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Increased white matter hyperintensities in male methamphetamine abusers

https://doi.org/10.1016/j.drugalcdep.2005.05.016Get rights and content

Abstract

Background

The current study was conducted to compare the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance (MR) imaging in methamphetamine (MA) abusers.

Methods

Thirty-three MA abusers and 32 age- and gender-matched healthy comparison subjects were studied. Axial T-2 weighted images and fluid attenuated inversion recovery axial images were obtained using 3.0 T MR scanner. The severity of WMH was assessed separately for deep and periventricular WMH. Ordinal logistic regression models were used to assess the odds ratio for WMH.

Results

MA abusers had greater severity of WMH than the healthy comparison subjects (odds ratio: 7.06, 8.46, and 4.56 for all, deep, and periventricular WMH, respectively). Severity of deep WMH correlated with total cumulative dose of MA (p = 0.027). Male MA abusers had greater severity of WMH than female MA abusers (odds ratio = 10.00). While male MA abusers had greater severity of WMH than male comparison subjects (odds ratio = 18.86), there was no significant difference in WMH severity between female MA abusers and female comparison subjects.

Conclusions

The current study reports increased WMH in MA abusers, which may be related to MA-induced cerebral perfusion deficits. In addition, female MA abusers had less severe WMH than male MA abusers, possibly due to estrogen's protective effect against ischemic or neurotoxic effects of MA.

Introduction

White matter signal hyperintensities (WMH) can be defined as patchy or diffuse white matter changes on T2-weighted magnetic resonance images (MRI) (Awad et al., 1986). Neuropathologic examination of WMH lesion has shown dilated perivascular spaces, perivascular demyelination, astrocytic gliosis and arteriosclerosis (Awad et al., 1986).

WMH increase with cardiovascular risk factors such as aging, hypertension, and diabetes mellitus (Awad et al., 1986, Coffey et al., 1988, Fazekas et al., 1988). The prevalence and significance of WMH has also been studied in major depression (Lyoo et al., 2002), bipolar disorder (Ahn et al., 2004), and schizophrenia (Keshavan et al., 1996).

Increased prevalence of WMH has been reported in cocaine and opiate abusers (Volkow et al., 1988, Bartzokis et al., 1999, Lyoo et al., 2004). Moreover, cerebral perfusion defects and ischemic lesions have been observed in animal studies (Wang et al., 2001) and in human MA abusers (Yen et al., 1994, Chang et al., 2002). Consequently, we hypothesised that subjects with MA dependence will have an increased severity of WMH relative to healthy comparison subjects.

MA-related neurotoxicity has been reported more frequently in males than in females in animal studies (Myers et al., 2003, Dluzen and McDermott, 2004). Estrogen has been reported to have a protective effect against cerebrovascular accidents (Paganini-Hill et al., 1988) and possibly for WMH (Schmidt et al., 1996). In addition, gender differences of MA effects on cerebral blood flow and glucose metabolism have been reported (Chang et al., 2002, Kim et al., 2005). Consequently, we also hypothesised that increased WMH would be more pronounced in male MA abusers than in female MA abusers, as compared to respective gender-matched comparison subjects.1

Section snippets

Subjects

Study subjects were recruited in Seoul, South Korea. Inclusion criteria were: (1) ages: 19–49, (2) lifetime diagnosis of DSM-IV methamphetamine dependence, as determined by Structured Clinical Interview for DSM-IV (SCID-IV), (3) an abstinence period longer than 4 weeks, and (4) cumulative intravenous MA use over 50.0 g. Exclusion criteria were: (1) current or past significant medical or neurological illness, (2) current or lifetime Axis I psychiatric disorders, (3) antisocial or borderline

Diagnosis and WMH

The prevalence and severity of WMH were presented in Fig. 1. MA abusers had greater severity of all WMH (deep and periventricular WMH combined) than healthy comparison subjects (ordinal logistic regression: z = 3.06, p = 0.002, odds ratio = 7.06) controlling for age. Age and gender were controlled in all the following ordinal regression models since it was a significant predictor for WMH. MA abusers had greater prevalence of WMH than healthy volunteers (33.3% versus 3.1%, respectively, Fisher's exact

Discussion

In the current study, we reported greater prevalence and severity of WMH in MA abusers relative to healthy volunteers. In addition, these findings were found only in male, not in female, MA abusers relative to respective gender-matched comparison subjects. To the best of our knowledge, this is the first report, which systemically measured the rates and severity of deep and periventricular WMH in MA abusers.

As we hypothesised, the prevalence and severity of WMH in MA abusers were greater than

Acknowledgements

This work was supported, in part, by grants from the National Institute on Drug Abuse (DA09448-09S1), Stanley Medical Research Institute, NARSAD and the Harvard-MIT CITP, National Institute on Drug Abuse (DA09448) (I.K.L. and P.F.R.), the National Institute on Drug Abuse (DA14178, DA15116) (P.F.R.), and Seoul National University Hospital (21-2004-008) (I.K.L.).

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