Epidemiology, cohort and case-control studies provide evidence of several risk factors occurring in the teenage period that can further increase risk of onset of psychosis. Among them are drug abuse, bullying, social exclusion, sleep deprivation, stressful events, inflammatory conditions and immigration. At the same time, pilot studies on interventions in the preclinical period have been performed, that showed efficacy of cognitive behavioural therapy (CBT) (although not compared to an active control condition)8 and of nutritional supply of omega-3 fatty acids (although not replicated in a larger group)9. At present, we do not know everything we would like to know to act early to prevent transition to psychosis in vulnerable youngsters, but we do have some basic clues on which we can act already. Each year we wait to complete our knowledge, many youngsters go on to develop a schizophrenia spectrum disorder. This topic should be a high priority in psychiatric research, as even UHR individuals who do not develop psychosis tend to manifest (other) severe psychiatric problems. A psychiatric disease affecting an adolescent or young adult has a large impact on the per-
son himself, but also on his family, surrounding and society at large. There are several ways forward, both for researchers and for health care workers. For the latter, schools are the most important partners for collaboration, since cognition is such an important risk factor. Cognitive decline is first detected at school, and lower functioning than in previous years, with a prominent deviation from sibs, should be a reason to contact health care workers who can screen for (subclinical) psychotic features. When these are present, a working alliance between mental care workers, family and school should be made to prevent further hits, i.e. prevent the youngster from starting to abuse drugs, actively avoid (or stop) being bullied and socially isolated, regulate exposure to stress and sleep. For researchers, individual neurobiological deviations at the UHR stage need to be tested for correction with specific interventions, such as supplementation with n-acetylcysteine to restore glutathione function, glutamatergic or GABA-ergic agents to improve signaling of the inhibitory interneurons, and omega-3 fatty acids or anti-inflammatory agents to restore optimal brain condition. In addition, CBT for UHR needs to be compared to other
psychosocial interventions, and efficacy has to be tested at group level and in specific patient groups. In short, there is much work to do for all of us in order to prevent transition to psychosis of vulnerable youngsters, and we need to make haste. Iris E. Sommer1, Celso Arango2 1 Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; 2Department of Child and Adolescent Psychiatry, Hospital General Universitario n, CIBERSAM; IiSGM, School of MediGregorio Mara~ no cine, Universidad Complutense de Madrid, Madrid, Spain
1. 2. 3. 4. 5. 6. 7. 8. 9.
Cannon M, Caspi A, Moffitt TE et al. Arch Gen Psychiatry 2002;59:449-56. Poulton R, Caspi A, Moffitt TE et al. Arch Gen Psychiatry 2000;57:1053-8. Fisher HL, Caspi A, Poulton R et al. Psychol Med 2013;43:2077-86. Meier MH, Caspi A, Reichenberg A et al. Am J Psychiatry 2014;171:91-101. Kendler KS, Ohlsson H, Mezuk B et al. Schizophr Bull 2016;42:77-86. Niendam TA, Bearden CE, Johnson JK et al. Schizophr Res 2006;84:100-11. Velthorst E, Nieman DH, Becker HE et al. Schizophr Res 2009;109:60-5. Ising HK, Kraan TC, Rietdijk J et al. Schizophr Bull 2016;42:1243-52. McGorry PD, Nelson B, Markulev C et al. JAMA Psychiatry 2017;74:19-27.
DOI:10.1002/wps.20454
Early intervention in psychosis: much done, much more to do While the term dementia praecox is usually credited to Kraepelin, it was B.A. Morel who first used it in 1852 to describe a 14-year-old: “His brilliant intellectual faculties underwent in time a very distressing arrest. A kind of torpor akin to hebetude replaced the earlier activity. In the hospital, the adolescent improved physically, worsened mentally and eventually was considered a hopeless case”1. Morel was describing a presentation rather than a diagnostic category. The “hopeless”, chronic and progressively deteriorating course became for Kraepelin the unifying feature of some mental disorders included in the category of dementia praecox. Bleuler broadened the scope of the diagnosis, identifying a set of basic symptoms (the four As, now considered
276
negative symptoms). We now know that neither chronicity nor any set of basic symptoms is pathognomonic of schizophrenia. Our understanding of many aspects of the condition remains uncertain; we can claim neither accuracy nor precision in our diagnosis. Schizophrenia seems to capture Pearson’s concept of uncertainty not due to limits of technology or measurement but inherent in the nature of the phenomenon being studied2. Fusar-Poli et al3 remind us of many areas of uncertainty that still linger in the diagnosis, management and outcome prediction of first-episode psychosis, where the development of early intervention services has raised several new questions while partially answering some old ones. These services improve short- to medium-
term outcomes of first-episode psychosis. Some forms of targeted interventions for “at risk mental states” appear to delay the emergence of frank psychosis. A staging approach to the broad category of psychosis might offer new opportunities and avenues for research and clinical practice. Of all this we can be certain. The rest is in a state of equipoise, and we are some way from understanding this most human of all conditions. Psychosis (including schizophrenia) is basically a disorder of the self. The subjective self remains elusive to the observer, just like disorders of the self do. Despite the uncertainties and contentious debates about the boundaries and limits of diagnostic categories of psychosis, we can still be proud of some of the changes heralded by the early interven-
World Psychiatry 16:3 - October 2017
tion movement. We were lucky in the UK to receive significant new investment for the establishment of early intervention services in 2004 and have recently been set a highly ambitious target to reduce the duration of untreated psychosis. From April 1, 2016, more than 50% of people experiencing first-episode psychosis should commence on the package of care recommended by the National Institute for Health and Care Excellence (NICE) within two weeks of referral. In the intervening decade, we have learnt interesting and unexpected lessons from the development of early intervention services. A surprising contributor to duration of untreated psychosis is delays within generic secondary mental health services, especially if sufferers have first sought help from child and adolescent mental health services4. Duration of untreated psychosis is malleable; developing a direct care pathway combined with a public awareness campaign can almost halve its length5. Just developing early intervention services, even when these do not have a specific early detection function, can reduce duration of untreated psychosis and hence ensure prompt and early treatment of first-episode psychosis6. We should not be surprised by how much remains uncertain. Kraepelin thought that schizophrenia was a single disease entity, akin to tertiary syphilis with its progressive decline and deterioration. Bleuler recognized the heterogeneity of the disorder, regarding it as a genus rather than a species7. Early intervention services deal with broad psychosis rather than narrow
World Psychiatry 16:3 - October 2017
schizophrenia. No wonder that this has increased areas of uncertainty. We are at the same stage of our understanding of the pathophysiology of psychosis as the ancient world was about dropsy, which for centuries was treated by mechanical removal of fluids from the body (bleeding, leeching, lancing, etc.)8. It was only when the renal and cardiac causes of dropsy were differentiated that medicine started developing treatments specific to aetiology. Psychosis is very likely the final common outcome of a number of different psychopathological processes. If our current treatments are symptomatic rather than curative, this simply reflects our limited understanding of the underlying causes. Dopamine dysfunction is a mechanism of symptom production, not a cause of psychosis, hence antipsychotics only relieve symptoms. Fundamentally altering the course of the disorder or preventing it in the first place will take several new advances in neuroscience. Social epidemiology has confirmed several environmental factors that increase the risk of psychosis. The biological underpinnings of psychosis are likely to be epigenetic rather than DNA sequence based, and the “prism of epigenetics” may yield clues where traditional genetic or environmental paradigms have fallen short9. Early intervention services have had a profound impact on clinical practice and user experience, which is rarely measured, often intangible, not factored into trial designs and hence rarely commented upon, but one that is evident to those who have worked before and after
these services have become available. We no longer consider a 14-year-old with emerging psychosis as a “hopeless case”. The UK Schizophrenia Commission Report10 noted: “We have seen what can be achieved with the approaches to care and treatment in the early intervention in psychosis services which focus on solutions. Today, instead of a life sentence, young people in early intervention services are given hope. They are supported to recover, with many returning to college or the workplace to live an ordinary life like everyone else”. This is a fundamental clinical, conceptual and philosophical shift, and its effect is experiential, like psychosis itself. Swaran Singh Division of Health Sciences, Warwick Medical School, University of Warwick, Warwick, UK 1.
Adityanjee A, Aderidigbe Y, Theodoridis D et al. Psychiatry Clin Neurosci 1999;53:43748. 2. Laudanski LM. Between certainty and uncertainty. Heidelberg: Springer, 2013. 3. Fusar-Poli P, McGorry PD, Kane JM. World Psychiatry 2017;16:251-65. 4. Birchwood M, Connor C, Lester H et al. Br J Psychiatry 2013;203:58-64. 5. Connor C, Birchwood M, Freemantle N et al. BMC Psychiatry 2016;16:127. 6. Marshall M, Hussain N, Bork N et al. Schizophr Res 2014;159:1-6. 7. Odegaard O. Br J Psychiatry 1967;113:81322. 8. Eknoyan G. Kidney Int Suppl 1997;59:S11826. 9. Oh G, Petronis A. Schizophr Bull 2008;34:1122-9. 10. Schizophrenia Commission. The abandoned illness. London: Rethink Mental Illness, 2012.
DOI:10.1002/wps.20455
277
son himself, but also on his family, surrounding and society at large. There are several ways forward, both for researchers and for health care workers. For the latter, schools are the most important partners for collaboration, since cognition is such an important risk factor. Cognitive decline is first detected at school, and lower functioning than in previous years, with a prominent deviation from sibs, should be a reason to contact health care workers who can screen for (subclinical) psychotic features. When these are present, a working alliance between mental care workers, family and school should be made to prevent further hits, i.e. prevent the youngster from starting to abuse drugs, actively avoid (or stop) being bullied and socially isolated, regulate exposure to stress and sleep. For researchers, individual neurobiological deviations at the UHR stage need to be tested for correction with specific interventions, such as supplementation with n-acetylcysteine to restore glutathione function, glutamatergic or GABA-ergic agents to improve signaling of the inhibitory interneurons, and omega-3 fatty acids or anti-inflammatory agents to restore optimal brain condition. In addition, CBT for UHR needs to be compared to other
psychosocial interventions, and efficacy has to be tested at group level and in specific patient groups. In short, there is much work to do for all of us in order to prevent transition to psychosis of vulnerable youngsters, and we need to make haste. Iris E. Sommer1, Celso Arango2 1 Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; 2Department of Child and Adolescent Psychiatry, Hospital General Universitario n, CIBERSAM; IiSGM, School of MediGregorio Mara~ no cine, Universidad Complutense de Madrid, Madrid, Spain
1. 2. 3. 4. 5. 6. 7. 8. 9.
Cannon M, Caspi A, Moffitt TE et al. Arch Gen Psychiatry 2002;59:449-56. Poulton R, Caspi A, Moffitt TE et al. Arch Gen Psychiatry 2000;57:1053-8. Fisher HL, Caspi A, Poulton R et al. Psychol Med 2013;43:2077-86. Meier MH, Caspi A, Reichenberg A et al. Am J Psychiatry 2014;171:91-101. Kendler KS, Ohlsson H, Mezuk B et al. Schizophr Bull 2016;42:77-86. Niendam TA, Bearden CE, Johnson JK et al. Schizophr Res 2006;84:100-11. Velthorst E, Nieman DH, Becker HE et al. Schizophr Res 2009;109:60-5. Ising HK, Kraan TC, Rietdijk J et al. Schizophr Bull 2016;42:1243-52. McGorry PD, Nelson B, Markulev C et al. JAMA Psychiatry 2017;74:19-27.
DOI:10.1002/wps.20454
Early intervention in psychosis: much done, much more to do While the term dementia praecox is usually credited to Kraepelin, it was B.A. Morel who first used it in 1852 to describe a 14-year-old: “His brilliant intellectual faculties underwent in time a very distressing arrest. A kind of torpor akin to hebetude replaced the earlier activity. In the hospital, the adolescent improved physically, worsened mentally and eventually was considered a hopeless case”1. Morel was describing a presentation rather than a diagnostic category. The “hopeless”, chronic and progressively deteriorating course became for Kraepelin the unifying feature of some mental disorders included in the category of dementia praecox. Bleuler broadened the scope of the diagnosis, identifying a set of basic symptoms (the four As, now considered
276
negative symptoms). We now know that neither chronicity nor any set of basic symptoms is pathognomonic of schizophrenia. Our understanding of many aspects of the condition remains uncertain; we can claim neither accuracy nor precision in our diagnosis. Schizophrenia seems to capture Pearson’s concept of uncertainty not due to limits of technology or measurement but inherent in the nature of the phenomenon being studied2. Fusar-Poli et al3 remind us of many areas of uncertainty that still linger in the diagnosis, management and outcome prediction of first-episode psychosis, where the development of early intervention services has raised several new questions while partially answering some old ones. These services improve short- to medium-
term outcomes of first-episode psychosis. Some forms of targeted interventions for “at risk mental states” appear to delay the emergence of frank psychosis. A staging approach to the broad category of psychosis might offer new opportunities and avenues for research and clinical practice. Of all this we can be certain. The rest is in a state of equipoise, and we are some way from understanding this most human of all conditions. Psychosis (including schizophrenia) is basically a disorder of the self. The subjective self remains elusive to the observer, just like disorders of the self do. Despite the uncertainties and contentious debates about the boundaries and limits of diagnostic categories of psychosis, we can still be proud of some of the changes heralded by the early interven-
World Psychiatry 16:3 - October 2017
tion movement. We were lucky in the UK to receive significant new investment for the establishment of early intervention services in 2004 and have recently been set a highly ambitious target to reduce the duration of untreated psychosis. From April 1, 2016, more than 50% of people experiencing first-episode psychosis should commence on the package of care recommended by the National Institute for Health and Care Excellence (NICE) within two weeks of referral. In the intervening decade, we have learnt interesting and unexpected lessons from the development of early intervention services. A surprising contributor to duration of untreated psychosis is delays within generic secondary mental health services, especially if sufferers have first sought help from child and adolescent mental health services4. Duration of untreated psychosis is malleable; developing a direct care pathway combined with a public awareness campaign can almost halve its length5. Just developing early intervention services, even when these do not have a specific early detection function, can reduce duration of untreated psychosis and hence ensure prompt and early treatment of first-episode psychosis6. We should not be surprised by how much remains uncertain. Kraepelin thought that schizophrenia was a single disease entity, akin to tertiary syphilis with its progressive decline and deterioration. Bleuler recognized the heterogeneity of the disorder, regarding it as a genus rather than a species7. Early intervention services deal with broad psychosis rather than narrow
World Psychiatry 16:3 - October 2017
schizophrenia. No wonder that this has increased areas of uncertainty. We are at the same stage of our understanding of the pathophysiology of psychosis as the ancient world was about dropsy, which for centuries was treated by mechanical removal of fluids from the body (bleeding, leeching, lancing, etc.)8. It was only when the renal and cardiac causes of dropsy were differentiated that medicine started developing treatments specific to aetiology. Psychosis is very likely the final common outcome of a number of different psychopathological processes. If our current treatments are symptomatic rather than curative, this simply reflects our limited understanding of the underlying causes. Dopamine dysfunction is a mechanism of symptom production, not a cause of psychosis, hence antipsychotics only relieve symptoms. Fundamentally altering the course of the disorder or preventing it in the first place will take several new advances in neuroscience. Social epidemiology has confirmed several environmental factors that increase the risk of psychosis. The biological underpinnings of psychosis are likely to be epigenetic rather than DNA sequence based, and the “prism of epigenetics” may yield clues where traditional genetic or environmental paradigms have fallen short9. Early intervention services have had a profound impact on clinical practice and user experience, which is rarely measured, often intangible, not factored into trial designs and hence rarely commented upon, but one that is evident to those who have worked before and after
these services have become available. We no longer consider a 14-year-old with emerging psychosis as a “hopeless case”. The UK Schizophrenia Commission Report10 noted: “We have seen what can be achieved with the approaches to care and treatment in the early intervention in psychosis services which focus on solutions. Today, instead of a life sentence, young people in early intervention services are given hope. They are supported to recover, with many returning to college or the workplace to live an ordinary life like everyone else”. This is a fundamental clinical, conceptual and philosophical shift, and its effect is experiential, like psychosis itself. Swaran Singh Division of Health Sciences, Warwick Medical School, University of Warwick, Warwick, UK 1.
Adityanjee A, Aderidigbe Y, Theodoridis D et al. Psychiatry Clin Neurosci 1999;53:43748. 2. Laudanski LM. Between certainty and uncertainty. Heidelberg: Springer, 2013. 3. Fusar-Poli P, McGorry PD, Kane JM. World Psychiatry 2017;16:251-65. 4. Birchwood M, Connor C, Lester H et al. Br J Psychiatry 2013;203:58-64. 5. Connor C, Birchwood M, Freemantle N et al. BMC Psychiatry 2016;16:127. 6. Marshall M, Hussain N, Bork N et al. Schizophr Res 2014;159:1-6. 7. Odegaard O. Br J Psychiatry 1967;113:81322. 8. Eknoyan G. Kidney Int Suppl 1997;59:S11826. 9. Oh G, Petronis A. Schizophr Bull 2008;34:1122-9. 10. Schizophrenia Commission. The abandoned illness. London: Rethink Mental Illness, 2012.
DOI:10.1002/wps.20455
277
