The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects.

To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes.

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.

To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP), a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.

Methamphetamine (MA) use rates in the United States (US) have consistently demonstrated geographical variation and have been higher in the West and Midwest. This uneven pattern of use could be explained by regional differences in MA manufacturing and distribution, but may also result from differences in altitude. The hypobaric hypoxia found at high altitude alters neurotransmitter synthesis in the brain, which may contribute to MA use. The present study investigated the relationship between mean altitude and MA use rate in the 48 contiguous US states and the District of Columbia.

Internet use and on-line game play stimulate corticostriatal-limbic circuitry in both healthy subjects and subjects with Internet gaming disorder (IGD). We hypothesized that increased fractional anisotropy (FA) with decreased radial diffusivity (RD) would be observed in IGD subjects, compared with healthy control subjects, and that these white matter indices would be associated with clinical variables including duration of illness and executive function. We screened 181 male patients in order to recruit a large number (n = 58) of IGD subjects without psychiatric co-morbidity as well as 26 male healthy comparison subjects. Multiple diffusion-weighted images were acquired using a 3.0 Tesla magnetic resonance imaging scanner. Tract-based spatial statistics was applied to compare group differences in diffusion tensor imaging (DTI) metrics between IGD and healthy comparison subjects. IGD subjects had increased FA values within forceps minor, right anterior thalamic radiation, right corticospinal tract, right inferior longitudinal fasciculus, right cingulum to hippocampus and right inferior fronto-occipital fasciculus (IFOF) as well as parallel decreases in RD value within forceps minor, right anterior thalamic radiation and IFOF relative to healthy control subjects. In addition, the duration of illness in IGD subjects was positively correlated with the FA values (integrity of white matter fibers) and negatively correlated with RD scores (diffusivity of axonal density) of whole brain white matter. In IGD subjects without psychiatric co-morbidity, our DTI results suggest that increased myelination (increased FA and decreased RD values) in right-sided frontal fiber tracts may be the result of extended game play.

Background and aims Given the similarities in clinical symptoms, Internet gaming disorder (IGD) is thought to be diagnostically similar to Internet-based gambling disorder (ibGD). However, cognitive enhancement and educational use of Internet gaming suggest that the two disorders derive from different neurobiological mechanisms. The goal of this study was to compare subjects with ibGD to those with IGD. Methods Fifteen patients with IGD, 14 patients with ibGD, and 15 healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging data for all participants were acquired using a 3.0 Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the three brain networks of default mode, cognitive control, and reward circuitry, were performed. Results Both IGD and ibGD groups demonstrated decreased functional connectivity (FC) within the default-mode network (DMN) (family-wise error p < .001) compared with healthy control subjects. However, the IGD group demonstrated increased FC within the cognitive network compared with both the ibGD (p < .01) and healthy control groups (p < .01). In contrast, the ibGD group demonstrated increased FC within the reward circuitry compared with both IGD (p < .01) and healthy control subjects (p < .01). Discussion and conclusions The IGD and ibGD groups shared the characteristic of decreased FC in the DMN. However, the IGD group demonstrated increased FC within the cognitive network compared with both ibGD and healthy comparison groups.

Metabolite-specific, scalar spin-spin coupling constant (J)-editing 1H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) 1H MRS technology offers an attractive alternative as it significantly alleviates the problem of severe metabolite signal overlap associated with standard 1D MRS and retains spectroscopic information for all MRS-detectable species. However, for metabolites found at low concentration, a direct, in vivo, comprehensive methods comparison is challenging and has not been reported to date. Here, we document an assessment of comparability between 2D 1H MRS and J-editing methods for measuring GABA in human brain. This clinical study is unique in that it involved chronic administration a GABA-amino transferase (AT) inhibitor (CPP-115), which induces substantial increases in brain GABA concentration, with normalization after washout. We report a qualitative and quantitative comparison between these two measurement techniques. In general, GABA concentration changes detected using J-editing were closely mirrored by the 2D 1H MRS time courses. The data presented are particularly encouraging considering recent 2D 1H MRS methodological advances are continuing to improve temporal resolution and spatial coverage for achieving whole-brain, multi-metabolite mapping.

Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children and adolescents. Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD. Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response.

Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein.

The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear.

The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.

Creatine monohydrate is actively being researched for its antidepressant effects, yet little is known about the link between dietary creatine and depression risk. This study examines the association between dietary creatine and depression in U.S. adults, using data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Patient health questionnaire, dietary creatine intake and covariates were obtained on 22,692 NHANES participants ≥20 years of age. Depression prevalence was calculated within quartiles of dietary creatine intake. Adjusted logistic regression models were formulated to determine the relationship between dietary creatine intake and depression risk. Additional covariates included income to poverty ratio, race/ethnicity, sex, age, education level, body mass index, healthcare access, smoking status, physical activity, and antidepressant/anxiolytic medication use. Models were further stratified by sex, age group, and antidepressant/anxiolytic medication use. Depression prevalence was 10.23/100 persons (95% CI: 8.64-11.83) among NHANES participants in the lowest quartile of dietary creatine intake compared with 5.98/100 persons (95% CI: 4.97-6.98) among participants in the highest quartile (p < 0.001). An inverse association was measured between dietary creatine and depression (adjusted odds ratio (AOR) = 0.68, 95% CI: 0.52-0.88). Dietary creatine's negative association with depression was strongest in females (AOR = 0.62, 95% CI: 0.40-0.98), participants aged 20-39 years (AOR = 0.52, 95% CI: 0.34-0.79) and participants not taking antidepressant/anxiolytic medication (AOR = 0.58, 95% CI: 0.43-0.77). Study results indicate a significant negative relationship between dietary creatine and depression in a nationally representative adult cohort. Further research is warranted to investigate the role creatine plays in depression, particularly among women and across the lifespan.

Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.

Wnts were previously shown to regulate the neurogenesis of neural stem or progenitor cells. Here, we explored the underlying molecular mechanisms through which Wnt signaling regulates neurotrophins (NTs) in the NT-induced neuronal differentiation of human mesenchymal stem cells (hMSCs). NTs can increase the expression of Wnt1 and Wnt7a in hMSCs. However, only Wnt7a enables the expression of synapsin-1, a synaptic marker in mature neurons, to be induced and triggers the formation of cholinergic and dopaminergic neurons. Human recombinant (hr)Wnt7a and general neuron makers were positively correlated in a dose- and time-dependent manner. In addition, the expression of synaptic markers and neurites was induced by Wnt7a and lithium, a glycogen synthase kinase-3β inhibitor, in the NT-induced hMSCs via the canonical/β-catenin pathway, but was inhibited by Wnt inhibitors and frizzled-5 (Frz5) blocking antibodies. In addition, hrWnt7a triggered the formation of cholinergic and dopaminergic neurons via the non-canonical/c-jun N-terminal kinase (JNK) pathway, and the formation of these neurons was inhibited by a JNK inhibitor and Frz9 blocking antibodies. In conclusion, hrWnt7a enhances the synthesis of synapse and facilitates neuronal differentiation in hMSCS through various Frz receptors. These mechanisms may be employed widely in the transdifferentiation of other adult stem cells.

Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD.

Although Internet gaming disorder (IGD) is included as a condition in the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, little is known about its nature or treatment response. This study is a follow-up of 755 patients who received professional treatment for IGD over a 5-year period.

Childhood overweight/obesity has been associated with negative consequences related to brain function and may involve alterations in white matter pathways important for cognitive and emotional processing. Aerobic physical activity is a promising lifestyle factor that could restore white matter alterations. However, little is known about either regional white matter alterations in children with overweight/obesity or the effects of aerobic physical activity targeting the obesity-related brain alterations in children. Using a large-scale cross-sectional population-based dataset of US children aged 9 to 10 years (n = 8019), this study explored the associations between overweight/obesity and microstructure of limbic white matter tracts, and examined whether aerobic physical activity may reduce the overweight/obesity-related white matter alterations in children. The primary outcome measure was restriction spectrum imaging (RSI)-derived white matter microstructural integrity measures. The number of days in a week that children engaged in aerobic physical activity for at least 60 minutes per day was assessed. We found that females with overweight/obesity had lower measures of integrity of the fimbria-fornix, a major limbic-hippocampal white matter tract, than their lean peers, while this difference was not significant in males. We also found a positive relationship between the number of days of aerobic physical activity completed in a week and integrity measures of the fimbria-fornix in females with overweight/obesity. Our results provide cross-sectional evidence of sex-specific microstructural alteration in the fimbria-fornix in children with overweight/obesity and suggest that aerobic physical activity may play a role in reducing this alteration. Future work should examine the causal direction of the relationship between childhood overweight/obesity and brain alterations and evaluate potential interventions to validate the effects of aerobic physical activity on this relationship.

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion.