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Effects of prenatal methamphetamine exposure: a review of cognitive and neuroimaging studies

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Abstract

Prenatal methamphetamine exposure (PME) is a significant problem in several parts of the world and poses important health risks for the developing fetus. Research on the short- and long-term outcomes of PME is scarce, however. Here, we summarize present knowledge on the cognitive and behavioral outcomes of PME, based on a review of the neuroimaging, neuropsychology, and neuroscience literature published in the past 15 years. Several studies have reported that the behavioral and cognitive sequelae of PME include broad deficits in the domains of attention, memory, and visual-motor integration. Knowledge regarding brain-behavior relationships is poor, however, in large part because imaging studies are rare. Hence, the effects of PME on developing neurocircuitry and brain architecture remain speculative, and are largely deductive. Some studies have implicated the dopamine-rich fronto-striatal pathways; however, cognitive deficits (e.g., impaired visual-motor integration) that should be associated with damage to those pathways are not manifested consistently across studies. We conclude by discussing challenges endemic to research on prenatal drug exposure, and argue that they may account for some of the inconsistencies in the extant research on PME. Studies confirming predicted brain-behavior relationships in PME, and exploring possible mechanisms underlying those relationships, are needed if neuroscience is to address the urgency of this growing public health problem.

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References

  • Abar B, LaGasse LL, Wouldes T, Derauf C, Newman E, Shah R et al (2013) Cross-national comparison of prenatal methamphetamine exposure on infant and early child physical growth: a natural experiment. Prev Sci 1:1–10

    Google Scholar 

  • Ahmadlou M, Ahmadi K, Rezazade M, Azad-Marzabadi E (2013) Global organization of functional brain connectivity in methamphetamine abusers. Clin Neurophysiol 124:1122–1131

    Article  PubMed  Google Scholar 

  • Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18

    Article  PubMed  Google Scholar 

  • Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T (2006) The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci 31:301–313

    PubMed Central  PubMed  Google Scholar 

  • Behnke M, Smith VC, Levy S, Ammerman SD, Gonzalez PK, Ryan SA et al (2013) Prenatal substance abuse: short-and long-term effects on the exposed fetus. Pediatrics 131:1009–1024

    Article  Google Scholar 

  • Billing L, Eriksson M, Larsson G, Zetterström R (1980) Amphetamine addiction and pregnancy. Acta Paediatr 69:675–680

    Article  CAS  Google Scholar 

  • Billing L, Eriksson M, Steneroth G, Zetterström R (1988) Predictive indicators for adjustment in 4-year-old children whose mothers used amphetamine during pregnancy. Child Abuse Negl 12:503–507

    Article  CAS  PubMed  Google Scholar 

  • Billing L, Eriksson M, Jonsson B, Steneroth G, Zetterström R (1994) The influence of environmental factors on behavioural problems in 8-year-old children exposed to amphetamine during fetal life. Child Abuse Negl 18:3–9

    Article  CAS  PubMed  Google Scholar 

  • Brown JM, Hanson GR, Fleckenstein AE (2001) Regulation of the vesicular monoamine transporter-2: a novel mechanism for cocaine and other psychostimulants. J Pharmacol Exp Ther 296:762–767

    CAS  PubMed  Google Scholar 

  • Bubenikova-Valesova V, Kacer P, Syslova K, Rambousek L, Janovsky M, Schutova B et al (2009) Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring. Int J Dev Neurosci 27:525–530

    Article  CAS  PubMed  Google Scholar 

  • Cadet JL, Krasnova IN (2009) Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol 88:101–119

    Article  CAS  PubMed  Google Scholar 

  • Cass WA (1997) Decreases in evoked overflow of dopamine in rat striatum after neurotoxic doses of methamphetamine. J Exp Ther 280:105–113

    CAS  Google Scholar 

  • Cernerud L, Eriksson M, Jonsson B, Steneroth G, Zetterstrom R (1996) Amphetamine addiction during pregnancy: 14-year follow-up of growth and school performance. Acta paediatrica 85:204–208

    Article  CAS  PubMed  Google Scholar 

  • Chang L, Smith LM, LoPresti C, Yonekura ML, Kuo J, Walot I, Ernst T (2004) Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatry Res Neuroimaging 132:95–106

    Article  CAS  Google Scholar 

  • Chang L, Alicata D, Ernst T, Volkow N (2007) Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 102:16–32

    Article  PubMed  Google Scholar 

  • Chang L, Cloak C, Jiang CS, Farnham S, Tokeshi B, Buchthal S et al (2009) Altered neurometabolites and motor integration in children exposed to methamphetamine in utero. Neuroimage 48:391–397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cloak CC, Ernst T, Fujii L, Hedemark B, Chang L (2009) Lower diffusion in white matter of children with prenatal methamphetamine exposure. Neurology 72:2068–2075

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Cui C, Sakata Haga H, Ohta KI, Nishida M, Yashiki M, Sawada K, Fukui Y (2006) Histological brain alterations following prenatal methamphetamine exposure in rats. Congenit Anom 46:180–187

    Article  CAS  Google Scholar 

  • Cummings JL (1993) Frontal-subcortical circuits and human behavior. Arch Neurol 50:873

    Article  CAS  PubMed  Google Scholar 

  • Degenhardt L, Hall W (2012) Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet 375:55–70

    Article  Google Scholar 

  • Della Grotta S, LaGasse LL, Arria AM, Derauf C, Grant P, Smith LM et al (2010) Patterns of methamphetamine use during pregnancy: results from the Infant Development, Environment, and Lifestyle (IDEAL) Study. Matern Child Health J 14:519–527

    Article  PubMed Central  PubMed  Google Scholar 

  • Eriksson M, Zetterström R (1994) Amphetamine addiction during pregnancy: 10-year follow-up. Acta Paediatr 83:27–31

    Article  Google Scholar 

  • Eriksson M, Larsson G, Winbladh B, Zetterström R (1978) The influence of amphetamine addiction on pregnancy and the newborn infant. Acta paediatrica Scandinavica 67:95

    Article  CAS  PubMed  Google Scholar 

  • Eriksson M, Larsson G, Zetterström R (1981) Amphetamine addiction and pregnancy: ii. pregnancy, delivery and the neonatal period. Socio-medical aspects. Acta Obstet Gynecol Scand 60:253–259

    Article  CAS  PubMed  Google Scholar 

  • Eriksson M, Billing L, Steneroth G, Zetterstrom R (1989) Health and development of 8-Year-old children whose mothers abused amphetamine during pregnancy. Acta Paediatr 78:944–949

    Article  CAS  Google Scholar 

  • Eriksson M, Jonsson B, Steneroth G, Zetterström R (1994) Cross-sectional growth of children whose mothers abused amphetamines during pregnancy. Acta Paediatr 83:612–617

    Article  CAS  PubMed  Google Scholar 

  • Eriksson M, Jonsson B, Steneroth G, Zetterström R (2000) Amphetamine abuse during pregnancy: Environmental factors and outcome after 14-15 years. Scand J Public Health 28:154–157

    Article  CAS  PubMed  Google Scholar 

  • Flames N, Hobert O (2011) Transcriptional control of the terminal fate of monoaminergic neurons. Annu Rev Neurosci 34:153–184

    Article  CAS  PubMed  Google Scholar 

  • Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Front Syst Neurosci 4:19

    PubMed Central  PubMed  Google Scholar 

  • Frost DO, Cadet JL (2000) Effects of methamphetamine-induced neurotoxicity on the development of neural circuitry: a hypothesis. Brain Res Rev 34:103–118

    Article  CAS  PubMed  Google Scholar 

  • Golub M, Costa L, Crofton K, Frank D, Fried P, Gladen B et al (2005) NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of amphetamine and methamphetamine. Birth Defects Res B Dev Reprod Toxicol 74:471–584

    Article  CAS  PubMed  Google Scholar 

  • Gomes-da-Silva J, Pérez-Rosado A, Miguel R, Fernández-Ruiz J, Silva M, Tavares MA (2002) Prenatal Exposure to Methamphetamine in the Rat. Ann N Y Acad Sci 965:68–77

    Article  CAS  PubMed  Google Scholar 

  • Graham D, Amos-Kroohs R, Braun A, Grace C, Schaefer T, Skelton M et al (2011) Long-term receptor alterations from developmental methamphetamine exposure in rats by use of selective pharmacological agonists and antagonists. Neurotoxicol Teratol 33:497–498

    Google Scholar 

  • Graham DL, Amos-Kroohs RM, Braun AA, Grace CE, Schaefer TL, Skelton MR et al (2013) Neonatal (+)-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists. Int J Neuropsychopharmacol 16:377–391

    Article  CAS  PubMed  Google Scholar 

  • Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A 100:253–258

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Helmich RC, Derikx LC, Bakker M, Scheeringa R, Bloem BR, Toni I (2010) Spatial remapping of cortico-striatal connectivity in Parkinson's disease. Cereb Cortex 20:1175–1186

    Google Scholar 

  • Jedynak JP, Uslaner JM, Esteban JA, Robinson TE (2007) Methamphetamine-induced structural plasticity in the dorsal striatum. Eur J Neurosci 25:847–853

    Article  PubMed  Google Scholar 

  • Jeng W, Wong AW, Ting-A-Kee R, Wells PG (2005) Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental deficits. Free Radic Biol Med 39:317–326

    Article  CAS  PubMed  Google Scholar 

  • Johnston MV, Ishida A, Ishida WN, Matsushita HB, Nishimura A, Tsuji M (2009) Plasticity and injury in the developing brain. Brain Dev 31:1–10

    Article  PubMed Central  PubMed  Google Scholar 

  • Kaewsuk S, Sae-ung K, Phansuwan-Pujito P, Govitrapong P (2009) Melatonin attenuates methamphetamine-induced reduction of tyrosine hydroxylase, synaptophysin and growth-associated protein-43 levels in the neonatal rat brain. Neurochem Int 55:397–405

    Article  CAS  PubMed  Google Scholar 

  • Kaltenbach KA, Finnegan LP (1993) Studies of prenatal drug exposure and environmental research issues: the benefits of integrating research within a treatment program. NIDA Res Monogr 117:259–259

    Google Scholar 

  • Khoshbouei H, Wang H, Lechleiter JD, Javitch JA, Galli A (2003) Amphetamine-induced dopamine efflux. A voltage-sensitive and intracellular Na + -dependent mechanism. J Biol Chem 278:12070

    Article  CAS  PubMed  Google Scholar 

  • Kish SJ (2008) Pharmacologic mechanisms of crystal meth. CMAJ 178:1679–1682

    Article  PubMed Central  PubMed  Google Scholar 

  • Kreis R, Ernst T, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. II: metabolite concentrations. J Magn Reson 102:9–19

    Article  CAS  Google Scholar 

  • LaGasse LL, Wouldes T, Newman E, Smith LM, Shah RZ, Derauf C et al (2011) Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand. Neurotoxicol Teratol 33:166–175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • LaGasse LL, Derauf C, Smith LM, Newman E, Shah R, Neal C et al (2012) Prenatal methamphetamine exposure and childhood behavior problems at 3 and 5 years of age. Pediatrics 129:681–688

    Article  PubMed Central  PubMed  Google Scholar 

  • Lester BM, Andreozzi L, Appiah L (2004) Substance use during pregnancy: time for policy to catch up with research. Harm Reduct J 1:5

    Article  PubMed Central  PubMed  Google Scholar 

  • Lewis SJ, Dove A, Robbins TW, Barker RA, Owen AM (2004) Striatal contributions to working memory: a functional magnetic resonance imaging study in humans. Eur J Neurosci 19:755–760

    Article  PubMed  Google Scholar 

  • Little BB, Snell LM, Gilstrap LC (1988) Methamphetamine abuse during pregnancy: outcome and fetal effects. Obstet Gynecol 72:541–544

    CAS  PubMed  Google Scholar 

  • Lu LH, Johnson A, O’Hare ED, Bookheimer SY, Smith LM, O’Connor MJ, Sowell ER (2009) Effects of prenatal methamphetamine exposure on verbal memory revealed with fMRI. J Dev Behav Pediatr 30:185

    Article  PubMed Central  PubMed  Google Scholar 

  • Maisto SA, McKay JR, Connors GJ (1990) Self-report issues in substance abuse: State of the art and future directions. Behavioral Assessment 12:117–134

    Google Scholar 

  • McKetin R, Kozel N, Douglas J et al (2008) The rise of methamphetamine in Southeast and East Asia. Drug and Alcohol Review 27:220–228

    Article  PubMed  Google Scholar 

  • Melo P, Moreno VZ, Vázquez SP, Pinazo-Durán MD, Tavares MA (2006) Myelination changes in the rat optic nerve after prenatal exposure to methamphetamine. Brain Res 1106:21–29

    Article  CAS  PubMed  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2010) Treatment episode data set (TEDS): 1998–2008. State admissions to substance abuse treatment services. DASIS Series: S-55 (HHS Publication No. SMA 10-4613). Rockville, MD: Author

  • Meredith CW, Jaffe C, Ang-Lee K, Saxon AJ (2005) Implications of chronic methamphetamine use: A literature review. Harv Rev Psychiatry 13:141–154

    Article  PubMed  Google Scholar 

  • Morrow BA, Roth RH, Redmond DE, Elsworth JD (2011) Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson’s disease. Neurosci 189:277–285

    Article  CAS  Google Scholar 

  • Nguyen D, Smith LM, LaGasse LL, Derauf C, Grant P, Shah R et al (2010) Intrauterine growth of infants exposed to prenatal methamphetamine: results from the infant development, environment, and lifestyle study. J Pediatr 157:337–339

    Article  PubMed Central  PubMed  Google Scholar 

  • Nordahl TE, Salo R, Leamon M (2003) Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: A review. J Neuropsychiatry Clin Neurosci 15:317–325

    Article  CAS  PubMed  Google Scholar 

  • Ondersma SJ, Simpson SM, Brestan EV, Ward M (2000) Prenatal drug exposure and social policy: the search for an appropriate response. Child Maltreat 5:93–108

    Article  CAS  PubMed  Google Scholar 

  • Oro AS, Dixon SD (1987) Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J Pediatr 111:571–578

    Article  CAS  PubMed  Google Scholar 

  • Poland ML, Dombrowski MP, Ager JW, Sokol RJ (1993) Punishing pregnant drug users: enhancing the flight from care. Drug Alcohol Depend 31:199–203

    Article  CAS  PubMed  Google Scholar 

  • Roberts S, Nuru-Jeter A (2010) Women’s perspectives on screening for alcohol and drug use in prenatal care. Women Health Iss 20:193–200

    Article  Google Scholar 

  • Roussotte FF, Bramen JE, Nunez SC, Quandt LC, Smith L, O’Connor MJ et al (2011) Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure. NeuroImage 54:3067–3075

    Article  CAS  PubMed  Google Scholar 

  • Salisbury AL, Ponder KL, Padbury JF, Lester BM (2009) Fetal effects of psychoactive drugs. Clin Perinatol 36:595

    Article  PubMed Central  PubMed  Google Scholar 

  • Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D (2001) Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 autoreceptors, transporters, and synaptic vesicle stores. J Neurosci 21:5916–5924

    CAS  PubMed  Google Scholar 

  • Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, Grant I (2007) Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol Rev 17:275–297

    Article  PubMed  Google Scholar 

  • Semple SJ, Grant I, Patterson TL (2005) Female methamphetamine users: social characteristics and sexual risk behavior. Women & Health 40:35–50

    Article  Google Scholar 

  • Šlamberová R, Pometlová M, Charousová P (2006) Postnatal development of rat pups is altered by prenatal methamphetamine exposure. Prog Neuropsychopharmacol Biol Psychiatry 30:82–88

    Article  PubMed  Google Scholar 

  • Smith LM, Chang L, Yonekura ML, Grob C, Osborn D, Ernst T (2001) Brain proton magnetic resonance spectroscopy in children exposed to methamphetamine in utero. Neurol 57:255–260

    Article  CAS  Google Scholar 

  • Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A et al (2006) The infant development, environment, and lifestyle study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics 118:1149–1156

    Article  PubMed  Google Scholar 

  • Smith DK, Johnson AB, Pears KC, Fisher PA, DeGarmo DS (2007) Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use. Child Maltreat 12:150–160

    Article  PubMed  Google Scholar 

  • Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A et al (2008) Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol 30:20–28

    Google Scholar 

  • Smith LM, LaGasse LL, Derauf C, Newman E, Shah R, Haning W et al (2011) Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine. Neurotoxicol Teratol 33:176–184

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315

    Article  CAS  PubMed  Google Scholar 

  • Sowell ER, Leow AD, Bookheimer SY, Smith LM, O’Connor MJ, Kan E et al (2010) Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis. J Neurosci 30:3876–3885

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stanwood GD, Levitt P (2004) Drug exposure early in life: functional repercussions of changing neuropharmacology during sensitive periods of brain development. Curr Opin Pharmacol 4:65–71

    Article  CAS  PubMed  Google Scholar 

  • Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75:406–433

    Article  CAS  PubMed  Google Scholar 

  • Suzuki T, Mizuo K, Nakazawa H, Funae Y, Fushiki S, Fukushima S et al (2003) Prenatal and neonatal exposure to bisphenol-A enhances the central dopamine D1 receptor-mediated action in mice: enhancement of the methamphetamine-induced abuse state. Neurosci 117:639–644

    Article  CAS  Google Scholar 

  • Terplan M, Smith EJ, Glavin SH (2010) Trends in injection drug use among pregnant women admitted into drug treatment: 1994–2006. J Womens Health 19:499–505

    Article  Google Scholar 

  • Thompson BL, Levitt P, Stanwood GD (2009) Prenatal exposure to drugs: effects on brain development and implications for policy and education. Nat Rev Neurosci 10:303–312

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Twomey J, LaGasse L, Derauf C, Newman E, Shah R, Smith L et al (2013) Prenatal methamphetamine exposure, home environment, and primary caregiver risk factors predict child behavioral problems at 5 Years. Am J Orthopsychiatry 83:64–72

    Article  PubMed Central  PubMed  Google Scholar 

  • United Nations Office on Drugs, & Crime (2010) World Drug Report 2010. United Nations Publications

  • United Nations Office on Drugs, and Crime (2013) World Drug Report 2013. United Nations Publications

  • Vaccarino FM, Ment LR (2004) Injury and repair in developing brain. Arch Dis Child Fetal Neonatal Ed 89:190–192

    Article  Google Scholar 

  • Weiss K, Melkus G, Jakob PM, Faber C (2009) Quantitative in vivo (1)H spectroscopic imaging of metabolites in the early postnatal mouse brain at 17.6 T. MAGMA 22:53–62

    Article  CAS  PubMed  Google Scholar 

  • Won L, Bubula N, McCoy H, Heller A (2001) Methamphetamine concentrations in fetal and maternal brain following prenatal exposure. Neurotoxicol Teratol 23:349–354

    Article  CAS  PubMed  Google Scholar 

  • Wouldes TA, LaGasse LL, Derauf C, Newman E, Shah R, Smith LM et al (2013) Co-morbidity of substance use disorder and psychopathology in women who use methamphetamine during pregnancy in the US and New Zealand. Drug Alcohol Depend 127:101–107

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The South African National Research Foundation (NRF) and the Medical Research Council (MRC) of South Africa supported this research.

Conflict of interest statement

We declare no conflict of interest. The material contained herein is original; it is not currently submitted elsewhere, and has not been published previously.

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  1. University of Cape Town, Rondebosch, Western Cape, South Africa

    Maja A. Kwiatkowski, Annerine Roos, Dan J. Stein, Kevin G. F. Thomas & Kirsty Donald

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  1. Maja A. Kwiatkowski
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Kwiatkowski, M.A., Roos, A., Stein, D.J. et al. Effects of prenatal methamphetamine exposure: a review of cognitive and neuroimaging studies. Metab Brain Dis 29, 245–254 (2014). https://doi.org/10.1007/s11011-013-9470-7

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