Search

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a U.S. pediatric prevalence of 8-10%. It presents with inattention and hyperactivity/impulsivity; frequently associated with emotional dysregulation (ED) symptoms common in Oppositional Defiant Disorder and Disruptive Mood Dysregulation Disorder. The etiology of ADHD is multi-factorial; symptom severity is associated with diet. This study examines the association of diet quality with ADHD and ED symptoms within a pediatric research cohort.Baseline data were analyzed for 134 children aged 6-12 years with symptoms of ADHD and ED enrolled in an RCT of multinutrient supplementation. Diet quality was based on Healthy Eating Index-2015 (HEI-2015). ADHD and ED symptoms were assessed using Child and Adolescent Symptom Inventory-5 and Strengths and Difficulties Questionnaire. Linear regression models, adjusting for covariates when necessary, determined association.The mean HEI Total Score of 63.4 (SD = 8.8) was not significantly associated with any outcome symptoms. However, after adjusting for covariates, HEI component scores for total fruit intake (β = -0.158,The lack of association with total diet quality could be explained by the relatively good baseline diet quality and mild symptom severity in this sample, along with measurement error from dietary intake estimates and relatively small sample size. These findings suggest that dietary intake may impact inattention in children with ADHD and ED: those eating less fruits and vegetables were likely to have more severe symptoms of inattention. Causality is not established by this cross-sectional analysis.

OBJECTIVE: To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD: A three-site 8-week placebo-controlled randomized clinical trial of micronutrients was conducted in unmedicated children ages 6-12 with ADHD and at least one impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS: Of 135 randomized (mean age 9.8 years), 126 (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (Risk Ratio=2.97, 97.5% CI: 1.50, 5.90, p

INTRODUCTION: Mass incarceration, particularly of the mentally ill, continues to pervade our criminal justice system. Jails in many areas have become the largest mental health facilities, especially in large urban communities, despite increasing societal recognition that those with mental illness are not best served behind bars. Misdemeanors are an often-overlooked contributor to mass incarceration, and may be preventable for those with chronic severe mental illness. METHODS: This Northeast Florida pilot program, the Mental Health Offenders Program (MHOP), is based on the successful Miami Eleventh Circuit Court Criminal Mental Health Project. MHOP provided pretrial release from custody, through diversion with a customized plan of care to stabilize defendants, using court supervision to ensure compliance. RESULTS: With community partners, the MHOP pilot enrolled 20 individuals with chronic severe mental illness and recurrent misdemeanor charges; 15 were able to continue in the program with stabilization of their mental health and reduction of county costs both documented. CONCLUSION: The MHOP pilot demonstrates that community resources can be successfully shifted to benefit mentally ill, non-violent offenders and the larger community by helping severely mentally ill clients achieve stability by providing healthcare, housing, and income, while decreasing costs for the community in a humane way.

The association of household food insecurity with symptoms of attention deficit hyperactivity disorder (ADHD) and emotional dysregulation in children was examined in this study. We utilized baseline data from 134 children aged 6–12 years who were enrolled in a clinical trial investigating multinutrient supplementation as a treatment for ADHD and emotional dysregulation. Household food security status was assessed using the 18-item US Household Food Security Survey Module. The symptoms of ADHD and emotional dysregulation disorders (oppositional defiant disorder (ODD) and disruptive mood dysregulation disorder (DMDD)) were assessed using the Child and Adolescent Symptom Inventory-5 and other comorbid emotional dysregulation symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression determined associations between household food security status and symptoms of ADHD, ODD and DMDD, emotional symptoms and conduct problems. Household food insecurity was associated with more severe emotional symptoms (β = 2.30; 95% CI = 0.87–3.73; p = 0.002), conduct problems (β = 1.15; 95% CI = 0.01–2.30; p = 0.049) and total difficulties scores (β = 4.59; 95% CI = 1.82–7.37; p = 0.001) after adjusting for covariates (child’s sex, parent marital status, household income, parental anxiety and other parental psychopathology). In unadjusted analyses, household food insecurity was also associated with increased ODD (β = 0.58; 95% CI = 0.21–0.95; p = 0.003) and DMDD symptoms (β = 0.69; 95% CI = 0.20–1.19; p = 0.006), but these associations attenuated to non-significance after adjusting for all covariates. Household food insecurity was associated with more severe emotional dysregulation symptoms. Discussing and addressing food insecurity may be appropriate initial steps for youths with ADHD and emotional dysregulation.

Background Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Background Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns. Aims This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms. Study design 90-day randomized, double blinded, placebo-controlled trial. Subjects 31 children aged 18–38 months who were born at ≤ 29 weeks' gestation. Outcome measure Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP). Results Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above = 0%, below = 65%), vestibular (above = 13%, below = 48%), tactile (above = 3%, below = 35%), oral sensory (above = 10%; below = 26%), visual (above = 10%, below = 16%); sensory processing quadrants: low registration (above = 3%; below = 71%), sensation avoiding (above = 3%; below = 39%), sensory sensitivity (above = 3%; below = 35%), and sensation seeking (above = 10%; below = 19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant ( p = 0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size = 0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32). Conclusions The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm.

Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.

These comments include established behavioral treatment preceding and augmenting stimulant use to prevent or reduce dosing, nutritional approaches with placebo-controlled evidence, and possible effects of stimulant on micronutrient levels.

Background According to the Alzheimer’s Association, in the United States more than 16 million adult family members provide care for a relative with Alzheimer’s disease or other dementia. The economic value contributed by unpaid caregivers is $234 billion dollars. Such caregivers are vital to the ability of the U.S. to meet caretaking needs, as the projected number of individuals suffering from dementia will nearly triple over the next 30 years. A meta-analysis found that decisions to provide family caretaking are rooted in long-standing family relationships. This essay explores one family’s decision to move from long-term institutional care back to family-based care in the home setting. https://www.alz.org Greenwood N, Smith R. Motivations for being informal carers of people living with dementia: a systematic review of qualitative literature. BMC Geriatr. 2019;19(1):169. Published 2019 Jun 17. https://doi.org/10.1186/s12877-019-1185-0

Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.

Perampanel is an anti-epileptic drug reported to exert its effects in the central never system (CNS) by inhibiting post-synaptic glutamate receptors. The most commonly reported neuropsychiatric side effects are affective dysregulation with some reports of psychosis. However, the precise therapeutic mechanism is unknown. We report on a 32-year-old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, subsequent to adding perampanel to his antiepileptic medications. On presentation, perampanel administration was temporarily withheld, and subsequently, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk: benefit ratio with little knowledge of the long-term effects. A broad-spectrum multi-nutrient formula has shown promise in children, but its effects on nutrient status and the underlying metabolome interactions have not been characterized. METHODS: Blood samples from medication-free children (n = 74) with ADHD enrolled in a double–blind randomized placebo-controlled multinutrient trial (RCT) were collected at baseline and 8 weeks post-intervention. Following RCT is an 8-week open label phase during which all participants took the active supplement. Symptoms were assessed using the Child and Adolescent Symptom Inventory 5. Double-blinded plasma samples will be analyzed for tyrosine, phenylalanine, tryptophan, magnesium, and zinc. Untargeted LC-MS metabolomics using HILIC chromatography and a high resolution QTof will assess very polar analytes in plasma extracts. Linear modeling will elucidate the influence of treatment, sampling time, and ADHD symptom score on plasma nutrient and plasma metabolite concentration. RESULTS: Preliminary findings of the open label phase show a significant improvement in inattention (P = 0.0435), hyperactivity (P = 0.0068), ODD (P = 0.0108) and DMDD (P = 0.0119). We hypothesize that these improvements in ADHD symptoms will be correlated with increased circulating concentrations of tyrosine, phenylalanine, tryptophan, magnesium, zinc, and metabolites involved in neurotransmitter synthesis and/or branched chain amino acid metabolism. CONCLUSIONS: Preliminary findings indicate improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD following 8 weeks of open label multi-nutrient supplementation. Results of the double-blinded phase are expected to mirror those observed in the open label phase, with increases in nutrients in those receiving the multinutrient. FUNDING SOURCES: The sample analyses were supported by NIH Award Number Grant P30 CA016058, OSU, and OSUCCC. Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.

BACKGROUND: Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns. AIMS: This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms. STUDY DESIGN: 90-day randomized, double blinded, placebo-controlled trial. SUBJECTS: 31 children aged 18–38 months who were born at ≤ 29 weeks’ gestation. OUTCOME MEASURE: Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP). RESULTS: Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above = 0%, below = 65%), vestibular (above = 13%, below = 48%), tactile (above = 3%, below = 35%), oral sensory (above = 10%; below = 26%), visual (above = 10%, below = 16%); sensory processing quadrants: low registration (above = 3%; below = 71%), sensation avoiding (above = 3%; below = 39%), sensory sensitivity (above = 3%; below = 35%), and sensation seeking (above = 10%; below = 19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant (p = 0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size = 0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32). CONCLUSIONS: The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm.

No child psychiatric disorder has a single treatment that is completely satisfactory. Combinations are sometimes more beneficial than single treatments. This is well established for medication + behavioral treatment for depression and ADHD. There is wide variability in the evidence base for various treatments, from FDA-approved RCTs to open pilots. In the search for additional or alternative treatments, essential fatty acids seem especially to pass the SECS criterion: a treatment that is safe, easy, cheap, and sensible does not need as much evidence to justify patient trials as one that is risky, unrealistic, difficult, or expensive (RUDE). Not only do omega-3 fatty acids have some RCT evidence for a small effect in several psychiatric disorders, but they also are believed useful in preventing cardiac morbidity and excessive inflammation. Therefore, for ADHD, we recommend a combination of behavioral treatment (e.g., parent training, cognitive-behavioral therapy (CBT) for older patients), FDA-approved medication, (primarily stimulants), an RDI/RDA multivitamin/mineral to compensate for stimulant appetite suppression, and about a gram a day of EPA/DHA, possibly supplemented with 50–100 mg GLA. For mood disorders, we recommend a combination of mood stabilizer or antidepressant (depending on which mood disorder), CBT, RDA/RDI multivitamin/mineral (in view of reported vitamin D deficiencies and vitamin wasting from some anticonvulsant mood stabilizers), and a gram per day of EPA/DHA. For autism, we recommend applied behavior analysis, RDA/RDI multivitamin/mineral in view of the often idiosyncratic unbalanced diet, ADHD medication if a problem with hyperactivity, antipsychotic if a problem with irritability/aggression, and omega-3 for anti-inflammatory effect. For learning disorder and developmental coordination disorder, we recommend remedial tutoring or occupational therapy and EPA/DHA. For children at high risk for psychosis or mood disorder, we recommend counseling, monitoring for early indication of low-dose antipsychotic, and general nutritional support, including EPA/DHA. For Tourette’s and aggression, EPA/DHA and other nutritional support can be added to standard treatment. When using fish oil, it is important to make sure it was refined to eliminate contaminants such as mercury. The effect accumulates gradually over months. There is no convincing evidence of greater benefit but some risk from amounts over a gram or two per day.

Genetic, dietary, and inflammatory factors contribute to the etiology of major mood disorders (MMD), thus impeding the identification of specific biomarkers to assist in diagnosis and treatment. We tested association of vitamin D and inflammatory markers in 36 adolescents with bipolar disorder (BD) and major depressive disorder (MDD) forms of MMD and without MMD (non-mood control). We also assessed the overall level of inflammation using a cell-based reporter assay for nuclear factor kappa-B (NFκB) activation and measuring antibodies to oxidized LDL. We found that these factors were similar between non-mood and MMD youth. To identify potential biomarkers, we developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFβ). We discovered that a homolog of GMFβ in human plasma is vitamin D-binding protein (DBP) and validated this finding using immunoprecipitation with anti-DBP antibodies and mass spectrometry/sequencing analysis. We quantified DBP levels in participants by western blot. DBP levels in BD participants were significantly higher (136%) than in participants without MMD (100%). The increase in DBP levels in MDD participants (121.1%) was not statistically different from these groups. The DBP responds early to cellular damage by binding of structural proteins and activating inflammatory cells. A product of enzymatic cleavage of DBP has been described as macrophage-activating factor. Circulating DBP is comprised of heterogenous high and low molecular fractions that are only partially recognized by mono- and polyclonal ELISA and are not suitable for the quantitative comparison of DBP in non-mood and MDD participants. Our data suggest DBP as a marker candidate of BD warranting its validation in a larger cohort of adolescent and adult MMD patients.

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental disorder affecting up to 9% of children and substantial numbers of adults. Existing pharmacologic treatments often improve symptoms, but concerns exist over side effects, stigma, potential long-term health effects, and residual irritability, often treated with adjunctive antipsychotics. To address public and clinician demand for non-pharmacologic evidence-based treatments, this study will examine efficacy of a 36-ingredient micronutrient (vitamin/mineral) supplement as treatment for children with ADHD and irritability. Methods: An international team of experts in ADHD, mood dysregulation, nutrition, epidemiology, and clinical trials conferred to develop/refine a protocol powered to detect a medium effect. The study will employ a fully-blind randomized controlled trial (RCT) design, comparing the micronutrient supplement to matched placebo in 135 children aged 6–12 with ADHD symptoms and irritability, based on the parent-rated Child and Adolescent Symptom Inventory-5 (CASI-5). Irritability will be measured by at least one symptom of oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD). Based on research suggesting an irritable ADHD subtype, the primary outcome will be a composite score comprised of the CASI-5 subscales: ADHD, ODD, DMDD, and the Peer Conflict Scale, which assesses anger and aggression perpetrated towards peers. Participants will provide biological samples (blood, urine, saliva, hair and stool) to explore the micronutrients’ mechanisms of action. Discussion: This study is the first adequately powered RCT in North America to examine both behavioral responses to, and biological mechanisms of, micronutrients for ADHD and irritability in children. If found efficacious, broad-spectrum micronutrients, given at therapeutic doses, may provide an evidence-based alternative to prescription medications for ADHD and associated irritability. Trial registration: NCT03252522. Registered 26 July 2017 Keywords: ADHD, Micronutrients, Vitamins, Minerals, Irritability

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder with increasing global prevalence and high heritability commonly diagnosed in childhood. Current pharmaceutical treatment options provide a poor long-term risk: benefit ratio. Nutrition has significant effects on neurological functioning, and increasing evidence exists to support the use of multinutrients as alternative treatment for ADHD. The goal of this study is to assess the efficacy and tolerability of a multinutrient supplement as an alternative treatment for ADHD and co-occurring mood dysregulation symptoms. METHODS: The Multinutrients in ADHD Youth study is a fully-funded, multi-site, randomized double-blinded clinical trial for adolescents ages 6–12 years (n = 135). The study is 16 weeks in total, with an 8-week randomized controlled trial (RCT) followed by an 8-week open label (OL) phase. During the RCT phase, participants are assigned to either the treatment or placebo group at a 3:2 ratio. Study outcomes of ADHD symptoms include child's inattention, hyperactivity and mood dysregulation, which are assessed using validated questionnaires. Outcome data for the OL phase of the study were analyzed using end of RCT phase as baseline given that the RCT component of the study is still blinded. RESULTS: Preliminary findings based on the OL phase compared ADHD symptoms following 8 weeks of open label supplementation (n = 27 families). A significant decrease in symptom count was found for inattention (P ≤ 0.001), hyperactivity (P ≤ 0.001), ODD (P ≤ 0.001) and DMDD (P ≤ 0.001). CONCLUSIONS: This study is the first adequately powered RCT in North America to investigate the effects of multinutrients supplements on ADHD symptoms among children. Preliminary findings indicate a trend in the improvements of ADHD symptoms of inattention, hyperactivity, ODD and DMDD in the OL phase of the study. FUNDING SOURCES: Foundation for the Center of Excellence in Mental Health, Canada; The Ohio State University Department of Human Sciences, College of Education and Human Ecology; The Ohio State University Wexner Medical Center, Clinical Research Center.

To the Editor: The very useful case report by Wong et al1 illustrates the potential harm of psychosis resulting from concurrent administration of over 50 ingredients, including 18 unregulated herbal agents, 19 digestive enzymes, 6 probiotic strains, and other over-the-counter substances. This is a valuable cautionary message, but the title and abstract lead readers astray. Instead of using specific language to identify the offending agents as herbs, the authors use the general term dietary supplements, an erroneous rubric often used in marketing herbs. By publishing evidence for an adverse herbal interaction with the term dietary supplements, this article inadvertently leads readers (many of whom read only the title and abstract) to believe that this case demonstrates harm from consumption of nutrients fundamental for human health. Without careful reading of the full text and Table 1, readers will not recognize that only 4 of the > 50 ingredients this patient consumed were minerals or vitamins (chromium, vitamin B6, folate, vitamin B12). And, given that the patient’s B12 levels, when tested, were in the low normal range, resulting in treatment with cyanocobalamin 1,000 μg, there is good reason to suspect that even these few nutrients were not very bioavailable or had trivial physiologic impact. It is unlikely that the patient’s psychosis resulted from the direct or combined effects of minerals, vitamins, enzymes, or probiotics. Rather, it is most likely that the patient’s physical and mental impairments resulted from the concurrent use of 18 botanicals, each with its own complex, nonspecific, and largely unmapped pharmacologic actions. Humans have evolved to need dietary nutrients such as minerals and vitamins for the function of every mitochondrion (and hence every cell) of our brains and bodies. In contrast, there is no evidence of evolutionary need of herbs. In fact, physiologically active herbs could be more accurately described as crude drugs that have been misclassified as dietary supplements (eg, St John’s wort, tobacco, marijuana, coca leaf, and poppies are plant parts with psychoactive chemicals). The signatories to this letter have contributed to the rapidly growing empirical literature demonstrating mental health benefits from nutrients (not herbs)2–8 as well as establishing safety of these nutrients,9 even when multiple nutrients are used in combination. It concerns us that the nonspecific use of the term dietary supplements could prejudice interpretation of the scientifically valid studies on nutritional approaches to treating psychiatric conditions. In addition to our own work, there is a large literature supporting the association between dietary patterns and mental health in population studies,10 and a new international society of scientists has formed to study this area (International Society for Nutritional Psychiatry Research; ISNPR.org).11 If the title and abstract of the report had accurately specified that it was primarily about the risk of the concurrent use of multiple unregulated botanical substances, there would be no confusion. Given the present situation, we respectfully ask that a correction be issued.

OBJECTIVE Pediatric obesity (body mass index [BMI] > or = 95th percentile for sex and age) and overweight (BMI > or = 85th percentile < 95% percentile) are priority public health targets for the prevention of diabetes and cardiovascular disease. We examined the prevalence and risk of overweight and obesity in adolescents with serious mental disorders. METHOD Height, weight, demographic, diagnostic, and treatment data were reviewed for 114 adolescents attending a partial hospitalization program over 18 consecutive months between January 2003 and July 2004. Sample data were compared to normative National Health and Nutrition Examination Survey data and regional county data for BMI. Unadjusted odds ratios and their 95% CIs were calculated for each categorical risk factor using the chi-squared test. A logistic regression model was conducted to detect the effects of these risk factors on the occurrence of overweight and obesity. RESULTS The combined prevalence of overweight and obesity was 55.4% (n = 63); the prevalence for obesity alone was 30% (n = 34), approximately double the rate in national and county norms. Lack of private insurance, smoking, and antidepressant and antipsychotic treatment were associated with overweight and obese status. CONCLUSIONS Adolescents with severe mental illness are at increased risk for overweight and obesity. Identification of elevated BMI, associated risk factors, and efforts to prevent weight gain should begin at initiation of mental health treatment.

Objective: To determine if divalproex sodium was superior to placebo in the treatment of symptomatic youths who suffer from a bipolar spectrum disorder and who also have a parent with a diagnosis of a bipolar illness. Method: Youths, ages 5 to 17 years, meeting DSM-IV criteria for bipolar disorder not otherwise specified (NOS) or cyclothymia who also had at least 1 biological parent with bipolar illness were randomly assigned in a double-blind fashion to receive treatment with either divalproex sodium or placebo for up to 5 years. Study participation ended if the subject required additional clinical intervention, if the patient developed treatment-related adverse events, or if the participant was not adherent with study procedures. The primary outcome measure was time to study discontinuation for any reason. The study was conducted from August 1997 to April 2003. Results: Fifty-six youths with a mean (SD) age of 10.7 (3.1) years were randomly assigned and received either divalproex sodium (N = 29) or placebo (N = 27). In spite of statistical power of 80% to detect hazard ratios of 2.2 or larger, the treatment groups did not significantly differ in survival time for discontinuation for any reason (p = .93) or discontinuation due to a mood event (p = .55). Changes in mood symptom ratings and psychosocial functioning from baseline to study discontinuation did not differ between groups (most significant p >.14). However, both groups did show improvements in mood symptoms and psychosocial functioning over time (all p values

Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic because of the greater prevalence of obesity. Despite implications for youth with severe mental disorders, little has been published in the psychiatric literature about this increasingly common medical comorbidity. The goals of this article are to: 1) provide an overview of the epidemiology and pathophysiology of NAFLD, including progression to nonalcoholic steatohepatitis (NASH); 2) describe two clinical cases illustrating difficulties faced in management; and 3) review screening recommendations, differential diagnosis, and monitoring and intervention approaches.A literature review was conducted, including guidelines and recommendations, with case presentations including case and control liver histology biopsy photographs.NAFLD in childhood and adolescence, as a precursor to NASH, progresses to fibrosis in a small percentage of youth, leading to risk for early onset cirrhosis and the need for transplantation. The cases presented raise concern that youth with severe mental health disorders, already at greater risk for obesity and its sequelae, may be at higher risk for progression to NASH, potentially because of greater rates of weight gain on top of overweight or obese status, and to liver metabolism changes from psychotropic medications favoring fat deposition.Patients with rapid weight gain into the overweight or obese categories, or who develop elevated liver transaminases that persist across 3-6 months, should be screened or referred for screening by their psychotropic-providing clinicians for early detection, diagnosis, and co-management by a pediatric gastroenterologist, to decrease risk of progression to NASH, which is reversible if early and sufficient lifestyle change results in significant weight loss. There is urgent need for controlled research on the relationships among weight gain, psychotropic medications, ultrasound and biopsy findings, and rates of progression to NAFLD and NASH in youth taking weight-gain-inducing psychotropic medications.

Therapeutic benefits of omega-3 fatty acids (Ω3) for mood disorders, psychosis, and anxiety have been reported in the literature. The purpose of the present article is to provide a literature review of Ω3 supplementation for affective disorders and to illustrate the benefits of Ω3 with a case presentation of a young girl with a history of bipolar disorder-type 1 with psychotic features and generalized anxiety disorder.Reviewed literature includes treatment studies of the impact of Ω3 on child mood disorders supplemented by review of meta-analyses within the adult mood disorders literature. The subject of this case report participated in 11 in-depth diagnostic and functional assessments over 5 years as part of an unrelated study. Three years were presupplementation and 2 years were with supplementation with no other medication changes, thus making a naturalistic multiple-baseline single-subject experiment.Augmentation over a 2 year period was notable for clinically significant and sustained improvement in depressive, manic, and psychotic symptoms.Ω3 supplementation may be a safe, adjunct intervention for treating bipolar disorder in children and adolescents, even in the presence of psychotic and anxious features. The 2 year follow-up in this case offers hope of an accumulating and enduring benefit. Further research into mechanisms of Ω3 action and of combination treatment with other well-known interventions for mood disorders would be beneficial.

Objective: The study was designed to determine the validity of the Mood Disorder Questionnaire-Adolescent Version (MDQ-A) as a screening instrument for bipolar disorders (I, II, not otherwise specified, and cyclothymia) in an adolescent outpatient psychiatric population. Method: 104 adolescents and their parents completed the MDQ-A. Three versions of the MDQ-A were compared: (1) self report of symptoms by adolescent, (2) attributional report-how the adolescent believed teachers or friends would report his/her symptoms, and (3) parent report of adolescent's symptoms. DSM-IV diagnosis was made based upon the clinician-administered Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), a semistructured diagnostic interview. MDQ-A items were summed, yielding a score for each adolescent ranging from 0 to 13 on each of the 3 MDQ-A versions. Each possible scoring threshold, in combination with co-occurrence of symptoms and behaviors and with moderate to serious problems caused by symptoms, was crossed with the results of the K-SADS-PL diagnostic interview to assess sensitivity and specificity. The study was conducted from April 2002 to September 2003. Results: A score of 5 or more items on the parent version yielded a sensitivity of 0.72 and specificity of 0.81, which were superior to self and attributional versions. Conclusions: The MDQ-A completed by parents about their adolescents' symptoms may be a useful screening instrument for bipolar disorders in an adolescent psychiatric outpatient population.

Objective To compare the diagnostic efficiency of six index tests as predictors of juvenile bipolar disorder in two large outpatient samples, aged 5 to 10 and 11 to 17 years, gathered from 1997 to 2002. Method DSM-IV diagnosis was based on a semistructured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children) with the parent and youth sequentially, blind to scores on the index tests. Participants were 318 youths aged 5 to 10 (50% with bipolar diagnoses) and 324 youths aged 11 to 17 (41% with bipolar diagnoses). Areas under the curve (AUCs) from receiver operating characteristic analyses and multilevel likelihood ratios quantified test performance. Results Parent report (AUCs from 0.78 to 0.84 in both age groups) outperformed teacher (AUCs 0.57 in the younger sample and 0.70 in the older sample) or adolescent measures (AUCs 0.67 [General Behavior Inventory] and 0.71 [Youth Self-Report]) at identifying bipolar disorders. Combining tests did not produce clinically meaningful classification improvement. Conclusions Parent report was more useful than teacher report or adolescent self-report on the index tests studied. Results generally replicated across both age groups. Parent report on these instruments could facilitate differential diagnosis of bipolar disorder in youths aged 5 to 17 years, especially by decreasing the rate of false-positive diagnoses.

The aim of this study was to examine the effectiveness of quetiapine in adolescents suffering from autistic disorder (AD).This was a 12-week, open-label study, for which medically healthy patients with AD between the ages of 10 and 17 years were eligible. Quetiapine treatment was gradually increased over the first 6 weeks of the study, to a total daily dose of 300 mg/day. Doses could then be increased to a maximum daily dose of 750 mg/day. Outcome measures included the Children's Psychiatric Rating Scale (CPRS) and the Clinical Global Impressions (CGI) scale.Nine (9) males were enrolled. Six (6) patients had previously been treated with other psychotropic agents. Although improvements in several symptom domains were observed on quetiapine, only 2 patients met a priori criteria for response ("much" or "very much improved" on the Clinical Global Impressions-Improvement Scale). In addition, only these same 2 patients' parents/guardians chose to continue quetiapine pharmacotherapy after study participation.These data suggest that quetiapine may not be a particularly effective agent in the treatment of adolescent patients with AD. However, should future studies be performed, it seems reasonable that they be conducted with more rigor, less treatment-resistant cohorts, and, possibly, a different dosing strategy.

To examine the effect of combined lithium and divalproex sodium on thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorders and to identify risk factors for lithium-induced hypothyroidism.Bipolar youths aged 5 to 17 years participating in an open-label clinical trial received treatment with lithium and divalproex sodium for up to 20 weeks. TSH levels were measured at baseline and at the end of the study. Subjects were divided into two groups for analysis: group 1 had TSH levels of less than 10.0 mU/L at the end of the study and group 2 had TSH levels of 10.0 mU/L or more at end of the study.Twenty of the 82 subjects (24.4%) showed TSH elevations of at least 10 mU/L within an average exposure of less than 3 months. The mean baseline TSH level for group 2 was significantly higher than for group 1 (2.97 [SD = 1.48] versus 2.05 [SD = 0.89], p.05). Mean lithium levels at the end of the study were 1.00 mEq/L for group 2 compared to 0.76 mEq/L for group 1 (t = -2.41, p =.019).Lithium is associated with significant rates of thyrotropin elevation in bipolar youths. Factors associated with elevation in TSH in lithium-treated subjects include a higher baseline TSH level and a higher lithium level. Close monitoring of thyroid function in children and adolescents taking lithium is recommended.

Background: The Young Mania Rating Scale (YMRS) has validity in the assessment of mania in adults. The purpose of this study was to examine how the YMRS might optimally be used in the assessment of youths. Methods: Children and adolescents between the ages of 5 and 17 years of age participated in this study. All youths were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Based on the K-SADS results, subjects were then assigned to one of five groups: a bipolar I group, another bipolar spectrum group, a depressive disorders group, a disruptive behaviors disorders group, and a no diagnosis group. Guardians completed a version of the YMRS modified for parent reporting. Clinicians completed the YMRS on all participating youths. Results: Both parent and clinician ratings on the YMRS assigned patients ( n =117) to the appropriate diagnostic group with 71–98% accuracy. Combining information from multiple informants did not significantly improve diagnostic group assignment. Limitations: The same raters completed the clinician YMRS and the K-SADS interview involving the parent. Findings need replication in an independent sample with lower base rates of bipolar disorder, less rigorously trained and supervised raters, and using a prospective design to provide maximum generalizability of results. Current results should be interpreted as a ‘best case’ scenario. Conclusions: These data suggest that the YMRS may be a useful adjunct in assessing the severity of mania in youths. Tentative cutting scores are proposed to maximize efficiency, sensitivity, and specificity.

Objective Lithium carbonate (Li) or divalproex sodium (DVPX) may be effective for some juveniles with bipolar disorder. Many youths with bipolar disorder do not respond to DVPX or Li monotherapy. An open-label study was conducted to examine the effectiveness of combination DVPX and Li therapy with youths diagnosed with bipolar disorder. Method Patients meeting DSM-IV criteria for bipolar I or bipolar II disorder, ages 5 to 17 years, were treated prospectively for up to 20 weeks with DVPX + Li. Assessments included the Young Mania Rating Scale (YMRS), Children's Depression Rating Scale–Revised (CDRS-R), and the Children's Global Assessment Scale (CGAS). The a priori definition of clinical remission utilized included four contiguous weekly ratings of YMRS ≤12.5, CDRS-R ≤40, CGAS ≥51, clinical stability, and no evidence of mood cycling. Results Ninety patients (66 males, 24 females) were treated. Significant improvement (p < .0001) in all outcome measures was observed by week 8 as well as at the end of study. The mean time in study was 11.3 weeks. Forty-seven percent (n = 42) met a priori criteria for remission. Conclusions Symptoms of mania and depression in juvenile bipolar disorder may be safely and effectively treated acutely with DVPX + Li.

OBJECTIVE This study examines the association between antidepressant use and risk of fracture in depressed youth and assesses whether fracture incidence varies over the course of antidepressant treatment. METHOD A retrospective cohort analysis of Ohio Medicaid claims data was conducted for youth ages 6-17 years with a new episode of ICD-9-diagnosed depression from 2001-2009. The primary outcome variable was time to fracture. Fracture rates were compared between depressed youth treated with antidepressant medication and untreated depressed youth. Time categories of no use, past use, and current use were compared. RESULTS Of 50,673 depressed youths, 5,872 (11.6%) experienced a fracture. Of those who had a fracture, 2,228 (37.9%) were exposed to antidepressants, 80% of which were selective serotonin reuptake inhibitors. The adjusted hazard ratio (HR) was 3% higher in those currently prescribed antidepressants (HR = 1.03; 95% CI, 1.00-1.06; P = .03). The risk ratio (RR) for adjusted fracture rates per 10,000 persons was twice as high during the first 30 days of antidepressant use compared to the other time periods (RR = 2.0; 95% CI, 1.2-3.3; P = .007). The number of fractures for those with past antidepressant use did not differ from those with no history of antidepressant use. CONCLUSIONS Antidepressant use may be associated with a small but significant increase in fracture risk, particularly within the first 30 days of treatment. Findings underscore a need for additional prospective and mechanistic research. Prescribers should consider other risks for fracture in antidepressant-treated youth, particularly disability and the concomitant use of other medications that increase fracture risk.

Objective: To examine the usefulness of a parent report version of the Young Mania Rating Scale (P-YMRS) in distinguishing bipolar disorder from other mental health conditions in children and adolescents. Method: Parents of 117 youths aged 5 to 17 years presenting to an outpatient research center completed an adapted Young Mania Rating Scale (P-YMRS). Eligible subjects underwent a diagnostic evaluation including a semistructured instrument (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and also a clinical evaluation by a child and adolescent psychiatrist in more than 75% of the subjects. Results: Factor analyses of the P-YMRS suggested one dimension, with a total score showing acceptable internal consistency (α = .75). Logistic regressions discriminated bipolar mood disorder versus unipolar disorder, versus disruptive behavior disorder, and versus any other diagnosis. Classification rates exceeded 78%, and receiver operating characteristics analyses showed good diagnostic efficiency, with areas under the curve greater than 0.82. Conclusions: The P-YMRS may be used to derive clinically meaningful information about mood disorders in youths.

Assessed the factor structure of the Young Mania Rating Scale (YMRS). Youths presenting to a research program specializing in the pharmacological treatment of mood and disruptive behavioral disorders (N = 612) were administered a semistructured diagnostic interview. Based on the interview, youths were placed into diagnostic groups. Highly trained raters completed the YMRS for each youth. YMRS ratings were internally consistent (alpha = .91), and exploratory and confirmatory factor analyses yielded a 1-factor solution for boys and girls in both young (5 to 11 years) and older (12 to 17 years) subsamples. However, the young male group showed higher scores on several items as well as the total YMRS score. Results suggest that the YMRS total score can be meaningfully interpreted in child and adolescent samples.

Objectives: The primary purpose of this study was to describe the clinical presentation of bipolar I disorder (BP-I) as it occurs in children and adolescents and to assess whether the manifestations of BP-I were similar in both age groups. Method: Ninety youths between the ages of 5 and 17 years meeting full diagnostic symptom criteria for BP-I were included in this study. The diagnosis of BP-I was established for these youths based on the results of a semi-structured diagnostic interview and a clinical assessment by a child and adolescent psychiatrist. The course of a subset of these youngsters’ illnesses was assessed using the Life Charting Method (LCM). Data regarding the clinical presentation, longitudinal history, psychiatric co-morbidities and parental psychopathology were also obtained. Results: The clinical presentation of BP-I was similar in children and adolescents. Youths meeting diagnostic criteria for BP-I developed an average of approximately 5.8 of the 7 symptoms of mania during periods of elevated or irritable mood. BP-I was found to be a cyclic disorder characterized by high rates of rapid cycling (50%) with almost no inter-episode recovery. Almost 75% of these subjects also met diagnostic symptom criteria for a disruptive behavior disorder. High rates of mood disorders were found in fathers. Conclusions: These data suggest that the presentation of juvenile BP-I is a cyclic and valid clinical condition with manifestations on a continuum with the later-onset forms of this illness.

A 13-year-old African-American female taking sertraline for obsessive compulsive disorder was diagnosed with her first episode of atrioventricular (AV) nodal re-entrant tachycardia five days after beginning Mixed Salts of a Single-Entity Amphetamine Product (Adderall) for treatment of attention-deficit hyperactivity disorder (ADHD). She received successful cardioversion with 6 mg of intravenous adenosine, but developed a second episode of possible AV nodal re-entrant tachycardia twelve days after Adderall was reinitiated at half the previous dose. The patient had clinically similar cardiac episodes five and six months after treatment was changed to slow-release methylphenidate. Stimulant medication may evoke onset of AV nodal tachyarrhythmias in patients who have the potential to develop them, possibly in combination with a selective serotonergic reuptake inhibitor (SSRI).

Little is known about the use of monoamine oxidase inhibitors (MAOIs) during pregnancy and the postpartum period. We present a literature review with what we believe is the second case report of phenelzine exposure throughout pregnancy and the postpartum period. Potential indications for use and principles of the clinical management of the pregnant patient treated with an MAOI are also discussed and include: documenting informed consent, MAOI dose adjusting during pregnancy, monitoring of maternal and fetal outcome, and appropriate analgesia and anesthesia during labor and delivery. Our patient tolerated phenelzine well throughout her pregnancy but experienced recurring depressive symptoms during periods of significant weight gain requiring dose adjustment. Labor, delivery, and the perinatal period progressed without complication for our patient and her infant, in whom no congenital malformation was detected. Additional case reports and animal studies of MAOI use during gestation may help determine safety and refine clinical management guidelines.

The purpose of this study was to report the safety, tolerability, and serum micronutrient concentrations and their correlations with mood changes from an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement, EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD).Ten children ages 6-12 received EMP+ escalating from one to four capsules t.i.d., with four children increased to the maximum suggested dose, five capsules t.i.d. Outcome measures were micronutrient concentrations in serum and red blood cells, vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire and 24 hour dietary recall interview), and mood and global functioning ratings.Seven children (70%) completed the study. Three (30%) terminated early for tolerability and compliance issues. Adverse effects were mild and transient, and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No differences occurred in BMI (p = 0.310) or waist-hip ratio (WHR; p = 0.674) pre- to postsupplementation. Four of the tested serum vitamin concentrations increased from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-α-tocopherol; and folate (all p0.05). The increase in serum 25-OH vitamin D approached significance (p = 0.063). No differences were found in dietary intake pre- to postsupplementation, suggesting that blood nutrient level increases were caused by EMP+.In this open prospective study, short-term use of EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action, combined with documentation of increased serum concentrations of specific micronutrients.

Diagnosis of major depressive disorder is entirely clinical at present, and based on criteria such as DSM-IV. The classes of medications include antidepressants, selective serotonin reuptake inhibitors (SSRIs), older dual-action reuptake inhibitors, newer dual-action antidepressants, norepinephrine reuptake inhibitors (NRIs) and monoamine oxidase inhibitors. Successful treatment of major depression may require a multi-modal approach including pharmacotherapy, education, and psychotherapy. Patient response to treatment needs systematic monitoring, not only to improve compliance, but to make sound decisions about the need to raise the dose to achieve an optimal antidepressant effect and to monitor side effects. A history of episodes lasting more than 6 months require longer continuation treatment of up to 12 months, and generally continuation treatment will be longer for psychotic depression. Antidepressant and adjunctive pharmacological agents allow successful acute treatment and prevention of future episodes of major depression in most patients.

Over-the-counter (OTC) and prescription medication abuse has been rapidly increasing, yet publications on OTC abuse in adolescents are limited. We present a brief literature review and a novel report of antihistamine dependence emerging after admission in an adolescent, subsequently treated with naltrexone. This case highlights the need to take a thorough history of OTC, herbal, and prescription drug use from parents and patients separately and repeatedly, at initial presentation, and again if withdrawal symptoms emerge. General strategies for combating OTC and prescription abuse are given.