Illness versus substance use effects on the frontal white matter in early phase schizophrenia: A 4Tesla (1)H-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. (1)H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4Tesla scanner (LASER sequence, TR/TE 3200/46ms).

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.