Platform for systems medicine research and diagnostic applications in psychotic disorders—The METSY project

2018 ◽  
Vol 50 ◽  
pp. 40-46 ◽  
Author(s):  
Elisabeth Frank ◽  
Dieter Maier ◽  
Juha Pajula ◽  
Tommi Suvitaival ◽  
Faith Borgan ◽  
...  
Keyword(s):  
At Risk ◽  
Lipid Metabolism ◽  
Psychotic Disorders ◽  
Clinical Decision Making ◽  
Endocannabinoid System ◽  
First Episode Psychosis ◽  
First Episode ◽  
Glucose And Lipid Metabolism ◽  
Episode Psychosis ◽  
Patients At Risk

AbstractPsychotic disorders are associated with metabolic abnormalities including alterations in glucose and lipid metabolism. A major challenge in the treatment of psychosis is to identify patients with vulnerable metabolic profiles who may be at risk of developing cardiometabolic co-morbidities. It is established that both central and peripheral metabolic organs use lipids to control energy balance and regulate peripheral insulin sensitivity. The endocannabinoid system, implicated in the regulation of glucose and lipid metabolism, has been shown to be dysregulated in psychosis. It is currently unclear how these endocannabinoid abnormalities relate to metabolic changes in psychosis. Here we review recent research in the field of metabolic co-morbidities in psychotic disorders as well as the methods to study them and potential links to the endocannabinoid system. We also describe the bioinformatics platforms developed in the EU project METSY for the investigations of the biological etiology in patients at risk of psychosis and in first episode psychosis patients. The METSY project was established with the aim to identify and evaluate multi-modal peripheral and neuroimaging markers that may be able to predict the onset and prognosis of psychiatric and metabolic symptoms in patients at risk of developing psychosis and first episode psychosis patients. Given the intrinsic complexity and widespread role of lipid metabolism, a systems biology approach which combines molecular, structural and functional neuroimaging methods with detailed metabolic characterisation and multi-variate network analysis is essential in order to identify how lipid dysregulation may contribute to psychotic disorders. A decision support system, integrating clinical, neuropsychological and neuroimaging data, was also developed in order to aid clinical decision making in psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic understanding of psychotic and metabolic disorders, facilitate early disease detection, aid treatment selection and elucidate new targets for pharmacological treatments.

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

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.

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

2020 ◽  
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.

Differences in coping, self-efficacy, and external control beliefs between patients at-risk for psychosis and patients with first-episode psychosis

2014 ◽  
Vol 219 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Stefanie J. Schmidt ◽  
Vera-Maria Grunert ◽  
Benno G. Schimmelmann ◽  
Frauke Schultze-Lutter ◽  
Chantal Michel
Keyword(s):  
At Risk ◽  
Self Efficacy ◽  
First Episode Psychosis ◽  
Control Beliefs ◽  
External Control ◽  
First Episode ◽  
Episode Psychosis ◽  
Patients At Risk

scholarly journals Mental health-related stigma and pathways to care for people at risk of psychotic disorders or experiencing first-episode psychosis: a systematic review

2017 ◽  
Vol 47 (11) ◽  
pp. 1867-1879 ◽  
Author(s):  
P. C. Gronholm ◽  
G. Thornicroft ◽  
K. R. Laurens ◽  
S. Evans-Lacko
Keyword(s):  
At Risk ◽  
Help Seeking ◽  
Psychotic Disorders ◽  
First Episode Psychosis ◽  
Current Evidence ◽  
Pathways To Care ◽  
First Episode ◽  
Early Stages ◽  
Episode Psychosis ◽  
Service Contact

BackgroundStigma associated with mental illness can delay or prevent help-seeking and service contact. Stigma-related influences on pathways to care in the early stages of psychotic disorders have not been systematically examined.MethodThis review systematically assessed findings from qualitative, quantitative and mixed-methods research studies on the relationship between stigma and pathways to care (i.e. processes associated with help-seeking and health service contact) among people experiencing first-episode psychosis or at clinically defined increased risk of developing psychotic disorder. Forty studies were identified through searches of electronic databases (CINAHL, EMBASE, Medline, PsycINFO, Sociological Abstracts) from 1996 to 2016, supplemented by reference searches and expert consultations. Data synthesis involved thematic analysis of qualitative findings, narrative synthesis of quantitative findings, and a meta-synthesis combining these results.ResultsThe meta-synthesis identified six themes in relation to stigma on pathways to care among the target population: ‘sense of difference’, ‘characterizing difference negatively’, ‘negative reactions (anticipated and experienced)’, ‘strategies’, ‘lack of knowledge and understanding’, and ‘service-related factors’. This synthesis constitutes a comprehensive overview of the current evidence regarding stigma and pathways to care at early stages of psychotic disorders, and illustrates the complex manner in which stigma-related processes can influence help-seeking and service contact among first-episode psychosis and at-risk groups.ConclusionsOur findings can serve as a foundation for future research in the area, and inform early intervention efforts and approaches to mitigate stigma-related concerns that currently influence recognition of early difficulties and contribute to delayed help-seeking and access to care.

QUALITY OF INDIVIDUAL AND GROUP LEVEL INTERVENTIONS FOR FIRST EPISODE PSYCHOSIS AT THE TERTIARY PSYCHIATRIC HOSPITAL IN UGANDA.

2020 ◽  
Author(s):  
Emmanuel Kiiza Mwesiga ◽  
Noeline Nakasujja ◽  
Lawrence Nankaba ◽  
Juliet Nakku ◽  
Seggane Musisi
Keyword(s):  
Psychiatric Hospital ◽  
Psychotic Disorders ◽  
First Episode Psychosis ◽  
First Episode ◽  
Group Level ◽  
Group Interventions ◽  
Episode Psychosis ◽  
Essential Components ◽  
The Individual

Introduction: Individual and group level interventions have the largest effect on outcomes in patients with the first episode of psychosis. The quality of these individual and group level interventions provided to first-episode psychosis patients in Uganda is unclear.Methods: The study was performed at Butabika National Psychiatric Teaching and referral hospital in Uganda. A retrospective chart review of recently discharged adult in-patients with the first episode of psychosis was first performed to determine the proportion of participants who received the different essential components for individual and group level interventions. From the different proportions, the quality of the services across the individual and group interventions was determined using the first-Episode Psychosis Services Fidelity Scale (FEPS-FS). The FEPS-FS assigns a grade of 1-5 on a Likert scale depending on the proportion of patients received the different components of the intervention. Results: The final sample included 156 first-episode psychosis patients. The median age was 27 years [IOR (24-36)] with 55% of participants of the female gender. 13 essential components across the individual and group interventions were assessed and their quality quantified. All 13 essential components had poor quality with the range of scores on the FEPS-FS of 1-3. Only one essential component assessed (use of single antipsychotics) had moderate quality.Discussion: Among current services at the National psychiatric hospital of Uganda, the essential for individual and group level interventions for psychotic disorders are of low quality. Further studies are required on how the quality of these interventions can be improved.

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.

Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition

2020 ◽  
pp. 1-10
Author(s):  
Deepak K. Sarpal ◽  
Goda Tarcijonas ◽  
Finnegan J. Calabro ◽  
William Foran ◽  
Gretchen L. Haas ◽  
...  
Keyword(s):  
Cognitive Control ◽  
Psychotic Disorders ◽  
First Episode Psychosis ◽  
First Episode ◽  
Cognitive State ◽  
Cognitive States ◽  
Episode Psychosis ◽  
Dorsolateral Prefrontal ◽  
Parietal Lobule ◽  
Context Specific

Abstract Background Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with ‘background connectivity’ following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders. Thus, here we examine background connectivity during executive processing in a cohort of participants with first-episode psychosis (FEP). Methods The following fMRI study examined background connectivity of the dorsolateral prefrontal cortex (DLPFC), during working memory engagement in a group of 43 patients with FEP, relative to 35 healthy controls (HC). Findings were also examined in relation to measures of executive function. Results The FEP group relative to HC showed significantly lower background DLPFC connectivity with bilateral superior parietal lobule (SPL) and left inferior parietal lobule. Background connectivity between DLPFC and SPL was also positively associated with overall cognition across all subjects and in our FEP group. In comparison, resting-state frontoparietal connectivity did not differ between groups and was not significantly associated with overall cognition, suggesting that psychosis-related alterations in executive networks only emerged during states of goal-oriented behavior. Conclusions These results provide novel evidence indicating while frontoparietal connectivity at rest appears intact in psychosis, when engaged during a cognitive state, it is impaired possibly undermining cognitive control capacities in FEP.

scholarly journals Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
Author(s):  
Kirsten B. Bojesen ◽  
Bjørn H. Ebdrup ◽  
Kasper Jessen ◽  
Anne Sigvard ◽  
Karen Tangmose ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Poor Response ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Resonance Spectroscopy ◽  
Reference Levels ◽  
Clinical Prognosis ◽  
Episode Psychosis

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

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