National Institute of Mental Health

Ets2 Is an Activity‐Dependent Transcriptional Regulator of a Fast‐Twitch Muscle Program

The functional properties of excitable cells, including skeletal muscle, are regulated by electrical activity. Distinct motoneuron firing patterns control contraction speed, strength, and endurance of fast- and slow-twitch myofibers by activating transcriptional programs that spe...

Single-nucleus atlas of cell-type specific genetic regulation in the human brain

Abstract Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of th...

Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer’s disease

Alzheimer’s disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on populatio...

AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data

The complexity of Alzheimer’s disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-n...

Single-nucleus transcriptome-wide association study of human brain disorders

Abstract Common brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging 1 . Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many...

Lifespan single-cell transcriptomic atlas of the human prefrontal cortex

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease1,2. Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal...

Single-cell atlas of transcriptomic vulnerability across brain disorders

Abstract Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited 1,2 . Here, to gain deeper insights into the aetiolo...

Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper

Abstract Psychiatric drug development remains constrained by diagnostic heterogeneity, insufficient and inconsistent drug response, high placebo response rates, and the absence of validated biomarkers that can reliably guide patient stratification, trial design, and regulatory de...

Appraising familial prediction of proband outcomes in neurogenetic disorders

Abstract Background Gene dosage disorders impact cognition and psychopathology, but outcomes vary widely amongst carriers of the same variant. Recent work has sought to better predict proband outcomes using measures of corresponding traits in family members. However, family-based...

Artificial Intelligence Across the PET Reconstruction Pipeline: An Update

PET reconstruction has evolved from analytic and iterative physics-based methods toward hybrid approaches that increasingly incorporate artificial intelligence (AI). As digital detectors, long-axial FOV systems, and time-of-flight technology increase data richness and computation...

Opportunities and challenges of generative AI in the research lifecycle

Artificial intelligence (AI) is increasingly being explored and adopted across the research lifecycle, from idea generation and literature discovery to data analysis, manuscript preparation, and editorial and peer-review processes. This perspective provides an overview of AI’s ro...

Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling, often irreversible toxicity that affects millions of patients, limits life-saving cancer therapy, and lacks proven treatment. In this work, we show that as little as two doses of psilocybin before chemotherapy dura...

Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness

Abstract Many bipolar disorder (BD) patients are non-responsive to lithium. The mechanisms underlying lithium (non-)responsiveness are largely unknown. By using gene-set enrichment analysis methods, we found that core clock gene-sets are significantly associated with lithium resp...

Altered thalamo–prefrontal synchrony dynamics during spatial working memory task performance in a SETD1A loss-of-function mouse model of schizophrenia predisposition

ABSTRACT Schizophrenia is associated with profound working memory deficits, for which there are no approved treatments. Rare heterozygous null mutations in SETD1A , a gene encoding a key epigenetic regulatory protein, have been definitively linked to increased risk for schizophre...