Skip to main content

Advertisement

Log in

Cigarette smoking and white matter microstructure

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

Abstract

Rationale

Diffusion tensor imaging has been used before in testing associations between cigarette smoking and white matter integrity, with inconsistent results. Published reports indicate higher fractional anisotropy (FA, a measure of linear water diffusion) in some brain regions and lower FA in others in adult smokers compared to nonsmokers. Adolescent smokers exhibited elevated FA at several brain regions and a positive correlation of FA in the genu corpus callosum with exposure to smoking (pack-years).

Objective

To help resolve prior discrepancies, we studied adults, sampling multiple brain regions, and testing for relationships to clinical features of nicotine dependence and exposure to smoking.

Methods

Brain MRI scans (1.5 T) were acquired, and FA and apparent diffusion coefficient (ADC, a measure of random diffusion) were assayed in corpus callosum and prefrontal white matter, corona radiata, internal capsule, cingulum bundle, and hippocampal perforant fibers in 18 smokers (33.7 ± 7.9 years of age) and 18 age- and gender-matched nonsmokers.

Results

ADC showed no group difference, but smokers had higher (4.3–21.1%) FA than nonsmokers. The differences were significant in right prefrontal white matter, cingulum, and genu corpus callosum. FA in several regions was negatively correlated with nicotine dependence or cigarettes/day.

Conclusions

Combined with earlier findings, these results suggest a model of changing trajectories whereby FA is higher with tobacco exposure during adolescence and declines with continued smoking in adulthood. This notion is supported by the observation that, at multiple sampling sites, participants who had started smoking earlier in life had higher FA than those who had started later.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Almeida OP, Garrido GJ, Lautenschlager NT, Hulse GK, Jamrozik K, Flicker L (2008) Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease. Am J Geriatr Psychiatry 16:92–98

    Article  PubMed  Google Scholar 

  • Azizian A, Monterosso J, O’Neill J, London ED (2009) Magnetic resonance imaging studies of cigarette smoking. Handb Exp Pharmacol 192:113–143

    Article  PubMed  CAS  Google Scholar 

  • Bartzokis G (2007) Acetylcholinesterase inhibitors may improve myelin integrity. Biol Psychiatry 62:294–301

    Article  PubMed  CAS  Google Scholar 

  • Bartzokis G, Lu PH (2009) Brain volume: age-related changes. In: Squire LR (ed) Encyclopedia of neuroscience. Academic, Oxford, pp 417–427

    Chapter  Google Scholar 

  • Bartzokis G, Lu PH, Stewart SB, Oluwadara B, Lucas AJ, Pantages J et al (2009) In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia. Schizophr Res 113:322–331

    Article  PubMed  Google Scholar 

  • Behrens TE, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S et al (2003) Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 50:1077–1088

    Article  PubMed  CAS  Google Scholar 

  • Benes FM (1989) Myelination of cortical-hippocampal relays during late adolescence. Schizophr Bull 15:585–593

    PubMed  CAS  Google Scholar 

  • Brody AL, Mandelker MA, Jarvik ME, Lee GS, Smith E, Huang JC et al (2004) Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiatry 55:77–84

    Article  PubMed  Google Scholar 

  • Bürgel U, Amunts K, Hoemke L, Mohlberg H, Gilsbach JM, Zilles K (2006) White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability. NeuroImage 29:1092–1105

    Article  PubMed  Google Scholar 

  • Chung A, Lyoo IK, Kim SJ, Hwang J, Bae SC, Sung YH et al (2007) Decreased frontal white-matter integrity in abstinent methamphetamine abusers. Int J Neuropsychopharmacol 10:765–775

    Article  PubMed  CAS  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(24):2068–2075

    Article  PubMed  CAS  Google Scholar 

  • Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJL, Ezzati M (2009) The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6:e1000058

    Article  PubMed  Google Scholar 

  • Ding YS, Fowler JS, Logan J, Wang GJ, Telang F, Garza V et al (2004) 6-[18 F]Fluoro-A-85380, a new PET tracer for the nicotinic acetylcholine receptor: studies in the human brain and in vivo demonstration of specific binding white matter. Synapse 53:184–189

    Article  PubMed  CAS  Google Scholar 

  • Domino EF, Ni L, Xu Y, Koeppe RA, Guthrie S, Zubieta J-K (2004) Regional cerebral blood flow and plasma nicotine after smoking tobacco cigarettes. Prog Neuro-Psychopharmacol Biol Psychiatry 28:319–327

    Article  CAS  Google Scholar 

  • Due DL, Huettel SA, Hall WG, Rubin DC (2002) Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging. Am J Psychiatry 159:954–960

    Article  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (2002) Structured clinical interview for DSM-IV Axis I Disorders—Patient Edition (SCID-I/P, version 2.0)

  • Gallinat J, Meisenzahl E, Jacobsen LK, Kalus P, Bierbrauer J, Kienast T et al (2006) Smoking and structural brain deficits: a volumetric MR investigation. Eur J Neurosci 24:1744–1750

    Article  PubMed  Google Scholar 

  • Gallinat J, Lang U, Jacobsen L, Bajbouj M, Kalus P, von Haebler D et al (2007) Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3T. J Clin Psychopharmacol 27:80–84

    Article  PubMed  CAS  Google Scholar 

  • Garrido R, King-Pospisil K, Son KW, Hennig B, Toborek M (2003) Nicotine upregulates nerve growth factor expression and prevents apoptosis of cultured spinal cord neurons. Neurosci Res 47:349–355

    Article  PubMed  CAS  Google Scholar 

  • Gazdzinski S, Durazzo TC, Studholme C, Song E, Banys P, Meyerhoff DJ (2005) Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes. Alcohol Clin Exp Res 29:1484–1495

    Article  PubMed  CAS  Google Scholar 

  • Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E (2007) Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. Am J Neuroradiol 28:226–235

    PubMed  CAS  Google Scholar 

  • Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO (1991) The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict 86:1119–1127

    Article  PubMed  CAS  Google Scholar 

  • Hoeft F, Barnea-Goraly N, Haas BW, Golarai G, Ng D, Mills D, Korenberg J, Bellugi U, Galaburda A, Reiss A (2007) More is not always better: Increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams Syndrome. J Neurosci 27(44):11960–11965

    Article  PubMed  CAS  Google Scholar 

  • Horti A, Scheffel U, Stathis M, Finley P, Ravert HT, London ED, Dannals RF (1997) Fluorine-18-FPH for PET imaging of nicotinic acetylcholine receptors. J Nucl Med 38:1260–1265

    PubMed  CAS  Google Scholar 

  • Hsu JL, Leemans A, Bai CH, Lee CH, Tsai YF, Chiu HC, Chen WH (2008) Gender differences and age-related white matter changes of the human brain: a diffusion tensor imaging study. NeuroImage 39:566–577

    Article  PubMed  Google Scholar 

  • Jacobsen LK, Picciotto MR, Heath CJ, Frost SJ, Tsou KA, Dwan RA et al (2007) Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure. J Neurosci 27:13491–13498

    Article  PubMed  CAS  Google Scholar 

  • Jenkinson M, Smith S (2001) A global optimisation method for robust affine registration of brain images. Med Image Anal 5:143–156

    Article  PubMed  CAS  Google Scholar 

  • Kimes AS, Horti AG, London ED, Chefer SI, Contoreggi C, Ernst M et al (2003) 2-[18 F]F-A85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans. FASEB J 17:1331–1333

    PubMed  CAS  Google Scholar 

  • Kohno M, Morales A, London ED (2010) Cigarette exposure associated with abnormal white matter development in adolescent smokers. Society for Neuroscience Abstracts

  • Kühn S, Schubert F, Gallinat J (2010) Reduced Thickness of Medial Orbitofrontal Cortex in Smokers. Biol Psychiatry 68:1061–1065

    Article  PubMed  Google Scholar 

  • Lim KO, Ardekani BA, Nierenberg J, Butler PD, Javitt DC, Hoptman MJ (2006) Voxelwise correlational analyses of white matter integrity in multiple cognitive domains in schizophrenia. Am J Psychiatry 163:2008–2010

    Article  PubMed  Google Scholar 

  • Liu JJ, Mohila CA, Gong Y, Govindarajan N, Onn SP (2005) Chronic nicotine exposure during adolescence differentially influences calcium-binding proteins in rat anterior cingulate cortex. Eur J Neurosci 22:2462–2474

    Article  PubMed  Google Scholar 

  • McClellan AT, Luborsky L, Woody GE, O’Brien CP (1980) An improved diagnostic evaluation instrument for substance abuse patients: the addiction severity index. Journal of Nervous and Mental Diseases 168:26–33

    Article  Google Scholar 

  • Medina D, DeToledo-Morrell L, Urresta F, Gabrieli JD, Moseley M, Fleischman D et al (2006) White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study. Neurobiol Aging 27:663–672

    Article  PubMed  Google Scholar 

  • Nolte J, Angevine JB (2000) The human brain: in photographs and diagrams. Mosby, St. Louis

    Google Scholar 

  • Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113

    Article  PubMed  CAS  Google Scholar 

  • Opanashuk LA, Pauly JR, Hauser KF (2001) Effect of nicotine on cerebellar granule neuron development. Eur J Neurosci 13:48–56

    Article  PubMed  CAS  Google Scholar 

  • Paul RH, Grieve SM, Niaura R, David SP, Laidlaw DH, Cohen R et al (2008) Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: a diffusion tensor imaging study. Nicotine Tob Res 10:137–147

    Article  PubMed  CAS  Google Scholar 

  • Ringman JM, O’Neill J, Geschwind D, Medina L, Apostolova LG, Rodriguez Y et al (2007) Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer’s disease mutations. Brain 130:1767–1776

    Article  PubMed  Google Scholar 

  • Rogers SW, Gregori NZ, Carlson N, Gahring LC, Noble M (2001) Neuronal nicotinic acetylcholine receptor expression by O2A/oligodendrocyte progenitor cells. Glia 33:306–313

    Article  PubMed  CAS  Google Scholar 

  • Salat DH, Tuch DS, Hevelone ND, Fischl B, Corkin S, Rosas HD, Dale AM (2005) Age-related changes in prefrontal white matter measured by diffusion tensor imaging. Ann NY Acad Sc 1064:37–49

    Article  CAS  Google Scholar 

  • Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23:S208–S219

    Article  PubMed  Google Scholar 

  • Teipel SJ, Meindl T, Wagner M, Kohl T, Bürger K, Reiser MF et al (2009) White matter microstructure in relation to education in aging and Alzheimer’s disease. J Alzheimers Dis 17:571–583

    PubMed  Google Scholar 

  • Tobias MC, O’Neill J, Hudkins M, Bartzokis G, Dean AC, London ED (2010) White-matter abnormalities in brain during early abstinence from methamphetamine abuse. Psychopharmacol 209:13–24

    Article  CAS  Google Scholar 

  • Wang JJ, Durazzo TC, Gazdzinski S, Yeh PH, Mon A, Meyerhoff DJ (2009) MRSI and DTI: a multimodal approach for improved detection of white matter abnormalities in alcohol and nicotine dependence. NMR Biomed 22:516–522

    Article  PubMed  CAS  Google Scholar 

  • Witter MP (2007) The perforant path: projections from the entorhinal cortex to the dentate gyrus. Prog Brain Res 163:43–61

    Article  PubMed  Google Scholar 

  • Zachary RA, Paulson MJ, Gorsuch RL (1985) Estimating WAIS IQ from the Shipley Institute of Living Scale using continuously adjusted age norms. J Clin Psychol 41:820–831

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Stein EA, Hong LE (2010) Smoking and schizophrenia independently and additively reduce white matter integrity between striatum and frontal cortex. Biol Psychiatry 68:674–677

    Article  PubMed  Google Scholar 

  • Zhang X, Salmeron BJ, Ross TJ, Geng X, Yang Y, Stein EA (2011) Factors underlying prefrontal and insula structural alterations in smokers. NeuroImage 54:42–48

    Article  PubMed  Google Scholar 

  • Zubieta J-K, Heitzeg MM, Xu Y, Koeppe RA, Ni L, Guthrie S, Domino EF (2005) Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence. Am J Psychiatry 162:567–577

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Institutes of Health [P20DA022539, R01DA020726—EDL; R03DA20512, R21DA023192 —JON; and MOIRR00865 (UCLA General Clinical Research Center)]. Additional funding was provided by endowments from the Katherine K. and Thomas P. Pike Chair in Addiction Studies and the Marjorie Green Family Trust (EDL). Research support for projects other than the one reported here was supplied to Dr. Edythe London under UCLA contract (number 20063287) with Philip Morris USA.

Financial disclosures

Research support for projects other than the one reported here was supplied to Dr. Edythe London under UCLA contract (number 20063287) with Philip Morris USA. There was no involvement of Philip Morris USA in this project. None of the other authors have any conflicts of interest or financial disclosures to report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph O’Neill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hudkins, M., O’Neill, J., Tobias, M.C. et al. Cigarette smoking and white matter microstructure. Psychopharmacology 221, 285–295 (2012). https://doi.org/10.1007/s00213-011-2621-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2621-9

Keywords

Navigation