scholarly journals Focusing on drug versus disease mechanisms and on clinical subgrouping to advance personalised medicine in psychiatry

2013 ◽  
Vol 26 (6) ◽  
pp. 327-333 ◽  
Author(s):  
Jose de Leon
Keyword(s):  
Psychiatric Disorders ◽  
Treatment Response ◽  
Personalised Medicine ◽  
Pharmacological Approach ◽  
Disease Mechanisms ◽  
Personalise Treatment

Personalised medicine has finally been featured in psychiatric journals, but psychiatrists have mainly focused on the promise of using disease mechanisms to personalise treatment. Psychiatric disorders such as schizophrenia and depression are not diseases, in the medical sense, and are probably more like syndromes. Instead of spending much time and effort focusing on the mechanisms of diseases that may instead be syndromes, the author believes that psychiatrists should (1) learn more about personalising prescription via drug mechanisms, a pharmacological approach to personalised medicine; and (2) reconsider prior attempts by traditional clinical psychopharmacologists to use sophisticated clinical approaches that try to subdivide psychiatric syndromes into groups that may be more homogenous for treatment response.

Liquid biopsy in the clinical management of hepatocellular carcinoma

Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2025-2034 ◽  
Author(s):  
Johann von Felden ◽  
Teresa Garcia-Lezana ◽  
Kornelius Schulze ◽  
Bojan Losic ◽  
Augusto Villanueva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Clinical Management ◽  
Early Stage ◽  
Personalised Medicine ◽  
Precision Oncology ◽  
Early Hepatocellular Carcinoma ◽  
Populations At Risk ◽  
Circulating Tumour Dna

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field.In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.

scholarly journals The Impact of Alexithymia on Treatment Response in Psychiatric Disorders: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Federica Pinna ◽  
Mirko Manchia ◽  
Pasquale Paribello ◽  
Bernardo Carpiniello
Keyword(s):  
Systematic Review ◽  
Psychiatric Disorders ◽  
Treatment Response ◽  
The Impact

Fooling Mother Nature: Epigenetics and Novel Treatments for Psychiatric Disorders

CNS Spectrums ◽  
2010 ◽  
Vol 15 (6) ◽  
pp. 358-366 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Disease ◽  
Gene Products ◽  
Risk Genes ◽  
Mother Nature ◽  
Novel Treatments ◽  
Brain Circuits ◽  
Disease Mechanisms ◽  
Normal Gene ◽  
Altered Gene

Modern formulations of psychiatric disorders hypothesize that mother nature goes awry, causing both genetic and epigenetic disease actions. Genetic disease actions are the consequences of naturally inherited risk genes that have an altered sequence of DNA. This altered DNA sequence theoretically leads to the production of altered gene products in neurons, causing inefficient information processing in various brain circuits, and biasing those circuits towards developing symptoms of a mental illness. Epigenetic disease actions are theorized either to activate risk genes to make an altered gene product or to activate normal genes to make normal gene products but at the wrong time. Epigenetic disease mechanisms theoretically turn normal genes into risk genes by causing normal genes to be expressed in neurons when these genes should be silenced or by causing normal genes to be silenced when they should be expressed.

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

2019 ◽  
Vol 38 (3) ◽  
pp. 232-239 ◽  
Author(s):  
Vijay Gayam ◽  
Oluwole Jegede ◽  
Benjamin Tiongson ◽  
Amrendra Kumar Mandal ◽  
Jasdeep Sidhu ◽  
...  
Keyword(s):  
Substance Use ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Psychiatric Disorders ◽  
Treatment Response ◽  
Psychiatric Diagnosis ◽  
Psychiatric Patients ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Direct Acting

Background: The highest burden of hepatitis C virus (HCV) infection is seen in patients with psychiatric disorders who have been excluded from traditional treatments with Interferon due to treatment-emergent neuropsychiatric adverse effects. The goal of this study is to determine the tolerability, treatment retention, and efficacy of direct-acting antivirals with psychiatric disorders and comorbid substance use disorders in real-life settings. Methods: This is a retrospective cohort observational study of HCV patients treated with direct-acting antivirals between January 2016 and December 2018. Patients were stratified and sub-stratified based on their psychiatric diagnosis and substance use. The primary assessment was the sustained virologic response at 12 weeks post-treatment (SVR12). Results: Among the 291 patients analyzed, patients with psychiatric diagnosis and non-psychiatric patients made up 51.2% (n = 149) and 48.8% (n = 142) respectively. Majority of the patients included in the study were African-Americans (68.7%, n = 200). Overall, 95.3% (142/149) and 94.4% (134/142) of psychiatric and non-psychiatric patients, respectively, achieved SVR12 and treatment response was similar between the groups (p = 0.72). Among psychiatric patients, only the prior treatment status was identified as a predictor of treatment response (OR 0.153, 95% CI 0.03–0.79; p = 0.05). No statistical difference was observed among the patients with SVR12 based on their primary psychiatric diagnoses or by comorbid substance abuse. Conclusion: The results of our study show that direct-acting antiviral treatments are well tolerated in psychiatric patients, and an overwhelming majority of patients achieved SVR12. Our study highlights the need to integrate HCV screening with treatment linkage in psychiatry and primary care practice.

Neurocognitive and Perceptual Processing in Genetic Mouse Models of Schizophrenia: Emerging Lessons

2019 ◽  
Vol 25 (6) ◽  
pp. 597-619
Author(s):  
Anastasia Diamantopoulou ◽  
Joseph A. Gogos
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Perceptual Processing ◽  
Great Promise ◽  
Biological Targets ◽  
The Past ◽  
Disease Mechanisms ◽  
Consistent Approach ◽  
Genetic Mouse Models

During the past two decades, the number of animal models of psychiatric disorders has grown exponentially. Of these, genetic animal models that are modeled after rare but highly penetrant mutations hold great promise for deciphering critical molecular, synaptic, and neurocircuitry deficits of major psychiatric disorders, such as schizophrenia. Animal models should aim to focus on core aspects rather than capture the entire human disease. In this context, animal models with strong etiological validity, where behavioral and neurophysiological phenotypes and the features of the disease being modeled are in unambiguous homology, are being used to dissect both elementary and complex cognitive and perceptual processing deficits present in psychiatric disorders at the level of neurocircuitry, shedding new light on critical disease mechanisms. Recent progress in neuroscience along with large-scale initiatives that propose a consistent approach in characterizing these deficits across different laboratories will further enhance the efficacy of these studies that will ultimately lead to identifying new biological targets for drug development.

scholarly journals Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Katrien Skorobogatov ◽  
Livia De Picker ◽  
Robert Verkerk ◽  
Violette Coppens ◽  
Marion Leboyer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Psychiatric Disorders ◽  
Treatment Response ◽  
Clinical Symptoms ◽  
Psychiatric Patients ◽  
Kynurenine Pathway ◽  
Primary Objective ◽  
Original Research ◽  
Psychiatric Illnesses ◽  
Predictive And Prognostic Biomarker

ObjectiveDisturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It remains uncertain however to what extent metabolite levels detectable in plasma or serum reflect brain kynurenine metabolism and other disease-specific pathophysiological changes. The primary objective of this systematic review was to investigate the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites. As secondary aims we describe their correlation with illness course, treatment response, and neuroanatomical abnormalities in psychiatric diseases.MethodsWe performed a systematic literature search until February 2021 in PubMed. We included 27 original research articles describing a correlation between peripheral and central kynurenine metabolite measures in preclinical studies and human samples from patients suffering from neuropsychiatric disorders and other conditions. We also included 32 articles reporting associations between peripheral KP markers and symptom severity, CNS pathology or treatment response in schizophrenia, bipolar disorder or major depressive disorder.ResultsFor kynurenine and 3-hydroxykynurenine, moderate to strong concordance was found between peripheral and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions. Despite discordant findings for other metabolites (mainly tryptophan and kynurenic acid), blood metabolite levels were associated with clinical symptoms and treatment response in psychiatric patients, as well as with observed neuroanatomical abnormalities and glial activity.ConclusionOnly kynurenine and 3-hydroxykynurenine demonstrated a consistent and reliable concordance between peripheral and central measures. Evidence from psychiatric studies on kynurenine pathway concordance is scarce, and more research is needed to determine the validity of peripheral kynurenine metabolite assessment as proxy markers for CNS processes. Peripheral kynurenine and 3-hydroxykynurenine may nonetheless represent valuable predictive and prognostic biomarker candidates for psychiatric disorders.

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