ArticlePsychopharmacology2015
Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Effect of amphetamines on blood pressure.The Cochrane database of systematic reviews · 2025Pooled it
- Psychostimulant-induced aberrant DNA methylation in an in vitro model of human peripheral blood mononuclear cells.Clinical epigenetics · 2022Article
- Dysmorphic contribution of neurotransmitter and neuroendocrine system polymorphisms to subtherapeutic mood states.Brain and behavior · 2019Article
- Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial.Alcohol and alcoholism (Oxford, Oxfordshire) · 2019Article
- Interplay Between Amphetamine and Activity Level in Gene Networks of the Mouse Striatum.Bioinformatics and biology insights · 2018Article
- Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.Journal of psychopharmacology (Oxford, England) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleResearchers studying behavioral and physiologic effects of d-amphetamine have explored individual response differences to the drug. Concurrently, genome-wide analyses have identified several single-nucleotide polymorphisms (SNPs) associated with these traits. Univariate methods can identify SNPs associated with behavioral and physiological traits, but multivariate analyses allow identification of clusters of related biologically relevant SNPs and behavioral components.
objectivesThe aim of the study was to identify clusters of related biologically relevant SNPs and behavioral components in the responses of healthy individuals to d-amphetamine using multivariate analysis.
methodsIndividuals (N = 375) without substance abuse histories completed surveys and detailed cardiovascular monitoring during randomized, blinded sessions: d-amphetamine (10 and 20 mg) and placebo. We applied parallel independent component analysis (Para-ICA) to data previously analyzed with univariate approaches, revealing new associations between genes and behavioral responses to d-amphetamine.
resultsThree significantly associated (p < .001) phenotype-genotype pairs emerged. The first component included physiologic measures of systolic and diastolic blood pressure (BP) and mean arterial pressure (MAP) along with SNPs in calcium and glutamatergic signaling pathways. The second associated components included the "Anger" items from the Profile of Mood States (POMS) questionnaire and the marijuana effects from the Addiction Research Center Inventory (Cuyas, Verdejo-Garcia et al.), with enriched genetic pathways involved in cardiomyopathy and MAPK signaling. The final pair included "Anxious," "Fatigue," and "Confusion" items from the POMS questionnaire, plus functional pathways related to cardiac muscle contraction and cardiomyopathy.
conclusionsMultifactorial genetic networks related to calcium signaling, glutamatergic and dopaminergic synapse function, and amphetamine addiction appear to mediate common behavioral and cardiovascular responses to d-amphetamine.
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