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Bracken B.K.,Behavioral Psychopharmacology Research Laboratory | Bracken B.K.,an Imaging Center | Bracken B.K.,Harvard University | Bracken B.K.,Charles River Analytics Inc. | And 7 more authors.
Psychiatry Research - Neuroimaging | Year: 2013

Over the past two decades, many magnetic resonance spectroscopy (MRS) studies reported lower N-acetylaspartate (NAA) in key brain regions of patients with schizophrenia (SZ) compared to healthy subjects. A smaller number of studies report no difference in NAA. Many sources of variance may contribute to these discordant results including heterogeneity of the SZ subject populations and methodological differences such as MRS acquisition parameters, and post-acquisition analytic methods. The current study reviewed proton MRS literature reporting measurements of NAA in SZ with a focus on methodology. Studies which reported lower NAA were significantly more likely to have used longer echo times (TEs), while studies with shorter TEs reported no concentration difference. This suggests that NAA quantitation using MRS was affected by the choice of TE, and that published MRS literature reporting NAA in SZ using a long TE is confounded by apparent differential T2 relaxation effects between SZ and healthy control groups. Future MRS studies should measure T2 relaxation times. This would allow for spectral concentration measurements to be appropriately corrected for these relaxation effects. In addition, as metabolite concentration and T2 relaxation times are completely independent variables, this could offer distinct information about the metabolite of interest. © 2013 Elsevier Ireland Ltd.

Joshi G.,Massachusetts General Hospital | Joshi G.,Harvard University | Biederman J.,Massachusetts General Hospital | Biederman J.,Harvard University | And 11 more authors.
European Archives of Psychiatry and Clinical Neuroscience | Year: 2013

The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 ± 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 ± 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample. © 2012 Springer-Verlag.

Gruber S.A.,an Imaging Center | Gruber S.A.,Harvard University | Dahlgren M.K.,an Imaging Center | Sagar K.A.,an Imaging Center | And 4 more authors.
Psychopharmacology | Year: 2014

Rationale: Marijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population. Objectives: The aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers. Methods: Twenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables. Results: MJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers. Conclusions: MJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers. © 2013 The Author(s).

Mashhoon Y.,Behavioral Psychopharmacology Research Laboratory | Mashhoon Y.,Harvard University | Czerkawski C.,an Imaging Center | Crowley D.J.,Harvard University | And 7 more authors.
Alcoholism: Clinical and Experimental Research | Year: 2014

Background: The brain undergoes dynamic and requisite changes into the early 20s that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking (BD) during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. Methods: Twenty-three binge drinking (11 females, mean age 22.0 ± 1.2) and 31 light drinking (15 females, mean age 21.5 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using FreeSurfer for 3 a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between binge drinker (BD) and light drinker (LD) groups. Results: Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p ≤ 0.05) and in the left dorsal PCC (dPCC; p ≤ 0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p < 0.01) and positively with the number of days elapsed since most recent use (p < 0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p ≤ 0.05). Conclusions: Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e., "thinness") of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects that interfere with the finalization of neuromaturational processes in the vulnerable frontal cortex, resulting in increased microarchitectural pruning. © 2014 Research Society on Alcoholism.

Meade C.S.,Duke University | Meade C.S.,Duke Global Health Institute | Meade C.S.,Behavioral Psychopharmacology Research Laboratory | Meade C.S.,Harvard University | And 4 more authors.
Journal of Behavioral Medicine | Year: 2011

Cocaine abuse among HIV patients is associated with faster disease progression and mortality. This study examined the relationship between neurocognitive functioning and medication adherence in HIV patients with (n = 25) and without (n = 39) current cocaine dependence. Active users had greater neurocognitive impairment (mean T-score = 35.16 vs. 40.97, p < .05) and worse medication adherence (mean z-score = -0.44 vs. 0.27, p < .001). In a multiple regression model, neurocognitive functioning (β = .33, p < .01) and cocaine dependence (β = -.36, p < .01) were predictive of poorer adherence. There was a significant indirect effect of cocaine dependence on medication adherence through neurocognitive impairment (estimate = -0.15, p < .05), suggesting that neurocognitive impairment partially mediated the relationship between cocaine dependence and poorer adherence. These results confirm that cocaine users are at high risk for poor HIV outcomes and underscore the importance of treating both neurocognitive impairment and cocaine dependence among HIV patients. © 2010 Springer Science+Business Media, LLC.

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