- Email: [email protected]
4th International Conference on Early Psychosis: ‘Translating the Evidence’
Schizophrenia Research 79 (2005) 1 – 4 www.elsevier.com/locate/schres
Guest editorial
4th International Conference on Early Psychosis: ‘Translating the Evidence’ Over the past decade, there has been tremendous progress in both clinical work and research in early psychosis. The first International Early Psychosis Association conference (IEPA) was held in 1996 with the theme of an overdue need and emerging opportunity for a range of preventive strategies in psychotic disorders, notably early intervention. This Special Issue presents the papers from eight Keynote and Plenary addresses at the 4th International Conference on Early Psychosis, bTranslating the EvidenceQ held in Vancouver, Canada, September 28th–October 1st 2004. The Vancouver Conference highlighted the rapid progress across the full spectrum of biological, epidemiological, psychological and sociological research into early psychosis with approximately 500 scientific communications (Schizophrenia Research, 2004). This scientific material did indeed demonstrate the translation of new evidence into clinical advances that can enhance early detection, expert clinical care and sustained recovery. In doing so, it addressed some of the controversy that has surrounded the belated introduction of early diagnosis in serious mental illness. This was reflected in the atmosphere of the meeting, which was calm, and focused with the balance having shifted from debate to data. The first papers focus on the epidemiology of risk. It is becoming increasingly evident that early risk factors for psychosis can possibly be detected years before the onset of the psychosis. Studying such risk factors as childhood developmental abnormalities, the early rearing environment, obstetric complications, prenatal factors, and adolescent development may provide information about etiological mechanisms 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.06.006
and, ultimately, perhaps, the possibility for preventive interventions. In her keynote address in Vancouver Dr. Mary Cannon suggested that these early risk factors rather than having an independent impact more likely interact with genetic or other environmental risk factors both individual and societal. This suggestion is supported by several lines of evidence in the Cannon and Clarke paper (Cannon and Clarke, 2005). One particular piece of evidence includes using a general population birth cohort study from Dunedin, New Zealand, to trace the developmental trajectory from infancy to adolescence, of individuals destined to develop schizophreniform disorder and bipolar disorder in adulthood. Analyzing such multilevel aspects of risk may lead to exploring causation over a much longer course within an individual’s development. Birth cohorts have yielded extremely useful information, but are expensive if we want to follow large numbers of subjects. Since most individuals with schizophrenia do not have first degree relatives who are affected, studying only persons at genetic high risk of such a low prevalence illness is difficult. An alternative way is to use historical-prospective research designs that utilize existing population-based databases to assess pre-morbid functioning, and allow the follow-up of large populations for long periods, at relatively low cost. In his commentary on risk factors for schizophrenia Dr. Mark Weiser presents a unique data set from historical-prospective studies with the Israeli army that provides important information on cognitive and behavioral functioning, pre-morbid psychiatric disorders, substance abuse and cigarette smoking present years before the onset of illness (Weiser et al., 2005).
2
Guest editorial
The theme of the next group of papers is the biology of onset. Concerned that the neurodevelopmental model does not explain the onset of psychosis or the nature of the positive symptoms of the disorder Dr. Robin Murray in his Keynote address challenged this model of schizophrenia that has been prominent for the past 15 years. This has been elaborated on in the paper by Dr. Mathew Broome (Broome et al., 2005). With a focus on prodromal symptoms, this paper first reviews their developmental and epidemiological context. The authors’ argument then includes the role of dopamine dysregulation in the onset of psychosis describing dopamine as bthe wind of psychotic fireQ. Finally, they draw on recent evidence first from social psychiatry that emphasizes the impact of factors such as migration, urban upbringing and social isolation and secondly from cognitive psychology in order to integrate the genetic, developmental and epidemiological data. In the next paper (Cannon, 2005), Dr. Tyrone Cannon presents recent work that suggests that alterations in brain function and structure in schizophrenia are primarily genetically mediated and appear in some unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk. The primarily genetically mediated deficits shared by at-risk but non-symptomatic relatives are not likely to show differential change in the pre-morbid period, and may be necessary but clearly not sufficient for the development of psychotic symptoms. Alternatively, deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. It is within this framework that Dr. Tyrone Cannon examines preliminary evidence from longitudinal studies of individuals ascertained initially in a prodromal state. Considering prospective studies of young relatives who are genetically at risk for schizophrenia (high risk (HR) studies) can shed light on the possible premorbid precursors of schizophrenia. Ongoing work in Pittsburgh (Keshavan et al., 2005) suggests that adolescent non-psychotic HR relatives have neurobehavioral, brain structural, physiological, and neurochemical deficits that may date back to childhood or earlier. The paper from Dr. Keshevan’s group in
Pittsburgh suggests that from prospective studies we can identify not only phenotypic commonalities in high risk adolescents across diagnoses, but also possibly distinct neural circuitries that may be involved (Keshavan et al., 2005). Collectively, it is hoped that such data may help us to predict the eventual emergence of a spectrum of psychopathology including schizophrenia, mood and addiction disorders among individuals genetically predisposed to these disorders. In the final paper in this section Dr. Shitij Kapur from the University of Toronto presents his hypothesis that in the context of psychosis a dysregulated hyperdopaminergic state leads to a process of heightened novelty and aberrant assignment of salience to environmental stimuli and their internal representations (Kapur et al., 2005). The implication is that delusions are a cognitive effort by the individual to make sense of these aberrantly salient experiences and associations, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. The antipsychotics exert their antipsychotic effect by bdampeningQ the motivational salience of these abnormal experiences and associations—and by doing so provide a means for psychological resolution of symptoms. The final two papers consider two psychosocial areas each of which is gaining importance in clinical and services research. The first paper by Dr. Helene Verdoux from Bordeaux University in France addresses the question of the direction of the association between substance use and psychosis onset (Verdoux et al., 2005). In her paper she presents evidence challenging the self-medication hypothesis through several prospective studies carried out in population-based samples, showing a dose–response relationship between cannabis exposure and risk of psychosis. As a large percentage of subjects from the general population are now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. The second paper from Dr. Jean Addington summarizes work from the Early Psychosis Programs at the Universities of Calgary and Toronto demonstrating a need for family work in early psychosis (Addington et al., 2005a). She describes a framework for a family program such that family programs within
Guest editorial
first episode services can offer individual and group family work, education, coping strategies, and communication and problem solving training. This is supported by recent evidence from a large longitudinal study which suggests that such a model of family work can help families with their distress and concerns. These keynote presentations from the Vancouver meeting illuminate the current state of affairs in early intervention work. What is most notable first of all is the bringing together of data within presentations from genetics, pathophysiology, epidemiology and both neurological and social development in attempting to put the pieces together to further our understanding of the development of psychotic disorders. Secondly, the need to study this illness in order to improve the quality of life and functioning of these young people and their families undermines all of this work. Since the IEPA meeting in Vancouver, papers have developed from several of the presentations and have been independently submitted to and accepted for publication in Schizophrenia Research. To complement the Keynote papers we have included in this Special Issue several of these papers. The first three are from Australia, Denmark and Canada that very much reflect the theme of the conference. Harris et al. (2005) in a large ongoing follow-up of first episode patients examine the impact of a long duration of untreated psychosis (DUP) eight years after admission and show that even after eight years DUP continues to appear to be an independent predictor of prognosis. The Danish OPUS trial headed by Dr. Merete Nordentoft is one of the very few randomized control trials of first episode treatment. In the paper from the OPUS group by Thorup et al. (2005) it is demonstrated that their large sample of first episode patients receiving the integrated treatment evidence reduced positive and in particular negative symptoms compared to the first episode patients who received standard care. Finally, the paper by Addington et al. (2005b) demonstrates significant improvement in distress in a large sample of family members three years after the first episode, supporting the acceptability and potential effectiveness of this family intervention. The final three papers represent ongoing clinical and research work in the United States, Australia and
3
Europe that focuses on the pre-psychotic period, defined as a period of ultra high risk. Loewy et al. (2005) present preliminary validation of a self-report screening measure for prodromal and psychotic symptoms, a much needed tool to complement the well-developed structured interviews already available for this population. Neurocognitive deficits are well documented in psychotic illness and there is evidence that such deficits are present long before the onset of full-blown psychosis. Thus, in the second paper, Francey et al. (2005) from the PACE clinic investigate the potential of a neurocognitive vulnerability indicator, namely sustained attention, to improve the prediction of psychosis in those at ultra high risk of transition to psychosis. The final paper, from the Cologne group (Bechdolf et al., 2005), supports the notion that these ultra high risk patients are not only help seeking but also have clear functional deficits. The papers in this issue are representative of the exciting scientific developments in the field of early psychosis that hopefully will facilitate and safeguard the development of evidenced-based practice and ultimately lead to the necessary changes in mental health care delivery internationally. In addition to these excellent papers captured here, the conference contained a vast array of quality data and clinical experience from around the world. These are summarized in the book of abstracts (Schizophrenia Research, 2004 v 70) and cover the full spectrum from basic science, applied biological psychiatry, psychopharmacology, psychosocial therapies, health services research and epidemiological research. This balance and uniform quality across so many research domains is most unusual in international conferences. A series of international links and collaborations have emerged from this and earlier forums which will continue not only to produce quality scientific data to guide progress in treatment and understanding in early psychosis but to advocate around the world for further reform and the wider application of early diagnosis and proactive and comprehensive care from the beginning of these potentially serious disorders. We encourage all readers to attend the next IEPA conference, which will be held in Birmingham in 2006 and will feature particularly the progress occurring in the UK in expanding and extending services for young people with early psychosis.
4
Guest editorial
Jean Addington, Associate Professor, University of Toronto; Chair, Scientific Executive Committee, 4th International Conference on Early psychosis; and Vice-president North America, IEPA. Patrick, McGorry MD, Professor, University of Melbourne, Director ORYGEN Youth Health (incorporating EPPIC), and President, IEPA References Addington, J., Collins, A., McCleery, A., Addington, D., 2005a. The role of family work in early psychosis. Schizophr. Res. 79, 77 – 83. Addington, J., McCleery, A., Addington, D., 2005b. Three year outcome of family work in an early psychosis program. Schizophr. Res. 79, 107 – 116. Bechdolf, A., Pukrop, R., Ko¨hn, D., Tschinkel, S., Veith, V., Schultze-Lutter, F., Ruhrmann, S., Geyer, C., Pohlmann, B., Klosterko¨tter, J., 2005. Subjective quality of life in subjects at risk for a first episode of psychosis. Schizophr. Res. 79, 137 – 143. Broome, M.R., Woolley, J., Tabraham, P., Johns, L.C., Bramon, E., Murray, G.K., Pariante, C., McQuire, P.K., Murray, R.M., 2005. What causes the onset of schizophrenia? Schizophr. Res. 79, 23 – 34. Cannon, T., 2005. Clinical and genetic high risk strategies in understanding vulnerability to psychosis. Schizophr. Res. 79, 35 – 44. Cannon, M., Clarke, M.C., 2005. Risk for schizophrenia—broadening the concepts, pushing back the boundaries. Schizophr. Res. 79, 5 – 13. Francey, S.M., Jackson, H.J., Phillips, L.J., Wood, S.J., Yung, A.R., McGorry, P.D., 2005. Sustained attention in young people at high risk of psychosis does not predict transition to psychosis. Schizophr. Res. 79, 127 – 136.
Harris, M.G., Henry, L.P., Harrigan, S.M., Purcell, R., Orli, S., Schwartz, O.S., Farrelly, S.E., Prosser, A.L., Jackson, H.J., McGorry, P.D., 2005. The relationship between duration of untreated psychosis and outcome: an eight-year prospective study. Schizophr. Res. 79, 85 – 93. Kapur, S., Mizrahi, R., Ming, Li, 2005. From dopamine to salience in psychosis linking biology, pharmacology and phenomenology of psychosis. Schizophr. Res. 79, 59 – 68. Keshavan, M.S., Diwadkar, V.A., Montrose, D.M., Rajarethinam, R., Sweeney, J.A., 2005. Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr. Res. 79, 45 – 57. Loewy, R.L., Bearden, C.E., Johnson, J.K., Raine, A., Cannon, T.D., 2005. The Prodromal Questionnaire (PQ): preliminary validation of a self-report screening measure for prodromal and psychotic syndromes. Schizophr. Res. 79, 117 – 125. Schizophrenia Research 2004. Supplement 1 to Schizophrenia Research V70, Issue 1 pages 1–175. Thorup, A., Peterson, L., Jeppesen, P., Ohlenschlaeger, J., Christensen, T., Karup, G., Jorgensen, P., Nordentoft, M., 2005. Integrated treatment ameliorates negative symptoms in first episode psychosisresults from the Danish OPUS trial. Schizophr. Res. 79, 95 – 105. Verdoux, H., Tournier, M., Cougnard, A., 2005. Impact of substance use on the onset and course of early psychosis. Schizophr. Res. 79, 69 – 75. Weiser, M., Davidson, M., Noy, S., 2005. Comments on risk for schizophrenia. Schizophr. Res. 79, 15 – 21.
Jean Addington University of Toronto, Psychiatry, CAMH, 250 College Street, Toronto, Canada M5T 1R8 E-mail address: [email protected] Tel.: +1 416 535 8501x4360
Guest editorial
4th International Conference on Early Psychosis: ‘Translating the Evidence’ Over the past decade, there has been tremendous progress in both clinical work and research in early psychosis. The first International Early Psychosis Association conference (IEPA) was held in 1996 with the theme of an overdue need and emerging opportunity for a range of preventive strategies in psychotic disorders, notably early intervention. This Special Issue presents the papers from eight Keynote and Plenary addresses at the 4th International Conference on Early Psychosis, bTranslating the EvidenceQ held in Vancouver, Canada, September 28th–October 1st 2004. The Vancouver Conference highlighted the rapid progress across the full spectrum of biological, epidemiological, psychological and sociological research into early psychosis with approximately 500 scientific communications (Schizophrenia Research, 2004). This scientific material did indeed demonstrate the translation of new evidence into clinical advances that can enhance early detection, expert clinical care and sustained recovery. In doing so, it addressed some of the controversy that has surrounded the belated introduction of early diagnosis in serious mental illness. This was reflected in the atmosphere of the meeting, which was calm, and focused with the balance having shifted from debate to data. The first papers focus on the epidemiology of risk. It is becoming increasingly evident that early risk factors for psychosis can possibly be detected years before the onset of the psychosis. Studying such risk factors as childhood developmental abnormalities, the early rearing environment, obstetric complications, prenatal factors, and adolescent development may provide information about etiological mechanisms 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.06.006
and, ultimately, perhaps, the possibility for preventive interventions. In her keynote address in Vancouver Dr. Mary Cannon suggested that these early risk factors rather than having an independent impact more likely interact with genetic or other environmental risk factors both individual and societal. This suggestion is supported by several lines of evidence in the Cannon and Clarke paper (Cannon and Clarke, 2005). One particular piece of evidence includes using a general population birth cohort study from Dunedin, New Zealand, to trace the developmental trajectory from infancy to adolescence, of individuals destined to develop schizophreniform disorder and bipolar disorder in adulthood. Analyzing such multilevel aspects of risk may lead to exploring causation over a much longer course within an individual’s development. Birth cohorts have yielded extremely useful information, but are expensive if we want to follow large numbers of subjects. Since most individuals with schizophrenia do not have first degree relatives who are affected, studying only persons at genetic high risk of such a low prevalence illness is difficult. An alternative way is to use historical-prospective research designs that utilize existing population-based databases to assess pre-morbid functioning, and allow the follow-up of large populations for long periods, at relatively low cost. In his commentary on risk factors for schizophrenia Dr. Mark Weiser presents a unique data set from historical-prospective studies with the Israeli army that provides important information on cognitive and behavioral functioning, pre-morbid psychiatric disorders, substance abuse and cigarette smoking present years before the onset of illness (Weiser et al., 2005).
2
Guest editorial
The theme of the next group of papers is the biology of onset. Concerned that the neurodevelopmental model does not explain the onset of psychosis or the nature of the positive symptoms of the disorder Dr. Robin Murray in his Keynote address challenged this model of schizophrenia that has been prominent for the past 15 years. This has been elaborated on in the paper by Dr. Mathew Broome (Broome et al., 2005). With a focus on prodromal symptoms, this paper first reviews their developmental and epidemiological context. The authors’ argument then includes the role of dopamine dysregulation in the onset of psychosis describing dopamine as bthe wind of psychotic fireQ. Finally, they draw on recent evidence first from social psychiatry that emphasizes the impact of factors such as migration, urban upbringing and social isolation and secondly from cognitive psychology in order to integrate the genetic, developmental and epidemiological data. In the next paper (Cannon, 2005), Dr. Tyrone Cannon presents recent work that suggests that alterations in brain function and structure in schizophrenia are primarily genetically mediated and appear in some unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk. The primarily genetically mediated deficits shared by at-risk but non-symptomatic relatives are not likely to show differential change in the pre-morbid period, and may be necessary but clearly not sufficient for the development of psychotic symptoms. Alternatively, deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. It is within this framework that Dr. Tyrone Cannon examines preliminary evidence from longitudinal studies of individuals ascertained initially in a prodromal state. Considering prospective studies of young relatives who are genetically at risk for schizophrenia (high risk (HR) studies) can shed light on the possible premorbid precursors of schizophrenia. Ongoing work in Pittsburgh (Keshavan et al., 2005) suggests that adolescent non-psychotic HR relatives have neurobehavioral, brain structural, physiological, and neurochemical deficits that may date back to childhood or earlier. The paper from Dr. Keshevan’s group in
Pittsburgh suggests that from prospective studies we can identify not only phenotypic commonalities in high risk adolescents across diagnoses, but also possibly distinct neural circuitries that may be involved (Keshavan et al., 2005). Collectively, it is hoped that such data may help us to predict the eventual emergence of a spectrum of psychopathology including schizophrenia, mood and addiction disorders among individuals genetically predisposed to these disorders. In the final paper in this section Dr. Shitij Kapur from the University of Toronto presents his hypothesis that in the context of psychosis a dysregulated hyperdopaminergic state leads to a process of heightened novelty and aberrant assignment of salience to environmental stimuli and their internal representations (Kapur et al., 2005). The implication is that delusions are a cognitive effort by the individual to make sense of these aberrantly salient experiences and associations, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. The antipsychotics exert their antipsychotic effect by bdampeningQ the motivational salience of these abnormal experiences and associations—and by doing so provide a means for psychological resolution of symptoms. The final two papers consider two psychosocial areas each of which is gaining importance in clinical and services research. The first paper by Dr. Helene Verdoux from Bordeaux University in France addresses the question of the direction of the association between substance use and psychosis onset (Verdoux et al., 2005). In her paper she presents evidence challenging the self-medication hypothesis through several prospective studies carried out in population-based samples, showing a dose–response relationship between cannabis exposure and risk of psychosis. As a large percentage of subjects from the general population are now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. The second paper from Dr. Jean Addington summarizes work from the Early Psychosis Programs at the Universities of Calgary and Toronto demonstrating a need for family work in early psychosis (Addington et al., 2005a). She describes a framework for a family program such that family programs within
Guest editorial
first episode services can offer individual and group family work, education, coping strategies, and communication and problem solving training. This is supported by recent evidence from a large longitudinal study which suggests that such a model of family work can help families with their distress and concerns. These keynote presentations from the Vancouver meeting illuminate the current state of affairs in early intervention work. What is most notable first of all is the bringing together of data within presentations from genetics, pathophysiology, epidemiology and both neurological and social development in attempting to put the pieces together to further our understanding of the development of psychotic disorders. Secondly, the need to study this illness in order to improve the quality of life and functioning of these young people and their families undermines all of this work. Since the IEPA meeting in Vancouver, papers have developed from several of the presentations and have been independently submitted to and accepted for publication in Schizophrenia Research. To complement the Keynote papers we have included in this Special Issue several of these papers. The first three are from Australia, Denmark and Canada that very much reflect the theme of the conference. Harris et al. (2005) in a large ongoing follow-up of first episode patients examine the impact of a long duration of untreated psychosis (DUP) eight years after admission and show that even after eight years DUP continues to appear to be an independent predictor of prognosis. The Danish OPUS trial headed by Dr. Merete Nordentoft is one of the very few randomized control trials of first episode treatment. In the paper from the OPUS group by Thorup et al. (2005) it is demonstrated that their large sample of first episode patients receiving the integrated treatment evidence reduced positive and in particular negative symptoms compared to the first episode patients who received standard care. Finally, the paper by Addington et al. (2005b) demonstrates significant improvement in distress in a large sample of family members three years after the first episode, supporting the acceptability and potential effectiveness of this family intervention. The final three papers represent ongoing clinical and research work in the United States, Australia and
3
Europe that focuses on the pre-psychotic period, defined as a period of ultra high risk. Loewy et al. (2005) present preliminary validation of a self-report screening measure for prodromal and psychotic symptoms, a much needed tool to complement the well-developed structured interviews already available for this population. Neurocognitive deficits are well documented in psychotic illness and there is evidence that such deficits are present long before the onset of full-blown psychosis. Thus, in the second paper, Francey et al. (2005) from the PACE clinic investigate the potential of a neurocognitive vulnerability indicator, namely sustained attention, to improve the prediction of psychosis in those at ultra high risk of transition to psychosis. The final paper, from the Cologne group (Bechdolf et al., 2005), supports the notion that these ultra high risk patients are not only help seeking but also have clear functional deficits. The papers in this issue are representative of the exciting scientific developments in the field of early psychosis that hopefully will facilitate and safeguard the development of evidenced-based practice and ultimately lead to the necessary changes in mental health care delivery internationally. In addition to these excellent papers captured here, the conference contained a vast array of quality data and clinical experience from around the world. These are summarized in the book of abstracts (Schizophrenia Research, 2004 v 70) and cover the full spectrum from basic science, applied biological psychiatry, psychopharmacology, psychosocial therapies, health services research and epidemiological research. This balance and uniform quality across so many research domains is most unusual in international conferences. A series of international links and collaborations have emerged from this and earlier forums which will continue not only to produce quality scientific data to guide progress in treatment and understanding in early psychosis but to advocate around the world for further reform and the wider application of early diagnosis and proactive and comprehensive care from the beginning of these potentially serious disorders. We encourage all readers to attend the next IEPA conference, which will be held in Birmingham in 2006 and will feature particularly the progress occurring in the UK in expanding and extending services for young people with early psychosis.
4
Guest editorial
Jean Addington, Associate Professor, University of Toronto; Chair, Scientific Executive Committee, 4th International Conference on Early psychosis; and Vice-president North America, IEPA. Patrick, McGorry MD, Professor, University of Melbourne, Director ORYGEN Youth Health (incorporating EPPIC), and President, IEPA References Addington, J., Collins, A., McCleery, A., Addington, D., 2005a. The role of family work in early psychosis. Schizophr. Res. 79, 77 – 83. Addington, J., McCleery, A., Addington, D., 2005b. Three year outcome of family work in an early psychosis program. Schizophr. Res. 79, 107 – 116. Bechdolf, A., Pukrop, R., Ko¨hn, D., Tschinkel, S., Veith, V., Schultze-Lutter, F., Ruhrmann, S., Geyer, C., Pohlmann, B., Klosterko¨tter, J., 2005. Subjective quality of life in subjects at risk for a first episode of psychosis. Schizophr. Res. 79, 137 – 143. Broome, M.R., Woolley, J., Tabraham, P., Johns, L.C., Bramon, E., Murray, G.K., Pariante, C., McQuire, P.K., Murray, R.M., 2005. What causes the onset of schizophrenia? Schizophr. Res. 79, 23 – 34. Cannon, T., 2005. Clinical and genetic high risk strategies in understanding vulnerability to psychosis. Schizophr. Res. 79, 35 – 44. Cannon, M., Clarke, M.C., 2005. Risk for schizophrenia—broadening the concepts, pushing back the boundaries. Schizophr. Res. 79, 5 – 13. Francey, S.M., Jackson, H.J., Phillips, L.J., Wood, S.J., Yung, A.R., McGorry, P.D., 2005. Sustained attention in young people at high risk of psychosis does not predict transition to psychosis. Schizophr. Res. 79, 127 – 136.
Harris, M.G., Henry, L.P., Harrigan, S.M., Purcell, R., Orli, S., Schwartz, O.S., Farrelly, S.E., Prosser, A.L., Jackson, H.J., McGorry, P.D., 2005. The relationship between duration of untreated psychosis and outcome: an eight-year prospective study. Schizophr. Res. 79, 85 – 93. Kapur, S., Mizrahi, R., Ming, Li, 2005. From dopamine to salience in psychosis linking biology, pharmacology and phenomenology of psychosis. Schizophr. Res. 79, 59 – 68. Keshavan, M.S., Diwadkar, V.A., Montrose, D.M., Rajarethinam, R., Sweeney, J.A., 2005. Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr. Res. 79, 45 – 57. Loewy, R.L., Bearden, C.E., Johnson, J.K., Raine, A., Cannon, T.D., 2005. The Prodromal Questionnaire (PQ): preliminary validation of a self-report screening measure for prodromal and psychotic syndromes. Schizophr. Res. 79, 117 – 125. Schizophrenia Research 2004. Supplement 1 to Schizophrenia Research V70, Issue 1 pages 1–175. Thorup, A., Peterson, L., Jeppesen, P., Ohlenschlaeger, J., Christensen, T., Karup, G., Jorgensen, P., Nordentoft, M., 2005. Integrated treatment ameliorates negative symptoms in first episode psychosisresults from the Danish OPUS trial. Schizophr. Res. 79, 95 – 105. Verdoux, H., Tournier, M., Cougnard, A., 2005. Impact of substance use on the onset and course of early psychosis. Schizophr. Res. 79, 69 – 75. Weiser, M., Davidson, M., Noy, S., 2005. Comments on risk for schizophrenia. Schizophr. Res. 79, 15 – 21.
Jean Addington University of Toronto, Psychiatry, CAMH, 250 College Street, Toronto, Canada M5T 1R8 E-mail address: [email protected] Tel.: +1 416 535 8501x4360