Nikolaos P. Daskalakis
A5084393367- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Birth, Development, and Health
- Health, Environment, Cognitive Aging
- Neuroendocrine regulation and behavior
- Epigenetics and DNA Methylation
- Posttraumatic Stress Disorder Research
- Resilience and Mental Health
- Anesthesia and Neurotoxicity Research
- Genetic Associations and Epidemiology
- Migration, Health and Trauma
- Genetics and Neurodevelopmental Disorders
- Traumatic Brain Injury Research
- Hormonal Regulation and Hypertension
- Adipose Tissue and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Child and Adolescent Psychosocial and Emotional Development
- Maternal Mental Health During Pregnancy and Postpartum
- Bioinformatics and Genomic Networks
- Memory and Neural Mechanisms
- Childhood Cancer Survivors' Quality of Life
- Suicide and Self-Harm Studies
- Functional Brain Connectivity Studies
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
McLean Hospital
2017-2025
Harvard University
2017-2025
Broad Institute
2019-2025
European Graduate School of Neuroscience
2025
Maastricht University
2025
Cohen Veterans Bioscience
2018-2024
Stanley Center for Psychiatric Research
2023-2024
Boston University
2024
National Center for PTSD
2023
Faculdade de Medicina de Jundiaí
2023
Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring Holocaust survivors both glucocorticoid receptor sensitivity vulnerability to psychiatric disorder. The authors examined the relative influences PTSD on DNA methylation exon 1F promoter (GR-1F) gene (NR3C1) peripheral blood mononuclear cells its relationship offspring.Adult with at least one survivor parent (N=80) demographically similar participants without parental...
Epigenetic alterations offer promise as prognostic or diagnostic markers, but it is not known whether these measures associate with, predict, clinical state. These questions were addressed in a pilot study with combat veterans PTSD to determine cytosine methylation promoter regions of the glucocorticoid related NR3C1 and FKBP51 genes would predict treatment outcome. Veterans received prolonged exposure (PE) psychotherapy, yielding responders (n=8), defined by no longer meeting criteria for...
The complexity and heterogeneity of schizophrenia have hindered mechanistic elucidation the development more effective therapies. Here, we performed single-cell dissection schizophrenia-associated transcriptomic changes in human prefrontal cortex across 140 individuals two independent cohorts. Excitatory neurons were most affected cell group, with transcriptional converging on neurodevelopment synapse-related molecular pathways. Transcriptional alterations included known genetic risk...
Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays primary human cells from mid-gestation cortex cerebral organoids, we interrogated the cis-regulatory activity 102,767 open chromatin regions, including thousands sequences with cell type-specific accessibility variants associated brain regulation. In cells, identified 46,802 active enhancer 164 that alter activity. Activity was comparable...
The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study posttraumatic stress disorder (PTSD) and major depressive (MDD) included the central nucleus amygdala, hippocampal dentate gyrus, medial prefrontal cortex (mPFC). Genes exons within mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal synaptic regulation, hormones. Multiomic factor gene network analyses provided...
The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data...
Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment regulatory elements in the developing brain. However, prioritizing risk genes mechanisms is challenging without a unified atlas. Across 672 diverse human brains, we identified 15,752 harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely...
Mutations in the synaptic gene SHANK3 lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is relatively common monogenic and highly penetrant cause of autism spectrum (ASD) intellectual disability (ID), frequently presents with attention deficits. The underlying neurobiology not fully pharmacological treatments for core symptoms do exist. Here, we report production characterization Shank3-deficient rat model PMS, genetic alteration similar human mutation. We...
In order to determine the impact of epigenetic response traumatic stress on post-traumatic disorder (PTSD), this study examined longitudinal changes genome-wide blood DNA methylation profiles in relation development PTSD symptoms two prospective military cohorts (one discovery and one replication data set). first cohort consisting male Dutch servicemen (n=93), emergence over a deployment period combat zone was significantly associated with alterations levels at 17 genomic positions 12...
Delineating the molecular basis of individual differences in stress response is critical to understanding pathophysiology and treatment posttraumatic disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male female rats were classified into vulnerable (i.e., "PTSD-like") resilient minimally affected) phenotypes on their performance a variety behavioral measures. Genome-wide expression profiling blood two limbic brain regions (amygdala hippocampus), followed by...