Association between early suicidal trajectories in first-episode psychosis and 10-year follow-up: TIPS registry-linked study.

Although the risk of suicidality is high in first-episode psychosis, patterns and individual variability in suicidal thoughts and behaviours over time are under-researched. We aimed to identify early trajectories of suicidality over a 2-year follow-up, assess their baseline predictors, and explore associations between those trajectories and later suicidality. This longitudinal follow-up study was a part of the Early Treatment and Intervention in Psychosis (TIPS)study. Participants, linked to Norwegian and Danish death registries, were recruited from four catchment areas (665 000 inhabitants) in Norway and Denmark (both inpatient and outpatient). We included participants aged 15-65 years, with an intelligence quotient of more than 70, willing to give informed consent, and with a first episode of active psychotic symptoms. Individuals with comorbid neurological or endocrinal disorders, or those with contraindications to antipsychotics, were excluded. Growth mixture modelling was used to identify trajectories of suicidal thoughts and behaviours over the first 2 years. Multinomial logistic regression was applied to examine the baseline predictors of those trajectories and their associations with suicidality at 10-year follow-up. A total of 301 participants were recruited from Jan 1, 1997, to Dec 31, 2000. Of the 299 with completed suicidality data at baseline, 271 participated in 1-year follow-up, 250 in 2-year follow-up, 201 in 5-year follow-up, and 186 at 10-year follow-up. At baseline, 176 (58%) were male, 125 (42%) were female. The mean age was 27·80 years (SD 9·64; range 15-63). 280 (93%) participants were of Scandinavian origin. Four trajectories over 2 years were identified: stable non-suicidal (217 [72%]), stable suicidal ideation (45 [15%]), decreasing suicidal thoughts and behaviours (21 [7%]), and worsening suicidal thoughts and behaviours (18 [6%]). A longer duration of untreated psychosis (odds ratio [OR] 1·24, 95% CI 1·02-1·50, p=0·033), poorer premorbid childhood social adjustment (1·33, 1·01-1·73, p=0·039), more severe depression (1·10, 1·02-1·20, p=0·016), and substance use (2·33, 1·21-4·46, p=0·011) at baseline predicted a stable suicidal ideation trajectory. Individuals in the stable suicidal ideation trajectory tended to have suicidal thoughts and behaviours at 10-year follow-up (3·12, 1·33-7·25, p=0·008). Individuals with a worsening suicidal trajectory were at a higher risk of death by suicide between 2 and 10 years (7·58, 1·53-37·62, p=0·013). Distinct suicidal trajectories in first-episode psychosis were associated with specific predictors at baseline and distinct patterns of suicidality over time. Our findings call for early and targeted interventions for at-risk individuals with persistent suicidal ideation or deteriorating patterns of suicidal thoughts and behaviours, or both. Health West, Norway; the Norwegian National Research Council; the Norwegian Department of Health and Social Affairs; the National Council for Mental Health and Health and Rehabilitation; the Theodore and Vada Stanley Foundation; the Regional Health Research Foundation for Eastern Region, Denmark; Roskilde County, Helsefonden, Lundbeck Pharma; Eli Lilly; Janssen-Cilag Pharmaceuticals, Denmark; a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and The National Institute of Mental Health grant; a National Alliance for Research on Schizophrenia & Depression Young Investigator Award from The Brain & Behavior Research Foundation; Health South East; Health West; and the Regional Centre for Clinical Research in Psychosis.

Gohar SM ，Hegelstad WTV ，Auestad B ，Haahr UH ，Joa I ，Johannessen JO ，Larsen TK ，Opjordsmoen S ，Rund BR ，Røssberg JI ，Simonsen E ，Friis S ，Melle I ... -  《Lancet Psychiatry》

Trajectories of suicidal ideation in patients with first-episode psychosis: secondary analysis of data from the OPUS trial.

Heterogeneity in suicidal ideation over time in patients with first-episode psychosis is expected, but prototypical trajectories of this have not yet been established. We aimed to identify trajectories of suicidal ideation over a 3-year period and to examine how these trajectories relate to subsequent suicidality. We used longitudinal data from the prospective 10-year follow-up OPUS trial of young Danish patients with first-episode psychosis. Participants were recruited between January, 1998, and December, 2000, from all inpatient and outpatient mental health services in Copenhagen and Aarhus County, were aged between 18 and 45 years, and had a diagnosis in the schizophrenia spectrum. Randomisation was done by a computer-generated randomisation list, stratified in alternating blocks for five centres. In Aarhus, a secretary drew lots when the researcher phoned her. Patients were randomly assigned to a treatment group (modified assertive community treatment) or a control group (standard treatment at community mental health centres) and assessed at treatment initiation, and after 1, 2, 5, and 10 years. We included all patients' data on suicidal ideation from the first three assessments in a latent growth mixture modelling analysis to empirically identify trajectories of suicidal ideation. Multivariable logistic regression analyses were applied to estimate associations between trajectories and subsequent suicidality. This trial is registered with ClinicalTrials.gov, number NCT00157313. Three trajectories for suicidal ideation were identified in 521 patients. 317 of 521 members (61%) of the largest trajectory, low-decreasing, consisted of patients who initially reported suicidal ideation once-to-a-few-times in the past year followed by a decrease in suicidal ideation. 172 of 521 (33%) members of the frequent-stable trajectory reported suicidal ideation sometimes-to-frequently at the first assessment and remained stable over time. Finally, 32 of 521 (6%) members of the frequent-increasing trajectory reported frequent suicidal ideation initially followed by worsening. Compared with the low-decreasing class, the risk of persistent suicidal ideation was higher for patients in the frequent-stable and frequent-increasing classes at 5 years (Odds ratio=4·5, 95% CI 2·50-8·02 and 4·7, 1·55-14·24 respectively) and at 10 years (4·2, 2·42-7·13 and 3·2, 1·20-8·70 respectively). Also the risk of suicide attempt at 5 years was higher for patients in the frequent-stable (2·8, 1·07-7·43) and frequent-increasing classes (6·6, 1·69-25·54) compared with the low-decreasing class. There was no difference in suicide rate at 5 or 10 years between trajectories. Because up to 40% of patients experienced frequent suicidal ideations that persisted or increased during the first years of treatment, our findings warrant special focus on suicidal issues as an integral part of treatment along with treatment to target psychotic symptoms. The Danish Council for Independent Research (Medical Sciences), Trygfonden, The Mental Health Services of the Capital Region of Denmark, The Danish Ministry of Health, The Danish Ministry of Social Affairs, the Psychiatry and Social Service Department in Central Denmark Region, and The Lundbeck Foundation.

Madsen T ，Karstoft KI ，Secher RG ，Austin SF ，Nordentoft M ... -  《Lancet Psychiatry》

[Suicidal risk during the first psychotic episode].

Suicide is the most common cause of early mortality during the course of schizophrenia. The most recent data in the literature show that the risk of suicide is greater at the beginning of the course of schizophrenia. The risk of suicide during the first year is 12 times higher than that of the general population. Specifically, 2-5 % of people with first-episode psychosis will die by suicide in long-term follow-up studies. Regarding the presence of suicidal ideation that are a major factor of suicide in subjects suffering from psychotic disorders, their prevalence remains extremely worrying, since they are substantial and persistent. Consequently, suicide prevention should be a major and immediate objective in the management of the disease, as soon as the diagnosis has been made. Suicidal ideas are a potential precursor to the evolution towards acting out. Their evolution must be specifically assessed in each individual. Indeed, in the influential Danish OPUS study the authors reported heterogeneity in suicidal ideations in young patients with first episode of psychosis and identified three prototypical trajectories of suicidal ideations over the first 2 years in treatment. Particularly, nearly 40 % of patients with first-episode psychosis have persisting suicidal thoughts over the initial treatment period. Consequently, the authors recommend routine screening for suicidality when providing treatment for first-episode psychosis. The main risk factors for suicidal behavior in patients with a first episode are classical ones. Previous research has suggested that, in addition to young age and early course of illness, other important clinical predictors of suicide in individuals with schizophrenia include presence of depressive symptoms and misuse of substances, which are very common conditions in these patients. Lack of social support, loss, rejection, stigma, insight, fear of future losses, are all negative experiences experienced by patients starting a psychotic disorder. Negative connotations of the diagnosis of psychotic disorders, feelings of being trapped that can be directly related to feeling a burden can lead to suicidal crisis in these individuals. Then, the painful experience of the disease and its consequences associated with self-stigmatization and social rejection may induce hopelessness and suicidal thoughts in these young subjects. The quality of the insight and its evolution may worsen the depressive experience and suicidal risk and they therefore also require to be measured regularly. Thus, the clinical evaluation of patients entering psychosis should focus on those dimensions that are not directly related to the psychotic symptoms. At the precise evaluation of each patient must be associated personalized measures of prevention. It is now proposed that prevention strategies targeting suicidal behaviour in first-episode psychosis should not be universal. On a more general level, evidence-based data to support specific care programs are still lacking, and only few data are in favor of integrated care in patients presenting with first episode. It should also be kept in mind that the risk of suicide is extraordinarily high for all psychiatric patients during the first few months after discharge from hospital. This should encourage caregivers to offer intensive follow-up programs to their patients and to embrace recontact and follow-up initiatives using the tools of e-health. Last, programs for the early detection of schizophrenia seem to be beneficial for the prevention of suicide in these subjects.

Courtet P 《ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE》

Trajectories of suicidal ideation after first-episode psychosis: a growth mixture modeling approach.

The period immediately after the onset of first-episode psychosis (FEP) may present with high risk for suicidal ideation (SI) and attempts, although this risk may differ among patients. Thus, we aimed to identify trajectories of SI in a 2-years follow-up FEP cohort and to assess baseline predictors and clinical/functional evolution for each trajectory of SI. We included 334 FEP participants with data on SI. Growth mixture modeling was used to identify trajectories of SI. Putative sociodemographic, clinical, and cognitive predictors of the distinct trajectories were examined using multinomial logistic regression. We identified three distinct trajectories: Non-SI trajectory (85.53% sample), Improving SI trajectory (9.58%), and Worsening SI trajectory (6.89%). Multinomial logistic regression model revealed that greater baseline pessimistic thoughts, anhedonia, and worse perceived family environment were associated with higher baseline SI followed by an Improving trajectory. Older age, longer duration of untreated psychosis, and reduced sleep predicted Worsening SI trajectory. Regarding clinical/functional evolution, individuals within the Improving SI trajectory displayed moderate depression at baseline which ameliorated during the study period, while the Worsening SI subgroup exhibited persistent mild depressive symptoms and greater functional impairment at follow-up assessments. Our findings delineated three distinct trajectories of SI among participants with FEP, one experiencing no SI, another in which SI might depend on acute depressive symptomatology, and a last subset where SI might be associated with mild but persistent clinical and functional impairments. These data provide insights for the early identification and tailored treatment of suicide in this at-risk population.

Salagre E ，Grande I ，Jiménez E ，Mezquida G ，Cuesta MJ ，Llorente C ，Amoretti S ，Lobo A ，González-Pinto A ，Carballo JJ ，Corripio I ，Verdolini N ，Castro-Fornieles J ，Legido T ，Carvalho AF ，Vieta E ，Bernardo M ，PEPs Group ... -  《-》

Right care, first time: a highly personalised and measurement-based care model to manage youth mental health.

Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change. Consequently, the effects of adolescent-onset mood and psychotic syndromes can have long term consequences. A key clinical challenge for youth mental health is to develop and test new systems that align with current evidence for comorbid presentations and underlying neurobiology, and are useful for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. Our highly personalised and measurement-based care model includes three core concepts: ▶ A multidimensional assessment and outcomes framework that includes: social and occupational function; self-harm, suicidal thoughts and behaviour; alcohol or other substance misuse; physical health; and illness trajectory. ▶ Clinical stage. ▶ Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on proposed pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). The model explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within this highly personalised approach is the incorporation of other evidence-based processes, including real-time measurement-based care as well as utilisation of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality, mental health care for young people. CHAPTER 1: MULTIDIMENSIONAL OUTCOMES IN YOUTH MENTAL HEALTH CARE: WHAT MATTERS AND WHY?: Mood and psychotic syndromes present one of the most serious public health challenges that we face in the 21st century. Factors including prevalence, age of onset, and chronicity contribute to substantial burden and secondary risks such as alcohol or other substance misuse. Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change; thus, effects can have long term consequences. We propose five key domains which make up a multidimensional outcomes framework that aims to address the specific needs of young people presenting to health services with emerging mental illness. These include social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Impairment and concurrent morbidity are well established in young people by the time they present for mental health care. Despite this, services and health professionals tend to focus on only one aspect of the presentation - illness type, stage and trajectory - and are often at odds with the preferences of young people and their families. There is a need to address the disconnect between mental health, physical health and social services and interventions, to ensure that youth mental health care focuses on the outcomes that matter to young people. CHAPTER 2: COMBINING CLINICAL STAGE AND PATHOPHYSIOLOGICAL MECHANISMS TO UNDERSTAND ILLNESS TRAJECTORIES IN YOUNG PEOPLE WITH EMERGING MOOD AND PSYCHOTIC SYNDROMES: Traditional diagnostic classification systems for mental disorders map poorly onto the early stages of illness experienced by young people, and purport categorical distinctions that are not readily supported by research into genetic, environmental and neurobiological risk factors. Consequently, a key clinical challenge in youth mental health is to develop and test new classification systems that align with current evidence on comorbid presentations, are consistent with current understanding of underlying neurobiology, and provide utility for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. This chapter outlines a transdiagnostic framework for classifying common adolescent-onset mood and psychotic syndromes, combining two independent but complementary dimensions: clinical staging, and three proposed pathophysiological mechanisms. Clinical staging reflects the progression of mental disorders and is in line with the concept used in general medicine, where more advanced stages are associated with a poorer prognosis and a need for more intensive interventions with a higher risk-to-benefit ratio. The three proposed pathophysiological mechanisms are neurodevelopmental abnormalities, hyperarousal and circadian dysfunction, which, over time, have illness trajectories (or pathways) to psychosis, anxious depression and bipolar spectrum disorders, respectively. The transdiagnostic framework has been evaluated in young people presenting to youth mental health clinics of the University of Sydney's Brain and Mind Centre, alongside a range of clinical and objective measures. Our research to date provides support for this framework, and we are now exploring its application to the development of more personalised models of care. CHAPTER 3: A COMPREHENSIVE ASSESSMENT FRAMEWORK FOR YOUTH MENTAL HEALTH: GUIDING HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE USING MULTIDIMENSIONAL AND OBJECTIVE MEASURES: There is an urgent need for improved care for young people with mental health problems, in particular those with subthreshold mental disorders that are not sufficiently severe to meet traditional diagnostic criteria. New comprehensive assessment frameworks are needed to capture the biopsychosocial profile of a young person to drive highly personalised and measurement-based mental health care. We present a range of multidimensional measures involving five key domains: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Objective measures include: neuropsychological function; sleep-wake behaviours and circadian rhythms; metabolic and immune markers; and brain structure and function. The recommended multidimensional measures facilitate the development of a comprehensive clinical picture. The objective measures help to further develop informative and novel insights into underlying pathophysiological mechanisms and illness trajectories to guide personalised care plans. A panel of specific multidimensional and objective measures are recommended as standard clinical practice, while others are recommended secondarily to provide deeper insights with the aim of revealing alternative clinical paths for targeted interventions and treatments matched to the clinical stage and proposed pathophysiological mechanisms of the young person. CHAPTER 4: PERSONALISING CARE OPTIONS IN YOUTH MENTAL HEALTH: USING MULTIDIMENSIONAL ASSESSMENT, CLINICAL STAGE, PATHOPHYSIOLOGICAL MECHANISMS, AND INDIVIDUAL ILLNESS TRAJECTORIES TO GUIDE TREATMENT SELECTION: New models of mental health care for young people require that interventions be matched to illness type, clinical stage, underlying pathophysiological mechanisms and individual illness trajectories. Narrow syndrome-focused classifications often direct clinical attention away from other key factors such as functional impairment, self-harm and suicidality, alcohol or other substance misuse, and poor physical health. By contrast, we outline a treatment selection guide for early intervention for adolescent-onset mood and psychotic syndromes (ie, active treatments and indicated and more specific secondary prevention strategies). This guide is based on experiences with the Brain and Mind Centre's highly personalised and measurement-based care model to manage youth mental health. The model incorporates three complementary core concepts: ▶A multidimensional assessment and outcomes framework including: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness trajectory. ▶Clinical stage. ▶Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on three underlying pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). These core concepts are not mutually exclusive and together may facilitate improved outcomes through a clinical stage-appropriate and transdiagnostic framework that helps guide decisions regarding the provision of appropriate and effective care options. Given its emphasis on adolescent-onset mood and psychotic syndromes, the Brain and Mind Centre's model of care also respects a fundamental developmental perspective - categorising childhood problems (eg, anxiety and neurodevelopmental difficulties) as risk factors and respecting the fact that young people are in a period of major biological and social transition. Based on these factors, a range of social, psychological and pharmacological interventions are recommended, with an emphasis on balancing the personal benefit-to-cost ratio. CHAPTER 5: A SERVICE DELIVERY MODEL TO SUPPORT HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE IN YOUTH MENTAL HEALTH: Over the past decade, we have seen a growing focus on creating mental health service delivery models that better meet the unique needs of young Australians. Recent policy directives from the Australian Government recommend the adoption of stepped-care services to improve the appropriateness of care, determined by severity of need. Here, we propose that a highly personalised approach enhances stepped-care models by incorporating clinical staging and a young person's current and multidimensional needs. It explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within a highly personalised approach is the incorporation of other evidence-based processes, including real-time measurement-based care and use of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality of, mental health care for young people.

Hickie IB ，Scott EM ，Cross SP ，Iorfino F ，Davenport TA ，Guastella AJ ，Naismith SL ，Carpenter JS ，Rohleder C ，Crouse JJ ，Hermens DF ，Koethe D ，Markus Leweke F ，Tickell AM ，Sawrikar V ，Scott J ... -  《-》