Skip to main content

Advertisement

SpringerLink
Log in

Subjective responses to amphetamine in young adults with previous mood elevation experiences

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

Abstract

Rationale

One risk factor for alcohol and substance misuse is hypomanic experiences, or periods of mood elevation. Young people who report hypomanic states are more likely to develop bipolar disorder (BP), and BP and other mood disorders increase the risk of addiction. We recently reported that young adults with a history of mood elevation experience less subjective effects from a low dose of alcohol, which may be predictive of future alcohol use. The finding with alcohol raised the question of whether this dampened response to a drug also applies to other drugs, such as amphetamine.

Objective

This study assessed responses of d-amphetamine in healthy young adults with varying experiences of mood elevation, as measured by the Mood Disorders Questionnaire (MDQ).

Methods

Healthy 18–19-year-olds (N = 30) with a range of MDQ scores participated in three 4-h laboratory sessions in which they received placebo, 10 mg, or 20 mg d-amphetamine. They completed mood questionnaires and cardiovascular measures.

Results

Individuals with higher MDQ scores reported less stimulation and euphoria after 10 mg, but not 20 mg, d-amphetamine, than individuals with lower scores. MDQ scores were not related to cardiovascular responses to the drug.

Conclusions

A history of mood elevation experiences or hypomania states is related to dampened response to a low dose of a psychostimulant drug, extending previous findings with dampened response to alcohol. This phenotype for mood disorders of dampened responses to drugs may contribute to risk for subsequent drug use or misuse.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abi-Dargham A, Kegeles LS, Martinez D, Innis RB, Laruelle M (2003) Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naive healthy volunteers: results from a large cohort. Eur Neuropsychopharmacol 13:459–468

    Article  CAS  PubMed  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub

  • Anand A, Verhoeff P, Seneca N, Zoghbi SS, Seibyl JP, Charney DS, Innis RB (2000) Brain SPECT imaging of amphetamine-induced dopamine release in euthymic bipolar disorder patients. Am J Psychiatry 157:1108–1114

    Article  CAS  PubMed  Google Scholar 

  • Berghorst LH, Kumar P, Greve DN, Deckersbach T, Ongur D, Dutra SJ, Pizzagalli DA (2016) Stress and reward processing in bipolar disorder: a functional magnetic resonance imaging study. Bipolar Disord 18:602–611

    Article  PubMed  PubMed Central  Google Scholar 

  • Bergsholm P, Fasmer OB, Haavik J (2010) Bipolar symptoms in adult attention-deficit/hyperactivity disorder: a cross-sectional study of 510 clinically diagnosed patients and 417 population-based controls. J Clin Psychiatry 71:48–57

    Article  PubMed  Google Scholar 

  • Brown WA, Corriveau DP, Ebert MH (1978) Acute psychologic and neuroendocrine effects of dextroamphetamine and methylphenidate. Psychopharmacology 58:189–195

    Article  CAS  PubMed  Google Scholar 

  • Calabrese JR, Hirschfeld RM, Reed M, Davies MA, Frye MA, Keck PE, Lewis L, McElroy SL, McNulty JP, Wagner KD (2003) Impact of bipolar disorder on a U.S. community sample. J Clin Psychiatry 64:425–432

    Article  PubMed  Google Scholar 

  • Cardenas L, Tremblay LK, Naranjo CA, Herrmann N, Zack M, Busto UE (2002) Brain reward system activity in major depression and comorbid nicotine dependence. J Pharmacol Exp Ther 302:1265–1271

    Article  CAS  PubMed  Google Scholar 

  • Carlson GA, Loney J, Salisbury H, Kramer JR, Arthur C (2000) Stimulant treatment in young boys with symptoms suggesting childhood mania: a report from a longitudinal study. J Child Adolesc Psychopharmacol 10:175–184

    Article  CAS  PubMed  Google Scholar 

  • Caseras X, Lawrence NS, Murphy K, Wise RG, Phillips ML (2013) Ventral striatum activity in response to reward: differences between bipolar I and II disorders. Am J Psychiatry 170:533–541

    Article  PubMed  PubMed Central  Google Scholar 

  • Chandler RA, Wang PW, Ketter TA, Goodwin GM (2008) A new US-UK diagnostic project: mood elevation and depression in first-year undergraduates at Oxford and Stanford universities. Acta Psychiatr Scand 118:81–85

    Article  CAS  PubMed  Google Scholar 

  • Chiu JF, Chokka PR (2011) Prevalence of bipolar disorder symptoms in primary care (ProBiD-PC): a Canadian study. Can Fam Physician 57:e58–e67

    PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Eysenck SBG, Eysenck HJ, Barrett P (1985) A revised version of the psychoticism scale. Personal Individ Differ 6:21–29

    Article  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JB (2012) Structured clinical interview for DSM-IV axis I disorders (SCID-I) s, clinician version, administration booklet

  • Galanter CA, Carlson GA, Jensen PS, Greenhill LL, Davies M, Li W, Chuang SZ, Elliott GR, Arnold LE, March JS, Hechtman L, Pelham WE, Swanson JM (2003) Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial. J Child Adolesc Psychopharmacol 13:123–136

    Article  PubMed  Google Scholar 

  • Haertzen CA (1966) Development of scales based on patterns of drug effects, using the Addiction Research Center Inventory (ARCI). Psychol Rep 18:163–194

    Article  CAS  PubMed  Google Scholar 

  • Harvanko A, Martin C, Lile J, Kryscio R, Kelly TH (2016) Individual differences in the reinforcing and subjective effects of d-amphetamine: dimensions of impulsivity. Exp Clin Psychopharmacol 24:436–446

    Article  PubMed  PubMed Central  Google Scholar 

  • Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, Lewis L, McElroy SL, Post RM, Rapport DJ, Russell JM, Sachs GS, Zajecka J (2000) Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 157:1873–1875

    Article  CAS  PubMed  Google Scholar 

  • Hirschfeld RM, Holzer C, Calabrese JR, Weissman M, Reed M, Davies M, Frye MA, Keck P, McElroy S, Lewis L, Tierce J, Wagner KD, Hazard E (2003) Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry 160:178–180

    Article  PubMed  Google Scholar 

  • Janowsky DS, el-Yousef MK, Davis JM, Sekerke HJ (1972) A cholinergic-adrenergic hypothesis of mania and depression. Lancet 2:632–635

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • King AC, Roche DJ, Rueger SY (2011) Subjective responses to alcohol: a paradigm shift may be brewing. Alcohol Clin Exp Res 35:1726–1728

    Article  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacol 24:97–129

    Article  CAS  Google Scholar 

  • Lasagna L, Von Felsinger JM, Beecher HK (1955) Drug-induced mood changes in man. I. Observations on healthy subjects, chronically ill patients, and postaddicts. J Am Med Assoc 157:1006–1020

    Article  CAS  PubMed  Google Scholar 

  • Levey DF, Le-Niculescu H, Frank J, Ayalew M, Jain N, Kirlin B, Learman R, Winiger E, Rodd Z, Shekhar A, Schork N, Kiefer F, Wodarz N, Muller-Myhsok B, Dahmen N, Consortium G, Nothen M, Sherva R, Farrer L, Smith AH, Kranzler HR, Rietschel M, Gelernter J, Niculescu AB (2014) Genetic risk prediction and neurobiological understanding of alcoholism. Transl Psychiatry 4:e391

    Article  CAS  PubMed  PubMed Central  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 12:245–258

    Article  CAS  PubMed  Google Scholar 

  • McNair DM (1971) Manual profile of mood states. Educational & Industrial testing service, San Diego, CA

  • Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68:241–251

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller ME, Badger GJ, Heil SH, Higgins ST, Sigmon SC (2015) Associations between sensation seeking and d-amphetamine reinforcement. Am J Addict 24:435–442

    Article  PubMed  Google Scholar 

  • Nusslock R, Young CB, Damme KS (2014) Elevated reward-related neural activation as a unique biological marker of bipolar disorder: assessment and treatment implications. Behav Res Ther 62:74–87

    Article  PubMed  PubMed Central  Google Scholar 

  • Overall JE, Gorham DR (1962) The brief psychiatric rating-scale. Psychol Rep 10:799–812

    Article  Google Scholar 

  • Patel SD, Le-Niculescu H, Koller DL, Green SD, Lahiri DK, McMahon FJ, Nurnberger JI Jr, Niculescu AB 3rd (2010) Coming to grips with complex disorders: genetic risk prediction in bipolar disorder using panels of genes identified through convergent functional genomics. Am J Med Genet B Neuropsychiatr Genet 153B:850–877

    CAS  PubMed  Google Scholar 

  • Pettorruso M, De Risio L, Di Nicola M, Martinotti G, Conte G, Janiri L (2014) Allostasis as a conceptual framework linking bipolar disorder and addiction. Front Psychiatry 5:173

    Article  PubMed  PubMed Central  Google Scholar 

  • Raven J (2000) The Raven’s progressive matrices: change and stability over culture and time. Cogn Psychol 41:1–48

    Article  CAS  PubMed  Google Scholar 

  • Rock PL, Chandler RA, Harmer CJ, Rogers RD, Goodwin GM (2013) The common bipolar phenotype in young people. Int J Bipolar Disord 1:19

    Article  PubMed Central  Google Scholar 

  • Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB (2003) The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 54:573–583

    Article  PubMed  Google Scholar 

  • Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 151:184–189

    Article  CAS  PubMed  Google Scholar 

  • Tremblay LK, Naranjo CA, Cardenas L, Herrmann N, Busto UE (2002) Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. Arch Gen Psychiatry 59:409–416

    Article  PubMed  Google Scholar 

  • Tremblay LK, Naranjo CA, Graham SJ, Herrmann N, Mayberg HS, Hevenor S, Busto UE (2005) Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch Gen Psychiatry 62:1228–1236

    Article  PubMed  Google Scholar 

  • Trost S, Diekhof EK, Mohr H, Vieker H, Kramer B, Wolf C, Keil M, Dechent P, Binder EB, Gruber O (2016) Investigating the impact of a genome-wide supported bipolar risk variant of MAD1L1 on the human reward system. Neuropsychopharmacol 41:2679–2687

    Article  CAS  Google Scholar 

  • Vasey MW, Thayer JF (1987) The continuing problem of false positives in repeated measures ANOVA in psychophysiology: a multivariate solution. Psychophysiology 24:479–486

    Article  CAS  PubMed  Google Scholar 

  • Waxmonsky J, Pelham WE, Gnagy E, Cummings MR, O’Connor B, Majumdar A, Verley J, Hoffman MT, Massetti GA, Burrows-MacLean L, Fabiano GA, Waschbusch DA, Chacko A, Arnold FW, Walker KS, Garefino AC, Robb JA (2008) The efficacy and tolerability of methylphenidate and behavior modification in children with attention-deficit/hyperactivity disorder and severe mood dysregulation. J Child Adolesc Psychopharmacol 18:573–588

    Article  PubMed  PubMed Central  Google Scholar 

  • Weafer J, de Wit H (2013) Inattention, impulsive action, and subjective response to D-amphetamine. Drug Alcohol Depend 133:127–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weafer J, Ross TJ, O’Connor S, Stein EA, de Wit H, Childs E (2018) Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers. Neuropsychopharmacol 43:2532–2538

    Article  CAS  Google Scholar 

  • White TL, Justice AJ, de Wit H (2002) Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73:729–741

    Article  CAS  PubMed  Google Scholar 

  • White TL, Lott DC, de Wit H (2006) Personality and the subjective effects of acute amphetamine in healthy volunteers. Neuropsychopharmacol 31:1064–1074

    Article  CAS  Google Scholar 

  • Yip SW, Doherty J, Wakeley J, Saunders K, Tzagarakis C, de Wit H, Goodwin GM, Rogers RD (2012) Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype. Neuropsychopharmacol 37:1808–1815

    Article  CAS  Google Scholar 

  • Yip SW, Worhunsky PD, Rogers RD, Goodwin GM (2015) Hypoactivation of the ventral and dorsal striatum during reward and loss anticipation in antipsychotic and mood stabilizer-naive bipolar disorder. Neuropsychopharmacol 40:658–666

    Article  CAS  Google Scholar 

  • Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 133:429–435

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann P, Bruckl T, Nocon A, Pfister H, Lieb R, Wittchen HU, Holsboer F, Angst J (2009) Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity. Arch Gen Psychiatry 66:1341–1352

    Article  PubMed  Google Scholar 

Download references

Funding

This research was supported by NIH grant R01DA02812 awarded to HdW. STS was supported by the NIDA Training Grant “Integrative Training in the Neurobiology of Addictive Behaviors” (T32DA043469) and DA was supported by the NIH Clinical Therapeutics Training Grant (T32GM007019).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, 5841 S Maryland Ave, MC3077, Chicago, IL, 60637, USA

    Scott T. Schepers, David L. Arndt & Harriet de Wit

  2. School of Psychology, Bangor University, Gwynedd, Wales, UK

    Robert D. Rogers

  3. Department of Public Health Sciences, University of Chicago, Chicago, IL, USA

    Donald Hedeker

Authors
  1. Scott T. Schepers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David L. Arndt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert D. Rogers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Donald Hedeker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harriet de Wit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harriet de Wit.

Ethics declarations

Study procedures were approved by the Institutional Review Board at the University of Chicago and were carried out in accordance with the Declaration of Helsinki.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schepers, S.T., Arndt, D., Rogers, R.D. et al. Subjective responses to amphetamine in young adults with previous mood elevation experiences. Psychopharmacology 236, 3363–3370 (2019). https://doi.org/10.1007/s00213-019-05295-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-019-05295-z

Keywords

Search

Navigation