- Email: [email protected]
IMPROVING FUNCTIONING WITH COGNITIVE REMEDIATION THERAPY
26
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
IMPROVING FUNCTIONING WITH COGNITIVE REMEDIATION THERAPY
Rafael Penades Hospital Clinic De Barcelona, Barcelona, Spain [email protected] Cognitive impairment has been shown to be linked to impairment in functional status (eg, social functioning, work performance, and activities of daily living) among patients with schizophrenia in crosssectional studies. While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established by now, the relationship between cognitive and functional change over time is far from complete. Moreover, little is known about the potential mechanisms that bridge the gap between cognition and functional outcome. To date, different controlled studies have now shown that large and lasting improvements in cognition can result from neurocognitive interventions. Cognitive remediation therapy (CRT) alone or together with work therapy can lead to large, lasting, and clinically relevant improvements not only in cognition but also in social and work functioning. CRT is guided by the view that metacognitive processes of scheme generation, self-monitoring and self-regulation are fundamental determinants of competent functioning in the real world and probably the most important targets in the achievement of improving functioning in patients with cognitive impairment. References [1] Reeder, C., Newton, E., Frangou, S., Wykes, T. (2004) Which executive skills should be target to affect social functioning and symptom change? Schizophrenia Bulletin. 30: 87-100. [2] Penadés, R., Catalán, R., Salamero, M. Boget, T., Puig, O., Guarch, J., G astó, C. (2006). Cognitive Remediation Therapy in chronic schizophrenia: a randomised and controlled study. Schizophrenia Research. 87: 323-331.
SESSION XV
June 24th, 2008
Late Breaking Genetic Findings STATUS REPORT OF THE GENOME-WIDE ASSOCIATION STUDY OF THE MOLECULAR GENETICS OF SCHIZOPHRENIA SAMPLE (MGS): PRELIMINARY ANALYSES OF THE GENETIC ASSOCIATION INFORMATION NETWORK (GAIN) SUBSAMPLE
Pablo V. Gejman Evanston Northwestern Healthcare and Northwestern University, Evanston, IL, USA [email protected] We are performing a GWAS study of total sample of 8160 subjects, 4284 cases and 3876 controls of European and African ancestry. In 2007, MGS was selected by GAIN (fnih.org) for GWAS genotyping and we submitted 5198 samples (2719 cases and 2479 controls (Wave 1) to be typed with the Affymetrix 6.0 array. Strict quality control procedures and Principal Components Analysis using EIGENSTRAT were applied, which eliminated many spurious findings. In the EA GAIN sample (∼1455 case control pairs), two of the best p-values are in a ∼450 Kb linkage disequilibrium block in 1p22.1 spanning FAM69A (hypothetical protein LOC388650; 1.04E-06) and the adjacent genes RPL5 (ribosomal protein L5; 7.35E-06), and EVI5 (ecotropic viral integration site 5). These three genes are among the top hits in a recent multi-stage GWAS of multiple sclerosis (Hafler et al., NEJM 2007). We performed bioinformatic analyses of FAM69A/RPL5/EVI5 region have initiated a deep resequencing (starting in FAM69A). In the AA GAIN sample (1278 cases and 1010 controls), the best p-value was in ERBB4, and another was in NRG1. ERBB4 encodes the receptor for neuregulin-1, which has been implicated in SZ by several lines of evidence. In our EA GAIN sample, the
lowest p-value observed in ERBB4 was 0.0038, and in NRG1 it was 0.003, similar to our previously reported results in an earlier dense LD mapping study of 14 SZ candidate genes in a slightly larger subset of the MGS sample, but we found some support for NOS1AP (not tested by us before). We are currently performing genome-wide CNV analysis in the total GAIN sample. The genotyping of another 2,962 subjects (under an R01 mechanism) has been completed but the results are not available yet. We plan to perform a final analysis of the total sample (8160 subjects) (each ancestry separately and both ancestries combined).
EPISODIC AND WORKING MEMORY FUNCTION IN MONOZYGOTIC AND DIZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA
Timothea Toulopoulou Institute of Psychiatry, King’s College London, University of London, London, UK [email protected] Introduction: Cognitive abnormalities are thought to be central to the pathophysiology of schizophrenia. These abnormalities include deficits in episodic memory, both in the verbal and the visual modalities. However, it is not clear to what extent these abnormalities relate to the genetic liability for schizophrenia. The objective of this study was to investigate verbal and visual episodic and working memory performance in monozygotic (MZ) and dizygotic (DZ) twins concordant and discordant for schizophrenia. Methods: A total of 252 twins participated in this study: 18 MZ twin pairs concordant for schizophrenia, 11 MZ twin pairs discordant for schizophrenia, 54 MZ twin pairs without schizophrenia, 7 DZ pairs discordant for schizophrenia and 36 DZ pairs without schizophrenia. Patients were drawn from in- and out-patient clinics across the UK. Controls were recruited through a UK twin register. Results: Twins with schizophrenia performed significantly worse than controls on most measures. Well co-twins from the MZ pairs discordant for schizophrenia were less able than controls to retain stories both immediately after presentation, and after a 30 minute delay. In addition they were slower in forming associations between words, and had more difficulty retaining visual representations over time. Their DZs counterparts performed less well than controls on backward digit span only, suggesting problems with working memory. Conclusions: Greater genetic loading for schizophrenia in the well co-twins was associated with more diverse memory impairments Acknowledgements: This work was supported by NARSAD through a Young Investigator Award to Dr Timothea Toulopoulou References [1] Substantial Genetic Overlap between Neurocognition and Schizophrenia: Genetic Modelling in Twin Samples Timothea Toulopoulou; Marco Picchioni; Fruhling Rijsdijk; Mei Hua-Hall; Ulrich Ettinger; Pak Sham; Robin Murray Arch Gen Psychiatry 2007;64 1348- 1355 SEMAPHORIN AND PLEXIN GENES SPECIFY LIMBIC AND CORTICAL CONNECTIVITY AND ARE IMPLICATED IN THE ETIOLOGY OF SCHIZOPHRENIA
Kevin Mitchell 1 , Annette Runker 1 , Graham Little 1 , Colm O’Tuathaigh 2 , Mark Dunleavy 2 , Derek Morris 4 , Aiden Corvin 4 , Michael Gill 4 , David Henshall 3 , John Waddington 2 1 Department of Genetics, Trinity College Dublin, Dublin, Ireland; 2 Department of Neuroscience, Royal College of Surgeons in Ireland, Dublin, Ireland; 3 Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland; 4 Department of Psychiatry, Trinity College Dublin, Dublin, Ireland [email protected] Introduction: Semaphorin and Plexin proteins play important roles in establ ishing the connectivity of the brain. Variation in several of these
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
IMPROVING FUNCTIONING WITH COGNITIVE REMEDIATION THERAPY
Rafael Penades Hospital Clinic De Barcelona, Barcelona, Spain [email protected] Cognitive impairment has been shown to be linked to impairment in functional status (eg, social functioning, work performance, and activities of daily living) among patients with schizophrenia in crosssectional studies. While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established by now, the relationship between cognitive and functional change over time is far from complete. Moreover, little is known about the potential mechanisms that bridge the gap between cognition and functional outcome. To date, different controlled studies have now shown that large and lasting improvements in cognition can result from neurocognitive interventions. Cognitive remediation therapy (CRT) alone or together with work therapy can lead to large, lasting, and clinically relevant improvements not only in cognition but also in social and work functioning. CRT is guided by the view that metacognitive processes of scheme generation, self-monitoring and self-regulation are fundamental determinants of competent functioning in the real world and probably the most important targets in the achievement of improving functioning in patients with cognitive impairment. References [1] Reeder, C., Newton, E., Frangou, S., Wykes, T. (2004) Which executive skills should be target to affect social functioning and symptom change? Schizophrenia Bulletin. 30: 87-100. [2] Penadés, R., Catalán, R., Salamero, M. Boget, T., Puig, O., Guarch, J., G astó, C. (2006). Cognitive Remediation Therapy in chronic schizophrenia: a randomised and controlled study. Schizophrenia Research. 87: 323-331.
SESSION XV
June 24th, 2008
Late Breaking Genetic Findings STATUS REPORT OF THE GENOME-WIDE ASSOCIATION STUDY OF THE MOLECULAR GENETICS OF SCHIZOPHRENIA SAMPLE (MGS): PRELIMINARY ANALYSES OF THE GENETIC ASSOCIATION INFORMATION NETWORK (GAIN) SUBSAMPLE
Pablo V. Gejman Evanston Northwestern Healthcare and Northwestern University, Evanston, IL, USA [email protected] We are performing a GWAS study of total sample of 8160 subjects, 4284 cases and 3876 controls of European and African ancestry. In 2007, MGS was selected by GAIN (fnih.org) for GWAS genotyping and we submitted 5198 samples (2719 cases and 2479 controls (Wave 1) to be typed with the Affymetrix 6.0 array. Strict quality control procedures and Principal Components Analysis using EIGENSTRAT were applied, which eliminated many spurious findings. In the EA GAIN sample (∼1455 case control pairs), two of the best p-values are in a ∼450 Kb linkage disequilibrium block in 1p22.1 spanning FAM69A (hypothetical protein LOC388650; 1.04E-06) and the adjacent genes RPL5 (ribosomal protein L5; 7.35E-06), and EVI5 (ecotropic viral integration site 5). These three genes are among the top hits in a recent multi-stage GWAS of multiple sclerosis (Hafler et al., NEJM 2007). We performed bioinformatic analyses of FAM69A/RPL5/EVI5 region have initiated a deep resequencing (starting in FAM69A). In the AA GAIN sample (1278 cases and 1010 controls), the best p-value was in ERBB4, and another was in NRG1. ERBB4 encodes the receptor for neuregulin-1, which has been implicated in SZ by several lines of evidence. In our EA GAIN sample, the
lowest p-value observed in ERBB4 was 0.0038, and in NRG1 it was 0.003, similar to our previously reported results in an earlier dense LD mapping study of 14 SZ candidate genes in a slightly larger subset of the MGS sample, but we found some support for NOS1AP (not tested by us before). We are currently performing genome-wide CNV analysis in the total GAIN sample. The genotyping of another 2,962 subjects (under an R01 mechanism) has been completed but the results are not available yet. We plan to perform a final analysis of the total sample (8160 subjects) (each ancestry separately and both ancestries combined).
EPISODIC AND WORKING MEMORY FUNCTION IN MONOZYGOTIC AND DIZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA
Timothea Toulopoulou Institute of Psychiatry, King’s College London, University of London, London, UK [email protected] Introduction: Cognitive abnormalities are thought to be central to the pathophysiology of schizophrenia. These abnormalities include deficits in episodic memory, both in the verbal and the visual modalities. However, it is not clear to what extent these abnormalities relate to the genetic liability for schizophrenia. The objective of this study was to investigate verbal and visual episodic and working memory performance in monozygotic (MZ) and dizygotic (DZ) twins concordant and discordant for schizophrenia. Methods: A total of 252 twins participated in this study: 18 MZ twin pairs concordant for schizophrenia, 11 MZ twin pairs discordant for schizophrenia, 54 MZ twin pairs without schizophrenia, 7 DZ pairs discordant for schizophrenia and 36 DZ pairs without schizophrenia. Patients were drawn from in- and out-patient clinics across the UK. Controls were recruited through a UK twin register. Results: Twins with schizophrenia performed significantly worse than controls on most measures. Well co-twins from the MZ pairs discordant for schizophrenia were less able than controls to retain stories both immediately after presentation, and after a 30 minute delay. In addition they were slower in forming associations between words, and had more difficulty retaining visual representations over time. Their DZs counterparts performed less well than controls on backward digit span only, suggesting problems with working memory. Conclusions: Greater genetic loading for schizophrenia in the well co-twins was associated with more diverse memory impairments Acknowledgements: This work was supported by NARSAD through a Young Investigator Award to Dr Timothea Toulopoulou References [1] Substantial Genetic Overlap between Neurocognition and Schizophrenia: Genetic Modelling in Twin Samples Timothea Toulopoulou; Marco Picchioni; Fruhling Rijsdijk; Mei Hua-Hall; Ulrich Ettinger; Pak Sham; Robin Murray Arch Gen Psychiatry 2007;64 1348- 1355 SEMAPHORIN AND PLEXIN GENES SPECIFY LIMBIC AND CORTICAL CONNECTIVITY AND ARE IMPLICATED IN THE ETIOLOGY OF SCHIZOPHRENIA
Kevin Mitchell 1 , Annette Runker 1 , Graham Little 1 , Colm O’Tuathaigh 2 , Mark Dunleavy 2 , Derek Morris 4 , Aiden Corvin 4 , Michael Gill 4 , David Henshall 3 , John Waddington 2 1 Department of Genetics, Trinity College Dublin, Dublin, Ireland; 2 Department of Neuroscience, Royal College of Surgeons in Ireland, Dublin, Ireland; 3 Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland; 4 Department of Psychiatry, Trinity College Dublin, Dublin, Ireland [email protected] Introduction: Semaphorin and Plexin proteins play important roles in establ ishing the connectivity of the brain. Variation in several of these