Douglas G. Kondo

The Epidemiology and Diagnostic Issues in Preschool Attention-Deficit/Hyperactivity Disorder: A Review

This study aims to review the nosology and epidemiology of attention-deficit/hyperactivity disorder (ADHD) in children aged 2 through 5 years. Studies, primarily in community or pediatric clinic settings, were reviewed. In studies using DSM diagnostic criteria, the prevalence of ADHD in preschool children ranges from 2.0% to 7.9%, with hyperactive-impulsive type and combined type significantly more common than pure inattentive type ADHD. Boys and older preschoolers (4- and 5-year-olds vs 2- and 3-year-olds) are more likely to meet criteria for ADHD. Preschoolers with ADHD are significantly impaired in their relationships with adults and other children, in their functioning at home and outside the home, and in cognitive and academic performance. Preschoolers with ADHD are significantly more likely to meet criteria for other psychiatric disorders and those who do meet criteria for other psychiatric disorders are more severely impaired than preschoolers with ADHD alone. Despite the severity of impairment, only about a quarter of preschoolers with ADHD are referred for mental health evaluation or treatment. Preschool ADHD predicts future ADHD and persistent impairment. Preschoolers with ADHD look like older children with ADHD with similar symptom presentations, associated features, and prognosis. These findings suggest that DSM-IV-TR ADHD is a reliable and valid diagnosis for children aged 2 through 5 years.

Review: Magnetic Resonance Spectroscopy Studies of Pediatric Major Depressive Disorder

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 Healths 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.

Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms.

Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover trial employed the Wender—Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and Connor’s Adult ADHD Rating Scale (CAARS) and two measures of adult ODD. Treatment responses of all participants and four subgroups (ADHDalone, ADHD + ED, ADHD + ODD, and ADHD + ED + ODD) were assessed. Results: Around 23% of baseline participants were ADHD alone, 31% were ADHD + ED, 10% were ADHD + ODD, and 36% were ADHD + ED + ODD. There was a significant treatment effect for all symptom areas and all four subgroups. MTS was associated with significantly more adverse events, especially dermatologic side effects. Conclusions: MTS was effective in treating adult ADHD. This clinical trial included numerous participants meeting criteria for ED and ODD. All ADHD symptoms responded positively to treatment with MTS.

Incidence of major depressive episode correlates with elevation of substate region of residence

BACKGROUND Major depressive disorder (MDD) is a common disorder that is often associated with suicide. We have recently suggested that elevation may play a role in regional variations in rates of suicide. We hypothesize that there is also a significant correlation between incidence of MDD and elevation of residence. METHODS The substate estimates from the 2004 to 2006 National Surveys on Drug Use and Health (NSDUH) report from SAMHSA was used to extract substate level data related to percentages of people 18 years or older who experienced serious psychological distress or a major depressive episode in the past year. Mean elevation of each substate region was calculated by averaging the weighted elevations of its relevant counties. Average elevation for United States counties was calculated using the Shuttle Radar Topography Mission (SRTM) elevation dataset. Pearson correlation coefficients were computed to investigate the association between average substate elevation and rate of serious psychological distress or major depressive episode. RESULTS There was a significant correlation between percentage of people experiencing serious psychological distress in the past year in a substate region and that substate regions mean elevation (r=0.18; p=0.0005), as well as between the percentage of people having at least one major depressive episode in the past year in a substate region and that substate regions mean elevation (r=0.27; p0.0001). CONCLUSIONS Elevation appears to be a significant risk factor for MDD. Further studies are indicated to determine whether the increased incidence of depression with increased elevation may be due to the hypoxic effects on subjects with MDD.

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.

Cocaine Use in the Past Year is Associated with Altitude of Residence

Objectives:Recently, increased rates of suicide in US counties at higher altitudes have been noted. Because of the documented association between cocaine use and suicide, we hypothesized that there would be a correlation between incidence of cocaine use and altitude of residence. Methods:Cocaine use data were obtained from the Substate Substance Abuse Estimates from the 1999–2001 National Surveys on Drug Use and Health. Data related to the percentages of people 12 years or older who used cocaine in the past year. Average elevation for US counties was calculated using the Shuttle Radar Topography Mission elevation data set, and subject region elevation was calculated by averaging the weighted elevations of each regions relevant counties. The correlation between elevation of a substate region and incidence of cocaine use in that region was calculated using Pearson correlation coefficients. Results:A significant correlation exists between mean altitude of a substate region and incidence of cocaine use in that region (r = 0.34; P < 0.0001). Regression analysis controlling for age, sex, race, education level, income, unemployment, and population density was performed. Altitude remained a significant factor (P = 0.007), whereas male sex (P = 0.008) and possessing less than a college education (P < 0.0001) were also significant predictors of self-reported cocaine use in the past year. It is important to note that cocaine use was assessed in isolation of other drugs of abuse, an additional confounding variable. Conclusions:This study demonstrates a significant correlation between altitude of substate region of residence and incidence of cocaine use. It is possible that stress response due to hypoxia is responsible; however, this requires further investigation. However, because other substance use was not assessed, specificity of this association is unknown. In addition, this correlation may help explain the increased rate of suicide in areas of higher elevation.

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.

Open-label uridine for treatment of depressed adolescents with bipolar disorder

This report is an open-label case series of seven depressed adolescents with bipolar disorder treated with uridine for 6 weeks. Treatment response was measured with the Childrens Depression Rating Scale-Revised and the Clinical Global Impressions scale. Uridine was associated with decreased depressive symptoms, and was well tolerated by study participants. Further systematic studies of uridine are warranted.

Eating disorders in primary care. A guide to identification and treatment.

PREVIEW Awareness of the signs and symptoms of eating disorders is essential for primary care physicians who work with children, adolescents, and young adults. In this article, Drs Kondo and Sokol describe the clinical manifestations of eating disorders such as anorexia nervosa, bulimia nervosa, and binge-eating disorder, which usually occur in adolescence and early adulthood, and pica and rumination disorder, which are more characteristic of infancy and early childhood. The authors also discuss risk factors for and medical complications of eating disorders and present current treatment methods.