Working From Within: The Rural Community Participatory Design Framework.

OBJECTIVE: This article describes the development of the rural community-based participatory design framework to guide healthcare design teams in their integration of rural community and clinical voice during the planning, design, and construction of a healthcare facility. BACKGROUND: Rural communities are facing an alarming rate of healthcare facility closures, provider shortages, and dwindling resources, which are negatively impacting population health outcomes. A prioritized focus on rural care access and delivery requires design teams to have a deeper understanding of the contextual considerations necessary for a successful healthcare facility project, made possible through engagement and partnership with rural dwelling community members and healthcare teams. METHOD: The rural community participatory design framework is adapted from the rural participatory research model, selected due to its capture of key concepts and characteristics of rural communities. Underpinning theories included rural nursing theory and theory of the built environment. RESULTS: The framework encompasses healthcare facility project phases, key translational concepts, and common traits across rural communities and cultures. As a middle-range theoretical framework, it is being tested in a current healthcare project with a Critical Access Hospital in Montana to facilitate design team and stakeholder collaboration. CONCLUSION: The rural community participatory design framework may be utilized by design teams as a means of familiarization with rural cultures, norms, values, and critical needs, which relate to meaningful design. The framework further enables design teams to critically appraise best practices of stakeholder engagement throughout the project lifecycle.

Systematic Review of Barriers to and Facilitators of Screening for Postpartum Depression at Well-Child Visits in the United States.

OBJECTIVE: To identify and evaluate barriers to and facilitators of screening for postpartum depression (PPD) during well-child visits in the United States. Additionally, to describe prior work on PPD screening tool evaluation and outcomes from PPD screenings conducted within the well-child setting. DATA SOURCES: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Five databases (Pub Med, PsycINFO, Web of Science, CINAHL, and Cochrane Library) were searched. STUDY SELECTION: Randomized controlled trials, case studies, cross-sectional studies, case-control studies, cohort studies, qualitative studies, and quasi-experimental studies conducted in the United States were included. The Standard Quality Assessment Criteria Tool (QualSyst) was used to assess the methodologic quality of each included study. DATA EXTRACTION: Sample, setting, methods, screening tools used, location of study setting, intervention, and salient findings were extracted and summarized for further analysis and synthesis. DATA SYNTHESIS: Quantitative studies were rated on 14 aspects, and qualitative studies were rated on 10 aspects, per QualSyst. Studies received a score of 2, 1, 0, or not applicable based on scoring criteria, with higher scores indicating greater methodologic quality. CONCLUSION: We found that barriers to PPD screening included concerns regarding time for screening, adequate training, and limited ability for referral. Facilitators of PPD screening included electronic prompts for providers, as well as tool availability and familiarity. Our results indicate that education and training about PPD screening in the pediatric setting are important next steps in addressing the rising concern of PPD in the United States.

Our Patients Need Empathy Training across Healthcare Professions.

Vulnerable populations are those who experience disparity at a disproportionate rate. For this article, specific vulnerable populations of interest include people who experience intellectual or developmental disorders, mental illness, or substance misuse. Vulnerable populations are some of the most stigmatized populations in our society. Research shows that vulnerable populations receive less empathic care than general health care populations, resulting in reduced quality of care and disparities in health outcomes. Empathy, a necessary health care competency, is associated with improved patient outcomes, enhanced job satisfaction, and increased retention and resilience across health care professions. However, there is no current standard for how empathy is taught, assessed, or sustained. Even when empathy education is implemented in healthcare professions curricula, research has demonstrated that it appears to erode with experience and time. In addition, the COVID-19 pandemic has exacerbated inequities in health care systems, with consequences for both patients and providers. There is an urgent need to develop efficacious training in empathy across health care professions to foster and sustain a robust workforce and improve health care experiences and outcomes.

Rapid Scoping Review: Empathy in Health Sciences Curriculum.

Empathy, the process of coming to know, understand, and care for another person, is a skill that can be learned; however, there is not a shared definition of empathy or understanding of how to operationalize empathy into practice. Healthcare worker empathy has been shown to have a beneficial effect on both patient health outcomes and the emotional wellness of healthcare workers. Empathic care is associated with more efficient, cost-effective, improved healthcare, and increased provider trust. The purpose of this rapid scoping review is to identify, compare, and contrast empathy training offered to select healthcare professional students (e.g., nurses, nurse practitioners, and pharmacists) as part of the general curriculum or as an elective. We utilized a rapid scoping review approach to identify potentially relevant peer-reviewed articles and studies for inclusion. Six electronic databases were searched, including: MEDLINE; EMBASE; PUBMed; CINAHL; EBSCOHOST; and ERIC, covering the past 10 years. A total of 4977 citations, 3480 abstracts, and 428 papers were screened. Fifty studies fulfilled the eligibility criteria. Of those, 21 primarily non-randomized experimental studies published between 2012 and 2021 were included in the final review. Over 80 percent of the training took place in the classroom setting and utilized active learning strategies. There is little consensus on how to best train future healthcare providers to provide empathic care to patients.

Suicide and altitude: A systematic review of global literature.

OBJECTIVE: The purpose of this systematic review was to synthesize the existing global literature examining the relationship between altitude and suicide. METHOD: Using the electronic databases PubMed, CINAHL, EMBASE, and PsychInfo published articles in English that addressed the relationship between altitude and suicide as a primary or secondary aim, and included human subjects, where identified. Studies were assessed for quality based on methodological approach and data relevance on a three-point scale (strong, moderate, or weak). RESULTS: Of the 19 studies related to the purpose and aims, 17 reported evidence of a positive correlation between altitude and increased suicide. Vast design differences were employed within the literature, individual-level suicide data was identified as the preferred level of analysis. DISCUSSION: The relationship between altitude and suicide is an evolving science with a small but growing body of literature suggesting altitude is associated with an increased risk of suicide. This review identifies the need for additional studies examining both individual-level suicide data and improving geographic precision. Public health nurses have a responsibility to carefully examine the quality of studies and the strength of the evidence when addressing variables associated with suicide.

National Internet-Based Survey of the Use, Barriers, Reasons and Beliefs of Mind-Body Practices During the Early Months of the COVID-19 Pandemic.

The purpose of this study was to learn about the use, barriers, reasons and beliefs regarding mind-body practices among adults living in the United States during the beginning months of the 2019 novel coronavirus disease (COVID-19) pandemic. An on-line survey was developed following the Checklist for Reporting Results of Internet e-Surveys (CHERRIES) guidelines and using the online survey software program, Qualtrics®XM, platform. Pilot testing of the survey was conducted for usability and functionality. The final 24-item survey was distributed via email and social media. A total of 338 adults responded to the survey, with 68.8% indicating that they participated in mind-body activities since the start of the pandemic. Physical activity was the most frequently (61.5%, n = 227) used mind-body practice. Further, 2 of the common barriers to engaging in mind-body practices were lack of motivation and wandering mind. Frequently listed reasons for using mind-body practices were to promote health, reduce stress and relaxation. Respondents believed that mind-body practices resulted in less stress. These findings may be applicable for reducing psychological stress related to the pandemic, as the pandemic continues to impact many areas of the United States.

The emotional dance with depression: A longitudinal investigation of OULA® for depression in women.

The primary purpose of this pilot study was to evaluate OULA®, a dance fitness program with a strong emphasis on processing emotions through dance, as an intervention for depression in women diagnosed with major or persistent depressive disorders. 53 women were eligible for participation. Women attended OULA® for 12 weeks and then abstained from OULA® during week 13. For the primary outcome, depression severity was measured using the Hamilton Depression Rating Scale (HAM-D), and secondary outcomes were measured using the Beck Anxiety Index (BAI) and the Subjective Happiness Scale (SHS). After the abstinence week, women were offered 3-months of optional additional OULA®. HAM-D, BAI and SHS scores were collected at weeks 2, 4, 5-14 and at the end of the 3-month optional OULA® phase. Results from linear mixed effects repeated models show that during the 12-week intervention period and at week 26, HAM-D scores significantly decrease each week compared to baseline. Further, BAI scores significantly decrease starting at week 5 and through the end of the intervention period and at week 26. Moreover, SHS scores increased significantly for four of the weeks during the intervention period and at week 26. The results from this study suggest that OULA® may be a useful intervention for decreasing depression and anxiety severity in women with depression but may not be helpful for improving subjective happiness.

An Internet-based survey of the dance fitness program OULA.

BACKGROUND: OULA is a high-energy dance workout to top 40 hits that is inspired by yoga and non-impact aerobics. Created in Missoula, Montana, the program has been gaining national and international popularity. To understand the demographic composition, reasons for attending OULA, and experiences with depression/anxiety, we conducted an Internet-based survey. METHODS: A pilot descriptive cross-sectional Internet-based survey was created in Qualtrics and distributed through social media and flyers. RESULTS: The 38-item survey received responses from 302 participants. Current OULA participants chose "exercise" as the primary reason for attending (40.2%, 95% confidence interval: 33.3-48.2), followed by "stress relief/improve mood" (28.8%, 95% confidence interval: 23.0-35.6). Participants listed "stress relief/improve mood" as the most common secondary (35.6%, 95% confidence interval: 29.0-43.2) and tertiary (38.6%, 95% confidence interval: 31.7-46.7) reason for attending OULA. A majority of the participants said that OULA makes them feel like part of a community (93.2%, 95% confidence interval: 82.5-105.1) and increases their energy outside of class (80.1%, 95% confidence interval: 70.2-91.1). In our sample, 12.5% (95% confidence interval: 8.8-17.1) and 9.0% (95% confidence interval: 5.9-12.9) were currently taking antidepressants and anxiolytics, respectively. CONCLUSION: These results suggest that current OULA participants are already using the program to relieve stress or improve mood. Further research should be conducted to understand the relationship between OULA and depression/anxiety.

Preliminary Psychometric Evaluation of the Hamilton Depression Rating Scale in Methamphetamine Dependence.

OBJECTIVE: The purpose of this study was to test the initial psychometric properties of the 17-item Hamilton Depression Rating Scale (HAM-D) in individuals with and without major depressive disorder who use methamphetamine. We used data from two completed studies and two ongoing clinical trials. The HAM-D has well established reliability and validity in a variety of populations. However, there are no published reports of reliability and validity of the HAM-D in a methamphetamine-using population. METHODS: HAM-D and depression status data were extracted from four separate studies for this psychometric assessment. Using these data, we evaluated three measures of construct validity: internal consistency, contrasted group validity, and factorial validity. RESULTS: We found potential concerns with the construct validity of the HAM-D in users of methamphetamine. Intercorrelations between items were primarily less than 0.20 and the Cronbach's alpha value in this sample was 0.58, indicating potential issues with internal consistency. The results of two-sample t-tests suggest concerns with contrasted group validity, as no significant difference in average scores were found for nine items. Consistent with previous studies, a principal component analysis indicates that the HAM-D is multidimensional. CONCLUSIONS: The 17-item HAM-D might not reliably and validly measure depression severity in a methamphetamine-using population. Given our small sample, additional research is needed, though, to further test the psychometric properties of the HAM-D in individuals who use methamphetamine.

A Review of Methamphetamine Dependence and Withdrawal Treatment: A Focus on Anxiety Outcomes.

Rates of anxiety disorders among individuals who use methamphetamine are estimated to be as high as 30.2%. The presence of an anxiety disorder in methamphetamine users is associated with higher rates of relapse, non-adherence to treatment and poorer outcomes relative to methamphetamine users without an anxiety disorder. A review investigating current treatment options for methamphetamine dependence or withdrawal from methamphetamine was conducted using PubMed, CINAHL and PsycINFO. The focus of the review was trials that utilized an intervention and collected anxiety as an outcome measure. Seven studies were included in the review, and five of these studies examined a pharmacotherapy option, one studied a psychosocial intervention and one study investigated exercise as an intervention. Some of the pharmacotherapy studies and the study of exercise were associated with improvements in mood and/or a reduction in methamphetamine use. Concerns of sample size and measurement of anxiety were raised. Future well-designed research with large sample sizes is warranted to examine how to manage anxiety among methamphetamine users.

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.

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).

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.

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.

Gender differences in the effect of tobacco use on brain phosphocreatine levels in methamphetamine-dependent subjects.

BACKGROUND: A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may ease depression and improve cognitive performance in animals and humans. OBJECTIVES: To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. METHODS: Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. RESULTS: Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p = 0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p = 0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. CONCLUSION: These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism.

A review of treatment options for co-occurring methamphetamine use disorders and depression.

Co-occurring methamphetamine use and depression interferes with treatment outcomes. Female methamphetamine users are known to have higher rates of depression than male methamphetamine users, although this is also true for the general population. There are limited treatment options for the management of depression among methamphetamine users. In this integrative review, we summarize data on treatment strategies for co-occurring depression and methamphetamine use disorders. English-language articles were identified from PsychINFO, CINAHL, PubMed, and Medline as well as from reference lists of key articles. Search terms included "methamphetamine," "depression," and "treatment." Research articles describing psychological (n = 3), pharmacological (n = 6), nutritional supplement (n = 1), and psychological combined with pharmacological (n = 3) approaches for the treatment of methamphetamine use or withdrawal and/or depression are included in this review. Psychological and combination of psychological with pharmacological approaches have not been shown to be effective in treating these co-occurring conditions. Antidepressants have been determined to be ineffective and/or to introduce side effects. Gender differences with response to treatment were examined in only one of the published studies. There is a large gap in knowledge regarding treatment of co-occurring methamphetamine use disorders and depression. Considering that female methamphetamine users experience higher rates of depression than men, a focus on gender-specific treatment approaches is warranted.

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: a potential new tool for diagnosis.

BACKGROUND: Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology. Case-control studies utilizing proton-1 magnetic resonance spectroscopy ((1)H-MRS) have found increased total choline levels in several brain regions in MDD. However, there are no published (1)H-MRS reports directly comparing adolescents with MDD and BD. We hypothesized that ACC choline levels would be increased in adolescents with unipolar versus bipolar depression. METHODS: We studied depressed adolescents with MDD (n=28; mean age 17.0±2.1 years) and BD (n=9; 17.3±3.1 years). A Siemens Verio 3-Tesla clinical MRI system was used to acquire scans, using a single-voxel PRESS sequence. The voxel (18.75 cm(3)) was positioned on the ACC in the midsagittal plane. To remove potential gender effects, only female adolescent participants were included. Data were analyzed using the ANOVA and post-hoc Tukey tests. RESULTS: A significantly increased ACC choline/creatine ratio was observed in participants with MDD (mean=0.253±0.021) compared to BD (mean=0.219±0.020) (p=0.0002). There were no significant differences in the other (1)H-MRS metabolites. LIMITATIONS: Cross sectional design, single gender sample, limited sample size. CONCLUSIONS: The present findings suggest that ACC total choline may have the potential to serve as a diagnostic biomarker in adolescent mood disorders.

Effect of altitude on brain intracellular pH and inorganic phosphate levels.

Normal brain activity is associated with task-related pH changes. Although central nervous system syndromes associated with significant acidosis and alkalosis are well understood, the effects of less dramatic and chronic changes in brain pH are uncertain. One environmental factor known to alter brain pH is the extreme, acute change in altitude encountered by mountaineers. However, the effect of long-term exposure to moderate altitude has not been studied. The aim of this two-site study was to measure brain intracellular pH and phosphate-bearing metabolite levels at two altitudes in healthy volunteers, using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS). Increased brain pH and reduced inorganic phosphate (Pi) levels were found in healthy subjects who were long-term residents of Salt Lake City, UT (4720ft/1438m), compared with residents of Belmont, MA (20ft/6m). Brain intracellular pH at the altitude of 4720ft was more alkaline than that observed near sea level. In addition, the ratio of inorganic phosphate to total phosphate signal also shifted toward lower values in the Salt Lake City region compared with the Belmont area. These results suggest that long-term residence at moderate altitude is associated with brain chemical changes.

Decreased frontal lobe phosphocreatine levels in methamphetamine users.

BACKGROUND: Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with high-energy phosphate metabolism have not been investigated in METH users. Phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and ß-nucleoside triphosphate (ß-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS: Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS: METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0g) of METH use than males (1.4±1.7g), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=.02). CONCLUSIONS: The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels.

Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study.

OBJECTIVES: To compare the concentrations of high-energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC). METHODS: We used in vivo phosphorus-31 magnetic resonance spectroscopy ((31) P-MRS) at 3 Tesla to measure phosphocreatine (PCr), beta-nucleoside triphosphate (ß-NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs. RESULTS: Analysis of covariance, including age as a covariate, revealed differences in PCr (p=0.037), Pi (p=0.017), and PCr/Pi (p=0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post-hoc Tukey-Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p=0.038) and medicated BD (24%; p=0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p=0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p=0.013) and with medicated BD (39%; p=0.002). No differences in ß-NTP or pH were observed. CONCLUSIONS: Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n-acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD.