Translational Research In Psychiatry Research Articles

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Trends in big data analyses by multicenter collaborative translational research in psychiatry.

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory‐based research that incorporates the latest findings, it is necessary to conduct large‐sample‐size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders.

Inflammatory Biomarkers for Mood Disorders - A Brief Narrative Review.

The nervous system and the immune system interact consistently in the brain and peripheries. Inflammation in the brain not only alters the metabolism of neurotransmitters, but also causes network dysfunction, structural changes, and the development of mood symptomology in patients with mood disorders. In addition, the dysregulation of the neuroimmune axis in mood disorders drives multiple-system comorbidities. Furthermore, patients with low-grade inflammation are more likely to exhibit treatment resistance with both pharmacotherapy and non-pharmacotherapy. The aim of this review was to examine the available data regarding not only evidence of inflammation in the pathophysiology of mood disorders and their comorbid conditions, but also potential inflammatory biomarkers of mood disorders. Studies of the use of adjunct anti-inflammatory medications in mood disorders, and inflammatory biomarkers that may guide treatment outcomes in mood disorders, were summarized. Studies have demonstrated that certain adjunct anti-inflammatory medications might help to improve mood symptoms and reduce comorbidities, and the baseline levels of inflammatory biomarkers, such as peripheral C-reactive protein (CRP), could be used to stratify the treatment outcome. All results suggested that the identification of peripheral and brain inflammatory biomarkers for the diagnosis, outcome prediction, staging, and stratification of interventions of mood disorders has emerged as an important area of translational research in psychiatry. Inflammatory biomarkers could guide interventions and enhance treatment response in patients with mood disorders. The main challenge is that substantial complexities might hamper the attainment of this goal.

Trends in MD/PhD Graduates Entering Psychiatry: Assessing the Physician-Scientist Pipeline.

The goal of this study was to identify trends in MD/PhD graduates entering psychiatry, to compare these trends with other specialties, and to review strategies for enhancing the physician-scientist pipeline. Data on 226,588 medical students graduating from Liaison Committee on Medical Education accredited programs between 1999 and 2012 (6626 MD/PhDs) were used to evaluate the number, percentage, and proportion of MD/PhDs entering psychiatry in comparison with other specialties (neurology, neurosurgery, internal medicine, family medicine, and radiation oncology). Linear regression and multiple linear regression determined whether these values increased over time and varied by sex. Over 14years, an average of 18 MD/PhDs (range 13-29) enrolled in psychiatry each year. The number of MD/PhDs going into psychiatry significantly increased, although these gains were modest (less than one additional MD/PhD per year). The proportion of students entering psychiatry who were MD/PhDs varied between 2.9 and 5.9 per 100 residents, with no significant change over time. There was also no change in the percentage of MD/PhDs entering psychiatry from among all MD/PhD graduates. The rate of increase in the number of MD/PhDs going into psychiatry did not differ significantly from other specialties except for family medicine, which is decreasing. The rate of MD/PhDs going into psychiatry was higher for women, suggesting closure of the sex gap in 17years. Despite the increase in the number of MD/PhDs entering psychiatry, these numbers remain low. Expanding the cohort of physician-scientists dedicated to translational research in psychiatry will require a multipronged approach.

The Impact of Translational Neuroscience on Revisiting Psychiatric Diagnosis: State of the Art and Conceptual Analysis.

This paper reviews translational research in psychiatry, focusing on those programs addressing the problem of the validity of psychiatric diagnoses. In medicine in general, and in psychiatry in particular, the term “translational” is used with different meanings. A conceptual analysis suggests that there are at least seven different types of translational research in psychiatry: T1 (“bench-to-bedside” development of tools and treatments), T2 (application of animal models to human psychiatry), T3 (papers focusing on the mind-brain gap, studying biological, neurobiological and cognitive dysfunctions), T4 (personalised therapies and prediction of treatment responses), T5 (“bedside-to-bench” translation of population data for laboratories), T6 (implementation of treatments at the population level, including accessibility and quality of services), and T7 (improving translational knowledge in residents’ trainings and researchers’ careers).Concerning the problem of validity of psychiatric diagnoses, new neurocognitive models like the Research Domain Criteria project are considered, in particular the translational program of cross-validation aimed at reducing the gap between neuroimaging data and psychopathological scores derived from rating-scales. It is shown that these programs are useful, filling some of the current research gaps, but it is also stressed that they carry implicit realist and reductionist assumptions. It is finally suggested that the formation of mental symptoms is a complex process involving both neurocognitive and semantic factors, which raises doubts about the possibility of complete translations, without residuals.

Measuring alterations in oscillatory brain networks in schizophrenia with resting-state MEG: State-of-the-art and methodological challenges.

Neuroimaging studies provide evidence of disturbed resting-state brain networks in Schizophrenia (SZ). However, untangling the neuronal mechanisms that subserve these baseline alterations requires measurement of their electrophysiological underpinnings. This systematic review specifically investigates the contributions of resting-state Magnetoencephalography (MEG) in elucidating abnormal neural organization in SZ patients. A systematic literature review of resting-state MEG studies in SZ was conducted. This literature is discussed in relation to findings from resting-state fMRI and EEG, as well as to task-based MEG research in SZ population. Importantly, methodological limitations are considered and recommendations to overcome current limitations are proposed. Resting-state MEG literature in SZ points towards altered local and long-range oscillatory network dynamics in various frequency bands. Critical methodological challenges with respect to experiment design, and data collection and analysis need to be taken into consideration. Spontaneous MEG data show that local and global neural organization is altered in SZ patients. MEG is a highly promising tool to fill in knowledge gaps about the neurophysiology of SZ. However, to reach its fullest potential, basic methodological challenges need to be overcome. MEG-based resting-state power and connectivity findings could be great assets to clinical and translational research in psychiatry, and SZ in particular.

Can Interoception Improve the Pragmatic Search for Biomarkers in Psychiatry?

Disrupted interoception is a prominent feature of the diagnostic classification of several psychiatric disorders. However, progress in understanding the interoceptive basis of these disorders has been incremental, and the application of interoception in clinical treatment is currently limited to panic disorder. To examine the degree to which the scientific community has recognized interoception as a construct of interest, we identified and individually screened all articles published in the English language on interoception and associated root terms in Pubmed, Psychinfo, and ISI Web of Knowledge. This search revealed that interoception is a multifaceted process that is being increasingly studied within the fields of psychiatry, psychology, neuroscience, and biomedical science. To illustrate the multifaceted nature of interoception, we provide a focused review of one of the most commonly studied interoceptive channels, the cardiovascular system, and give a detailed comparison of the most popular methods used to study cardiac interoception. We subsequently review evidence of interoceptive dysfunction in panic disorder, depression, somatic symptom disorders, anorexia nervosa, and bulimia nervosa. For each disorder, we suggest how interoceptive predictions constructed by the brain may erroneously bias individuals to express key symptoms and behaviors, and outline questions that are suitable for the development of neuroscience-based mental health interventions. We conclude that interoception represents a viable avenue for clinical and translational research in psychiatry, with a well-established conceptual framework, a neural basis, measurable biomarkers, interdisciplinary appeal, and transdiagnostic targets for understanding and improving mental health outcomes.

Taking the long view: an emerging framework for translational psychiatric science.

Understood in their historical context, current debates about psychiatric classification, prompted by the publication of the DSM-5, open up new opportunities for improved translational research in psychiatry. In this paper, we draw lessons for translational research from three time slices of 20th century psychiatry. From the first time slice, 1913 and the publication of Jaspers' General Psychopathology, the lesson is that translational research in psychiatry requires a pluralistic approach encompassing equally the sciences of mind (including the social sciences) and of brain. From the second time slice, 1959 and a conference in New York from which our present symptom-based classifications are derived, the lesson is that, while reliability remains the basis of psychiatry as an observational science, validity too is essential to effective translation. From the third time slice, 1997 and a conference on psychiatric classification in Dallas that brought together patients and carers with researchers and clinicians, the lesson is that we need to build further on collaborative models of research combining expertise-by-training with expertise-by-experience. This is important if we are to meet the specific challenges to translation presented by the complexity of the concept of mental disorder, particularly as reflected in the diversity of desired treatment outcomes. Taken together, these three lessons - a pluralistic approach, reliability and validity, and closer collaboration among relevant stakeholders - provide an emerging framework for more effective translation of research into practice in 21st century psychiatry.

P3-7. Neurophysiological profile of acoustic startle response in Japanese children with autism spectrum disorders

The acoustic startle response (ASR) is considered the promising neurophysiological measurements for translational research in psychiatry. A numbers of individuals with autism spectrum disorders (ASD) exhibit enhanced auditory perception; however, ASR to weak stimuli remains unclear. Here, we evaluated the basic profile of ASR with weak and strong stimuli in Japanese children with ASD. The subjects were 10 Japanese children with ASD and 34 with typical development (TD). The electromyographic activity of the left orbicularis oculi muscle to pulse stimuli of 65–110 dB SPL, in increments of 5 dB, was measured to evaluate ASR. The electroencephalogram (EEG) was also recorded during the testing. Quantitative autistic traits were assessed by Social Responsive Scale (SRS). Magnitude of ASR to weak stimuli (70 dB) was greater in ASD individuals, and was associated with SRS social awareness subscale scores. The peak startle latency was prolonged in ASD individuals, and was associated with SRS social cognition and autistic mannerism subscales. The EEG current source density distribution was atypical in ASD compared to TD group. A comprehensive investigation of ASR, including the magnitude of startle responses to weak stimuli and peak startle latency, might enhance understanding of the atypical neurophysiological mechanisms underlying ASD.

Epigenetic Mechanisms in Psychiatry

Epigenetic Mechanisms in Psychiatry

Prepulse Inhibition of Startle Response: Recent Advances in Human Studies of Psychiatric Disease

Prepulse inhibition (PPI) is considered to be one of the most promising neurophysiological indexes for translational research in psychiatry. Impairment of PPI has been reported in several psychiatric diseases, particularly schizophrenia, where PPI is considered a candidate intermediate phenotype (endophenotype) of the disease. Recent findings from a variety of research areas have provided important evidence regarding PPI impairment. Human brain imaging studies have demonstrated the involvement of the striatum, hippocampus, thalamus and frontal and parietal cortical regions in PPI. In addition, several genetic polymorphisms, including variations in the genes coding for Catechol O-methyltransferase, Neuregulin 1, nuclear factor kappa-B subunit 3 and serotonin-2A receptor were related to PPI; and these findings support PPI as a polygenetic trait that involves several neurotransmitter pathways. Early psychosis studies suggest that PPI disruption is present before the onset of psychosis. Also, discrepancy of PPI impairment between children and adults can be found in other psychiatric diseases, such as autistic spectrum disorders and posttraumatic stress disorder, and comprehensive investigation of startle response might contribute to understand the impairment of the neural circuitry in psychiatric diseases. Finally, recent studies with both Asian and Caucasian subjects indicate that patients with schizophrenia exhibit impaired PPI, and impaired sensorimotor gating might be a global common psychophysiological feature of schizophrenia. In conclusion, studies of PPI have successfully contributed to a better understanding of the fundamental neural mechanisms underlying sensorimotor gating and will certainly be most valuable in devising future approaches that aim to investigate the complex pathogenesis of psychiatric diseases.

Translational research in psychiatry: new developments in Brazil

Translational research in psychiatry: new developments in Brazil