Faculty Opinions recommendation of Unmet needs in patients with brief psychotic disorders: Too ill for clinical high risk services and not ill enough for first episode services.

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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Unmet needs in patients with brief psychotic disorders: Too ill for clinical high risk services and not ill enough for first episode services

European Psychiatry ◽

10.1016/j.eurpsy.2018.12.006 ◽

2019 ◽

Vol 57 ◽

pp. 26-32 ◽

Cited By ~ 14

Author(s):

Amedeo Minichino ◽

Grazia Rutigliano ◽

Sergio Merlino ◽

Cathy Davies ◽

Dominic Oliver ◽

...

Keyword(s):

Mental Health ◽

High Risk ◽

Clinical Outcomes ◽

Psychotic Disorders ◽

Pathways To Care ◽

First Episode ◽

Clinical High Risk ◽

Early Intervention Services

AbstractBackground:Patients with acute and transient psychotic disorders (ATPDs) are by definition remitting, but have a high risk of developing persistent psychoses, resembling a subgroup of individuals at Clinical High Risk for Psychosis (CHR-P). Their pathways to care, treatment offered and long-term clinical outcomes beyond risk to psychosis are unexplored. We conducted an electronic health record-based retrospective cohort study including patients with ATPDs within the SLaM NHS Trust and followed-up to 8 years.Methods:A total of 2561 ATPDs were included in the study. A minority were detected (8%) and treated (18%) by Early Intervention services (EIS) and none by CHR-P services. Patients were offered a clinical follow-up of 350.40 ± 589.90 days. The cumulative incidence of discharges was 40% at 3 months, 60% at 1 year, 69% at 2 years, 77% at 4 years, and 82% at 8 years. Treatment was heterogeneous: the majority of patients received antipsychotics (up to 52%), only a tiny minority psychotherapy (up to 8%).Results:Over follow-up, 32.88% and 28.54% of ATPDS received at least one mental health hospitalization or one compulsory hospital admission under the Mental Health Act, respectively. The mean number of days spent in psychiatric hospital was 66.39 ± 239.44 days.Conclusions:The majority of ATPDs are not detected/treated by EIS or CHR-P services, receive heterogeneous treatments and short-term clinical follow-up. ATPDs have a high risk of developing severe clinical outcomes beyond persistent psychotic disorders and unmet clinical needs that are not targeted by current mental health services.

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S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.216 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S93-S93

Author(s):

Irina Falkenberg ◽

Huai-Hsuan Tseng ◽

Gemma Modinos ◽

Barbara Wild ◽

Philip McGuire ◽

...

Keyword(s):

High Risk ◽

Emotion Recognition ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Healthy Controls ◽

Emotional Faces ◽

Facial Movements ◽

Episode Psychosis ◽

Ultra High Risk

Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.

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Circulating lipids associate with future weight gain in individuals with an at-risk mental state and in first-episode psychosis

10.1101/2020.01.30.20019711 ◽

2020 ◽

Author(s):

Santosh Lamichhane ◽

Alex M. Dickens ◽

Partho Sen ◽

Heikki Laurikainen ◽

Jaana Suvisaari ◽

...

Keyword(s):

At Risk ◽

Weight Gain ◽

High Risk ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

Molecular Signature ◽

First Episode ◽

Baseline Serum ◽

Average Life Span ◽

Episode Psychosis

AbstractPatients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic co-morbidities. Identification of individuals with psychotic disorders with a high risk of rapid weight gain, and the associated development of metabolic complications, is an unmet need as regards public health. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 controls (CTR), 44 first-episode psychosis (FEP) patients and 22 individuals at clinical-high-risk (CHR) for psychosis, from two study centers (Turku/Finland and London/UK). Baseline serum samples were analyzed by lipidomics, while body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols with low double bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of two triacylglycerols (TG(48:0) and TG(45:0)), was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals, and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic co-morbidities.

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Basic symptoms and gray matter volumes of patients at clinical high risk for psychosis

Psychological Medicine ◽

10.1017/s0033291720001282 ◽

2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Daniela Hubl ◽

Chantal Michel ◽

Frauke Schultze-Lutter ◽

Martinus Hauf ◽

Benno G. Schimmelmann ◽

...

Keyword(s):

High Risk ◽

Gray Matter ◽

First Episode ◽

Clinical High Risk ◽

Significant Group ◽

Basic Symptoms ◽

Conversion Rates ◽

Episode Psychosis ◽

Ultra High Risk ◽

Gray Matter Volumes

Abstract Background Clinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce. Methods We investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between. Results Significantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes. Conclusions This is the first study to demonstrate that patients who fulfill both UHR and BS criteria – a population that has been associated with higher conversion rates – exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.

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Reduced P3a amplitudes in antipsychotic naïve first-episode psychosis patients and individuals at clinical high-risk for psychosis

Journal of Psychiatric Research ◽

10.1016/j.jpsychires.2012.12.017 ◽

2013 ◽

Vol 47 (6) ◽

pp. 755-761 ◽

Cited By ~ 37

Author(s):

Alejandra Mondragón-Maya ◽

Rodolfo Solís-Vivanco ◽

Pablo León-Ortiz ◽

Yaneth Rodríguez-Agudelo ◽

Guillermina Yáñez-Téllez ◽

...

Keyword(s):

High Risk ◽

First Episode Psychosis ◽

First Episode ◽

Clinical High Risk ◽

Episode Psychosis

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O8.4. CORTICAL DOPAMINE RELEASE IN RESPONSE TO A COGNITIVE CHALLENGE: PRELIMINARY RESULTS IN FIRST EPISODE PSYCHOSIS AND CLINICAL HIGH RISK

Schizophrenia Bulletin ◽

10.1093/schbul/sbz021.236 ◽

2019 ◽

Vol 45 (Supplement_2) ◽

pp. S184-S184

Author(s):

Abanti Tagore ◽

Naren Rao ◽

Christin Schifani ◽

Huai-Hsuan Tseng ◽

Pablo Rusjan ◽

...

Keyword(s):

High Risk ◽

Dopamine Release ◽

First Episode Psychosis ◽

First Episode ◽

Clinical High Risk ◽

Preliminary Results ◽

Episode Psychosis ◽

Cognitive Challenge

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T39. IMPAIRED SENSORIMOTOR GATING USING THE ACOUSTIC PREPULSE INHIBITION PARADIGM IN INDIVIDUALS AT A CLINICAL HIGH RISK FOR PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.599 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S246-S246

Author(s):

Qijing Bo ◽

Zhen Mao ◽

Qing Tian ◽

Weidi Li ◽

Lei Zhao ◽

...

Keyword(s):

High Risk ◽

Prepulse Inhibition ◽

Clinical Characteristics ◽

Sensorimotor Gating ◽

Spatial Separation ◽

Structured Interview ◽

First Episode ◽

Clinical High Risk ◽

Neurocognitive Functions ◽

First Episode Schizophrenia

Abstract Background Many robust studies on prepulse inhibition (PPI) were conducted in patients with schizophrenia, and, increasingly, evidence has indicated individuals who are at clinical high risk for psychosis (CHR). The specificity of the PPI is insufficient with the classic paradigm. The current study investigated an improved perceived spatial separation PPI (PSSPPI) paradigm in CHR individuals, compared with patients of first-episode schizophrenia (FES) and healthy controls (HC), and the relationship between PPI, demographics, clinical characteristics, and cognitive performance. Methods We included 53 FESs, 55 CHR individuals, and 53 HCs. CHRs were rated on the Structured Interview for Prodromal Syndromes (SIPS). The prepulse inhibition measures of perceived spatial co-location PPI (PSCPPI) and PSSPPI paradigms were applied using 60- and 120-ms lead intervals. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess neurocognitive functions. Results Compared with HC, the CHR group had lower PSSPPI level (ISI=60 ms, P<0.001; ISI=120 ms, P<.001). PSSPPI showed a large effect size (ES) between CHR and HC (ISI=60 ms, ES=0.91; ISI=120 ms, ES=0.98); on PSSPPI using 60-ms lead interval, ES ranged from small to large from CHR to FES. PPI deficits in CHR were unrelated to demographics, clinical characteristics, and cognition. Discussion CHR individuals show a sensorimotor gating deficit similar to FES patients on PSSPPI of the startle response, with greater sensitivity than the classic PPI paradigm. PSSPPI appears a promising objective approach for identifying individuals at clinical high risk for psychosis related to a high risk of transition to schizophrenia.

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