Skip to main content

Advertisement

SpringerLink
Log in

Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Researchers 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.

Objectives

The 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.

Methods

Individuals (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.

Results

Three 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.

Conclusions

Multifactorial 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Alibakhshi R, Moradi K, Mohebbi Z, Ghadiri K (2013) Mutation analysis of PAH gene in patients with PKU in western Iran and its association with polymorphisms: identification of four novel mutations. Metab Brain Dis 29:131-138

  • Billings SE, Pierzchalski K, Butler Tjaden NE, Pang XY, Trainor PA, Kane MA, Moise AR (2013) The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development. FASEB J 27(12):4877–4889

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bramness JG, Gundersen OH, Guterstam J, Rognli EB, Konstenius M, Loberg EM, Medhus S, Tanum L, Franck J (2012) Amphetamine-induced psychosis–a separate diagnostic entity or primary psychosis triggered in the vulnerable? BMC Psychiatr 12:221

    Article  Google Scholar 

  • Calhoun VD, Adali T, Pearlson GD, Pekar JJ (2001) A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp 14(3):140–151

    Article  CAS  PubMed  Google Scholar 

  • Calhoun VD, Liu J, Adali T (2009) A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data. Neuroimage 45(1 Suppl):S163–S172

    Article  PubMed Central  PubMed  Google Scholar 

  • Chait LD, Uhlenhuth EH, Johanson CE (1985) The discriminative stimulus and subjective effects of d-amphetamine in humans. Psychopharmacology (Berl) 86(3):307–312

    Article  CAS  Google Scholar 

  • Chen JC, Chen PC, Chiang YC (2009) Molecular mechanisms of psychostimulant addiction. Chang Gung Med J 32(2):148–154

    PubMed  Google Scholar 

  • Cherner M, Bousman C, Everall I, Barron D, Letendre S, Vaida F, Atkinson JH, Heaton R, Grant I, Group H (2010) Cytochrome P450-2D6 extensive metabolizers are more vulnerable to methamphetamine-associated neurocognitive impairment: preliminary findings. J Int Neuropsychol Soc 16(5):890–901

    Article  PubMed Central  PubMed  Google Scholar 

  • Choi DS, Wang D, Dadgar J, Chang WS, Messing RO (2002) Conditional rescue of protein kinase C epsilon regulates ethanol preference and hypnotic sensitivity in adult mice. J Neurosci 22(22):9905–9911

    CAS  PubMed  Google Scholar 

  • Conrod PJ, Peterson JB, Pihl RO (2001) Reliability and validity of alcohol-induced heart rate increase as a measure of sensitivity to the stimulant properties of alcohol. Psychopharmacology (Berl) 157(1):20–30

    Article  CAS  Google Scholar 

  • Crabbe JC, Jarvik LF, Liston EH, Jenden DJ (1983) Behavioral responses to amphetamines in identical twins. Acta Genet Med Gemellol (Roma) 32(2):139–149

    CAS  Google Scholar 

  • Cruickshank CC, Dyer KR (2009) A review of the clinical pharmacology of methamphetamine. Addiction 104(7):1085–1099

    Article  PubMed  Google Scholar 

  • Cuyas E, Verdejo-Garcia A, Fagundo AB, Khymenets O, Rodriguez J, Cuenca A, de Sola Llopis S, Langohr K, Pena-Casanova J, Torrens M, Martin-Santos R, Farre M, de la Torre R (2011) The influence of genetic and environmental factors among MDMA users in cognitive performance. PLoS One 6(11):e27206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • de Wit H, Phillips TJ (2012) Do initial responses to drugs predict future use or abuse? Neurosci Biobehav Rev 36(6):1565–1576

    Article  PubMed Central  PubMed  Google Scholar 

  • Deng PY, Xiao Z, Yang C, Rojanathammanee L, Grisanti L, Watt J, Geiger JD, Liu R, Porter JE, Lei S (2009) GABA(B) receptor activation inhibits neuronal excitability and spatial learning in the entorhinal cortex by activating TREK-2 K+ channels. Neuron 63(2):230–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Derogatis LR (1977) SCL-90-R (Revised) Version Manual: I. Johns Hopkins University School of Medicine

  • Di Battista ME, Pascale E, Purcaro C, Passarelli F, Passarelli E, Guglielmi R, Vanacore N, Meco G (2013) Clinical subtypes in Parkinson's disease: the impact of MAPT haplotypes. J Neural Transm 121:353-356

  • Dick DM, Edenberg HJ, Xuei X, Goate A, Kuperman S, Schuckit M, Crowe R, Smith TL, Porjesz B, Begleiter H, Foroud T (2004) Association of GABRG3 with alcohol dependence. Alcohol Clin Exp Res 28(1):4–9

    Article  CAS  PubMed  Google Scholar 

  • Edenberg HJ, Foroud T (2006) The genetics of alcoholism: identifying specific genes through family studies. Addict Biol 11(3–4):386–396

    Article  PubMed  Google Scholar 

  • Edwards AC, Aliev F, Bierut LJ, Bucholz KK, Edenberg H, Hesselbrock V, Kramer J, Kuperman S, Nurnberger JI Jr, Schuckit MA, Porjesz B, Dick DM (2012) Genome-wide association study of comorbid depressive syndrome and alcohol dependence. Psychiatr Genet 22(1):31–41

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eker HK, Derinkuyu BE, Unal S, Masliah-Planchon J, Drunat S, Verloes A (2013) Cerebro-fronto-facial syndrome type 3 with polymicrogyria: A clinical presentation of Baraitser-Winter syndrome. Eur J Med Genet 57:32-36

  • Elhayek D, Perez de Nanclares G, Chouchane S, Hamami S, Mlika A, Troudi M, Leban N, Ben Romdane W, Gueddiche MN, El Amri F, Mrabet S, Ben Chibani J, Castano L, Haj Khelil A, Ariceta G (2013) Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes. BMC Med Genet 14(1):119

    Article  PubMed Central  PubMed  Google Scholar 

  • Engelhardt BE, Stephens M (2010) Analysis of population structure: a unifying framework and novel methods based on sparse factor analysis. PLoS Genet 6(9):e1001117

    Article  PubMed Central  PubMed  Google Scholar 

  • Eun LY, Song BW, Cha MJ, Song H, Kim IK, Choi E, Chang W, Lim S, Choi EJ, Ham O, Lee SY, Byun KH, Jang Y, Hwang KC (2010) Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium. Biochem Biophys Res Commun 402(2):272–279

    Article  CAS  PubMed  Google Scholar 

  • Fan J, Fossella J, Sommer T, Wu Y, Posner MI (2003) Mapping the genetic variation of executive attention onto brain activity. Proc Natl Acad Sci U S A 100(12):7406–7411

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferreira-Junior NC, Fedoce AG, Alves FH, Resstel LB (2013) Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses. J Neurosci Res 91(10):1338–1348

    Article  CAS  PubMed  Google Scholar 

  • First MBS, RL, Gibbon M, Williams, Janet BW (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP). Biometrics Research. New York State Psychiatric Institute New York

  • Flynn KM, Michaud M, Madri JA (2013) CD44 deficiency contributes to enhanced experimental autoimmune encephalomyelitis: a role in immune cells and vascular cells of the blood-brain barrier. Am J Pathol 182(4):1322–1336

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Freedman R (2013) alpha7-nicotinic acetylcholine receptor agonists for cognitive enhancement in schizophrenia. Annu Rev Med 65:245-261

  • Gelernter J, Sherva R, Koesterer R, Almasy L, Zhao H, Kranzler HR, Farrer L (2013) Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. Mol Psychiatry 19:717-723

  • Gotrick B, Giglio D, Tobin G (2009) Effects of amphetamine on salivary secretion. Eur J Oral Sci 117(3):218–223

    Article  PubMed  Google Scholar 

  • Greene SL, Kerr F, Braitberg G (2008) Review article: amphetamines and related drugs of abuse. Emerg Med Australas 20(5):391–402

    Article  PubMed  Google Scholar 

  • Hainsworth AH, Allsopp RC, Jim A, Potter JF, Lowe J, Talbot CJ, Prettyman RJ (2010) Death-associated protein kinase (DAPK1) in cerebral cortex of late-onset Alzheimer's disease patients and aged controls. Neuropathol Appl Neurobiol 36(1):17–24

    Article  CAS  PubMed  Google Scholar 

  • Hamidovic A, Dlugos A, Palmer AA, de Wit H (2010) Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine. Psychiatr Genet 20(3):85–92

    PubMed Central  PubMed  Google Scholar 

  • Hariri AR, Weinberger DR (2003) Imaging genomics. Br Med Bull 65:259–270

    Article  CAS  PubMed  Google Scholar 

  • Hart AB, de Wit H, Palmer AA (2013) Candidate gene studies of a promising intermediate phenotype: failure to replicate. Neuropsychopharmacology 38(5):802–816

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hart AB, Engelhardt BE, Wardle MC, Sokoloff G, Stephens M, de Wit H, Palmer AA (2012) Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). PLoS One 7(8):e42646

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Herrmann MJ, Walter A, Schreppel T, Ehlis AC, Pauli P, Lesch KP, Fallgatter AJ (2007) D4 receptor gene variation modulates activation of prefrontal cortex during working memory. Eur J Neurosci 26(10):2713–2718

    Article  CAS  PubMed  Google Scholar 

  • Hildreth CM, Goodchild AK (2010) Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat. BMC Neurosci 11:128

    Article  PubMed Central  PubMed  Google Scholar 

  • Hodgkinson CA, Enoch MA, Srivastava V, Cummins-Oman JS, Ferrier C, Iarikova P, Sankararaman S, Yamini G, Yuan Q, Zhou Z, Albaugh B, White KV, Shen PH, Goldman D (2010) Genome-wide association identifies candidate genes that influence the human electroencephalogram. Proc Natl Acad Sci U S A 107(19):8695–8700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Honjo Y, Ito H, Horibe T, Shimada H, Nakanishi A, Mori H, Takahashi R, Kawakami K (2012) Derlin-1-immunopositive inclusions in patients with Alzheimer's disease. Neuroreport 23(10):611–615

    Article  CAS  PubMed  Google Scholar 

  • Ishiguro H, Hall FS, Horiuchi Y, Sakurai T, Hishimoto A, Grumet M, Uhl GR, Onaivi ES, Arinami T (2012) NrCAM-regulating neural systems and addiction-related behaviors. Addict Biol

  • Ishiguro H, Liu QR, Gong JP, Hall FS, Ujike H, Morales M, Sakurai T, Grumet M, Uhl GR (2006) NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice. Neuropsychopharmacology 31:572–584

    Article  CAS  PubMed  Google Scholar 

  • Jayanthi S, Deng X, Ladenheim B, McCoy MT, Cluster A, Cai NS, Cadet JL (2005) Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci U S A 102(3):868–873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: d-amphetamine. Psychopharmacology (Berl) 71(3):275–279

    Article  CAS  Google Scholar 

  • Kalivas PW (2009) The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci 10(8):561–572

    Article  CAS  PubMed  Google Scholar 

  • Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M (2004) The KEGG resource for deciphering the genome. Nucleic Acids Res 32(Database issue):D277–D280

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M (2014) Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res 42(Database issue):D199–D205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khananshvili D (2013) The SLC8 gene family of sodium-calcium exchangers (NCX) - structure, function, and regulation in health and disease. Mol Aspects Med 34(2–3):220–235

    Article  CAS  PubMed  Google Scholar 

  • Khatri P, Sirota M, Butte AJ (2012) Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol 8(2):e1002375

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kitazono T, Kubo M, Hata J, Ibayashi S, Kiyohara Y, Iida M (2008) Molecular epidemiology of cerebrovascular diseases; the Hisayama study and the Fukuoka Stroke Registry (FSR). Rinsho Shinkeigaku 48(11):892–895

    Article  PubMed  Google Scholar 

  • Kuhar MJ, Jaworski JN, Hubert GW, Philpot KB, Dominguez G (2005) Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets. AAPS J 7(1):E259–E265

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kuo DS, Labelle-Dumais C, Gould DB (2012) COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Hum Mol Genet 21(R1):R97–R110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • LaBelle EF, Polyak F (1996) Phospholipase C beta 2 in vascular smooth muscle. J Cell Physiol 169(2):358–363

    Article  CAS  PubMed  Google Scholar 

  • Lalonde R, Strazielle C (2008) Discrimination learning in Rora(sg) and Grid2(ho) mutant mice. Neurobiol Learn Mem 90(2):472–474

    Article  CAS  PubMed  Google Scholar 

  • Li CY, Mao X, Wei L (2008) Genes and (common) pathways underlying drug addiction. PLoS Comput Biol 4(1):e2

    Article  PubMed Central  PubMed  Google Scholar 

  • Li Q, Yu K (2008) Improved correction for population stratification in genome-wide association studies by identifying hidden population structures. Genet Epidemiol 32(3):215–226

    Article  CAS  PubMed  Google Scholar 

  • Lipskaia L, Defer N, Esposito G, Hajar I, Garel MC, Rockman HA, Hanoune J (2000) Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase. Circ Res 86(7):795–801

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Demirci O, Calhoun VD (2008) A parallel independent component analysis approach to investigate genomic influence on brain function. IEEE Signal Proc Lett 15:413–416

    Article  Google Scholar 

  • Liu J, Pearlson G, Windemuth A, Ruano G, Perrone-Bizzozero NI, Calhoun V (2009) Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA. Hum Brain Mapp 30(1):241–255

    Article  PubMed Central  PubMed  Google Scholar 

  • Logue MW, Baldwin C, Guffanti G, Melista E, Wolf EJ, Reardon AF, Uddin M, Wildman D, Galea S, Koenen KC, Miller MW (2013) A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Mol Psychiatry 18(8):937–942

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lu JR, McKinsey TA, Xu H, Wang DZ, Richardson JA, Olson EN (1999) FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors. Mol Cell Biol 19(6):4495–4502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12(2):245–258

    CAS  PubMed  Google Scholar 

  • Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 100(10):6186–6191

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McGrath CL, Glatt SJ, Sklar P, Le-Niculescu H, Kuczenski R, Doyle AE, Biederman J, Mick E, Faraone SV, Niculescu AB, Tsuang MT (2009) Evidence for genetic association of RORB with bipolar disorder. BMC Psychiatr 9:70

    Article  Google Scholar 

  • McIntyre JC, Titlow WB, McClintock TS (2010) Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons. J Neurosci Res 88(15):3243–3256

    Article  CAS  PubMed  Google Scholar 

  • Meda SA, Narayanan B, Liu J, Perrone-Bizzozero NI, Stevens MC, Calhoun VD, Glahn DC, Shen L, Risacher SL, Saykin AJ, Pearlson GD (2012) A large scale multivariate parallel ICA method reveals novel imaging-genetic relationships for Alzheimer's disease in the ADNI cohort. Neuroimage 60(3):1608–1621

    Article  PubMed Central  PubMed  Google Scholar 

  • Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34(3):267–273

    Article  CAS  PubMed  Google Scholar 

  • Murphy SM, Ernst D, Wei Y, Laura M, Liu YT, Polke J, Blake J, Winer J, Houlden H, Hornemann T, Reilly MM (2013) Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2. Neurology 80(23):2106–2111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nekrasova T, Jobes ML, Ting JH, Wagner GC, Minden A (2008) Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion. Dev Biol 322(1):95–108

    Article  CAS  PubMed  Google Scholar 

  • Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, Wang Y, Lam VK, Chan JC, Ma RC (2010) Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab 95(5):2418–2425

    Article  CAS  PubMed  Google Scholar 

  • Nikpay M, Seda O, Tremblay J, Petrovich M, Gaudet D, Kotchen TA, Cowley AW Jr, Hamet P (2012) Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse. Hypertens Res 35(6):585–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Orsetti M, Di Brisco F, Canonico PL, Genazzani AA, Ghi P (2008) Gene regulation in the frontal cortex of rats exposed to the chronic mild stress paradigm, an animal model of human depression. Eur J Neurosci 27(8):2156–2164

    Article  CAS  PubMed  Google Scholar 

  • Procopio DO, Saba LM, Walter H, Lesch O, Skala K, Schlaff G, Vanderlinden L, Clapp P, Hoffman PL, Tabakoff B (2013) Genetic markers of comorbid depression and alcoholism in women. Alcohol Clin Exp Res 37(6):896–904

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ribases M, Bosch R, Hervas A, Ramos-Quiroga JA, Sanchez-Mora C, Bielsa A, Gastaminza X, Guijarro-Domingo S, Nogueira M, Gomez-Barros N, Kreiker S, Gross-Lesch S, Jacob CP, Lesch KP, Reif A, Johansson S, Plessen KJ, Knappskog PM, Haavik J, Estivill X, Casas M, Bayes M, Cormand B (2009) Case-control study of six genes asymmetrically expressed in the two cerebral hemispheres: association of BAIAP2 with attention-deficit/hyperactivity disorder. Biol Psychiatry 66(10):926–934

    Article  CAS  PubMed  Google Scholar 

  • Richardson RJ, Grkovic I, Anderson CR (2006) Cocaine- and amphetamine-related transcript peptide and somatostatin in rat intracardiac ganglia. Cell Tissue Res 324(1):17–24

    Article  CAS  PubMed  Google Scholar 

  • Rissanen J (1987) Minimum description length principle. Encyclopedia of Statistical Sciences

  • Roussos P, Bitsios P, Giakoumaki SG, McClure MM, Hazlett EA, New AS, Siever LJ (2013) CACNA1C as a risk factor for schizotypal personality disorder and schizotypy in healthy individuals. Psychiatry Res 206(1):122–123

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sarachana T, Hu VW (2013) Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder. Mol Autism 4(1):14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schep LJ, Slaughter RJ, Beasley DM (2010) The clinical toxicology of metamfetamine. Clin Toxicol (Phila) 48(7):675–694

    Article  CAS  Google Scholar 

  • Schilt T, Koeter MW, de Win MM, Zinkstok JR, van Amelsvoort TA, Schmand B, den Brink W (2009) The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene. Eur Neuropsychopharmacol 19(2):116–124

    Article  CAS  PubMed  Google Scholar 

  • Schoner K, Kohlhase J, Muller AM, Schramm T, Plassmann M, Schmitz R, Neesen J, Wieacker P, Rehder H (2013) Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent frequent associations in fetuses with Peters' plus syndrome and B3GALTL mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele. Prenat Diagn 33(1):75–80

    Article  CAS  PubMed  Google Scholar 

  • Schurz M, Radua J, Aichhorn M, Richlan F, Perner J (2014) Fractionating theory of mind: a meta-analysis of functional brain imaging studies. Neurosci Biobehav Rev 42:9-34

  • Shibasaki M, Mizuno K, Kurokawa K, Suzuki T, Ohkuma S (2011) Role of actin depolymerizing factor in the development of methamphetamine-induced place preference in mice. Eur J Pharmacol 671(1–3):70–78

    Article  CAS  PubMed  Google Scholar 

  • Singleton AB, Farrer MJ, Bonifati V (2013) The genetics of Parkinson's disease: progress and therapeutic implications. Mov Disord 28(1):14–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102(43):15545–15550

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Supriyanto I, Watanabe Y, Mouri K, Shiroiwa K, Ratta-Apha W, Yoshida M, Tamiya G, Sasada T, Eguchi N, Okazaki K, Shirakawa O, Someya T, Hishimoto A (2013) A missense mutation in the ITGA8 gene, a cell adhesion molecule gene, is associated with schizophrenia in Japanese female patients. Prog Neuropsychopharmacol Biol Psychiatry 40:347–352

    Article  CAS  PubMed  Google Scholar 

  • Terracciano A, Esko T, Sutin AR, de Moor MH, Meirelles O, Zhu G, Tanaka T, Giegling I, Nutile T, Realo A, Allik J, Hansell NK, Wright MJ, Montgomery GW, Willemsen G, Hottenga JJ, Friedl M, Ruggiero D, Sorice R, Sanna S, Cannas A, Raikkonen K, Widen E, Palotie A, Eriksson JG, Cucca F, Krueger RF, Lahti J, Luciano M, Smoller JW, van Duijn CM, Abecasis GR, Boomsma DI, Ciullo M, Costa PT Jr, Ferrucci L, Martin NG, Metspalu A, Rujescu D, Schlessinger D, Uda M (2011) Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. Transl Psychiatry 1:e49

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thomas EA, Foye PE, Alvarez CE, Usui H, Sutcliffe JG (2001) Insulin receptor substrate protein p53 localization in rats suggests mechanism for specific polyglutamine neurodegeneration. Neurosci Lett 309(3):145–148

    Article  CAS  PubMed  Google Scholar 

  • Toma C, Hervas A, Balmana N, Vilella E, Aguilera F, Cusco I, del Campo M, Caballero R, De Diego-Otero Y, Ribases M, Cormand B, Bayes M (2011) Association study of six candidate genes asymmetrically expressed in the two cerebral hemispheres suggests the involvement of BAIAP2 in autism. J Psychiatr Res 45(2):280–282

    Article  PubMed  Google Scholar 

  • Turdi S, Schamber RM, Roe ND, Chew HG Jr, Culver B, Ren J (2009) Acute methamphetamine exposure inhibits cardiac contractile function. Toxicol Lett 189(2):152–158

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Uhl GR, Drgon T, Liu QR, Johnson C, Walther D, Komiyama T, Harano M, Sekine Y, Inada T, Ozaki N, Iyo M, Iwata N, Yamada M, Sora I, Chen CK, Liu HC, Ujike H, Lin SK (2008) Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry 65(3):345–355

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Yuan W, Li MD (2011) Genes and pathways co-associated with the exposure to multiple drugs of abuse, including alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine, and/or nicotine: a review of proteomics analyses. Mol Neurobiol 44(3):269–286

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Zheng Y, Xu H, Yan X, Chang X (2013) Investigate pathogenic mechanism of TXNDC5 in rheumatoid arthritis. PLoS One 8(1):e53301

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wardle MC, Hart AB, Palmer AA, de Wit H (2013) Does COMT genotype influence the effects of d-amphetamine on executive functioning? Genes Brain Behav 12(1):13–20

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wolf A, Agnihotri S, Munoz D, Guha A (2011) Developmental profile and regulation of the glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme. Neurobiol Dis 44(1):84–91

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Loonam TM, Noailles PA, Angulo JA (2001) Comparison of cocaine- and methamphetamine-evoked dopamine and glutamate overflow in somatodendritic and terminal field regions of the rat brain during acute, chronic, and early withdrawal conditions. Ann N Y Acad Sci 937:93–120

    Article  CAS  PubMed  Google Scholar 

  • Zitman FM, Todorov B, Verschuuren JJ, Jacobs BC, Furukawa K, Furukawa K, Willison HJ, Plomp JJ (2011) Neuromuscular synaptic transmission in aged ganglioside-deficient mice. Neurobiol Aging 32(1):157–167

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All authors have read and approved the manuscript, and none have any conflicts of interest. Dr. de Wit received a research grant from Unilever for a project unrelated to this study. This work was supported by NIH Grants DA007255 (ABH), T32AA015496-08 (HLY), and DA002812 (HdW).

Author information

Authors and Affiliations

  1. Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, 200 Retreat Avenue, Hartford, CT, 06102, USA

    Haley L. Yarosh, Shashwath A. Meda & Godfrey D. Pearlson

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Haley L. Yarosh & Godfrey D. Pearlson

  3. Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA

    Godfrey D. Pearlson

  4. Department of Human Genetics, University of Chicago, Chicago, IL, USA

    Amy B. Hart

  5. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA

    Harriet de Wit

Authors
  1. Haley L. Yarosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shashwath A. Meda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harriet de Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amy B. Hart
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Godfrey D. Pearlson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shashwath A. Meda.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 76 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yarosh, H.L., Meda, S.A., de Wit, H. et al. Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations. Psychopharmacology 232, 2781–2794 (2015). https://doi.org/10.1007/s00213-015-3914-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-015-3914-1

Keywords

Search

Navigation