Rebekah S. Huber

Acute Air Pollution Exposure and Risk of Suicide Completion

Research into environmental factors associated with suicide has historically focused on meteorological variables. Recently, a heightened risk of suicide related to short-term exposure to airborne particulate matter was reported. Here, we examined the associations between short-term exposure to nitrogen dioxide, particulate matter, and sulfur dioxide and completed suicide in Salt Lake County, Utah (n = 1,546) from 2000 to 2010. We used a time-stratified case-crossover design to estimate adjusted odds ratios for the relationship between suicide and exposure to air pollutants on the day of the suicide and during the days preceding the suicide. We observed maximum heightened odds of suicide associated with interquartile-range increases in nitrogen dioxide during cumulative lag 3 (average of the 3 days preceding suicide; odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.04, 1.39) and fine particulate matter (diameter ≤2.5 μm) on lag day 2 (day 2 before suicide; OR = 1.05, 95% CI: 1.01, 1.10). Following stratification by season, an increased suicide risk was associated with exposure to nitrogen dioxide during the spring/fall transition period (OR = 1.35, 95% CI: 1.09, 1.66) and fine particulate matter in the spring (OR = 1.28, 95% CI: 1.01, 1.61) during cumulative lag 3. Findings of positive associations between air pollution and suicide appear to be consistent across study locations with vastly different meteorological, geographical, and cultural characteristics.

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 β-nucleoside triphosphate (β-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

Shi X‐F, Kondo DG, Sung Y‐H, Hellem TL, Fiedler KK, Jeong E‐K, Huber RS, Renshaw PF. Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus‐31 magnetic resonance spectroscopy study. Bipolar Disord 2012: 14: 607–617.

Altitude is a risk factor for completed suicide in bipolar disorder

Bipolar disorder (BD) is a severe brain disease that is associated with a significant risk for suicide. Recent studies indicate that altitude of residence significantly affects overall rate of completed suicide, and is associated with a higher incidence of depressive symptoms. Bipolar disorder has shown to be linked to mitochondrial dysfunction that may increase the severity of episodes. The present study used existing data sets to explore the hypothesis that altitude has a greater effect of suicide in BD, compared with other mental illnesses. The study utilized data extracted from the National Violent Death Reporting System (NVDRS), a surveillance system designed by the Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC). Data were available for 16 states for the years 2005-2008, representing a total of 35,725 completed suicides in 922 U.S. counties. Random coefficient and logistic regression models in the SAS PROC MIXED procedure were used to estimate the effect of altitude on decedents mental health diagnosis. Altitude was a significant, independent predictor of the altitude at which suicides occurred (F=8.28, p=0.004 and Wald chi-square=21.67, p<0.0001). Least squares means of altitude, independent of other variables, indicated that individuals with BD committed suicide at the greatest mean altitude. Moreover, the mean altitude at which suicides occurred in BD was significantly higher than in decedents whose mental health diagnosis was major depressive disorder (MDD), schizophrenia, or anxiety disorder. Identifying diagnosis-specific risk factors such as altitude may aid suicide prevention efforts, and provide important information for improving the clinical management of BD.

Dubowitz syndrome: a review and implications for cognitive, behavioral, and psychological features.

Dubowitz syndrome is a rare autosomal recessive disorder characterized by micorcephaly, short stature, abnormal faces, and mild to severe mental retardation. Growth retardation occurs both intrauterine and postnatal. Behavioral characteristics include hyperactivity, short attention span, and aggressiveness. Behavior problems include difficulty feeding, sleep disturbance, and bedwetting. Individuals with the disorder have displayed shyness, fear of crowds, and dislike of loud noises. A high-pitched or hoarse voice is common. Deficits have been found in speech and language skills, reasoning and memory skills, self-help skills, and psychomotor functioning. Ocular, dental, cutaneous, skeletal, cardiovascular, gastrointestinal, neurological, immunological, and hematological medical difficulties have been noted. Approximately 148 cases have been described in the literature. The cause of the disorder remains unknown, however, research suggests genetic origin. Past research emphasizes physical characteristics and medical complications. There is a lack of cognitive, behavioral, and psychological information available regarding the disorder. This article presents a review of the literature and provides assessment and treatment implications for the cognitive, behavioral, and psychological aspects of Dubowitz syndrome. Keywords Dubowitz; Syndrome; Autosomal; Recessive

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 31P magnetic resonance spectroscopy study

The aim of the present study was to measure brain phosphorus‐31 magnetic resonance spectroscopy (31P MRS) metabolite levels and the creatine kinase reaction forward rate constant (kf) in subjects with bipolar disorder (BD).

Association Between Altitude and Regional Variation of ADHD in Youth

Objective: The purpose of this study was to evaluate the effect of altitude on rates of ADHD. As decreased dopamine (DA) activity has been reported with ADHD and hypoxia has shown to be associated with increased DA, we hypothesized that states at higher altitudes would have lower rates of ADHD. Method: State estimates from the 2007 National Survey of Children’s Health (NSCH) report and 2010 National Survey of Children with Special Health Care Needs (NS-CSHCN) report were used to extract the percentages of youth ages 4 to 17 diagnosed with ADHD. Results: Both the datasets independently revealed that the prevalence of ADHD decreases with increasing altitude (R2 = .38, p < .001; R2 = .31, p < .001), respectively. This study controlled for potential confounds (e.g., low birth weight, ethnicity, and household size). Conclusion: These findings suggest a need for further investigation into the extent by which altitude may serve as a protective factor for ADHD.

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.

A review of MR spectroscopy studies of pediatric bipolar disorder.

Pediatric bipolar disorder is a severe mental illness whose pathophysiology is poorly understood and for which there is an urgent need for improved diagnosis and treatment. MR spectroscopy is a neuroimaging method capable of in vivo measurement of neurochemicals relevant to bipolar disorder neurobiology. MR spectroscopy studies of adult bipolar disorder provide consistent evidence for alterations in the glutamate system and mitochondrial function. In bipolar disorder, these 2 phenomena may be linked because 85% of glucose in the brain is consumed by glutamatergic neurotransmission and the conversion of glutamate to glutamine. The purpose of this article is to review the MR spectroscopic imaging literature in pediatric bipolar disorder, at-risk samples, and severe mood dysregulation, with a focus on the published findings that are relevant to glutamatergic and mitochondrial functioning. Potential directions for future MR spectroscopy studies of the glutamate system and mitochondrial dysfunction in pediatric bipolar disorder are discussed.