This Research Topic is the second volume of the 'Community Series in Genetic and Epigenetic Mechanisms Underpinning Vulnerability to Developing Psychiatric Disorders'. Please see the first volume
here.
Recent advances have highlighted the necessity of understanding both the genetic and the epigenetic mechanisms that underpin mental illnesses, with the ultimate aim being an attempt to answer the longstanding question of why some individuals are vulnerable to developing a psychiatric disease while others are not. The complex or multifactorial genetic model aims to explain how these polygenetic and environmental factors interact and strongly impact brain function both during development and throughout adulthood. As a result of the sum total of these interactions, the cognitive function, emotion regulation and personality of each individual is different and unique regardless of the level of genetic similarity. An interesting question emerging from these studies is why some genes are expressed in the brain in some environments but not in others. What is clear is that both genetic and epigenetic mechanisms influence the neurobiological substrate across the lifespan and that the resulting alterations to crucial aspects of brain function i.e. synaptic transmission or connectivity within neural circuits (among many others) can unfortunately manifest in individuals as a diverse set of debilitating psychiatric disorders. In this Research Topic we aim to attract studies interrogating the mechanisms of these interactions that enable this to come to be the case.
In the past, the findings of behavioral genetics were established using three types of classical approaches 1) comparing identical and fraternal twins, 2) studying family members, and 3) studying adoptees that had been raised together or apart. These studies showed that specific genes strongly influence not only personality, cognitive ability, and emotion regulation but also the risk of developing psychiatric disorders. However, although these types of studies identified specific genes that contribute to individual differences in brain function, they are limited by the fact that not a single gene has been identified to be causally involved in contributing to major mental disorders such as schizophrenia, addiction, depression or anxiety. Furthermore, most replication studies with those candidate genes have consistently failed, and those that have been replicated have been shown to participate in a small fraction of total variation. These results demonstrate that the rich complexity of human behavior cannot be explained simply by a linear relationship between a single gene and a complex behavior. This type of reductionist model has been successful for monogenic disorders such as Huntington disease but these types of disorders are extremely rare, so a different approach is required for polygenic disorders such as complex psychiatric conditions. The multifactorial complex model, based on the influence of gene networks and multiple environmental factors interacting and impacting in brain development and function to produce the phenotypic behavior, is a more heuristic model that better accounts for the current state of the field. Using that model, complex behavior, and the brain circuits that produce it, are the result of complex networks involving hundreds to thousands of genes working in concert with multiple environmental factors. Epigenetic research has established that an individual’s experience within an environment can alter the chromatin landscape within the brain in a region-specific and cell type specific manner and produce differences in gene expression even in individuals that are genetically identical such as monozygotic twins. Thus, targeting key environment-epigenetic modifications within the brain has immense therapeutic potential as a way of combating an individual’s vulnerability towards developing a pathological state.
In this Research Topic, we welcome contributions employing the multifactorial complex model, that seek to utilize a combination of genomics and epigenomics datasets to understand individual differences in vulnerability to developing psychiatric disorders. We welcome original research articles, reviews and mini-reviews of both clinical and preclinical studies involving research into:
• Genomics and epigenomics of personality disorders.
• Genomics and epigenomics of obesity.
• Genomics and epigenomics of substance use disorders.
• Genomics and epigenomics of depression.
• Genomics and epigenomics of anxiety.
• Genomics and epigenomics of schizophrenia.
• Genomics and epigenomics of ADHD.