scholarly journals Resurrection of the Follow-Back Method to Study the Transdiagnostic Origins of Psychosis

2021 ◽  
Author(s):  
Jim van Os ◽  
Annette Schaub ◽  
William T Carpenter
Keyword(s):  
High Risk ◽  
General Population ◽  
Psychotic Disorder ◽  
Help Seeking ◽  
Psychotic Disorders ◽  
Common Mental Disorders ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Representative Cohort ◽  
Representative Samples

Abstract There has been a major drive in research trying to understand the onset of psychosis. Clinical-high risk (CHR) studies focus on opportunistic help-seeking samples with non-psychotic disorders and a degree of psychosis admixture of variable outcome, but it is unlikely that these represent the population incidence of psychotic disorders. Longitudinal cohort studies of representative samples in the general population have focused on development and outcome of attenuated psychotic symptoms, but typically have low power to detect transition to clinical psychotic disorder. In this issue of Schizophrenia Bulletin, Cupo and colleagues resurrect a time-honored method to examine psychosis onset: the epidemiological follow-back study, modernizing it to fit the research framework of the early intervention era. The authors set out to investigate the hypothesis that psychotic disorder represents the poorest outcome fraction of initially non-psychotic, common mental disorders and present compelling findings, unifying previous opportunistic CHR and representative cohort-based work.

scholarly journals Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

2021 ◽  
Author(s):  
Meike Heurich ◽  
Melanie Föcking ◽  
David Mongan ◽  
Gerard Cagney ◽  
David R. Cotter
Keyword(s):  
High Risk ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Clinical Symptoms ◽  
First Episode Psychosis ◽  
Specific Protein ◽  
First Episode ◽  
Clinical High Risk ◽  
Blood Proteins ◽  
Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

scholarly journals What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?

2021 ◽  
Vol 30 ◽  
Author(s):  
Laila Hasmi ◽  
Lotta-Katrin Pries ◽  
Margreet ten Have ◽  
Ron de Graaf ◽  
Saskia van Dorsselaer ◽  
...  
Keyword(s):  
High Risk ◽  
Drug Use ◽  
Psychotic Disorder ◽  
Positive Family History ◽  
Mental Health Service Use ◽  
Psychotic Symptoms ◽  
Polygenic Risk Score ◽  
Clinical High Risk ◽  
Drug Use Disorders ◽  
Per Se

Abstract Aims Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired ‘comorbidity’ epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the ‘risk’ in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se. Methods We examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors. Results The incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use. Conclusions The risk in ‘clinical high risk’ states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the ‘pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.

Mortality in offspring of mothers with psychotic disorder

2007 ◽  
Vol 38 (8) ◽  
pp. 1203-1210 ◽  
Author(s):  
J. Suvisaari ◽  
L. Häkkinen ◽  
J. Haukka ◽  
J. Lönnqvist
Keyword(s):  
High Risk ◽  
General Population ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Suicide Attempts ◽  
Risk Group ◽  
High Risk Group ◽  
Suicide Mortality ◽  
Increased Risk ◽  
Maternal Suicide

BackgroundPrevious studies suggest that offspring of mothers with psychotic disorders have an almost two-fold higher mortality risk from birth until early adulthood. We investigated predictors of mortality from late adolescence until middle age in offspring of mothers with psychotic disorders.MethodThe Helsinki High-Risk Study follows up offspring (n=337) of women treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975. Factors related to mortality up to 2005 among offspring of these mothers was investigated with a survival model. Hazard rate ratios (HRR) were calculated using sex, diagnosis of psychotic disorder, childhood socio-economic status, maternal diagnosis, and maternal suicide attempts and aggressive symptoms as explanatory variables. The effect of family was investigated by including a frailty term in the model. We also compared mortality between the high-risk group and the Finnish general population.ResultsWithin the high-risk group, females had lower all-cause mortality (HRR 0.43, p=0.05) and mortality from unnatural causes (HRR 0.24, p=0.03) than males. Having themselves been diagnosed with a psychotic disorder was associated with higher mortality from unnatural causes (HRR 4.76, p=0.01), while maternal suicide attempts were associated with higher suicide mortality (HRR 8.64, p=0.03). Mortality in the high-risk group was over two-fold higher (HRR 2.44, p<0.0001) than in the general population, and remained significantly higher when high-risk offspring who later developed psychotic disorders were excluded from the study sample (HRR 2.30, p<0.0001).ConclusionsOffspring of mothers with psychotic disorder are at increased risk of several adverse outcomes, including premature death.

scholarly journals Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion

2016 ◽  
Vol 26 (3) ◽  
pp. 287-298 ◽  
Author(s):  
T. H. Zhang ◽  
H. J. Li ◽  
K. A. Woodberry ◽  
L. H. Xu ◽  
Y. Y. Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Symptom Onset ◽  
Help Seeking ◽  
Cox Regression ◽  
Clinical Population ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Chinese Sample ◽  
Over Time

Background.Chinese psychiatrists have gradually started to focus on those who are deemed to be at ‘clinical high-risk (CHR)’ for psychosis; however, it is still unknown how often those individuals identified as CHR from a different country background than previously studied would transition to psychosis. The objectives of this study are to examine baseline characteristics and the timing of symptom onset, help-seeking, or transition to psychosis over a 2-year period in China.Method.The presence of CHR was determined with the Structured Interview for Prodromal Syndromes (SIPS) at the participants' first visit to the mental health services. A total of 86 (of 117) CHR participants completed the clinical follow-up of at least 2 years (73.5%). Conversion was determined using the criteria of presence of psychotic symptoms (in SIPS). Analyses examined baseline demographic and clinical predictors of psychosis and trajectory of symptoms over time. Survival analysis (Kaplan–Meier) methods along with Log-rank tests were performed to illustrate the relationship of baseline data to either conversion or non-conversion over time. Cox regression was performed to identify baseline predictors of conversion by the 2-year follow-up.Results.In total 25 (29.1%) of 86 completers transitioned to a psychotic disorder over the course of follow-up. Among the CHR sample, the mean time between attenuated symptom onset and professional help-seeking was about 4 months on average, and converters developed fully psychotic symptoms about 12 months after symptom onset. Compared with those CHR participants whose risk syndromes remitted over the course of the study, converters had significantly longer delays (p = 0.029) for their first visit to a professional in search of help. At baseline assessment, the conversion subgroup was younger, had poorer functioning, higher total SIPS positive symptom scores, longer duration of untreated prodromal symptoms, and were more often given psychosis-related diagnoses and subsequently prescribed antipsychotics in the clinic.Conclusions.Chinese CHR identified primarily by a novel clinical screening approach had a 2-year transition rate comparable with those of specialised help-seeking samples world-wide. Early clinical intervention with this functionally deteriorating clinical population who are suffering from attenuated psychotic symptoms, is a next step in applying the CHR construct in China.

scholarly journals The reality of at risk mental state services: a response to recent criticisms

2019 ◽  
pp. 1-7 ◽  
Author(s):  
Alison R. Yung ◽  
Stephen J. Wood ◽  
Ashok Malla ◽  
Barnaby Nelson ◽  
Patrick McGorry ◽  
...  
Keyword(s):  
At Risk ◽  
High Risk ◽  
Psychotic Disorder ◽  
Mental State ◽  
Help Seeking ◽  
Psychotic Symptoms ◽  
Ultra High Risk ◽  
Psychological Medicine ◽  
Poor Outcomes ◽  
At Risk Mental State

AbstractBackgroundIn the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate.MethodsIn this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers.ResultsMany of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring.ConclusionsARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

scholarly journals From Speech Illusions to Onset of Psychotic Disorder: Applying Network Analysis to an Experimental Measure of Aberrant Experiences

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Lindy-Lou Boyette ◽  
Adela-Maria Isvoranu ◽  
Frederike Schirmbeck ◽  
Eva Velthorst ◽  
Claudia J P Simons ◽  
...  
Keyword(s):  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Clinical High Risk ◽  
Cross Sectional ◽  
Affective Symptoms ◽  
The Eu

Abstract Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.

Obstetric Complications and Transition to Psychosis in an ‘Ultra’ High Risk Sample

2005 ◽  
Vol 39 (6) ◽  
pp. 460-466 ◽  
Author(s):  
Yang Yun ◽  
Lisa J. Phillips ◽  
Sue Cotton ◽  
Alison R. Yung ◽  
Shona M. Francey ◽  
...  
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Functional Decline ◽  
Obstetric Complications ◽  
Psychotic Symptoms ◽  
Psychotic Episode ◽  
Degree Relative ◽  
Ultra High Risk

Objective: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. Method: The ‘ultra’ high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. Results: Obstetric complicationswere not associated with the later development of psychosis in the UHR group included in this study. Conclusions: This study does not suppor t a role for OCs as a risk factorfor the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.

scholarly journals M110. PREDICTING RISK OF PSYCHOSIS IN A GENERAL POPULATION SAMPLE

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S176-S177
Author(s):  
Daphne Kounali ◽  
Sarah Sullivan ◽  
Jon Heron ◽  
Jon McLeod ◽  
Mary Cannon ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Risk ◽  
General Population ◽  
Prediction Model ◽  
Psychotic Disorder ◽  
Help Seeking ◽  
Predictive Performance ◽  
Need For Care ◽  
Psychotic Experiences ◽  
Machine Learning Methods

Abstract Background At present clinical high-risk states for psychosis are determined by specialist mental health services using clinical tools such as the CAARMS, which largely rely on the detection of attenuated psychotic symptoms. However, the positive predictive value (PPV) of the CAARMS for transition to psychosis is only 25% in help seeking populations and as low as 5% in general population, non-help seeking samples. There is therefore a clear need to improve the prediction of psychotic disorder using other (non-symptom related) markers of risk. Our aim was to derive a risk prediction tool to determine risk of psychotic disorder using a large, population-based birth-cohort. Methods We used data from the ALSPAC birth cohort, with data on a comprehensive range of predictors ascertained from early childhood through early adulthood, and on psychotic disorder up to age 24 (imputed up to N≈7000 with any data on psychotic experiences). We use a two-stage risk prediction model, where different sets of predictors are used for outcomes of increasing severity. In the first stage, we predicted a clinical need for care in those who had self-reported psychotic-like experiences prior to age 17 years. We assumed that most of this need for care subsample would be help-seeking and that they therefore provide a more accessible risk-enriched sample for the second stage of our prediction model, where more difficult to measure predictors are included for estimating the risk of new onset psychotic disorder. Here we report on the first stage of our prediction model where we predict a clinical need for care (defined as presence of frequent and distressing interviewer-rated psychotic experiences) at age 17–24 years in participants who self-reported any psychotic-like experiences prior to age 17. The prediction set consisted of sixty-one features across 4 domains: socio-demographic (12 features); cognitive (10 features); non-psychotic psychopathology (24 features); behavioural (10 features). We used machine-learning methods for predictor selection and model fitting, employing resampling to assess and validate model calibration and discrimination. Results 13% of participants who self-reported psychotic experiences by age 17 were found to have a clinical need for care between ages 17–24, and 3.5% met criteria for newly ascertained psychotic disorder at 24 years. Use of two different machine learning methods for feature selection (random forests with a 10-fold cross-validation and elastic nets employing shrinkage) yielded similar results, although the elastic nets/ridge regression produced a more parsimonious model. The features selected included: adolescent self-harm, and childhood IQ, attention, processing speed and external locus of control. The AUC reduced very little compared to that of a model with 61 characteristics. This simpler model showed improved calibration and optimism-corrected predictive performance of AUC=0.73, sensitivity=0.75, specificity=0.60, and PPV=0.22. Discussion Our risk calculator is comparable in performance to those produced in studies of prodromal psychosis in high-risk samples. This first-stage model achieved promising predictive performance. We are currently developing a prognostic score for psychotic disorder in those with a clinical need for care and augment the predictor set with genetic, lipidomic and proteomic markers and further cognitive tests. We will then assess the model’s clinical utility and variation in predictive performance using linkage of ALSPAC data to clinical health care records with the aim to externally validate in other cohort studies.

scholarly journals Transdiagnostic Dimensions of Psychiatric Comorbidity in Individuals at Clinical High Risk for Psychosis: A Preliminary Study Informed by HiTOP

2021 ◽  
Vol 11 ◽  
Author(s):  
Henry R. Cowan ◽  
Vijay A. Mittal
Keyword(s):  
High Risk ◽  
Negative Symptom ◽  
Negative Symptoms ◽  
Psychiatric Comorbidity ◽  
Psychotic Disorders ◽  
Comparison Group ◽  
Dimensional Structure ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Clinical High Risk

Background: Although psychiatric comorbidity is the norm among individuals at clinical high risk for psychotic disorders (CHR), research has yet to examine transdiagnostic dimensional models of comorbidity in this critical population.Methods: This study analyzed quantitative measures of eleven psychiatric syndromes in a group at CHR (n = 71) and a matched healthy comparison group (n = 73) to determine these syndromes' dimensional structure and relationships to cognition, functioning, and risk of conversion to psychotic disorders.Results: Relative to the comparison group, the CHR group was elevated on all eleven psychiatric syndromes. Exploratory factor analysis found three psychopathology dimensions: internalizing, negative symptoms, and positive symptoms. Depression cross-loaded onto the internalizing and negative symptom dimensions. Hypomania loaded positively on positive symptoms but negatively on negative symptoms. The negative symptom factor was associated with poorer cognition and functioning and a higher risk of conversion to psychosis.Conclusions: These dimensions align with internalizing, detachment, and thought disorder, three of the five spectra in higher-order models such as the Hierarchical Taxonomy of Psychopathology (HiTOP). In the CHR state, detachment appears to be particularly insidious and predictive of psychosis. Further research is required to distinguish depression and hypomania from attenuated psychotic symptoms in this population.

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