Biomarkers For Mental Disorders Research Articles

Edge-centric analysis of time-varying functional brain networks with applications in autism spectrum disorder

The interaction between brain regions changes over time, which can be characterized using time-varying functional connectivity (tvFC). The common approach to estimate tvFC uses sliding windows and offers limited temporal resolution. An alternative method is to use the recently proposed edge-centric approach, which enables the tracking of moment-to-moment changes in co-fluctuation patterns between pairs of brain regions. Here, we first examined the dynamic features of edge time series and compared them to those in the sliding window tvFC (sw-tvFC). Then, we used edge time series to compare subjects with autism spectrum disorder (ASD) and healthy controls (CN). Our results indicate that relative to sw-tvFC, edge time series captured rapid and bursty network-level fluctuations that synchronize across subjects during movie-watching. The results from the second part of the study suggested that the magnitude of peak amplitude in the collective co-fluctuations of brain regions (estimated as root sum square (RSS) of edge time series) is similar in CN and ASD. However, the trough-to-trough duration in RSS signal is greater in ASD, compared to CN. Furthermore, an edge-wise comparison of high-amplitude co-fluctuations showed that the within-network edges exhibited greater magnitude fluctuations in CN. Our findings suggest that high-amplitude co-fluctuations captured by edge time series provide details about the disruption of functional brain dynamics that could potentially be used in developing new biomarkers of mental disorders.

The association of mitochondrial DNA copy number with incident mental disorders in women: A population-based follow-up study

BackgroundAvailable evidence suggests that mitochondrial DNA copy number (mtDNA-CN) may differ among patients with mental disorders compared to the general population. However, whether mtDNA-CN is independently associated with the subsequent incidence of mental disorders remains unclear. Material and methodsWe used droplet digital PCR to measure the absolute mtDNA-CN in DNA samples obtained from a population-based follow-up study, which included a total of 2354 middle-aged women (52–63 years) who were free of mental disorders at baseline. After 17 years (median) of follow-up, 727 participants were diagnosed with mental disorders. ResultsIn the univariate Cox regression, lower baseline mtDNA-CN (mtDNA-CN < 117) was associated with a higher risk of mental disorders (HR = 1.16, p = 0.047). In addition, smoking, marital status and sleeping quality were associated with both mtDNA-CN and mental disorders. After adjusting for these variables, the association between mtDNA-CN and mental disorders decreased and became non-significant (HR = 1.07, p = 0.36). Stratification of data according to the subtype of mental disorders, showed that low mtDNA-CN was associated with a higher risk of alcohol or drug use disorders (HR = 1.82, p = 0.045 after adjusting). ConclusionIn the present study, we could not find any independent association between mtDNA-CN blood and the most common mental disorders in a population-based follow-up study of Swedish women, except for alcohol and drug use disorders. The use of blood mtDNA-CN as a biomarker of mental disorders, in addition to other risk factors, needs to be further examined in future studies.

Theta-Range Oscillations in Stress-Induced Mental Disorders as an Oscillotherapeutic Target.

Emotional behavior and psychological disorders are expressed through coordinated interactions across multiple brain regions. Brain electrophysiological signals are composed of diverse neuronal oscillations, representing cell-level to region-level neuronal activity patterns, and serve as a biomarker of mental disorders. Here, we review recent observations from rodents demonstrating how neuronal oscillations in the hippocampus, amygdala, and prefrontal cortex are engaged in emotional behavior and altered by psychiatric changes such as anxiety and depression. In particular, we focus mainly on theta-range (4–12 Hz) oscillations, including several distinct oscillations in this frequency range. We then discuss therapeutic possibilities related to controlling such mental disease-related neuronal oscillations to ameliorate psychiatric symptoms and disorders in rodents and humans.

Comparison of plasma nucleotide metabolites and amino acids pattern in patients with binge eating disorder and obesity

Binge eating disorder (BED) increasingly affects population, but the mechanisms of the disease and its biomarkers are not well characterized. Recently, plasma purines, pyrimidines, amino acid and nicotinamide metabolites profiling attracted attention in studies on pathology and biomarkers of mental disorders but has not been adequately studied in BED. Blood and plasma samples were taken from patients with adult obese with BED (n = 20) and control adult obese without BED (n = 17). Plasma samples were analyzed for nucleotides and amino acid concentrations with high-performance liquid chromatography-mass spectrometry. BED had a significantly (p < 0.05) lower uridine and hypoxanthine to creatinine ratio compared to the control group. Among the amino acids BED patients had significantly (p < 0.05) lower concentrations of glutamic acid, leucine, isoleucine and the whole branched-chain amino acids group, while the concentration of citrulline was increased. Among nicotinamide metabolites, 1-methylnicotinamide levels were significantly (p < 0.05) lower. This study highlights potential use of profiling nucleotide metabolite and amino acid pattern in BED patients that may provide information on mechanisms and potential biomarkers. However, further investigation in larger population is necessary to identify clinical correlates of the observed changes.

Could structural changes in the retinal layers be a new biomarker of mental disorders? A systematic review and thematic synthesis

It has recently been suggested that alterations of the layers of the retina could be a biomarker of specific mental disorders since they originate in the same embryonic layer as the brain and both are interconnected through the optic nerve. The purpose of this article is to offer a systematic review of the literature and a thematic synthesis on the current state of the alterations of the retina layers identified by optical coherence tomography in patients with schizophrenia, bipolar disorder and major depression. For this purpose, we performed a bibliographic search, a systematic review of the studies and a thematic synthesis of the reported findings.Patients with schizophrenia have more abnormal findings followed by patients with bipolar disorder, with very few findings in depression. The nerve fibre layer is the retinal layer with more abnormal findings both in schizophrenia and in bipolar disorder, while no study in major depression found alterations in it. Of the clinical parameters, the duration of the illness correlates significantly and inversely with the thickness of the different layers in all disorders.When interpreting these data, it is necessary to take into account the limitations and differences of the studies, especially the mean length of the disorders. Given that this was very different among the 3 disorders (more than doubled in the case of schizophrenia respect to major depression), the differences in the results found could be due more to the effect of the length of illness than to the disorder itself.In summary, optical coherence tomography findings are promising, since they could provide biomarkers of neurodegeneration and/or neuroprogression of both schizophrenia and bipolar disorder.

A Theoretical Framework for Evaluating Psychiatric Research Strategies.

One of the major goals of basic studies in psychiatry is to find etiological mechanisms or biomarkers of mental disorders. A standard research strategy to pursue this goal is to compare observations of potential factors from patients with those from healthy controls. Classifications of individuals into patient and control groups are generally based on a diagnostic system, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD). Several flaws in these conventional diagnostic-based approaches have been recognized. The flaws are primarily due to the complexity in the relation between the pathogenetic factors (causes) and disorders: The current diagnostic categories may not reflect the underlying etiological mechanisms. To overcome this difficulty, the National Institute of Mental Health initiated a novel research strategy called Research Domain Criteria (RDoC), which encourages studies to focus on the neurobiological mechanisms and core aspects of behavior rather than to rely on traditional diagnostic categories. However, how RDoC can improve research in psychiatry remains a matter of debate. In this article, we propose a theoretical framework for evaluating psychiatric research strategies, including the conventional diagnostic category-based approaches and the RDoC approach. The proposed framework is based on the statistical modeling of the processes of how the disorder arises from pathogenetic factors. This framework provides the statistical power to quantify how likely relevant pathogenetic factors are to be detected under various research strategies. On the basis of the proposed framework, we can discuss which approach performs better in different types of situations. We present several theoretical and numerical results that highlight the advantages and disadvantages of the strategies. We also demonstrate how a computational model is incorporated into the proposed framework as a generative model of behavioral observations. This demonstration highlights how the computational models contribute to designing psychiatric studies.

Metabolomics studies in brain tissue: A review

Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions.

Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders.

Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC)/norepinephrine (NE) system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty). The reason for this discrepancy might be that NE is not only for flight (fear), but also for fight (anger). Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders.

Heterogeneity and individuality: microRNAs in mental disorders.

MicroRNAs are about 22 nucleotide long single-stranded RNA molecules, negatively regulating gene expression of a single gene or a gene network. In neural tissues, they have been implicated in developmental and neuroplasticity-related processes, such as neurogenesis, differentiation, apoptosis and long-term potentiation. Their molecular mode of action is reminiscent of findings of genome-wide association studies in mental disorders, unable to attribute the risk of disease to a specific gene, but rather to multiple genes, gene-networks and gene-environment interaction. As such, microRNAs are an attractive target for research. Here, we review clinical studies conducted in humans on microRNAs in mental disorders with a particular focus on schizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. The majority of clinical studies have focused on schizophrenia. The most robust finding has been reported for rs1625579 located in MIR137HG, which was associated with schizophrenia on a genome-wide level. Concerning bipolar disorder, major depression and anxiety disorders, promising results have been published, but only a considerably smaller number of clinical studies is available and genome-wide association studies did not suggest a direct link to microRNAs so far. Expression of microRNAs as biomarkers of mental disorders and treatment response is currently emerging with preliminary results. Larger-scaled genetic and functional studies along with translational research are needed to enhance our understanding of microRNAs in mental disorders. These studies will aid in disentangling the complex genetic nature of these disorders and possibly contribute to the development of novel, individualized diagnostic and therapeutic approaches.

EEG coherence analysis in depressive disorders and its possible use in clinical practice: a literature review

Recent reviews and meta-analyses of clinical data have revealed that there is a clear need in objective biomarkers of mental disorders and, in particular, of depression. There is a lot of evidence that EEG coherence can be an important marker of depressive disorders, and can predict response to different antidepressants. The most consistent finding is a decrease of frontal interhemispheric EEG coherence which is observed for most disorders related to depression. Methodological issues are discussed with a particular emphasis on use of statistical classifiers and on coupling EEG coherence with other methods of EEG analysis.

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.

S23 * NEUROBIOLOGICAL ENDOPHENOTYPES IN ALCOHOL DEPENDENCE * S23.1 * GENETIC DETERMINANTS OF ALCOHOL ADDICTION: SEARCHING FOR AN ENDOPHENOTYPE ASSOCIATED WITH SWEET LIKING IN POPULATION OF FAMILIES WITH HISTORY OF ALCOHOL ADDICTION

S23 * NEUROBIOLOGICAL ENDOPHENOTYPES IN ALCOHOL DEPENDENCE * S23.1 * GENETIC DETERMINANTS OF ALCOHOL ADDICTION: SEARCHING FOR AN ENDOPHENOTYPE ASSOCIATED WITH SWEET LIKING IN POPULATION OF FAMILIES WITH HISTORY OF ALCOHOL ADDICTION

A bridge to somewhere

A bridge to somewhere