Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of 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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

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

Download Full-text

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

Download Full-text

117.3 Imaging Microglial Activation in Clinical High Risk for Psychosis and Untreated First-Episode Psychosis: A PET StudyW [18F]FEPPA

Schizophrenia Bulletin ◽

10.1093/schbul/sbx021.170 ◽

2017 ◽

Vol 43 (suppl_1) ◽

pp. S64-S64 ◽

Cited By ~ 1

Author(s):

Romina Mizrahi ◽

Sina Hafizi ◽

Cory Gerritsen ◽

Michael Kiang ◽

Michael Bargby ◽

...

Keyword(s):

High Risk ◽

Microglial Activation ◽

First Episode Psychosis ◽

First Episode ◽

Clinical High Risk ◽

Episode Psychosis

Download Full-text

Predictors of treatment response to psychological interventions in people at clinical high risk of first-episode psychosis

Early Intervention in Psychiatry ◽

10.1111/eip.12460 ◽

2017 ◽

Vol 13 (1) ◽

pp. 120-127 ◽

Cited By ~ 2

Author(s):

Helen Wessels ◽

Michael Wagner ◽

Kathrin Kuhr ◽

Julia Berning ◽

Verena Pützfeld ◽

...

Keyword(s):

High Risk ◽

Treatment Response ◽

First Episode Psychosis ◽

First Episode ◽

Psychological Interventions ◽

Clinical High Risk ◽

Episode Psychosis

Download Full-text

Association Between Circulating Lipids and Future Weight Gain in Individuals With an At-Risk Mental State and in First-Episode Psychosis

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa087 ◽

2020 ◽

Cited By ~ 1

Author(s):

Santosh Lamichhane ◽

Alex M Dickens ◽

Partho Sen ◽

Heikki Laurikainen ◽

Faith Borgan ◽

...

Keyword(s):

At Risk ◽

Weight Gain ◽

High Risk ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

Molecular Signature ◽

First Episode ◽

Baseline Serum ◽

Average Life Span ◽

Episode Psychosis

Abstract Patients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic comorbidities. There is an unmet public health need to identify individuals with psychotic disorders who have a high risk of rapid weight gain and who are at risk of developing metabolic complications. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 healthy controls (CTR), 44 first-episode psychosis (FEP) patients, and 22 individuals at clinical high risk (CHR) for psychosis, from 2 study centers (Turku, Finland and London, UK). Baseline serum samples were analyzed using lipidomics, and body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols (TGs) 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 2 TGs (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 comorbidities.

Download Full-text

Poster #T180 THE COURSE OF COGNITIVE FUNCTIONING IN CLINICAL HIGH RISK AND FIRST-EPISODE PSYCHOSIS INDIVIDUALS

Schizophrenia Research ◽

10.1016/s0920-9964(14)70996-x ◽

2014 ◽

Vol 153 ◽

pp. S352-S353

Author(s):

Martina Papmeyer ◽

Erich Studerus ◽

Marlon Pflüger ◽

Sarah Ittig ◽

Avinash Ramyead ◽

...

Keyword(s):

High Risk ◽

Cognitive Functioning ◽

First Episode Psychosis ◽

First Episode ◽

Clinical High Risk ◽

Episode Psychosis

Download Full-text

O9.1. PROSPECTIVE MEMORY AND THE RELATIONSHIP TO SOCIAL FUNCTION AND NEGATIVE SYMPTOMS IN CLINICAL HIGH RISK, FIRST EPISODE PSYCHOSIS, AND SCHIZOPHRENIA

Schizophrenia Bulletin ◽

10.1093/schbul/sbz021.241 ◽

2019 ◽

Vol 45 (Supplement_2) ◽

pp. S186-S187

Author(s):

Anne Marie Teti ◽

Patricia C Graham ◽

Mallory Fergione ◽

Lawrence C Haber ◽

Joanna M Fiszdon ◽

...

Keyword(s):

High Risk ◽

Prospective Memory ◽

Negative Symptoms ◽

Social Function ◽

First Episode Psychosis ◽

First Episode ◽

Clinical High Risk ◽

Episode Psychosis ◽

The Relationship

Download Full-text

Change in cannabis use, clinical symptoms and social functioning among patients with first-episode psychosis: a 5-year follow-up study of patients in the OPUS trial

Psychological Medicine ◽

10.1017/s0033291713000433 ◽

2013 ◽

Vol 44 (1) ◽

pp. 117-126 ◽

Cited By ~ 30

Author(s):

L. Clausen ◽

C. R. Hjorthøj ◽

A. Thorup ◽

P. Jeppesen ◽

L. Petersen ◽

...

Keyword(s):

Antipsychotic Medication ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Cannabis Use ◽

Psychotic Symptoms ◽

First Episode ◽

Episode Psychosis

BackgroundSeveral studies indicate that cannabis use among patients with psychotic disorders is associated with worse outcome, but only a few studies have controlled for baseline condition and medication.MethodAt 5-year follow-up, interviews were carried out with 314 first-episode psychosis patients included in the OPUS trial. The patients included were in the age range of 18 to 45 years old and 59% were male. Cannabis use was extracted from the Schedule for Clinical Assessment in Neuropsychiatry. At follow-up, the patients were divided into different groups according to the variable cannabis use: abstainers, stoppers, starters and continuers. Psychotic, negative and disorganized dimensions (ranging from zero to five) were calculated for each of the four groups based on the Schedule for the Assessment of Positive and Negative Symptoms in Schizophrenia.ResultsCannabis users were younger (24.6 years v. 27.4 years, p < 0.001) and had a lower level of education. At the 5-year follow-up, users of cannabis had higher scores on the psychotic dimension [difference 0.97, 95% confidence interval (CI) 0.41–1.53, p = 0.001] and lower levels of the Global Assessment of Functioning (difference 8.26, 95% CI 2.13–14.39, p = 0.01). Those who stopped using cannabis between entry and 5-year follow-up had a significantly lower level of psychotic symptoms at 5-year follow-up even after controlling for baseline level of psychotic symptoms and for insufficient antipsychotic medication (adjusted difference in psychotic dimension –1.04, 95% CI –1.77 to –0.31, p = 0.006).ConclusionsContinuous cannabis use was associated with higher levels of psychotic symptoms after 5 years, and this association was only partly explained by insufficient antipsychotic medication.

Download Full-text