Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation.
Epigenetic chromatin remodeling and modifications of DNA represent central mechanisms for regulation of gene expression during brain development and in memory formation. Emerging evidence implicates epigenetic modifications in disorders of synaptic plasticity and cognition.
S-adenosyl L-methionine (SAMe) is the natural, universal methyl group donor, participating in transmethylation reactions, known and commonly used as a dietary supplement since 1952. It plays an important role in the synthesis of neuromediators and melatonin and mechanisms of epigenetic regulation. The aim of this article is to review the literature about possibilities of SAMe application in the therapy of CNS diseases: depression, dementia syndromes, schizophrenia and somatic disorders.
Clinical genetic studies propose a strong genetic contribution to the pathogenesis of anxiety disorders with a heritability of about 30-67%. The present review will give an overview of linkage studies, association studies and genome-wide association studies (GWAS) yielding support for some candidate genes. Additionally, first evidence for gene-environment interactions between candidate genes of anxiety disorders and stressful life events will be reported.
Child and Adolescent Psychiatric Clinics of North America
This article reviews the familiality, linkage, candidate gene, and genomewide association studies of obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, and other anxiety disorders (ie, generalized anxiety disorder, separation anxiety disorder, social phobia, and specific phobia). Studies involving children and adolescents are highlighted. Clinical and research implications are discussed.
Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects.
Seishin Shinkeigaku Zasshi = Psychiatria Et Neurologia Japonica
In addition to genetic factors, the role of epigenetic and other environmental factors in the promotion of anxiety disorder has attracted much attention in psychiatric research. When stress is encountered in the environment, the hypothalamus-pituitary adrenal system (HPA system) is activated and cortisol is secreted. CRHR gene function is closely related to this response. As a result of haplotype analysis of CRHR genes in depression and panic disorder patients, it was found that genetic polymorphism of CRHR1 and CRHR2 was related to both disorders.
Presently available clinical genetic studies point to a considerable heritability of anxiety disorders (30-67%), with multiple vulnerability genes such as 5-HT1A, 5-HTT, MAO-A, COMT, CCK-B, ADORA2A, CRHR1, FKBP5, ACE, RGS2/7 and NPSR1 suggested by molecular genetic association studies. These genes have been shown to partially interact with each other as well as with environmental factors to shape the overall disease risk in a complex genetic model.
Fear and anxiety are debilitating conditions that affect a significant number of individuals in their lifetimes. Understanding underlying mechanisms of these disorders affords us the possibility of therapeutic intervention. Such clarity in terms of mechanism and intervention can only come from an amalgamation of research from human to animal studies that attempt to mimic the human condition, both of which are discussed in this review. We begin by presenting an outline of our current understanding of the neurobiological basis of fear and anxiety.
Low socioeconomic position (SEP) has previously been linked to a number of negative health indicators, including poor mental health. The biologic mechanisms linking SEP and mental health remain poorly understood. Recent work suggests that social exposures influence DNA methylation in a manner salient to mental health. We conducted a pilot investigation to assess whether SEP, measured as educational attainment, modifies the association between genomic methylation profiles and traumatic stress in a trauma-exposed sample.