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) in some brain regions and lower FA in others in adult smokers compared to nonsmokers. Adolescent smokers exhibited elevated FA at several sites 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 (1.5T) were acquired, and FA and apparent diffusion coefficient (ADC) 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.

BackgroundPrevious studies revealed microstructural abnormalities in prefrontal white matter and corpus callosum of long-term abstinent chronic methamphetamine abusers. In view of the importance of the early abstinence period in treatment retention, we compared 23 methamphetamine-dependent subjects abstinent from methamphetamine for 7–13 days with 18 healthy comparison subjects. As certain metabolic changes in the brain first manifest after early abstinence from methamphetamine, it is also possible that microstructural white-matter abnormalities are not yet present during early abstinence.MethodsUsing diffusion tensor imaging at 1.5 T, fractional anisotropy (FA) was measured in prefrontal white matter at four inferior–superior levels parallel to the anterior commissure–posterior commissure (AC–PC) plane. We also sampled FA in the corpus callosum at the midline and at eight bilateral, fiber-tract sites in other regions implicated in effects of methamphetamine.ResultsThe methamphetamine group exhibited lower FA in right prefrontal white matter above the AC–PC plane (11.9% lower; p = 0.007), in midline genu corpus callosum (3.9%; p = 0.019), in left and right midcaudal superior corona radiata (11.0% in both hemispheres, p’s = 0.020 and 0.016, respectively), and in right perforant fibers (7.3%; p = 0.025). FA in left midcaudal superior corona radiata was correlated with depressive and generalized psychiatric symptoms within the methamphetamine group.ConclusionsThe findings support the idea that methamphetamine abuse produces microstructural abnormalities in white matter underlying and interconnecting prefrontal cortices and hippocampal formation. These effects are already present during the first weeks of abstinence from methamphetamine and are linked to psychiatric symptoms assessed during this period.

Background:The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon.Methods:We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment.Results:In the methamphetamine group, small but significant (5–15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex.Conclusions:Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery.

Rationale Findings from animal studies and human PET imaging indicate that nicotine and cigarette smoking affect glutamate (Glu) and related neurochemical markers in the brain, and imply that smoking reduces extracellular Glu. As Glu release is mediated by nicotinic acetylcholine receptors (nAChRs), which are present at high concentrations in the thalamus, we examined effects of smoking on thalamic Glu. Objective To determine the effects of tobacco smoking on thalamic glutamate levels. Methods Thalamic Glu levels were measured in vivo in 18 smokers and 16 nonsmokers using proton magnetic resonance spectroscopic imaging (1H MRSI) at 1.5 T. Results Mean Glu levels did not differ significantly between the subject groups. However, within smokers, Glu levels were negatively correlated with self-reports of both cigarettes/day over last 30 days (r = −0.64, p = 0.006) and pack-years of smoking (r = −0.66, p = 0.005). Conclusions Consistent with expectations based on preclinical studies, within smokers cigarettes/day and pack-years are associated with reduced Glu in thalamus, a brain region rich in nAchRs. These results encourage work on candidate glutamatergic therapies for smoking cessation and suggest a non-invasive metric for their action in the brain.