Dear Colleagues,

This Special Issue is the continuation of our 2019 Special Issue, "Genomics of Brain Disorders 2.0" (https://www.mdpi.com/journal/ijms/special_issues/genomics_brain2).

Brain disorders represent the third major problem of health and disability in developed countries after cardiovascular disorders and cancer. From a global health perspective, important issues to be addressed with regard to neuropsychiatric disorders (NPDs) are: (i) disease burden (DALYs: disability-adjusted life years; YLDs: years lived with disability; YLLs: years of life lost); (ii) the costs (direct, indirect) of disease; (iii) disease pathogenesis; (iv) the identification of presymptomatic biomarkers; (v) novel targets for drug development; and (vi) personalized treatments with pharmacogenetic procedures for optimizing drug efficacy and safety. NPDs contribute approximately 10% of the global burden of disease. About 30% of all YLDs are assigned to NPDs, especially depression, alcohol use disorders, schizophrenia, bipolar disorder, and dementia. NPDs are the leading cause of disease burden, responsible for 7.4% of global DALYs and 22.9% of global YLDs. Within NPDs, mental disorders account for 56.7% DALYs, followed by neurological disorders (28.6%) and substance use disorder (14.7%).

The global cost of NPDs is projected to be about US$6 trillion by 2030. An estimated eight million deaths annually are attributed to mental disorders. Approximately 127 million Europeans suffer brain disorders. The total annual cost of brain disorders in Europe is about €386 billion, with €135 billion in direct medical expenditures, €179 billion in indirect costs, and €72 billion in direct non-medical costs. Mental disorders represent €240 billion (62% of the total cost, excluding dementia), followed by neurological diseases (€84 billion, 22%).

The primary cause of most brain disorders is poorly understood. In NPDs there is a convergence of multiple genomic defects distributed across the human genome with epigenetic phenomena and environmental risk factors leading to the phenotypic expression of the disease. In children, neurodevelopmental disorders are determinant for abnormal brain maturation and early mental derailment. In age-related neurodegenerative disorders, a common feature is the presence of intracellular and/or extracellular deposits of abnormally processed proteins that represent prototypical hallmarks probably contributing to premature neuronal death. A better characterization of the genomic background of mental and neurological disorders is necessary for elucidating disease-specific pathogenesis, as well as the identification of accurate biomarkers, and the implementation of novel treatments addressing pathogenic, mechanistic, metabolic, transporter and pleiotropic genes, and their products, associated with specific NPDs.

Prof. Dr. Ramón Cacabelos
Guest Editor

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• Genomics of Brain Disorders 2.0 in International Journal of Molecular Sciences (9 articles)