Post‐COVID ‐19 psychosis: Cotard's syndrome and potentially high risk of harm and self‐harm in a first‐onset acute and transient psychotic disorder after resolution of COVID ‐19 pneumonia

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.

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Fluvoxamine may prevent onset of psychosis: a case report of a patient at ultra-high risk of psychotic disorder

Annals of General Psychiatry ◽

10.1186/1744-859x-10-26 ◽

2011 ◽

Vol 10 (1) ◽

pp. 26 ◽

Cited By ~ 7

Author(s):

Shigenori Tadokoro ◽

Nobuhisa Kanahara ◽

Shuichi Kikuchi ◽

Kenji Hashimoto ◽

Iyo Masaomi

Keyword(s):

Case Report ◽

High Risk ◽

Psychotic Disorder ◽

Ultra High Risk

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

Epidemiology and Psychiatric Sciences ◽

10.1017/s204579602100041x ◽

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.

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Factors associated with psychiatric admission and subsequent self-harm repetition: a cohort study of high-risk hospital-presenting self-harm

Journal of Mental Health ◽

10.1080/09638237.2021.1979488 ◽

2021 ◽

pp. 1-9

Author(s):

Grace Cully ◽

Paul Corcoran ◽

Dorothy Leahy ◽

Eugene Cassidy ◽

Sarah Steeg ◽

...

Keyword(s):

Cohort Study ◽

High Risk ◽

Psychiatric Admission ◽

Factors Associated ◽

Self Harm

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Ultra-high-risk paradigm: lessons learnt and new directions

Evidence-Based Mental Health ◽

10.1136/ebmental-2018-300061 ◽

2018 ◽

Vol 21 (4) ◽

pp. 131-133 ◽

Cited By ~ 17

Author(s):

Patrick D McGorry ◽

Cristina Mei

Keyword(s):

High Risk ◽

Mental Disorders ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Evidence Base ◽

Ultra High Risk ◽

Underlying Mechanisms ◽

Staging Model ◽

Definition Of ◽

New Generation

Within the embryonic early psychosis field in the early 1990s, the conceptualisation and definition of an at-risk or ultra-high-risk (UHR) mental state for psychosis was a breakthrough which transformed the clinical and research landscape in psychiatry. Twenty-five years later, we have a new evidence base that has illuminated the neurobiology of the onset phase of psychotic disorder, delivered Cochrane level 1 evidence showing that the onset of full-threshold sustained psychotic disorder can be at least delayed, and is paving the way to a new generation of transdiagnostic research. Here, we document the contribution of the UHR approach to understanding the underlying mechanisms of psychosis onset as well as the long-term outcomes. Particularly, we highlight that psychosis onset can be delayed in those meeting UHR criteria and that these criteria have a higher valence for subsequent psychotic disorders and some valence for persistent non-psychotic syndromes. Critiques have helped to identify some of the limitations of this paradigm, which are acknowledged. These include evidence that psychotic disorders can emerge more acutely and from other, as yet undefined, precursor states. Rather than defending, or alternatively questioning the value of, the UHR approach, we propose a broader, transdiagnostic staging model that is consistent with the pluripotent and variably comorbid trajectories for mental disorders. This approach moves beyond psychosis to capture a wider range of subthreshold symptoms and full-threshold disorders, thus enhancing prediction for the emergence and progression of a range of mental disorders, as well as providing new avenues for early intervention and prevention.

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Mortality in offspring of mothers with psychotic disorder

Psychological Medicine ◽

10.1017/s0033291707002383 ◽

2007 ◽

Vol 38 (8) ◽

pp. 1203-1210 ◽

Cited By ~ 9

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.

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Intelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis

10.31234/osf.io/45tpn ◽

2021 ◽

Author(s):

Nicholas Cheng ◽

Ashleigh Lin ◽

Stephen C. Bowden ◽

Caroline Gao ◽

Alison R. Yung ◽

...

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Fluid Intelligence ◽

Block Design ◽

Small Sample ◽

Linear Mixed Effects ◽

Ultra High Risk ◽

Matrix Reasoning

Background: Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition to a psychotic disorder. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data from three time-points, spanning an average of eight years.Methods: Participants (N=139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests.Results: The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (β=−0.12, 95% CI [−0.29, 0.05] for Vocabulary and β=−0.14, 95% CI [−0.33, 0.05] for Similarities). Conclusions: There was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. As the small sample of individuals who transitioned may have limited our ability to detect subtle differences, future studies with larger sample sizes are needed to explore potential differences in intelligence trajectories between UHR transition groups.

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Reflections on a project to prevent suicide and self-harm among prisoners identified as high risk in two prisons in Northern England

Health & Justice ◽

10.1186/s40352-018-0080-7 ◽

2018 ◽

Vol 6 (1) ◽

Author(s):

Paul Biddle ◽

Wendy Dyer ◽

Richard Hand ◽

Charlitta Strinati

Keyword(s):

High Risk ◽

Self Harm

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M21. THE STEP TRIAL: A SEQUENTIAL MULTIPLE ASSIGNMENT RANDOMISED TRIAL (SMART) OF INTERVENTIONS FOR PATIENTS AT ULTRA-HIGH RISK OF PSYCHOSIS - STUDY RATIONALE, DESIGN AND BASELINE DATA

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.333 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S141-S141

Author(s):

Barnaby Nelson ◽

G Paul Amminger ◽

Hok Pan Yuen ◽

Melissa Kerr ◽

Jessica Spark ◽

...

Keyword(s):

High Risk ◽

Case Management ◽

Psychotic Disorder ◽

Psychosocial Functioning ◽

Randomised Trial ◽

Antidepressant Medication ◽

Clinical Population ◽

Psychotic Symptoms ◽

Retention Data ◽

Cognitive Behavioural

Abstract Background Although approximately twenty randomised controlled trials have now been conducted with young people identified as being at high clinical risk of psychotic disorder, it remains unclear what the optimal type and sequence of treatments are for this clinical population. There has also been increased focus on clinical outcomes other than transition to psychotic disorder, such as psychosocial functioning, persistent attenuated psychotic symptoms and non-psychotic disorders. At Orygen, we are currently conducting a trial of a sequence of interventions consisting of two psychosocial therapies (support and problem solving [SPS] and cognitive-behavioural case management [CBCM]) and antidepressant medication. The primary outcome of the study is functional outcome after 6 months. This presentation will outline the background, rationale, design, recruitment and retention data and preliminary baseline results. Methods STEP is a sequential multiple assignment randomised trial (SMART) of treatments for young people (12–25 year olds) who meet ultra high risk for psychosis (UHR) criteria. Participants were recruited from primary (headspace) and secondary/tertiary (Orygen Youth Health) mental health services in Melbourne, Australia. The trial consists of three steps: Step 1: SPS (1.5 months); Step 2: SPS vs Cognitive Behavioural Case Management (4.5 months); Step 3: Cognitive Behavioural Case Management + Antidepressant Medication vs Cognitive Behavioural Case Management + Placebo (6 months). Patients who do not respond by the end of each step graduate to the next step in treatment. Responders are randomised to SPS or monitoring. Treatment response is based a combination of reduced attenuated psychotic symptoms, rated using the Comprehensive Assessment of At-Risk Mental States (CAARMS), and functional improvement (Social and Occupational Functioning Assessment Scale [SOFAS]) at the end of the treatment step. A ‘fast fail’ option is built into Step 3, whereby patients who deteriorate or have not responded 3 months into Step 3 are offered a choice of continuing existing treatment or commencing omega-3 fatty acids or low-dose antipsychotic medication. The intervention is for 12 months, with follow up at 18 and 24 months. A pilot study using the same design is currently being conducted at The University of California Davis. Results Recruitment has recently completed, with 342 patients recruited over a 2.4 year period, representing the largest UHR treatment study conducted to date. Preliminary results indicate an 8% response rate to Step 1 and a 23% response rate to Step 2. Discontinuation rates are 15% (step 1), 43% (step 2), 32% (step 3), primarily due to participants being lost to follow up or not wanting to start medication. The current transition to psychosis rate is 10.2%. Baseline clinical data are currently being analysed and will be presented at the conference. Discussion Preliminary results indicate high non-response rates following SPS and moderate non-response rates following extended SPS or CBCM, possibly partly due to the stringent definition of response, which required substantial and persistent improvement in both attenuated psychotic symptoms and functioning. Discontinuation rates are low to moderate, reflecting the complexity and severity of this clinical population. The recruitment and retention data show that it is possible to conduct large-scale and complex stepped care trials with this high risk population in a primary mental health care setting (headspace services). Outcomes will inform the most effective type and sequence of treatments for improving psychosocial functioning, symptoms and reducing risk of developing psychotic disorder in this group, as well as identify predictors of treatment response.

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