1. Yücel, M., Solowij, N., Respondek, C., et al. (2008) Arch Gen Psychiatry, 65, 694-701. doi:10.1016/j.schres.2010.02.784
Poster 24 BRIEF SCHIZOPHRENIA ADDICTION SCALE (BSAS): A PILOT STUDY Martin L. Vargas, Sonia Lopez-Lorenzo Complejo Asistencial de Zamora, Zamora, Spain Background: Addiction is a frequent comorbid diagnosis in schizophrenia, that can be either one aetiological factor or a consequence of the disease. But the systematic evaluation of the use of drugs of abuse is still not an habitual clinical practice in schizophrenia, except in the cases where one drug-induced psychosis is suspected. The lack of useful and brief scales specifically designed for the evaluation of addiction in schizophrenia could contribute to this problem. The objective is to present a new tool to briefly measure addiction in schizophrenia and to study its main psychometric characteristics. Methods: We conduct one cross-sectional study on 60 schizophrenia out-patients (43 male; average age: 38.9 years, SD 9.4). The diagnose were: paranoid schizophrenia 26.7%, schizoaffective disorder 25.0%, residual schizophrenia 21.7%, other subtypes of schizophrenia 26.6%. The BSAS reflects life use of drugs and addiction: tobacco, coffee, alcohol, cannabis, cocaine, amphetamines, hallucinogens, opiates and gambling. For every substance and gambling, one five-point scale (lower 0, higher 4) was applied regarding to five characteristics: first use, frequency, length of use, last time use and harmful consequences. PANNS, FCQ-3, CGI and GAF were applied as clinical variables. The composite score was obtained for every substance and gambling. One factor analysis using principal components (Varimax rotation) was performed to study the dimensionality of BSAS. It was also studied the correlation between the factors and the clinical variables. Results: Two factors were defined, that explains for 66.1 of the variance: 1) Illegal addiction: cocaine, opiates, cannabis, hallucinogens, cannabis, amphetamines (mean score: 16.4, SD:20.4); 2) Legal addiction: alcohol, coffee, tobacco, gambling (mean score: 41.7, SD: 19.2). The distribution of both factors do not adjust to the normal curve but they suggest three subgroups of patients: those without addiction, one second group with moderate addictive trend and a third group highly addictive. The correlation (Spearman's Rho) between both factors was r = 0.58 (p < 0.001). The legal addiction factor did not correlate with any clinical variable. The illegal addiction factor was associated only with the negative syndrome (r = -0.30, p = 0.18). Discussion: Addiction in schizophrenia has two factors (illegal and legal addiction), which are independent from symptoms and severity of the disease. The quantification of the addictive syndrome as one independent dimension from the psychotic one could contribute to a better differentiation between the different disorders that constitute the schizophrenia syndrome. We propose that