Pharmacoresistant Severe Mental Health Disorders in Children and Adolescents: Functional Abnormalities of Cytochrome P450 2D6

Thümmler, Susanne; Dor, E.; David, Renaud; Leali, G.; Battista, Michèle; David, A.; Askénazy, Florence; Verstuyft, Céline

doi:10.3389/fpsyt.2018.00002

Cited by 26 publications

(17 citation statements)

References 27 publications

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“…Environmental chemicals and toxicants: In the last few years, epidemiologic investigations indicated that prenatal exposure to chemical and toxic factors such as air pollution, pesticides, materials used in the plastic industry and heavy metals may increase the risk of ASD [39,40,62,63,64]. Possible mechanisms behind the association between these environmental risk factors and ASD are not only their interactions with genetic factors, and/or epigenetic marks leading to a diminished ability to detoxify xenobiotics [65,66] but also their potential role in triggering neuro-inflammation and oxidative stress that lead to neurobiological and neurotransmitter alterations and abnormalities in signaling pathways [63].…”

Section: Prenatal Periodmentioning

confidence: 99%

Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations

Gialloreti

Mazzone

Benvenuto

et al. 2019

JCM

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Autism Spectrum Disorder (ASD) is a complex condition with early childhood onset, characterized by a set of common behavioral features. The etiology of ASD is not yet fully understood; however, it reflects the interaction between genetics and environment. While genetics is now a well-established risk factor, several data support a contribution of the environment as well. This paper summarizes the conclusions of a consensus conference focused on the potential pathogenetic role of environmental factors and on their interactions with genetics. Several environmental factors have been discussed in terms of ASD risk, namely advanced parental age, assisted reproductive technologies, nutritional factors, maternal infections and diseases, environmental chemicals and toxicants, and medications, as well as some other conditions. The analysis focused on their specific impact on three biologically relevant time windows for brain development: the periconception, prenatal, and early postnatal periods. Possible protective factors that might prevent or modify an ASD trajectory have been explored as well. Recommendations for clinicians to reduce ASD risk or its severity have been proposed. Developments in molecular biology and big data approaches, which are able to assess a large number of coexisting factors, are offering new opportunities to disentangle the gene–environment interplay that can lead to the development of ASD.

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Section: Prenatal Periodmentioning

confidence: 99%

Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations

Gialloreti

Mazzone

Benvenuto

et al. 2019

JCM

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“…Administration of FLX by intranasal route is therefore expected to decrease the DDI at intestinal and hepatic tissues as well as to evade the BBB and the P-glycoprotein therein expressed and that has been suggested to be involved in pharmacoresistant depression. Moreover, the intranasal route also decreases drug systemic exposure, and consequently adverse effects [17]. As such, FLX is herein hypothesized as a SSRI model drug to be encapsulated within lipid nanoparticles for intranasal delivery.…”

mentioning

confidence: 99%

QbD-driven development of intranasal lipid nanoparticles for depression treatment

Vitorino

Silva

Gouveia

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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Depression is a life-threatening psychiatric disorder and a multifactorial global public health concern. Current pharmacological treatments present limited efficacy, and are associated with several harmful side effects and development of pharmacoresistance mechanisms. Developing more effective therapeutic options is therefore a priority. This work aims at efficiently designing an antidepressant therapeutic surrogate relying on a dual strategy supported on lipid nanoparticles and intranasal delivery. For that purpose, the formulation was comprehensively optimized following a quality by design perspective. Critical quality attributes (CQAs) ranged from physicochemical to intranasal performance features. The optimized formulation was administered to mice in order to assess the antidepressive and anxiolytic effects by applying the forced swimming and marble-burying tests, respectively. A cross-analysis of the predictive models established for the set of 12 CQAs elicited the formulation containing similar proportion of solid and liquid lipids and lower surfactant concentration as the optimal one. Despite increasing the liquid lipid amount yielded smaller and more homogeneous particle size, and higher release rate, nanostructured lipid carriers (NLCs) provided an earlier and superior pig nasal mucosa permeability than nanoemulsions, along with better stability and cytotoxic profiles. Importantly, the intranasal delivery of the optimal lipid nanoparticle formulation reduced both depressive and anxiety-like behaviors, which positions these intranasal nanosystems in line with the hypothesis of provisioning timely and better acting antidepressant therapies. 1. Introduction Depression is a life-threatening mental disorder and a major public health concern, affecting more than 300 million people of all ages worldwide [1]. It leads to disability, noteworthy health-related costs and decreased quality of life, being considered a prominent risk factor for many other diseases, including neuropsychiatric, cardiovascular, and metabolic conditions [2,3]. Conventional pharmacological treatments for depression are considered relatively well defined. Antidepressant standard-of-care comprises oral selective serotonin reuptake inhibitors (SSRIs, e.g. fluoxetine) and serotonin-norepinephrine reuptake inhibitors (SNRIs, e.g.

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“…GWAS analysis supports CACNA1C’s participation in bipolar disorder, a behavioral disorder related to abnormal depression and elevated moods 43 . Anxiety and substance related disorders are commonly associated with bipolar disorders 44 . This suggests some health conditions are connected.…”

Section: Resultsmentioning

confidence: 99%

Network-based approach highlighting interplay among anti-hypertensives: target coding-genes: diseases

Sharma

2020

Sci Rep

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Elucidating the relation between the medicines: targets, targets: diseases and diseases: diseases are of fundamental significance as-is for societal benefit. Hypertension is one of the dangerous health conditions prevalent in society, is a risk factor for several other diseases if left untreated and anti-hypertensives (AHs) are the approved drugs to treat it. The goal of the study is to decipher the connection between hypertension with other health conditions, however, is challenging due to the large interactome. To fulfill the aim, the strategy involves prior clustering of the AHs into groups as per our previous method, followed by the analyzing functional association of the target coding-genes (tc-genes) and health conditions for each group. Following our recently published work where the AHs are clustered into six groups such that molecules having similar patterns come together, here, the distribution of molecular functions and the cellular components adopted by the tc-genes of each group are analyzed. The analyses indicate that kidney, heart, brain or lung related ailments are commonly associated with the tc-genes. The association of selective tc-genes to health conditions suggests a preference for certain health conditions despite many possibilities. Analyses of experimentally validated drug–drug combinations indicate the trend in successful AHs combinations. Clinically validated combinations bind different targets. Our study provides a promising methodology in a network-based approach that considers the influence of structural diversity of AHs to the functional perspective of tc-genes concerning the health conditions. The method could be extended to explore disease–disease relationships.

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Pharmacoresistant Severe Mental Health Disorders in Children and Adolescents: Functional Abnormalities of Cytochrome P450 2D6

Cited by 26 publications

References 27 publications

Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations

Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations

QbD-driven development of intranasal lipid nanoparticles for depression treatment

Network-based approach highlighting interplay among anti-hypertensives: target coding-genes: diseases

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