Altered white matter microstructure in adolescent substance users.
Chronic marijuana use during adolescence is frequently comorbid with heavy alcohol consumption and associated with CNS alterations, yet the influence of early cannabis and alcohol use on microstructural white matter integrity is unclear. Building on evidence that cannabinoid receptors are present in myelin precursors and affect glial cell processing, and that excessive ethanol exposure is associated with persistently impaired myelination, we used diffusion tensor imaging (DTI) to characterize white matter integrity in heavy substance using and non-using adolescents. We evaluated 36 marijuana and alcohol-using (MJ+ALC) adolescents (ages 16-19) and 36 demographically similar non-using controls with DTI. The diffusion parameters fractional anisotropy (FA) and mean diffusivity (MD) were subjected to whole-brain voxelwise group comparisons using tract-based spatial statistics (Smith, S.M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T.E., Mackay, C.E., Watkins, K.E., Ciccarelli, O., Cader, M.Z., Matthews, P.M., Behrens, T.E., 2006. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31, 1487-1505). MJ+ALC teens had significantly lower FA than controls in 10 regions, including left superior longitudinal fasciculus (SLF), left postcentral gyrus, bilateral crus cerebri, and inferior frontal and temporal white matter tracts. These diminutions occurred in the context of increased FA in right occipital, internal capsule, and SLF regions. Changes in MD were less distributed, but increased MD was evident in the right occipital lobe, whereas the left inferior longitudinal fasciculus showed lower MD in MJ+ALC users. Findings suggest that fronto-parietal circuitry may be particularly impacted in adolescent users of the most prevalent intoxicants: marijuana and alcohol. Disruptions to white matter in this young group could indicate aberrant axonal and myelin maturation with resultant compromise of fiber integrity. Findings of increased anisotropic diffusion in alternate brain regions suggest possible neuroadaptive processes and can be examined in future studies of connectivity to determine how aberrancies in specific tracts might influence efficient cognitive processing.
Bava
Sunita
S
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
Frank
Lawrence R
LR
McQueeny
Tim
T
Schweinsburg
Brian C
BC
Schweinsburg
Alecia D
AD
Tapert
Susan F
SF
D000293:Adolescent; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D019966:Substance-Related Disorders / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
Neuroimage. 2004 Jan;21(1):329-39
14741671
Neuroimage. 2004 Nov;23(3):914-20
15528091
Magn Reson Med. 2004 Nov;52(5):979-93
15508154
Magn Reson Med. 2003 Jan;49(1):177-82
12509835
Magn Reson Imaging. 2000 Jul;18(6):659-69
10930775
Alcohol Clin Exp Res. 2008 Mar;32(3):395-404
18241319
Nat Protoc. 2007;2(3):499-503
17406613
FEBS Lett. 1998 Sep 25;436(1):6-10
9771884
Neuroimage. 2007 Apr 1;35(2):501-10
17258911
Brain. 2006 May;129(Pt 5):1096-112
16585053
Cereb Cortex. 2005 Dec;15(12):1848-54
15758200
QJM. 2000 Jul;93(7):449-56
10874054
Alcohol Clin Exp Res. 2008 Mar;32(3):386-94
18302722
Peptides. 2000 Nov;21(11):1735-42
11090929
Neuropsychopharmacology. 2005 Feb;30(2):423-32
15562292
Alcohol Clin Exp Res. 2000 Dec;24(12):1873-82
11141048
Hum Brain Mapp. 2005 Oct;26(2):139-47
15858815
Neurotoxicol Teratol. 2007 Jan-Feb;29(1):141-52
17169528
Nat Neurosci. 1999 Oct;2(10):859-61
10491602
Magn Reson Med. 2003 Jan;49(1):193-7
12509838
Brain Cogn. 2008 Jul;67(2):225-33
18346830
J Int Neuropsychol Soc. 2002 Nov;8(7):873-83
12405538
J Magn Reson Imaging. 2001 Apr;13(4):534-46
11276097
IEEE Trans Med Imaging. 1999 Aug;18(8):712-21
10534053
Chem Phys Lipids. 2002 Dec 31;121(1-2):257-66
12505705
J Stud Alcohol. 1998 Jul;59(4):427-38
9647425
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10422-7
10468624
Magn Reson Med. 1995 Jul;34(1):65-73
7674900
Magn Reson Med. 1999 Sep;42(3):515-25
10467296
Radiology. 2004 Jan;230(1):77-87
14645885
Alcohol Clin Exp Res. 2005 Sep;29(9):1590-600
16205359
Psychiatry Res. 2008 May 30;163(1):40-51
18356027
JAMA. 2002 Mar 6;287(9):1172-4
11879116
Proc Natl Acad Sci U S A. 2004 May 25;101(21):8174-9
15148381
J Neurosci. 2002 Nov 15;22(22):9742-53
12427829
Drug Alcohol Depend. 2005 Aug 1;79(2):201-10
16002029
Psychopharmacology (Berl). 2004 Nov;176(3-4):239-47
15205869
J Neurosci Res. 2002 Mar 15;67(6):829-36
11891798
Neuroimage. 2008 Jan 1;39(1):52-61
17919933
Psychopharmacology (Berl). 2007 Oct;194(2):173-83
17558500
Neuroreport. 1993 Feb;4(2):135-8
8453049
Arch Gen Psychiatry. 2008 Jun;65(6):694-701
18519827
J Neurol Sci. 1997 Mar 10;146(2):145-51
9077511
J Biol Chem. 1995 Jun 9;270(23):13973-80
7775459
Neuroreport. 2000 Feb 28;11(3):491-6
10718301
Nat Neurosci. 1999 Oct;2(10):861-3
10491603
J Neurosci. 2001 Feb 1;21(3):823-33
11157068
Drug Alcohol Depend. 2005 Jan 7;77(1):23-30
15607838
Med Image Anal. 2001 Jun;5(2):143-56
11516708
Neuroimage. 2005 Jul 15;26(4):1164-73
15961051
Drug Alcohol Depend. 2004 Nov 11;76(2):125-33
15488336
Am J Psychiatry. 2003 Jun;160(6):1078-85
12777265
Alcohol Clin Exp Res. 1995 Aug;19(4):1018-23
7485811
J Child Psychol Psychiatry. 2007 Jun;48(6):592-600
17537075
J Am Acad Child Adolesc Psychiatry. 2008 Feb;47(2):165-173
18176333
Psychol Addict Behav. 2007 Dec;21(4):478-87
18072830
Neuroimage. 2006 Jul 15;31(4):1487-505
16624579
Neuroimage. 2008 Jul 1;41(3):1067-74
18424082
Harm Reduct J. 2006 May 09;3:17
16684342
Magn Reson Med. 2003 Nov;50(5):1077-88
14587019
Br J Addict. 1991 Sep;86(9):1119-27
1932883
Ann N Y Acad Sci. 2004 Jun;1021:77-85
15251877
Comput Biomed Res. 1996 Jun;29(3):162-73
8812068
Schizophr Res. 2008 Feb;99(1-3):1-6
18248793
J Pharmacol Exp Ther. 1999 Mar;288(3):1357-66
10027878
Magn Reson Med. 2002 Jun;47(6):1083-99
12111955
Neurosci Biobehav Rev. 2006;30(6):718-29
16887188
Curr Drug Abuse Rev. 2008 Jan;1(1):99-111
19630709
Neuroimage. 2004;23 Suppl 1:S208-19
15501092
Neurosci Lett. 2006 Oct 2;406(1-2):76-80
16905253
Neuroimage. 2009 Feb 1;44(3):777-89
18992825
Neuroimage. 2002 Oct;17(2):825-41
12377157
Arch Gen Psychiatry. 2003 May;60(5):443-56
12742865
Biol Psychiatry. 2006 Feb 15;59(4):364-72
16125148
Alcohol Clin Exp Res. 2000 Feb;24(2):164-71
10698367
J Int Neuropsychol Soc. 2003 Jul;9(5):679-89
12901774
Radiology. 1999 Sep;212(3):770-84
10478246
Neuroreport. 2007 Oct 29;18(16):1735-9
17921878
Behav Brain Res. 2007 Jul 19;181(1):12-22
17467816
J Neurochem. 2002 May;81(4):802-13
12065639
Neuroimage. 2007 Jan 15;34(2):733-42
17092743
Cereb Cortex. 2005 Jun;15(6):854-69
15590909
Neurobiol Aging. 2006 Jul;27(7):994-1009
15964101
Brain Res Cogn Brain Res. 2005 Apr;23(1):107-18
15795138
Biol Psychiatry. 2008 Mar 1;63(5):512-8
17720147
Pediatrics. 2008 Apr;121 Suppl 4:S290-310
18381495
Neuroimage. 2002 May;16(1):177-99
11969328
J Abnorm Psychol. 2004 Nov;113(4):483-98
15535782
Radiology. 1996 Dec;201(3):637-48
8939209
Psychol Med. 2008 Jun;38(6):877-85
17949516
J Int Neuropsychol Soc. 2007 Sep;13(5):807-20
17697412
Addict Behav. 2004 Feb;29(2):413-23
14732431
Alcohol Clin Exp Res. 2008 Jun;32(6):1001-13
18422840
Magn Reson Med. 1996 Dec;36(6):893-906
8946355
J Int Neuropsychol Soc. 1999 Sep;5(6):481-93
10561928
Science. 1999 Mar 19;283(5409):1908-11
10082463
Trends Cogn Sci. 2005 Feb;9(2):60-8
15668098
J Neurosci. 2003 Feb 15;23(4):1398-405
12598628
Biol Psychiatry. 2007 Jan 1;61(1):31-40
16631130
J Psychiatr Res. 2009 Jan;43(3):189-204
19111160
Biol Psychiatry. 2005 Mar 1;57(5):448-55
15737658
Alcohol Clin Exp Res. 2004 Oct;28(10):1577-86
15597092