Biomarkers in Neuropsychiatry最新文献

{"title":"Retinal structural alterations in chronic versus first episode schizophrenia spectrum disorders","authors":"Adriann Lai ,&nbsp;Christen Crosta ,&nbsp;Michael Loftin ,&nbsp;Steven M. Silverstein","doi":"10.1016/j.bionps.2020.100013","DOIUrl":"10.1016/j.bionps.2020.100013","url":null,"abstract":"<div><h3>Background</h3><p>Recent studies have found evidence of retinal thinning in schizophrenia spectrum disorder patients; however, it is not known whether retinal thinning is present at the first episode of psychosis or whether it is a result of the progression of the disease or related factors (e.g., emergence of medical comorbidities). We hypothesized that first episode patients (FEP) would not differ on any retinal variables when compared to age matched controls, while chronically ill patients would show evidence of retinal thinning compared to age matched controls.</p></div><div><h3>Methods</h3><p>15 first episode patients, 20 control subjects age-matched to the FEP group, 18 chronically ill patients, and 18 control subjects age-matched to the chronically ill group participated in Spectral Domain OCT scans. We collected data on retinal nerve fiber layer (RNFL) thickness, macula thickness and volume, and ganglion cell-inner plexiform layer (GCL-IPL) thickness as well as cup-to-disc ratio at the optic nerve head.</p></div><div><h3>Results</h3><p>No evidence of retinal structural change was found in the first episode group. In contrast, chronic schizophrenia and schizoaffective disorder patients were characterized by GCL-IPL thinning and overall macula thinning and volume reduction. No evidence of RNFL thinning was observed in the chronic group, however.</p></div><div><h3>Discussion</h3><p>These data suggest that retinal structure is unaffected very early in the course of schizophrenia spectrum disorders but that thinning is an aspect of illness progression, medical comorbidity, and/or long-term antipsychotic medication use in schizophrenia spectrum disorders. Among retinal indices, macula thickness and volume appear to be the most sensitive to the changes associated with illness chronicity.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"99895776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysiological biomarkers for schizophrenia therapeutics","authors":"Gregory A. Light ,&nbsp;Yash B. Joshi ,&nbsp;Juan L. Molina ,&nbsp;Savita G. Bhakta ,&nbsp;John A. Nungaray ,&nbsp;Lauren Cardoso ,&nbsp;Juliana E. Kotz ,&nbsp;Michael L. Thomas ,&nbsp;Neal R. Swerdlow","doi":"10.1016/j.bionps.2020.100012","DOIUrl":"10.1016/j.bionps.2020.100012","url":null,"abstract":"<div><p>Chronic psychotic disorders, including schizophrenia (SZ), are highly heterogeneous at many levels of analysis, from genetics to clinical presentation and treatment sensitivity. This heterogeneity reflects both a divergence of shared biological pathways moving from over a hundred “risk genes” to many different clinical phenotypes, and the convergence of distinct biological pathways to a shared “phenocopies” of chronic psychosis. Successful strategies for developing “next generation” interventions in SZ – including “pro-cognitive” medications, cognitive remediation, neurostimulation and combinations thereof – will address these pathways to clinical heterogeneity by using biological signals, or “biomarkers” that characterize treatment-sensitive subpopulations. Identifying and detecting these meaningful signals in the complex biology of SZ is a vexing scientific challenge. We propose that rational starting points are neurophysiological measures of early auditory information processing (EAIP), based on their functional importance as strong mediators of both cognition and function in SZ, their plasticity in response to both pharmacologic and non-pharmacologic therapeutic “challenge”, and their experimental characteristics as highly quantitative, robust and reliable measures of brain activity. Here we describe some of our current approaches to developing neurophysiological biomarkers for “next generation” therapeutic sensitivity in SZ, and some potentially novel experimental strategies that we envision on the near horizon.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43203477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational neurophysiological biomarkers of N-methyl-d-aspartate receptor dysfunction in serine racemase knockout mice","authors":"Andrea Balla ,&nbsp;Stephen D. Ginsberg ,&nbsp;Atheir I. Abbas ,&nbsp;Henry Sershen ,&nbsp;Daniel C. Javitt","doi":"10.1016/j.bionps.2020.100019","DOIUrl":"10.1016/j.bionps.2020.100019","url":null,"abstract":"<div><p>Alterations in glutamatergic function are well established in schizophrenia (Sz), but new treatment development is hampered by the lack of translational pathophysiological and target engagement biomarkers as well as by the lack of animal models that recapitulate the pathophysiological features of Sz. Here, we evaluated the rodent auditory steady state response (ASSR) and long-latency auditory event-related potential (aERP) as potential translational markers. These biomarkers were assessed for their sensitivity to both the N-methyl-<span>d</span>-aspartate receptor (NMDAR) antagonist phencyclidine (PCP) and to knock-out (KO) of Serine Racemase (SR), which is known to lead to Sz-like alterations in function of parvalbumin (PV)-type cortical interneurons. PCP led to significant increases of ASSR that were further increased in SRKO-/-, consistent with PV interneuron effects. Similar effects were observed in mice with selective NMDAR KO on PV interneurons. By contrast, PCP but not SRKO reduced the amplitude of the rodent analog of the human N1 potential. Overall, these findings support use of rodent ASSR and long-latency aERP, along with previously described measures such as mismatch negativity (MMN), as translational biomarkers, and support SRKO mice as a potential rodent model for PV interneuron dysfunction in Sz.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39225988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal stress responsiveness and suicidal behavior: A risk phenotype","authors":"Louisa J. Steinberg ,&nbsp;J. John Mann","doi":"10.1016/j.bionps.2020.100011","DOIUrl":"10.1016/j.bionps.2020.100011","url":null,"abstract":"<div><p>Suicidal behavior is a major cause of morbidity and mortality in psychiatric illness. However, only a subset of patients with psychiatric illnesses, such as major depressive disorder (MDD), commit suicide. This raises the question of how those who manifest suicidal behavior differ from those who do not. In the context of a stress-diathesis model of suicidal behavior, the reaction to stress has often been overlooked. The hypothalamic-pituitary-adrenal (HPA) axis dysfunction is proposed as an index of a disordered response to stress that thereby is part of the pathogenesis of risk for suicide in major depression. Suicide attempters are distinguished from non-attempters by a cluster of traits that include greater mood dysregulation and subjective distress, more pronounced reactive aggressive traits, impaired problem solving and learning, and distortion of perceived social cues. In this review, we show how these traits and risk for suicide are potentially linked to HPA axis dysfunction, which in turn can be traced back to genetic predisposition, and early life stress-related epigenetic mechanisms.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48634494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical abnormalities and identification for first-episode schizophrenia via high-resolution magnetic resonance imaging","authors":"Lin Liu, Long-Biao Cui, Xu-Sha Wu, N. Fei, Ziliang Xu, Di Wu, Yi-bin Xi, Peng Huang, K. V. von Deneen, S. Qi, Ya-Hong Zhang, Huaning Wang, H. Yin, W. Qin","doi":"10.1101/2020.02.05.20020768","DOIUrl":"https://doi.org/10.1101/2020.02.05.20020768","url":null,"abstract":"Evidence from neuroimaging has implicated abnormal cerebral cortical patterns in schizophrenia. Application of machine learning techniques is required for identifying structural signature reflecting neurobiological substrates of schizophrenia at the individual level. We aimed to detect and develop a method for potential marker to identify schizophrenia via the features of cerebral cortex using high-resolution magnetic resonance imaging (MRI).In this study, cortical features were measured, including volumetric (cortical thickness, surface area, and gray matter volume) and geometric (mean curvature, metric distortion, and sulcal depth) features. Patients with first-episode schizophrenia (n = 52) and healthy controls (n = 66) were included from the Department of Psychiatry at Xijing Hospital. Multivariate computation was used to examine the abnormalities of cortical features in schizophrenia. Features were selected by least absolute shrinkage and selection operator (LASSO) method. The diagnostic capacity of multi-dimensional neuroanatomical patterns-based classification was evaluated based on diagnostic tests.Mean curvature (left insula and left inferior frontal gyrus), cortical thickness (left fusiform gyrus), and metric distortion (left cuneus and right superior temporal gyrus) revealed both group differences and diagnostic capacity. Area under receiver operating characteristic curve was 0.88, and the sensitivity, specificity, and accuracy of were 94%, 82%, and 88%, respectively. Confirming these findings, similar results were observed in the independent validation. There was a positive association between index score derived from the multi-dimensional patterns and the severity of symptoms (r = 0.40, P < .01) for patients.Our findings demonstrate a view of cortical differences with capacity to discriminate between patients with schizophrenia and healthy population. Structural neuroimaging-based measurements hold great promise of paving the road for their clinical utility in schizophrenia.","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41639414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder","authors":"Anilkumar Pillai ,&nbsp;Davide Bruno ,&nbsp;Jay Nierenberg ,&nbsp;Chirayu Pandya ,&nbsp;Tami Feng ,&nbsp;Chelsea Reichert ,&nbsp;Jaime Ramos-Cejudo ,&nbsp;Ricardo Osorio ,&nbsp;Henrik Zetterberg ,&nbsp;Kaj Blennow ,&nbsp;Nunzio Pomara","doi":"10.1016/j.bionps.2019.100007","DOIUrl":"10.1016/j.bionps.2019.100007","url":null,"abstract":"<div><p>Late-life major depression (LLMD) is a risk factor for the development of mild cognitive impairment and dementia, including Alzheimer’s disease (AD) and vascular dementia. Immune dysregulation and changes in innate immune responses in particular, have been implicated in the pathophysiology of both LLMD and AD. Complement system, a key component of the innate immune mechanism, is known to play an important role in synaptic plasticity and cognitive functions. However, its role in LLMD remains unknown. In the present study, we examined the levels of complement component 3 (C3, the convergence point of all complement activation pathways) in the cerebrospinal fluid (CSF) of elderly depressed subjects compared to healthy controls; as well as the relationship of CSF C3 levels with amyloid-beta (Aβ42 and Aβ40), total tau (T-tau) and phosphorylated tau (P-tau) proteins and cognition scores. CSF was obtained from 50 cognitively intact volunteers (major depression group, N = 30; comparison group, N = 20) and analyzed for levels of C3 by ELISA. C3 levels were marginally lower in the major depression group relative to the comparison group. We did not find any significant association of C3 with the AD biomarkers Aβ42 reflecting plaque pathology, P-tau related to tau pathology or the neurodegeneration biomarker T-tau. In contrast, C3 was positively correlated with CSF Aβ40, which may reflect Aβ deposition in cerebral vessel walls. We observed a negative correlation between C3 levels and Total Recall on the Buschke Selective Reminding Test (BSRT) for memory performance in the depressed subjects when controlling for education. This initial evidence on C3 status in LLMD subjects may have implications for our understanding of the pathophysiology of major depression especially in late life.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2019.100007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37548255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory biomarkers in schizophrenia: Implications for heterogeneity and neurobiology","authors":"Brian J. Miller ,&nbsp;David R. Goldsmith","doi":"10.1016/j.bionps.2019.100006","DOIUrl":"https://doi.org/10.1016/j.bionps.2019.100006","url":null,"abstract":"<div><p>The longstanding investigation of immune system abnormalities, including inflammation, in schizophrenia has tremendous renewed interest as an area of research. Presently, the field has an unparalleled opportunity to investigate inflammation as a potential biomarker in schizophrenia. In this review, we: 1) summarize evidence for inflammatory biomarkers across the course of illness, 2) discuss relationships between inflammatory markers and psychopathology, cognition, and illness relapse, 3) consider inflammation as a biomarker for metabolic comorbidity, 4) discuss neuroinflammatory imaging biomarkers, 5) consider inflammation as a biomarker of response to treatment in schizophrenia, as well as findings on adjunctive anti-inflammatory treatments in schizophrenia, and 6) review potential mechanisms for the effects of inflammation on the brain, and 7) discuss implications for the future research agenda. Although there is not evidence to support widespread clinical use of inflammation as a biomarker in schizophrenia, future studies in this area show promise towards a greater understanding of the etiopathophysiology of this heterogeneous syndrome, towards new potential diagnostics and therapeutics to reduce risk, alleviate symptoms and improve quality of life in both at-risk and established patient populations.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2019.100006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137411571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers in neuropsychiatric disorders: Translating research to clinical applications","authors":"Henry A. Nasrallah","doi":"10.1016/j.bionps.2019.100001","DOIUrl":"10.1016/j.bionps.2019.100001","url":null,"abstract":"","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2019.100001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"111892089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic neural activity differences in psychosis biotypes: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium","authors":"Olivia Thomas ,&nbsp;David Parker ,&nbsp;Rebekah Trotti ,&nbsp;Jennifer McDowell ,&nbsp;Elliot Gershon ,&nbsp;John Sweeney ,&nbsp;Matcheri S. Keshavan ,&nbsp;Sarah K. Keedy ,&nbsp;Elena Ivleva ,&nbsp;Carol A. Tamminga ,&nbsp;Godfrey D. Pearlson ,&nbsp;Brett A. Clementz","doi":"10.1016/j.bionps.2019.100002","DOIUrl":"10.1016/j.bionps.2019.100002","url":null,"abstract":"<div><h3>Intro</h3><p>The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) proposed “Biotypes,” subgroups of psychosis cases with neuro-cognitive homology. Neural activity unbound to stimulus processing (nonspecific or intrinsic activity) was important for differentiating Biotypes, with Biotype-2 characterized by high nonspecific neural activity. A precise estimate of intrinsic activity (IA) was not included in the initial Biotypes characterization. This report hypothesizes intrinsic activity is a critical differentiating feature for psychosis Biotypes.</p></div><div><h3>Method</h3><p>Participants were recruited at B-SNIP sites and included probands with psychosis (schizophrenia, schizoaffective disorder, bipolar I disorder), their first-degree biological relatives, and healthy persons (N = 1338). Probands were also sub-grouped by psychosis Biotype. 10-sec inter-stimulus intervals during an auditory paired-stimuli task were used to quantify intrinsic activity from 64 EEG sensors. Single-trial power and connectivity measures at empirically derived frequency bands were quantified. Multivariate discriminant and correlational analyses were used to summarize variables that efficiently and maximally differentiated groups by conventional diagnoses and Biotypes and to determine their relationship to clinical and social functioning.</p></div><div><h3>Results</h3><p>Biotype-1 consistently exhibited low IA, and Biotype 2 exhibited high IA relative to healthy persons across power frequency bands (delta/theta, alpha, beta, gamma) and alpha band connectivity estimates. DSM groups did not differ from healthy persons on any IA measure.</p></div><div><h3>Discussion</h3><p>Psychosis Biotypes, but not DSM syndromes, were differentiated by intrinsic activity; Biotype-2 was uniquely characterized by an accentuation of this measure. Neurobiologically defined psychosis subgroups may facilitate the use of intrinsic activity in translation models aimed at developing effective treatments for psychosis-relevant deviations in neural modulation.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2019.100002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10532455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: More research needed on predictive biomarkers related to clozapine treatment","authors":"Jonathan M. Meyer","doi":"10.1016/j.bionps.2019.100003","DOIUrl":"10.1016/j.bionps.2019.100003","url":null,"abstract":"","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2019.100003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"101104283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}