Biomarkers For Psychiatric Disorders Research Articles

Auditory and Visual Mismatch Negativity in Psychiatric Disorders: A Review

Event-related potentials (ERPs) provide an objective index of neurocognitive abnormality or dysfunction in neuropsychiatric disorders. Auditory mismatch negativity (aMMN), which was discovered in the 1980s, is one unique type of ERP. Several lines of evidence suggest that it reflects auditory preattentive (automatic) information processing and the function of glutamatergic N-methyl-D-aspartate receptors. Many studies also have suggested that aMMN is a promising biomarker for some psychiatric disorders such as schizophrenia. Prospective studies combining analyses of several biomarkers, including aMMN, in schizophrenia patients from the prodromal period, are underway. Meanwhile, the existence of a visual counterpart of aMMN (vMMN) has been disputed, and a genuine vMMN was only confirmed in the last decade. Thus, there have been a relatively small number of vMMN studies compared with studies of aMMN, and the mechanism underlying vMMN is still unclear. However, it is well known that abnormal auditory and visual sensory information processing is present in psychiatric disorders, and vMMN is an important component of ERPs studied in psychiatric patients. The aim of this review is to provide an overview of recent aMMN and vMMN findings in several psychiatric disorders, including schizophrenia, major depression, Alzheimer’s disease, and developmental disorders. In doing so, we highlight their potential use as biomarkers of psychiatric disorders.

S.01.02 Analysis of whole genome biomarker expression in blood and brain; peripheral biomarkers in psychiatric disorders

S.01.02 Analysis of whole genome biomarker expression in blood and brain; peripheral biomarkers in psychiatric disorders

Autism: from genetics to biomarkers.

The development of biomarkers for psychiatric disorders is particularly challenging, given the frequent clinical heterogeneity, and the subjective nature of symptoms which requires finely tuned quantification methods for accurate diagnosis. Yet the more clinically heterogeneous a disease, the more valuable becomes an objective measure of disease state or severity. While identifying biological markers for psychiatric disorders has thus far remained out of reach, groundbreaking progress in DNA sequencing technologies and the completed human genome sequence have set the foundation for a novel perspective on clinical care, which also brings promising new approaches for biomarker discovery. The aim of genomic medicine [1] is to take advantage of the wealth of information encoded in an individual’s genome regarding their disease risk and potential responses to therapy. For diseases having significant contribution of genetic factors, the possibility to quantify genetic variation with enough depth is expected to lead to the development of effective markers of disease risk. This special issue of Disease Markers is dedicated to autism spectrum disorders (ASD) and discusses the current understanding of ASD genetics, as well as the possibilities of translating genetic research toward biomarker development in ASD. ASD are a spectrum of neurodevelopmental conditions characterized by language deficits, dysfunctions of social-reciprocal interactions and repetitiverestrictive behaviors. The clinical manifestations of autism are highly variable, both between individuals, and along an individual’s developmental trajectory. Although some individualswith ASD are highly functional, many are severely impaired and require permanent care. The significant level of impairment combined with the fact that no specific therapy is yet available for ASD, make ASD a devastating illness for patients and families, and a heavy financial burden for the healthcare system. The most effective intervention for ASD has proven to be early behavioral therapy [2]. Thus the identification of biological markers for ASD, allowing very early detection, even before the onset of symptoms, would be of tremendous value At the same time, one of the most well established characteristics of ASD is it’s high heritability, and significant research efforts have been geared toward understanding the genetic basis of autism. Thefield ofASD genetic research is still far from fully elucidating the mechanisms that govern ASD heritability, but the last two decades have undoubtedly brought about remarkable progress. Currently it is believed that both common genetic variation and rare DNA sequence variants contribute to the ASD genetic susceptibility [3], and that the relative contribution of common and rare alleles is variable among ASD cases. In the first article of this issue, “Mutant mouse models of autism spectrum disorders”, Yuri Bozzi and colleagues review the phenotypic characteristics of currently available mouse models of ASD as well as the contribution of mouse models toward the development of pharmacological therapy for ASD. Of particular importance for dissecting out the cellular and molecular mechanisms of ASD are several genes that have been identified as causes of genetic syndromes with a high incidence of ASD (FMR1, the gene mutated in fragile X syndrome, TSC1/TSC2, the genes responsible for tuberous sclerosis and NF1, the gene implicated in neurofibromatosis are just a few examples). Despite the

Integrative Neuroscience and Personalized Medicineedited by GordonEvian and KoslowStephen. Oxford, United Kingdom, Oxford University Press, 2011, 322 pp., $89.95.

Integrative Neuroscience and Personalized Medicineedited by GordonEvian and KoslowStephen. Oxford, United Kingdom, Oxford University Press, 2011, 322 pp., $89.95.

Are the DNA methylation profiles within the CpG island at the promoter of exon I of the brain-derived neurotrophic factor (BDNF) gene a potent diagnostic biomarker in psychiatric disorders?

Are the DNA methylation profiles within the CpG island at the promoter of exon I of the brain-derived neurotrophic factor (BDNF) gene a potent diagnostic biomarker in psychiatric disorders?

Epigenetic biomarkers in psychiatric disorders

The discovery of biomarkers in psychiatric disorders may help in the diagnosis, prevention and treatment of patients with these disorders. Here, I discuss the potential role of epigenetic biomarkers, that is, epigenetically altered genes and/or expression patterns of proteins or metabolites, in psychiatric disorders. Before epigenetic biomarkers can be clinically applied in these disorders, several issues need to be addressed. These include establishing a connection between biomarkers and the disease process; determining the predictive quality of the biomarkers; determining the effects of disease heterogeneity on the biomarkers; and identifying sample sources for the biomarkers that are easily accessible for testing.

Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications

Converging lines of evidence implicate the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depression. Recent studies have begun to explore the relationship between serum BDNF and depression. We conducted meta-analyses of 11 studies examining differences in serum BDNF content between depressed and nondepressed subjects (N = 748), and eight studies comparing pre- and post-antidepressant treatment serum BDNF content (N = 220). The meta-analysis revealed strong evidence that BDNF levels were lower in depressed subjects than healthy control subjects (p < 6.8 x 10(-8)). Similarly, the second meta-analysis found significantly higher BDNF levels after antidepressant treatment (p = .003). There was no evidence of publication bias in the first (p = .376) or second (p = .571) meta-analysis and no evidence that either meta-analysis was unduly influenced by any one study. These findings provide strong evidence to suggest that serum BDNF levels are abnormally low in patients suffering from major depressive disorder and that the BDNF levels are elevated following a course of antidepressant treatment. Although the relationship of our findings to pathophysiology of depression and the mechanism of drug action remains to be determined, the measure may have potential use as a biomarker for psychiatric disorders or as a predictor of antidepressant efficacy.

The economic burden of schizophrenia in Russia

The search for immune biomarkers in psychiatric disorders has primarily focused on pro-inflammatory cytokines. Other immune proteins including chemokines have been relatively neglected in such studies. Recent evidence has implicated chemokines in many neurobiological processes potentially relevant to psychiatric disorders, beyond their classical chemotactic functions. These may include neuromodulator effects, neurotransmitter-like effects, and direct/indirect regulation of neurogenesis. This systematic review presents the existing early evidence which supports an association of many chemokines with the psychiatric disorders: depression, bipolar disorder, schizophrenia, mild cognitive impairment and Alzheimer's disease. The non-specific association of chemokines including CXCL8 (IL-8), CCL2 (MCP-1), CCL3 (MIP-1α) and CCL5 (RANTES) with these disorders across diagnostic categories implies a generalised involvement of many chemokine systemic with psychiatric disease. Additional chemokines with great mechanistic relevance including CXCL12 (SDF-1) and CX3CL1 (fractalkine) have been rarely reported in the existing human literature and should be included in future clinical studies. The potential utility of these proteins as pathologically relevant biomarkers or therapeutic targets should be considered by future clinical and translational research.