An Integrated Analysis of Anatomical and Sugar Contents Identifies How Night Temperatures Regulate the Healing Process of Oriental Melon Grafted onto Pumpkin.

Graft healing is a complex process affected by environmental factors, with temperature being one of the most important influencing factors. Here, oriental melon grafted onto pumpkin was used to study changes in graft union formation and sugar contents at the graft interface under night temperatures of 18 °C and 28 °C. Histological analysis suggested that callus formation occurred 3 days after grafting with a night temperature of 28 °C, which was one day earlier than with a night temperature of 18 °C. Vascular reconnection with a night temperature of 28 °C was established 2 days earlier than with a night temperature of 18 °C. Additionally, nine sugars were significantly enriched in the graft union, with the contents of sucrose, trehalose, raffinose, D-glucose, D-fructose, D-galactose, and inositol initially increasing but then decreasing. Furthermore, we also found that exogenous glucose and fructose application promotes vascular reconnection. However, exogenous sucrose application did not promote vascular reconnection. Taken together, our results reveal that elevated temperatures improve the process of graft union formation through increasing the contents of sugars. This study provides information to develop strategies for improving grafting efficiency under low temperatures.

Efficacy of Streptomyces murinus JKTJ-3 in Suppression of Pythium Damping-Off of Watermelon.

Damping-off caused by Pythium aphanidermatum (Pa) is one of the most destructive diseases for watermelon seedlings. Application of biological control agents against Pa has attracted the attention of many researchers for a long time. In this study, the actinomycetous isolate JKTJ-3 with strong and broad-spectrum antifungal activity was screened from 23 bacterial isolates. Based on the morphological, cultural, physiological, and biochemical characteristics as well as the feature of 16S rDNA sequence, isolate JKTJ-3 was identified as Streptomyces murinus. We investigated the biocontrol efficacy of isolate JKTJ-3 and its metabolites. The results revealed that seed and substrate treatments with JKTJ-3 cultures showed a significant inhibitory effect on watermelon damping-off disease. Seed treatment with the JKTJ-3 cultural filtrates (CF) displayed higher control efficacy compared to the fermentation cultures (FC). Treatment of the seeding substrate with the wheat grain cultures (WGC) of JKTJ-3 exhibited better control efficacy than that of the seeding substrate with the JKTJ-3 CF. Moreover, the JKTJ-3 WGC showed the preventive effect on suppression of the disease, and the efficacy increased with increase in the inoculation interval between the WGC and Pa. Production of the antifungal metabolite actinomycin D by isolate JKTJ-3 and cell-wall-degrading enzymes such as ß-1,3-glucanase and chitosanase were probably the mechanisms for effective control of watermelon damping-off. It was shown for the first time that S. murinus can produce anti-oomycete substances including chitinase and actinomycin D. This is the first report about S. murinus used as biocontrol agent against watermelon damping-off caused by Pa.

Tobacco nicotine promotes TRAIL resistance in lung cancer through SNHG5.

Tobacco nicotine use is carcinogenic and a well-known risk factor for lung cancer. However, whether tobacco nicotine can induce drug resistance in lung cancer is not clear. The objective of the present study was to identify the TNF-related apoptosis-inducing ligand (TRAIL) resistance of long noncoding RNAs (lncRNAs) that are differentially expressed in smokers and nonsmokers with lung cancer. The results suggested that the nicotine upregulated small nucleolar RNA host gene 5 (SNHG5) and markedly decreased the levels of cleaved caspase-3. The present study found that cytoplasm lncRNA SNHG5 overexpression was associated with TRAIL resistance in lung cancer and that SNHG5 can interact with X-linked inhibitor of apoptosis protein to promote TRAIL resistance. Therefore, nicotine promoted TRAIL resistance in lung cancer through SNHG5/X-linked inhibitor of apoptosis protein.

The complete mitochondrial genome of Fannia canicularis (Diptera: Fanniidae).

Fannia canicularis (Linnaeus, 1761) is a species from the family Fanniidae. In this study, we sequenced and analyzed the complete mitochondrial genome of F. canicularis for the first time. The circular mitogenome is 15,826 bp in length, and includes 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding control region. The family Fanniidae formed a monophyletic clade in the phylogenetic tree based on 13 concatenated PCGs, sister to three other families in Diptera.

Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming.

Background: Various comorbid psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD), have been reported in individuals with internet gaming disorder (IGD). Prior research has shown alterations in brain metabolites, including N-acetylaspartate (NAA), and combined glutamate and glutamine in patients with ADHD that were similar to those observed in patients with IGD. We hypothesized that the decreased NAA levels in the IGD group would be associated with a history of ADHD. Methods: Forty adults participated in this study. Participants were classified as having a high risk for IGD if they had a total score higher than 21 on the IGD Scale-short form. Proton magnetic resonance spectroscopy (1H-MRS) and high-resolution structural magnetic resonance imaging (MRI) data were acquired using a 3 Tesla Siemens Prisma scanner system. Results: Levels of NAA within the right prefrontal cortex were lower in the IGD group than those observed in the control group. In a multiple linear regression analysis, internet addiction test scores and history of ADHD were shown to predict increased game play. In addition, history of ADHD predicted lower levels of NAA within the right prefrontal cortex. Conclusion: The preliminary results of current study suggest a mediating effect of ADHD on the severity of internet game play as well as the levels of NAA within the dorsolateral prefrontal cortex (DLPFC). The inclusion of ADHD in IGD research is important and deserving of further consideration.

Sequencing and analysis of the complete mitochondrial genome of Mansonia uniformis (Dipera: Culicidae).

In this study, we sequenced and analyzed the complete mitochondrial genome of Mansonia uniformis, and this is the first report on the genus Mansonia. The circular mitogenome is 15,603 bp long and contains 13 protein-coding genes (PCGs), 22 tRNA genes, 2 ribosomal RNA genes, and a A + T-rich control region. Most PCGs start with ATN codons, and end with TAA, except for COX1 starting with TCG codons and COX2 ending with a single thymine stop codon. The phylogenetic tree based on the COX1 gene showed that M. uniformis formed a monophyletic clade, sister to other seven genus from the subfamily Culicinae.

Progastrin-Releasing Peptide Precursor and Neuron-Specific Enolase Predict the Efficacy of First-Line Treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Among Non-Small-Cell Lung Cancer Patients Harboring EGFR Mutations.

PURPOSE: Lung cancer is the leading cause of cancer-related mortality and non-small-cell lung cancer (NSCLC) accounts for 80-90% of all lung cancers. However, biomarkers to predict the prognosis of NSCLC patients upon treatment with tyrosine kinase inhibitors remain unreliable. Different types of EGFR mutations can help predict the efficacy of tyrosine kinase inhibitor (TKI) treatment among advanced NSCLC patients harboring them. However, survival varies among individuals harboring the same mutation after targeted therapy. This study aimed to investigate the value of serum tumor markers (STMs) and EGFR mutations in the prognostic assessment of progression-free survival (PFS) in advanced-stage EGFR-mutated NSCLC. PATIENTS AND METHODS: A retrospective clinical review was performed on 81 NSCLC patients harboring EGFR mutations and for whom STM data, measured before commencement of first-line treatment with tyrosine kinase inhibitors, were available. Associations among EGFR mutations, STMs, baseline clinical features, and PFS were analyzed. Kaplan-Meier method was used to plot survival curves, and Cox logistic regression models were used to identify independent prognostic factors. RESULTS: Exon 19 deletion (19-del) in EGFR, negative neuron-specific enolase (NSE), negative pro-gastrin-releasing peptide precursor (ProGRP) value, and "never smoking" status were significantly associated with improved PFS (P=0.007, P=0.001, P<0.001, and P<0.001, respectively). Multivariate Cox analysis revealed that 19-del in EGFR, never smoking, negative ProGRP value, and negative NSE were independent predictors of PFS. CONCLUSION: This study demonstrated that 19-del in EGFR may predict longer PFS in advanced-stage EGFR-mutated NSCLC treated with TKIs. Additionally, longer PFS can be predicted by serum tumor markers with negative ProGRP value, negative NSE value before initial treatment, and "never smoking." Therefore, in addition to the EGFR mutation type and smoking status, physicians can also prognosticate the PFS of tyrosine kinase inhibitors treatment according to the values of ProGRP and NSE before treatment.

MicroRNA-215-3p Suppresses the Growth, Migration, and Invasion of Colorectal Cancer by Targeting FOXM1.

Previous investigations have indicated that microRNA-215-3p is dysregulated in many kinds of cancers and functions as oncogene or tumor suppressor. However, the potential role of microRNA-215-3p in the progression of colorectal cancer remains not well known. Herein, we demonstrated that microRNA-215-3p was downregulated in human colorectal cancer tissues and was reversely correlated to the lymph node metastasis of colorectal cancer. Overexpression of microRNA-215-3p inhibited the clonogenic abilities and metastasis-relevant traits of colorectal cancer cell in vitro. Consistently, upregulation of microRNA-215-3p inhibited the growth and metastasis of colorectal cancer cell in vivo. Forkhead box protein M1 was identified as a direct target of microRNA-215-3p and reexpression of forkhead box protein M1 reversed the suppressive impacts of microRNA-215-3p on the growth, mobility, and invasion abilities of colorectal cancer cell. Altogether, these results revealed the vital role of microRNA-215-3p in the tumorigenesis and metastasis of colorectal cancer.

Cerebral bioenergetic differences measured by phosphorus-31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude.

AIM: Increased oxidative stress in cerebral mitochondria may follow exposure to the systemic hypobaric hypoxia associated with residing at higher altitudes. Because mitochondrial dysfunction is implicated in bipolar disorder (BD) pathophysiology, this may impact the cerebral bioenergetics in BD. In this study, we evaluated the cerebral bioenergetics of BD and healthy control (HC) subjects at two sites, located at sea level and at moderate altitude. METHODS: Forty-three veterans with BD and 33 HC veterans were recruited in Boston (n = 22) and Salt Lake City (SLC; n = 54). Levels of phosphocreatine, ß nucleoside triphosphate (ßNTP), inorganic phosphate, and pH over total phosphate (TP) were measured using phosphorus-31 magnetic resonance spectroscopy in the following brain regions: anterior cingulate cortex and posterior occipital cortex, as well as bilateral prefrontal and occipitoparietal (OP) white matter (WM). RESULTS: A significant main effect of site was found in ßNTP/TP (Boston > SLC) and phosphocreatine/TP (Boston < SLC) in most cortical and WM regions, and inorganic phosphate/TP (Boston < SLC) in OP regions. A main effect analysis of BD diagnosis demonstrated a lower pH in posterior occipital cortex and right OP WM and a lower ßNTP/TP in right prefrontal WM in BD subjects, compared to HC subjects. CONCLUSION: The study showed that there were cerebral bioenergetic differences in both BD and HC veteran participants at two different sites, which may be partly explained by altitude difference. Future studies are needed to replicate these results in order to elucidate the dysfunctional mitochondrial changes that occur in response to hypobaric hypoxia.

Continuous prospectively navigated multi-echo GRE for improved BOLD imaging of the kidneys.

The objective of this study is to develop improved methods for renal blood oxygenation level dependent (BOLD) imaging. T2* mapping of the kidneys, or renal BOLD imaging, may depict renal oxygen levels and may be valuable as a noninvasive means of following the progression of renal disease. Current renal BOLD data is limited by imaging in a single breath hold, which results in low resolution and low signal-to-noise ratio (SNR). We compare a new free-breathing renal BOLD method with conventional breath-hold BOLD (BH-BOLD). A multi-echo GRE sequence with continuous prospective respiratory navigation and real-time feedback was developed that allows high resolution and high SNR renal BOLD imaging with constant sequence repetition time (TR) during free-breathing BOLD (FB-BOLD). The sequence was evaluated in 10 normal volunteers and compared with conventional BH-BOLD. Scan time for the FB-BOLD sequence was approximately three minutes, compared with 15 seconds for the BH-BOLD sequence. SNR of source images and residual error of T2* fitting were compared between the two methods. The FB-BOLD sequence produced motion-free T2* maps of the kidneys with SNR 1.9 times higher than BH-BOLD images. Residual error of T2* fitting was consistently lower in the right kidney with FB-BOLD (30% less than BH-BOLD) but higher in the left kidney (80% more than BH-BOLD), likely related to placement of the navigator on the right hemidiaphragm. A free-breathing prospectively navigated renal BOLD sequence allows flexible tradeoff between scan time, resolution, and SNR.

iTRAQ-based quantitative proteomics analysis of cold stress-induced mechanisms in grafted watermelon seedlings.

Rootstock grafting can improve the cold tolerance of watermelon. However, the molecular mechanisms underlying this process remain unknown. Herein, we used an isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach for the comparative analysis of protein abundances in self-grafted (SG) and pumpkin rootstock-grafted (RG) watermelon seedlings in response to cold stress. A total of 4796 distinct proteins were identified, and 752 proteins were significantly differentially accumulated in grafted watermelon seedling leaves after 48 h cold stress. Based on bioinformatics analysis, the cold tolerance of RG watermelon seedlings might be related to more energy produced through photosynthesis, carbon metabolism, and oxidative phosphorylation, compared with that of SG watermelon seedlings. RG watermelon seedlings could cope with cold stress by improving the scavenging capacity of ROS and arginine biosynthesis. Posttranscriptional regulation and protein homeostasis also play important roles for grafted watermelon seedlings to adapt to cold stress. Several protein kinases involved in signal transduction may act as positive regulators in RG watermelon seedling leaves suffering from cold stress. In addition, iTRAQ data were confirmed to be reliable by the assays of physiological indicators and relative transcript levels of eight genes. BIOLOGICAL SIGNIFICANCE: Rootstock grafting is regarded as an effective method to enhance the cold tolerance of watermelon seedlings. To elucidate the cold tolerance mechanism of grafted watermelon, an iTRAQ-based quantitative proteomics approach combined with bioinformatics analysis was employed to identify differentially accumulated proteins in SG and RG watermelon seedlings between cold stress and control conditions. This study provided additional insight into the molecular basis of the grafted watermelon seedlings in response to cold stress.

Reduced lateral orbitofrontal cortex volume and suicide behavior in youth with bipolar disorder.

OBJECTIVES: Structural abnormalities in cortical and subcortical regions, including the orbitofrontal cortex (OFC), are altered during brain development in adolescents with bipolar disorder (BD), which may increase risk for suicide. Few studies have examined the neural substrates of suicidal behavior in BD youth. The aim of the present study was to investigate the relationship between suicide behavior and the OFC in youth with BD. METHODS: Thirty-seven participants with BD and 26 non-psychiatric controls, ages 13-21 years, completed a diagnostic interview and mood rating scales. Lifetime symptoms of suicide ideation and behavior were examined using the Columbia Suicide Severity Rating Scale. Participants underwent magnetic resonance imaging on a 3T Siemens Verio scanner. Morphometric analysis of brain images was performed using FreeSurfer. RESULTS: Eighteen participants with BD had a history of suicide attempt (SA). Bipolar youth with a history of SA showed reduced left lateral OFC volumes compared to controls, but there was no difference between BD attempters and non-attempters. Controls and BD non-attempters had significantly greater OFC cortical thickness than BD attempters. Additionally, there was a significant negative correlation between OFC volumes and suicide lethality, demonstrating that as suicide lethality increased, OFC volume in BD youth was reduced. CONCLUSIONS: The OFC is involved in decision-making, impulsivity, and reward circuitry which have shown to be impaired in BD. Reduced OFC volume and its association with lethality of suicide suggest that suicide behavior in BD may be related to the emerging neuroanatomical substrates of the disorder, particularly abnormalities of the OFC.

Relationship of executive functioning deficits to N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) in youth with bipolar disorder.

BACKGROUND: Although cognitive deficits in bipolar disorder (BD) have been repeatedly observed, our understanding of these impairments at a mechanistic level remains limited. Few studies that investigated cognitive impairments in bipolar illness have examined the association with brain biochemistry. This pilot study utilized proton magnetic resonance spectroscopy (1H-MRS) to evaluate the relationship between neurocognitive performance and brain metabolites in youth with BD. METHODS: Thirty participants, twenty depressed BD participants and ten healthy comparison participants, ages 13-21, completed mood and executive function measures. 1H-MRS data were also acquired from the anterior cingulate cortex (ACC) using two-dimensional (2D) J-resolved 1H-MRS sequence. Proton metabolites including N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) were quantified for both groups. RESULTS: Participants with BD performed significantly lower on executive functioning measures than comparison participants. There were significant positive correlations between Wisconsin Card Sorting Test (WCST) performance and NAA (p < .001) and GABA (p < .01) in the ACC in bipolar youth, such that as WCST performance increased, both NAA and GABA levels increased. LIMITATIONS: Small sample size and lack of control for medications. CONCLUSIONS: These findings build on previous observations of biochemical alterations associated with BD and indicate that executive functioning deficits in bipolar youth are correlated with NAA and GABA. These results suggest that cognitive deficits occur early in the course of illness and may reflect risk factors associated with altered neurochemistry. Further investigation of the relationship between brain metabolites and cognition in BD may lead to important information for developing novel, targeted interventions.

Two-dimensional single-shot diffusion-weighted stimulated EPI with reduced FOV for ultrahigh-b radial diffusion-weighted imaging of spinal cord.

PURPOSE: High-resolution diffusion-weighted imaging (DWI) of the spinal cord (SC) is problematic because of the small cross-section of the SC and the large field inhomogeneity. Obtaining the ultrahigh-b DWI poses a further challenge. The purpose of the study was to design and validate two-dimensional (2D) single-shot diffusion-weighted stimulated echo planar imaging with reduced field of view (2D ss-DWSTEPI-rFOV) for ultrahigh-b radial DWI (UHB-rDWI) of the SC. METHODS: A novel time-efficient 2D ss-DWSTEPI-rFOV sequence was developed based on the stimulated echo sequence. Reduced-phase field of view was obtained by using two slice-selective 90 ° radiofrequency pulses in the presence of the orthogonal slice selection gradients. The sequence was validated on a cylindrical phantom and demonstrated on SC imaging. RESULTS: Ultrahigh-b radial diffusion-weighted ( bmax = 7300 s/mm2) images of the SC with greatly reduced distortion were obtained. The exponential plus constant fitting of the diffusion-decay curve estimated the constant fraction (restricted water fraction) as 0.36 ± 0.05 in the SC white matter. CONCLUSION: A novel 2D ss-DWSTEPI-rFOV sequence has been designed and demonstrated for high-resolution UHB-rDWI of localized anatomic structures with significantly reduced distortion induced by nonlinear static field inhomogeneity. Magn Reson Med 77:2167-2173, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Neurochemical correlates of internet game play in adolescents with attention deficit hyperactivity disorder: A proton magnetic resonance spectroscopy (MRS) study.

Previous studies have examined the relationship of brain metabolic changes in patients with attention deficit hyperactivity disorder (ADHD) and internet gaming disorder (IGD). However, these studies have been limited by a small number of subjects, a large variance in subject age, and different brain regions of interest. The present study assessed the effects of chronic internet game play in ADHD children. Twenty eight ADHD adolescents with IGD (IGD+ADHD), 27 ADHD adolescents without problematic internet game playing (ADHD only) and 42 healthy comparison adolescents (HC) were included in the study. Magnetic resonance spectroscopy (MRS) was performed on a 3T MRI scanner. Our results indicate that the levels of NAA in both ADHD groups were lower than those observed in the HC group. The levels of Glu+Gln in the ADHD only group were increased, compared to those observed in the control group. However, Glu+Gln was not increased in the IGD+ADHD group. In addition, the levels of Glu+Gln in the IGD+ADHD group were positively correlated with K-ARS total and inattention scores. ADHD and IGD subjects were both characterized by decreased NAA levels within the frontal lobe, consistent with hypofrontality.

Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression.

Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted.

Synchronous Radial 1H and 23Na Dual-Nuclear MRI on a Clinical MRI System, Equipped With a Broadband Transmit Channel.

The purpose of this work was to synchronously acquire proton (1H) and sodium (23Na) image data on a 3T clinical MRI system within the same sequence, without internal modification of the clinical hardware, and to demonstrate synchronous acquisition with 1H/23Na-GRE imaging with Cartesian and radial k-space sampling. Synchronous dual-nuclear imaging was implemented by: mixing down the 1H signal so that both the 23Na and 1H signal were acquired at 23Na frequency by the conventional MRI system; interleaving 1H/23Na transmit pulses in both Cartesian and radial sequences; and using phase stabilization on the 1H signal to remove mixing effects. The synchronous 1H/23Na setup obtained images in half the time necessary to sequentially acquire the same 1H and 23Na images with the given setup and parameters. Dual-nuclear hardware and sequence modifications were used to acquire 23Na images within the same sequence as 1H images, without increases to the 1H acquisition time. This work demonstrates a viable technique to acquire 23Na image data without increasing 1H acquisition time using minor additional custom hardware, without requiring modification of a commercial scanner with multinuclear capability.

Decreased brain PME/PDE ratio in bipolar disorder: a preliminary (31) P magnetic resonance spectroscopy study.

OBJECTIVES: The aim of the present study was to measure brain phosphorus-31 magnetic resonance spectroscopy ((31) P MRS) metabolite levels and the creatine kinase reaction forward rate constant (kf ) in subjects with bipolar disorder (BD). METHODS: Subjects with bipolar euthymia (n = 14) or depression (n = 11) were recruited. Healthy comparison subjects (HC) (n = 23) were recruited and matched to subjects with BD on age, gender, and educational level. All studies were performed on a 3-Tesla clinical magnetic resonance imaging system using a (31) P/(1) H double-tuned volume head coil. (31) P spectra were acquired without (1) H-decoupling using magnetization-transfer image-selected in vivo spectroscopy. Metabolite ratios from a brain region that includes the frontal lobe, corpus callosum, thalamus, and occipital lobe are expressed as a percentage of the total phosphorus (TP) signal. Brain pH was also investigated. RESULTS: Beta-nucleoside-triphosphate (ß-NTP/TP) in subjects with bipolar depression was positively correlated with kf (p = 0.039, r(2) = 0.39); similar correlations were not observed in bipolar euthymia or HC. In addition, no differences in kf and brain pH were observed among the three diagnostic groups. A decrease in the ratio of phosphomonoesters to phosphodiesters (PME/PDE) was observed in subjects with bipolar depression relative to HC (p = 0.032). We also observed a trend toward an inverse correlation in bipolar depression characterized by decreased phosphocreatine and increased depression severity. CONCLUSIONS: In our sample, kf was not altered in the euthymic or depressed mood state in BD. However, decreased PME/PDE in subjects with bipolar depression was consistent with differences in membrane turnover. These data provide preliminary support for alterations in phospholipid metabolism and mitochondrial function in bipolar depression.

Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

OBJECTIVE: Depression among methamphetamine users is more prevalent in females than males, but gender-specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment-resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. METHODS: Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. RESULTS: The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t (9) = 2.905, p <.01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally, creatine was well tolerated and adverse events that were related to gastrointestinal symptoms and muscle cramping were determined as possibly related to creatine. CONCLUSIONS: The current study suggests that creatine treatment may be a promising therapeutic approach for females with depression and comorbid methamphetamine dependence. This study is registered on clinicaltrials.gov (NCT01514630).

The Utility of Magnetic Resonance Spectroscopy for Understanding Substance Use Disorders: A Systematic Review of the Literature.

The aim of this article is to present a systematic review of magnetic resonance spectroscopy (MRS) studies of substance use disorders. As a noninvasive and nonionizing imaging technique, MRS is being widely used in substance abuse research to evaluate the effects substances of abuse have on brain chemistry. Nearly 40 peer-reviewed research articles that focused on the utility of MRS in alcohol, methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, opiates, opioids, marijuana, and nicotine use disorders were reviewed. Findings indicate inconsistencies with respect to alterations in brain chemistry within each substance of abuse, and the most consistent finding across substances was decreased N-acetylaspartate and choline levels with chronic alcohol, methamphetamine, and nicotine use. Variation in the brain regions studied, imaging technique, as well as small sample sizes might explain the discrepancies in findings within each substance. Future well-designed MRS studies offer promise in examining novel treatment approaches in substance use disorders.