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Endophenotype

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https://read.qxmd.com/read/30892378/behavioral-affective-and-cognitive-alterations-induced-by-individual-and-combined-environmental-stressors-in-rats
#1
Francisco Diego Rabelo-da-Ponte, Jessica Maria Pessoa Gomes, Nathércia Lima Torres, João Ilo Coelho Barbosa, Geanne Matos de Andrade, Danielle Macedo, Bruno Ceppi
OBJECTIVE: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). METHODS: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds...
March 14, 2019: Revista Brasileira de Psiquiatria
https://read.qxmd.com/read/30874533/-the-role-of-family-studies-in-research-of-neurobiological-basis-of-depressive-disorders
#2
E D Kasyanov, G E Mazo, A O Kibitov
Depression belongs to a large class of multifactorial diseases and genetic factors play a significant role in its formation, development and clinical manifestations. The authors present an overview of current studies of recurrent depressive disorder (RDD), a heterogeneous group of disorders with phenotypically similar psychopathological symptoms. A study of families with a high risk for RDD using clinical and biological (including genetic) approaches can greatly help in understanding of the neurobiological basis of depressive disorders, as well as in the identification of endophenotypes of depression...
2019: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://read.qxmd.com/read/30873927/do-young-adolescents-with-first-episode-psychosis-or-adhd-show-sensorimotor-gating-deficits
#3
Jacob Rydkjaer, Jens Richardt Moellegaard Jepsen, Anne Katrine Pagsberg, Birgitte Fagerlund, Birte Yding Glenthoej, Bob Oranje
BACKGROUND: Early identification is important for patients with early-onset schizophrenia (SZ). Assessment of (candidate) endophenotypic markers for SZ, such as prepulse inhibition of the startle reflex (PPI), may help distinguish between the early-onset SZ and other psychiatric disorders. We explored whether PPI deficits usually seen in adult-onset SZ are present in young adolescents with either early-onset psychosis or attention deficit/hyperactivity disorder (ADHD). METHODS: Twenty-five adolescents with first-episode, non-affective psychosis (FEP), 28 adolescents with ADHD and 43 healthy controls (HC), aged 12-17 years, were assessed with an auditory PPI paradigm...
March 15, 2019: Psychological Medicine
https://read.qxmd.com/read/30865306/precision-medicine-for-the-discovery-of-treatable-mechanisms-in-severe-asthma
#4
REVIEW
Kian Fan Chung, Ian M Adcock
Although the complex disease of asthma has been defined as being heterogeneous, the extent of its endophenotypes remain unclear. The pharmacological approach to initiating treatment has, until recently, been based on disease control and severity. The introduction of antibody therapies targeting the Type2 inflammation pathway for patients with severe asthma has resulted in the recognition of an allergic and an eosinophilic phenotype, which are not mutually exclusive. Concomitantly, molecular phenotyping based on a transcriptomic analysis of bronchial epithelial and sputum cells has identified a Type-2-high inflammation cluster characterised by eosinophilia and recurrent exacerbations, as well as Type-2-low clusters linked with IL-6 trans-signalling, interferon pathways, inflammasome activation and mitochondrial oxidative phosphorylation pathways...
March 13, 2019: Allergy
https://read.qxmd.com/read/30864184/mapping-causal-pathways-from-genetics-to-neuropsychiatric-disorders-using-genome-wide-imaging-genetics-current-status-and-future-directions
#5
Brandon D Le, Jason L Stein
Imaging genetics aims to identify genetic variants associated with the structure and function of the human brain. Recently, collaborative consortia have been successful in this goal, identifying and replicating common genetic variants influencing gross human brain structure, as measured through MRI. In this review, we contextualize imaging genetic associations as one important link in understanding the causal chain from genetic variant to increased risk for neuropsychiatric disorders. We provide examples in other fields of how identifying genetic variant associations to disease and multiple phenotypes along the causal chain has revealed a mechanistic understanding of disease risk, with implications for how imaging genetics can be similarly applied...
March 13, 2019: Psychiatry and Clinical Neurosciences
https://read.qxmd.com/read/30863277/enhanced-global-brain-functional-connectivity-in-the-left-superior-frontal-gyrus-as-a-possible-endophenotype-for-schizophrenia
#6
Yudan Ding, Yangpan Ou, Qinji Su, Pan Pan, Xiaoxiao Shan, Jindong Chen, Feng Liu, Zhikun Zhang, Jingping Zhao, Wenbin Guo
The notion of dysconnectivity in schizophrenia has been put forward for many years and results in substantial attempts to explore altered functional connectivity (FC) within different networks with inconsistent results. Clinical, demographical, and methodological heterogeneity may contribute to the inconsistency. Forty-four patients with first-episode, drug-naive schizophrenia, 42 unaffected siblings of schizophrenia patients and 44 healthy controls took part in this study. Global-brain FC (GFC) was employed to analyze the imaging data...
2019: Frontiers in Neuroscience
https://read.qxmd.com/read/30859356/visual-disengagement-genetic-architecture-and-relation-to-autistic-traits-in-the-general-population
#7
Monica Siqueiros Sanchez, Erik Pettersson, Daniel P Kennedy, Sven Bölte, Paul Lichtenstein, Brian M D'Onofrio, Terje Falck-Ytter
Visual disengagement has been hypothesized as an endophenotype for autism. In this study we used twin modelling to assess the role of genetics in basic measures of visual disengagement, and tested their putative association to autistic traits in the general population. We used the Gap Overlap task in a sample of 492 twins. Results showed that most of the covariance among eye movement latencies across conditions was shared and primarily genetic. Further, there were unique genetic contributions to the Gap condition, but not to the Overlap condition-i...
March 11, 2019: Journal of Autism and Developmental Disorders
https://read.qxmd.com/read/30852411/excessive-discounting-of-delayed-reinforcers-as-a-trans-disease-process-update-on-the-state-of-the-science
#8
REVIEW
Warren K Bickel, Liqa N Athamneh, Julia C Basso, Alexandra M Mellis, William B DeHart, William H Craft, Derek Pope
Delay discounting, or the process by which reinforcers lose value with delay to their receipt, has been identified as a trans-disease process underlying addiction, other disorders, and maladaptive health behaviors. Delay discounting has been identified as an endophenotype for multiple psychiatric disorders including substance use disorder, ADHD, and major depressive disorder, with this endophenotype being linked to deficits in dopaminergic and serotonergic neurotransmission. In addition, neuroanatomical and neurophysiological deficits in areas of the executive and impulsive systems have been associated with both steeper discounting and substance use disorders...
February 6, 2019: Current Opinion in Psychology
https://read.qxmd.com/read/30839265/resting-state-electroencephalography-in-participants-with-sensory-overresponsiveness-an-exploratory-study
#9
Yelena Granovsky, Irit Weissman-Fogel, Tami Bar-Shalita
OBJECTIVE: People with sensory overresponsiveness (SOR) perceive nonpainful stimuli as noxious and demonstrate hyperalgesia and lingering sensation to laboratory pain stimuli. Electroencephalography (EEG) of cortical activity at rest is widely used to explore endophenotypes but has not yet been tested in people with SOR. Therefore, we investigated the characteristics of resting-state EEG in participants with SOR. METHOD: Resting-state EEG (5-min, eyes-closed recording) was compared in participants with (n = 9) and without (n = 12) SOR...
January 2019: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
https://read.qxmd.com/read/30838682/the-erring-brain-error-related-negativity-as-an-endophenotype-for-ocd-a-review-and-meta-analysis
#10
Anja Riesel
Obsessive-compulsive disorder (OCD) is a complex and heterogeneous disorder that is associated with high personal and societal costs. Feelings of doubt, worry, and repetitive behavior, key symptoms of OCD, have been linked to hyperactive error signals in the brain. The error-related negativity (ERN) represents a validated marker of error processing in the ERP. Increased ERN amplitudes in OCD have been reported very robustly over the last 20 years. This article integrates results from 38 studies analyzing the ERN in OCD, using a quantitative meta-analysis...
April 2019: Psychophysiology
https://read.qxmd.com/read/30819512/optogenetic-augmentation-of-the-hypercholinergic-endophenotype-in-dyt1-knock-in-mice-induced-erratic-hyperactive-movements-but-not-dystonia
#11
Franziska Richter, Anne Bauer, Stefanie Perl, Anja Schulz, Angelika Richter
BACKGROUND: The most prevalent inherited form of generalized dystonia is caused by a mutation in torsinA (DYT1, ∆GAG) with incomplete penetrance. Rodent models with mutated torsinA do not develop dystonic symptoms, but previous ex vivo studies indicated abnormal excitation of cholinergic interneurons (ChI) and increased striatal acetylcholine. METHODS: We used in vivo optogenetics to exacerbate this endophenotype in order to determine its capacity to trigger dystonic symptoms in freely behaving mice...
February 25, 2019: EBioMedicine
https://read.qxmd.com/read/30818145/cognitive-deficits-in-subjects-at-risk-for-psychosis-first-episode-and-chronic-schizophrenia-patients
#12
Yi Liu, Guodong Wang, Hua Jin, Hailong Lyu, Yong Liu, Wenbin Guo, Chuan Shi, Jordan Meyers, JiJun Wang, Jingping Zhao, Renrong Wu, Robert C Smith, John M Davis
BACKGROUND: Identifying the types and characteristics of cognitive deficits before the onset of schizophrenia and during its subsequent course could improve early detection and contribute to our understanding of the evolution of the core behavioral deficits underlying this disorder. METHODS: This study used the Measurement and Treatment Research to Improve Cognition In Schizophrenia (MATRICS) battery to identify cognitive deficits and their progression during the course of schizophrenia from genetic high risk (HRF) subjects, subjects with prodromal symptoms (prodromal), and patients with first episode (FSCZ) and multi-episode (CSCZ) schizophrenia, compared to controls, in a Chinese Han population of 267 subjects...
February 1, 2019: Psychiatry Research
https://read.qxmd.com/read/30807820/inhibiting-mglur5-activity-by-afq056-mavoglurant-rescues-circuit-specific-functional-connectivity-in-fmr1-knockout-mice
#13
Valerio Zerbi, Marija Markicevic, Fabrizio Gasparini, Aileen Schroeter, Markus Rudin, Nicole Wenderoth
Previous work has demonstrated that neuroimaging biomarkers which capture functional connectivity of the brain can be used to define a specific and robust endophenotype in Fmr1-/y mice, a well-established animal model of human Fragile-X Syndrome (FXS). However, it is currently unknown whether this macroscopic measure of brain connectivity is sufficiently sensitive to reliably detect changes caused by pharmacological interventions. Here we inhibited the activity of the metabotropic glutamate receptor-5 (mGluR5) using AFQ056/Mavoglurant, a drug that is assumed to normalize excitatory/inhibitory neural signaling imbalances in FXS...
February 23, 2019: NeuroImage
https://read.qxmd.com/read/30804328/genetic-risk-for-schizophrenia-and-developmental-delay-is-associated-with-shape-and-microstructure-of-midline-white-matter-structures
#14
Mark Drakesmith, Greg D Parker, Jacqueline Smith, Stefanie C Linden, Elliott Rees, Nigel Williams, Michael J Owen, Marianne van den Bree, Jeremy Hall, Derek K Jones, David E J Linden
Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia (Sz) and developmental delay (DD) that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter...
February 25, 2019: Translational Psychiatry
https://read.qxmd.com/read/30802869/differentiation-of-schizophrenia-by-combining-the-spatial-eeg-brain-network-patterns-of-rest-and-task-p300
#15
Fali Li, Jiu Ju Wang, Yuanyuan Liao, Chanlin Yi, Yuanling Jiang, Yajing Si, Wenjing Peng, Dezhong Yao, Yangsong Zhang, Wentian Dong, Peng Xu
The P300 is regarded as a psychosis endophenotype of schizophrenia and a putative biomarker of risk for schizophrenia. However, the brain activity (i.e., P300 amplitude) during tasks cannot always provide satisfying discrimination of patients with schizophrenia (SZs) from healthy controls (HCs). Spontaneous activity at rest indices the potential of the brain, such that if the task information can be efficiently processed, it provides a compensatory understanding of the cognitive deficits in SZs. In this study, based on the resting and P300 task electroencephalogram (EEG) data sets, we constructed functional EEG networks and then extracted the inherent Spatial Pattern of Network (SPN) features for both brain states...
February 22, 2019: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://read.qxmd.com/read/30793996/animal-models-of-major-depressive-disorder-and-the-implications-for-drug-discovery-and-development
#16
Konstantin A Demin, Maxim Sysoev, Maria V Chernysh, Anna K Savva, Mamiko Koshiba, Edina A Wappler-Guzzetta, Cai Song, Murilo S De Abreu, Brian Leonard, Matthew O Parker, Brian H Harvey, Li Tian, Eero Vasar, Tatyana Strekalova, Tamara G Amstislavskaya, Andrey D Volgin, Erik T Alpyshov, Dongmei Wang, Allan V Kalueff
Depression is a highly debilitating psychiatric disorder that affects the global population and causes severe disabilities and suicide. Depression pathogenesis remains poorly understood, and the disorder is often treatment-resistant and recurrent, necessitating the development of novel therapies, models and concepts in this field. Areas covered: Animal models are indispensable for translational biological psychiatry, and markedly advance the study of depression. Novel approaches continuously emerge that may help untangle the disorder heterogeneity and unclear categories of disease classification systems...
February 22, 2019: Expert Opinion on Drug Discovery
https://read.qxmd.com/read/30776455/refractory-diet-dependent-changes-in-neural-microstructure-implications-for-microstructural-endophenotypes-of-neurologic-and-psychiatric-disease
#17
Maribel Torres-Velázquez, Emily A Sawin, Jacqueline M Anderson, John-Paul J Yu
Alterations in gut microbiome populations via dietary manipulation have been shown to induce diet-dependent changes in white matter microstructure. The purpose of this study is to examine the durability of these diet-induced microstructural alterations. We implemented a crossover experimental design where post-weaned male rats were assigned to one of four experimental diets. Following the administration of experimental diets and again following crossover and resumption of a normal diet, brains were imaged ex-vivo with diffusion tensor imaging...
February 15, 2019: Magnetic Resonance Imaging
https://read.qxmd.com/read/30776391/bdnf-polymorphism-in-non-veridical-decision-making-and-differential-effects-of-rtms
#18
Jaan Tulviste, Elkhonon Goldberg, Kenneth Podell, Mariliis Vaht, Jaanus Harro, Talis Bachmann
Making decisions when an objectively correct option is not obvious, involves different neurobiological mechanisms than "veridical" decision making. The dorsolateral prefrontal cortex (DLPFC) exhibits a distinct pattern of prefrontal activation in non-veridical cognition, but little is known about the role of underlying neurobiological endophenotypes. A functional polymorphism in the brain-derived neurotrophic factor (BDNF) gene, causing a valine (Val) to methionine (Met) amino acid substitution at codon 66, has been shown to be associated with structural and functional changes in DLPFC and affect veridical decision making...
February 15, 2019: Behavioural Brain Research
https://read.qxmd.com/read/30770890/the-myeloarchitecture-of-impulsivity-premature-responding-in-youth-is-associated-with-decreased-myelination-of-ventral-putamen
#19
Camilla L Nord, Seung-Goo Kim, Mette Buhl Callesen, Timo L Kvamme, Mads Jensen, Mads Uffe Pedersen, Kristine Rømer Thomsen, Valerie Voon
Impulsivity has been suggested as a neurocognitive endophenotype conferring risk across a number of neuropsychiatric conditions, including substance and behavioural addictions, eating disorders, and attention deficit/hyperactivity disorder. We used a paradigm with interspecies translation validity (the four-choice serial reaction time task, 4CSRTT) to assess 'waiting' impulsivity in a youth sample (N = 99, aged 16-26 years). We collected magnetization prepared two rapid acquisition gradient echo (MP2RAGE) scans, which enabled us to measure R1, the longitudinal relaxation rate, a parameter closely related to tissue myelin content, as well as quantify grey matter volume...
February 15, 2019: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://read.qxmd.com/read/30767897/eeg-of-asymptomatic-first-degree-relatives-of-patients-with-juvenile-myoclonic-childhood-absence-and-rolandic-epilepsy-a-systematic-review-and-meta-analysis
#20
Mariam Tashkandi, Duaa Baarma, Andrea C Tricco, Cyrus Boelman, Reem Alkhater, Berge A Minassian
Rolandic (RE), childhood absence (CAE) and juvenile myoclonic (JME) epilepsy encompass centrotemporal sharp waves, 3-Hz spike waves and >3-Hz spike or polyspike waves, respectively. Evidence abounds for genetic roles in all three syndromes, yet involved genes for the vast majority of patients remain unknown. It has long been proposed that while each disease is genetically complex, its specific EEG trait may represent a genetically simpler endophenotype. This meta-analysis of the literature focuses on the frequency of EEG traits in clinically unaffected first-degree relatives towards determining inheritance patterns of the EEG endophenotypes...
February 15, 2019: Epileptic Disorders: International Epilepsy Journal with Videotape
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