Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a (1)H-magnetic resonance spectroscopy study.
In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy ((1)H-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel (1)H-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p = 0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p = 0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p < 0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. howellsfleur@gmail.com.
F M
FM
Howells
Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
K A
KA
Donald
Medical Research Council Anxiety and Stress Disorders Unit, University of Stellenbosch, Stellenbosch, South Africa.
A
A
Roos
Departments of Neurology and of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
R P
RP
Woods
Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
H J
HJ
Zar
Departments of Neurology and of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
K L
KL
Narr
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
D J
DJ
Stein
D000428:Alcohol Drinking / Q000009:adverse effects / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000378:metabolism*; D011522:Protons; D012727:Sex Characteristics; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
D011522:Protons; D018698:Glutamic Acid
Alcohol exposure; Gray matter; MRS; Oligodendrocytes; Thyroid hormone