T2 relaxation time abnormalities in bipolar disorder and schizophrenia.

There are substantial abnormalities in the number, density, and size of cortical neurons and glial cells in bipolar disorder and schizophrenia. Because molecule-microenvironment interactions modulate metabolite signals characteristics, these cellular abnormalities may impact transverse (T2) relaxation times. We measured T2 relaxation times for three intracellular metabolites (N-acetylaspartate+N-acetylaspartylglutamate, creatine+phosphocreatine, and choline-containing compounds) in the anterior cingulate cortex and parieto-occipital cortex from 20 healthy subjects, 15 patients with bipolar disorder, and 15 patients with schizophrenia at 4 T. Spectra used in T2 quantification were collected from 8-cc voxels with varying echo times (30 to 500 ms, in 10-ms steps). Both bipolar disorder and schizophrenia groups had numerically shorter T2 relaxation times than the healthy subjects group in both regions; these differences reached statistical significance for creatine+phosphocreatine and choline-containing compounds in bipolar disorder and for choline-containing compounds in schizophrenia. Metabolite T2 relaxation time shortening is consistent with reduced cell volumes and altered macromolecule structures, and with prolonged water T2 relaxation times reported in bipolar disorder and schizophrenia. These findings suggest that metabolite concentrations reported in magnetic resonance spectroscopy studies of psychiatric conditions may be confounded by T2 relaxation and highlight the importance of measuring and correcting for this variable.

In vivo proton magnetic resonance spectroscopic examination of benzodiazepine action in humans.

In an examination of the effect of benzodiazepines on brain chemistry, 44 healthy controls underwent a short echo-time proton magnetic resonance spectroscopy ((1)H MRS) session after induced sedation with intravenous midazolam (0.03mg/kg) plus fentanyl (2µg/kg). The regions of interest were the anterior cingulate cortex, right basal ganglia, right frontal lobe, and right hippocampus. Twenty-five of these subjects underwent the second (1)H MRS session while awake. The measured (1)H MRS metabolites included N-acetyl-aspartate, creatine-containing compounds (PCr+Cr), choline-containing compounds, myo-inositol, and glutamate plus glutamine, which were quantified both as absolute values and metabolite/PCr+Cr ratios. The results were analyzed using independent group t tests and repeated measures analysis of variance (ANOVA, with alpha values set at 0.025 to minimize the risk of false-positive findings arising from multiple comparisons. No significant difference between subjects under midazolam plus fentanyl induced sedation and awake could be detected with unpaired analyses. Paired comparisons by ANOVA with repeated measures found that neither drug (midazolam plus fentanyl) nor the drug by time (interval between two scan times) interaction had a significant effect on the quantified metabolites. These findings encourage utilization of benzodiazepine-induced brief sedation during in vivo (1)H MRS experiments of the brain, and may help with elucidation of state-dependent neurochemical alterations during the course of bipolar and schizoaffective disorders.

Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals.

Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color-word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N=50) and those who dropped out of the trial before completion (non-completers: N=24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p=0.02, Stroop model p=0.006, and Stroop and HDRS model p=0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance.

Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.

BACKGROUND: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examined whether a low-energy component of EP-MRSI (low-field magnetic stimulation [LFMS]) has antidepressant-like, locomotor-stimulating, or amnestic effects in rats. METHODS: We examined the effects of LFMS on immobility in the forced swim test (FST) and activity within an open field in separate groups of rats. After exposure to forced swimming, rats received LFMS (three 20-min sessions at 1.5 G/cm and .75 V/m) before behavioral testing. We also examined the effects of LFMS on fear conditioning (FC), a learning paradigm that also involves exposure to stressful conditions. RESULTS: Low-field magnetic stimulation reduced immobility in the FST, an antidepressant-like effect qualitatively similar to that of standard antidepressants. Low-field magnetic stimulation did not alter locomotor activity or FC. CONCLUSIONS: Low-field magnetic stimulation has antidepressant-like effects in rats that seem unrelated to locomotor-activating or amnestic effects. These findings raise the possibility that electromagnetic fields can affect the brain biology and might have physiologic consequences that offer novel approaches to therapy for psychiatric disorders. These same consequences might render MRI-based scans more invasive than previously appreciated.

T2 relaxation effects on apparent N-acetylaspartate concentration in proton magnetic resonance studies of schizophrenia.

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.

Reduced Plasma Nitric Oxide End Products in Cocaine-dependent Men.

Chronic cocaine abusers experience brain and peripheral vascular dysfunction, the severity of which tends to be greater in men than women. The mechanisms underlying these effects of cocaine are unknown. Because nitric oxide (NO) abnormalities play key roles in development of vascular dysfunction in several disorders, we determined whether vascular nitric oxide end product (NOx) levels, which can serve as markers of systemic vascular NO production, are reduced in cocaine-dependent (CD) subjects. Plasma samples from 24 CD men, 12 CD women, and matched comparison subjects (19 men, 14 women) were analyzed with a Sievers 280i nitric oxide chemiluminescence detection analysis system. NOx levels in comparison in women and men were 24.9 ± 6.6 and 23.3 ± 5.7 µmol/L, and in CD women and men were 22.5 ± 8.4 and 13.0 ± 9.6 µmol/L, respectively. ANCOVA analysis, adjusted for lifetime smoking, indicated group (P < 0.0005) and sex (P = 0.04) effects, both of which survived posthoc Scheffe tests. Reduced NOx levels in CD men drove the group difference. These data suggest that chronic cocaine abuse is associated with reduced NOx levels in men, although the finding also may be attributable to factors indirectly related to cocaine abuse, including cohort differences in other drug use or lifestyle factors. These findings warrant additional studies to more directly characterize vascular NO turnover in cocaine abusers and to establish whether NO abnormalities contribute to cocaine-associated vascular dysfunction and to sex differences in cocaine's effects.