Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

Glucocorticoid-immune response to acute stress in women and men living with HIV.

Despite high risk for serious non-AIDS events (SNAEs) and accelerated age-related increases in inflammatory markers relative to HIV+ men, HIV+ women have been understudied, particularly in terms of stress impacts on immune parameters. The purpose of this study was to examine sex differences in glucocorticoid-immune stress response in mid-life HIV+ individuals, as poor glucocorticoid control of stress-induced inflammation may contribute to health risk in HIV+ women. Male and female participants completed a threat of shock laboratory stressor. Serum cortisol and cytokines [interleukin (IL)-6, IL-8, IL-10, IL-1ß, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interferon (IFN)-γ] were assessed at six timepoints prior to and in response to the stressor. Participants included 8 HIV- controls (n = 5 female) and 9 HIV+ (n = 5 female) who were virally suppressed. Repeated measures mixed models revealed a significant sex by HIV status by time interaction for IL-10, IL-1ß, TNF-α, and cortisol. IL-10 response, an anti-inflammatory cytokine, was larger in males than females, regardless of HIV status. TNF-α response was blunted in HIV+ individuals compared with HIV-, and specifically in HIV+ women, IL-1ß and cortisol response were blunted. Individuals living with HIV may have impaired coordination between the immune system and hypothalamic pituitary adrenal (HPA) axis. HIV+ women in particular exhibited dysregulated IL-1ß and cortisol response to acute stress. Future work should focus on relationships among proinflammatory cytokines, stress, and SNAEs in HIV, with attention to sex as a biological variable.

Randomized controlled trial of transcranial magnetic stimulation in pregnant women with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) affects 10% of pregnancies. Because transcranial magnetic stimulation (TMS) is a nonmedication option, psychiatric patients who do not tolerate or prefer to avoid antidepressants are good candidates for TMS. METHOD: In a randomized controlled trial of twenty-two women with MDD in the second or third trimester of pregnancy, subjects were randomized to active TMS (n=11) or sham TMS (n=11). This study took place at a single academic center. Subjects received 20 sessions of TMS to the right dorsolateral prefrontal cortex at 1 Hz as a single train of 900 pulses per session at 100% motor threshold. Estradiol and progesterone and were measured before session 1 and after session 20. RESULTS: Results demonstrated significantly decreased Hamilton Depression Rating Scale (HDRS-17) scores for the active compared to the sham group (p=0.003). Response rates were 81.82% for the active and 45.45% for the sham coil (p=0.088). Remission rates were 27.27% for the active 18.18% for the sham coil (p=0.613). Late preterm birth (PTB) occurred in three women receiving active TMS. All other maternal and delivery outcomes were normal. CONCLUSIONS: Right-sided, low frequency TMS was effective in reducing depressive symptoms in this sample of pregnant women. There may be a possibility that TMS is associated with late PTB although a larger sample size would be needed for adequate power to detect a true difference between groups. This study demonstrated that TMS is low risk during pregnancy although larger trials would provide more information about the efficacy and safety of TMS in this population. This trial shows that an RCT of a biologic intervention in pregnant women with psychiatric illness can be conducted.

New onset executive function difficulties at menopause: a possible role for lisdexamfetamine.

RATIONALE: Reports of cognitive decline, particularly in the domains of executive functions (EFs), are common among menopausal women. OBJECTIVE: This study aims to determine the impact of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset EF complaints. METHODS: Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties as measured using the Brown Attention Deficit Disorder Scale (BADDS) were administered LDX 40-60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest. RESULTS: Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p = 0.0001) and for four out of the five BADDS subscales (all p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p = 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p = 0.017) and heart rate increased significantly (p = 0.006) when women were on LDX but remained, on average, within the normal range. CONCLUSIONS: LDX 40-60 mg/day was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women.