56 results match your criteria: "Johns Hopkins University Medical Campus[Affiliation]"
J Neurochem
January 2025
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA.
Preclinical behavioral testing is essential for drug discovery in neuropsychiatric disorders, yet translational challenges persist because of interspecies differences. Touchscreen-based behavioral tasks offer a promising solution for bridging this gap. These tasks provide flexibility across cognitive domains and species, facilitating rigorous comparisons.
View Article and Find Full Text PDFPediatr Res
July 2024
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Behav Processes
October 2023
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:
Attention is a cognitive domain often disrupted in neuropsychiatric disorders and continuous performance tests (CPTs) are common clinical assays of attention. In CPTs, participants produce a behavioral response to target stimuli and refrain from responding to non-target stimuli. Performance in CPTs is measured as the ability to discriminate between targets and non-targets.
View Article and Find Full Text PDFBr J Pharmacol
October 2023
Genetics of Cognition Laboratory, Neuroscience Area, Istituto Italiano di Tecnologia, Genoa, Italy.
Background And Purpose: Cognitive and motor functions are modulated by dopaminergic signalling, which is shaped by several genetic factors. The biological effects of single genetic variants might differ depending on epistatic interactions that can be functionally multi-directional and non-linear.
Experimental Approach: We performed behavioural and neurochemical assessments in genetically modified mice and behavioural assessments and genetic screening in human patients with 22q11.
Nat Commun
May 2023
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits.
View Article and Find Full Text PDFActa Neuropathol
April 2023
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.
Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs.
View Article and Find Full Text PDFNeuropsychopharmacology
September 2021
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets.
View Article and Find Full Text PDFBiol Psychiatry
September 2021
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
Background: Recent breakthroughs in psychiatric genetics have implicated biological pathways onto which genetic risk for psychiatric disorders converges. However, these studies do not reveal the developmental time point(s) at which these pathways are relevant.
Methods: We aimed to determine the relationship between psychiatric risk and developmental gene expression relating to discrete biological pathways.
Neurosci Lett
January 2021
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA; Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA. Electronic address:
Social isolation is a growing public health concern across the lifespan. Specifically, isolation early in life, during critical periods of brain development, increases the risk of psychiatric disorders later in life. Previous studies of isolation models in mice have shown distinct neurological abnormalities in various regions of the brain, but the mechanism linking the experience of isolation to these phenotypes is unclear.
View Article and Find Full Text PDFFront Behav Neurosci
May 2020
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, United States.
Effort-related choice (ERC) tasks allow animals to choose between high-value reinforcers that require high effort to obtain and low-value/low-effort reinforcers. Dopaminergic neuromodulation regulates ERC behavior. The enzyme catechol--methyltransferase (COMT) metabolizes synaptically-released dopamine.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2020
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Rationale: Cognitive impairment is a primary feature of many neuropsychiatric disorders and there is a need for new therapeutic options. Catechol-O-methyltransferase (COMT) inhibitors modulate cortical dopaminergic function and have been proposed as potential cognitive enhancers. Unfortunately, currently available COMT inhibitors are not good candidates due to either poor blood-brain barrier penetration or severe toxicity.
View Article and Find Full Text PDFTransl Psychiatry
May 2020
The Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Beyond being one the most widely used psychoactive drugs in the world, cannabis has been identified as an environmental risk factor for psychosis. Though the relationship between cannabis use and psychiatric disorders remains controversial, consistent association between early adolescent cannabis use and the subsequent risk of psychosis suggested adolescence may be a particularly vulnerable period. Previous findings on gene by environment interactions indicated that cannabis use may only increase the risk for psychosis in the subjects who have a specific genetic vulnerability.
View Article and Find Full Text PDFAm J Hum Genet
August 2019
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY 11004, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. Electronic address:
Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results.
View Article and Find Full Text PDFTransl Psychiatry
June 2019
Dartmouth College, Hanover, NH, 03755, USA.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFTransl Psychiatry
May 2019
Dartmouth College, Hanover, NH, 03755, USA.
Little is known about the molecular pathogenesis of schizophrenia, possibly because of unrecognized heterogeneity in diagnosed patient populations. We analyzed gene expression data collected from the dorsolateral prefrontal cortex (DLPFC) of post-mortem frozen brains of 189 adult diagnosed schizophrenics and 206 matched controls. Transcripts from 633 genes are differentially expressed in the DLPFC of schizophrenics as compared to controls at Bonferroni-corrected significance levels.
View Article and Find Full Text PDFNat Commun
May 2019
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
View Article and Find Full Text PDFNat Commun
August 2018
Department of Neuroscience and Brain Technologies, Genetics of Cognition laboratory, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genova, Italy.
In the original version of this Article, references in the Methods section incorrectly referred to references in the Supplementary References section. The relevant references (now numbered 20, 27, 42, 47, 69-80) have been removed from the Supplementary References section of the Supplementary Information file and added to the References section of the main manuscript, in both the PDF and HTML versions of the Article.
View Article and Find Full Text PDFTwin Res Hum Genet
October 2018
Division of Psychiatry Research, Zucker Hillside Hospital,Glen Oaks,NY,USA.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol.
View Article and Find Full Text PDFNat Genet
July 2018
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis.
View Article and Find Full Text PDFNat Commun
June 2018
Department of Neuroscience and Brain Technologies, Genetics of Cognition laboratory, Istituto Italiano di Tecnologia, via Morego, 30, 16163, Genova, Italy.
Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive.
View Article and Find Full Text PDFNat Commun
May 2018
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure.
View Article and Find Full Text PDFCell Rep
November 2017
Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA. Electronic address:
Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype.
View Article and Find Full Text PDFScience
November 2017
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.