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Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

ABSTRACT: Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer's disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics. Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyzed after treatment with a multifactorial regime in a natural setting. (i) Biochemical, hematological, and metabolic differences may contribute to changes in drug efficacy and safety; (ii) anxiety and depression are more frequent and severe in females than males; (iii) both females and males respond similarly to treatment, showing significant improvements in anxiety and depression; (iv) APOE-3 carriers are the best responders and APOE-4 carriers tend to be the worst responders to conventional treatments; and (v) among CYP2D6, CYP2C19, and CYP2C9 genophenotypes, normal metabolizers (NMs) and intermediate metabolizers (IMs) are significantly better responders than poor metabolizers (PMs) and ultra-rapid metabolizers (UMs) to therapeutic interventions that modify anxiety and depression phenotypes in dementia. APOE-4 carriers and CYP-related PMs and UMs deserve special attention for their vulnerability and poor response to current treatments.

SUBMITTER: Cacabelos R

PROVIDER: S-EPMC8071277 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

Cacabelos Ramón R Carril Juan C JC Corzo Lola L Fernández-Novoa Lucía L Pego Rocío R Cacabelos Natalia N Cacabelos Pablo P Alcaraz Margarita M Tellado Iván I Naidoo Vinogran V

Pharmaceuticals (Basel, Switzerland) 20210415 4

<h4>Background</h4>Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer's disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics.<h4>Methods</h4>Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyz ...[more]

PMID: 33920985

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Project description:Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin-angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.

Dataset Information

Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

Publications

Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer's Disease.

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