Illness versus substance use effects on the frontal white matter in early phase schizophrenia: A 4 Tesla ¹H-MRS study

Objective Young adults with early phase schizophrenia often report a past or current pattern of illicit substance use and/or alcohol misuse. Still, little is known about the cumulative and separate effects of each stressor on white matter tissue, at this vulnerable period of brain development. Methods Participants involved 24 healthy controls with a past or current history of sustained illicit drug use and/or alcohol misuse (users), 23 healthy controls without such history (normative data), and 27 users with early phase schizophrenia. ¹H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4 Tesla scanner (LASER sequence, TR/TE 3200/46 ms). Results Reduced levels of choline-containing compounds (Cho) were specific to the effect of illness (Cohen's d = 0.68), with 22% of the variance in Cho levels accounted for by duration of illness. Reduced levels of myoInositol (d = 1.10) and creatine plus phosphocreatine (d = 1.07) were specific to the effects of illness plus substance use. Effect of substance use on its own was revealed by reductions in levels of glutamate plus glutamine (d = 0.83) in control users relative to normative data. Conclusions The specific effect of illness on white matter might indicate a decreased synthesis of membrane phospholipids or alternatively, reduced membrane cellular density. In terms of limitations, this study did not include patients without a lifetime history of substance use (non-users), and the specific effect of each substance used could not be studied separately.