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Description The Cârța Monastery, a former Cistercian monastery, is pictured here from one of its sides, conjuring the romanticism that is beloved in medieval ruins. The photo was taken on a sunny fall afternoon in the Țara Făgărașului region of Romania in southern Transylvania. Cârța Monastery was started around 1202 by a group of Cistercian monks from Egres Abbey in the then-kingdom of Hungary. Cistercian architecture is considered some of the most beautiful of the Middle Ages, and walking the grounds of the Monastery indeed evoked a profound sense of gratitude, awe, and peace in the shadow of its beauty that I can call up to this day. Such experiences contribute to our resilience as individuals, and as communities, and reminds us as global members of society that seeking to consistently better ourselves and our planet is a constant evolution., Competing Interests: Conflicts of Interest Dr Gracious declares personal fees from Novo Nordisc., (© 2023 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Objectives: 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., Methods: 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., Results: 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, p  = .037) and total vegetable intake (β =  -0.118, p  = .004) were negatively associated with inattention., Conclusions: 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.

Description Obsessive-compulsive symptoms in schizophrenia are often initially unrecognized or missed entirely in the diagnostic process. Sexual obsession is common in patients with schizophrenia. Therefore, identifying sexual obsession early in treatment has significant implications for appropriate multidisciplinary management and prognosis. We report the case of a Hispanic male in his 20s who presented with self-injurious behavior and worsening psychotic symptoms in the context of a recent diagnosis of schizophrenia and without a past diagnosis or historical symptoms of obsessive-compulsive disorder (OCD). This report elucidates the importance of identifying the underlying cause of self-injurious behavior, which in this young man was due to new onset OCD presenting as sexual obsession comorbid with schizophrenia. Olanzapine, paroxetine, and cognitive behavioral therapy (CBT) were administered with good therapeutic response., Competing Interests: Conflicts of Interest Dr Gracious reports personal fees from Novo Nordisc, outside the submitted work., (© 2022 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Pulmonary emboli (PEs) occur when the pulmonary artery is blocked by foreign material. In one such instance, this foreign material can be a blood clot that may occur from patient risk factors inducing a prothrombotic state. The relationship between COVID-19 vaccines and a prothrombotic state is novel and changing as our understanding of the relationship between the two evolves. The patient in this case study presented with unrelenting and progressive dyspnea, tachycardia, and unilateral lower extremity swelling two days after receiving the second dose of the Pfizer COVID-19 vaccine. After diagnostic testing, the patient was found to have a submassive saddle pulmonary embolism with subsequent right heart strain. This patient was treated with appropriate anticoagulation therapies, including heparin and apixaban, as well as thrombectomy, and made a complete recovery. The possible relationship between COVID-19 vaccines and thrombotic events supports the need for increased awareness of a potential new risk factor behind the development of PE. It is our hope that this case report will help raise awareness of an association despite the lack of incident data at this time., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Borisoff et al.)

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., Competing Interests: Conflicts of Interest Drs Bell and Raza and Mr. Kilcrease declare they have no conflicts of interest., (© 2022 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Objective: To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample., Method: A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 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 youths (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 < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred., Conclusion: Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level., Clinical Trial Registration Information: Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

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.

Introduction: Attitudes of those in the homeless population toward testing, particularly during a pandemic, are critical to understand, so that they and their communities may be safely triaged and protected. Homeless persons are more likely to be exposed during viral epidemics, and have greater vulnerability for more severe viral illness, due to greater medical comorbidities. The literature reflects a dearth of published papers describing the perceptions, interest, and motivations of homeless people to seek or receive viral testing, despite their status as a high-risk population., Methods: A quality improvement project consisting of a cross-sectional survey took place at 8 SARS-CoV-2 infection testing sites (local shelters and drop-in sites) within Duval County, Jacksonville, FL., Results: The vast majority of homeless individuals approached for testing completed demographic data and a checklist of beliefs and attitudes about testing (N=764) and underwent COVID-19 nasopharyngeal swab testing (n=679). Mean age was 48; 66% were male, and the predominant race was Black (51%) with 89% of non-Hispanic ethnicity. Of the total participants, 59.2% wanted testing and 4.6% declined testing. Attitudes toward testing varied by site and by wanting vs. not wanting to be tested. Top reasons in those wanting testing included curiosity; a belief that faith would protect them from the virus; and having shelter encouragement to be tested. Top attitudes among those not wanting to be tested were: shelter encouraged me; curiosity; and receiving a gift card. For the total group of subjects, being offered a $10 gift card did not affect their desire to be tested. Those who were not faith-influenced were less likely to want testing., Conclusion: Findings from selected literature and this quality improvement study support the use of a variety of strategies to encourage participation in testing events with large numbers of homeless individuals, including education, gift cards, shelter staff encouragement, involvement of local faith leaders and more broad support by the community. An additional qualitative study would complement these findings, as populations appear to differ in beliefs and attitudes depending on their location and other demographics. Motivational strategies to influence testing rates can be fine-tuned if beliefs, perceptions and attitudes are better understood., Competing Interests: Conflicts of Interest Dr. Gracious reports personal fees from Novo Nordisk, outside the submitted work. Drs. Bell and Bosi declare they have no conflicts of interest., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Description Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe 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, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, 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., Competing Interests: Conflicts of Interest Dr. Gracious reports personal fees from Novo Nordisc not related to the submitted work., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

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., Competing Interests: Conflicts of Interest The author declares she has no conflicts of interest., (© 2020 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Guidelines for suggested intake of ω-3 polyunsaturated fatty acids (PUFAs) are limited in youth and rely primarily on age. However, body weight varies considerably within age classifications. The current analyses examined effects of body weight and body mass index (BMI) on fatty acid accumulation in 64 youth (7-14 years) with a diagnosed mood disorder in a double-blind randomized-controlled trial (2000mg ω-3 supplements or a control capsule) across 12 weeks. Weight and height were measured at the first study visit and EPA and DHA levels were determined using fasting blood samples obtained at both the first and end-of-study visits. In the ω-3 supplementation group, higher baseline body weight predicted less plasma accumulation of both EPA [B = -0.047, (95% CI = -0.077; -0.017), β = -0.54, p = 0.003] and DHA [B = -0.02, (95% CI = -0.034; -0.007), β = -0.52, p = 0.004]. Similarly, higher BMI percentile as well as BMI category (underweight, normal weight, overweight/obese) predicted less accumulation of EPA and DHA (ps≤0.01). Adherence to supplementation was negatively correlated with BMI percentile [B = -0.002 (95% CI = -0.004; 0.00), β = -0.44, p = 0.019], but did not meaningfully affect observed associations. As intended, the control supplement exerted no significant effect on plasma levels of relevant fatty acids regardless of youth body parameters. These data show strong linear relationships of both absolute body weight and BMI percentile with ω-3 PUFA accumulation in youth. A dose-response effect was observed across the BMI spectrum. Given increasing variability in weight within BMI percentile ranges as youth age, dosing based on absolute weight should be considered. Moreover, effects of weight should be incorporated into statistical models in studies examining clinical effects of ω-3 PUFAs in youth as well as adults, as weight-related differences in effects may contribute meaningfully to inconsistencies in the current literature., Trial Registration: WHO International Clinical Trial Registry Platform NCT01341925 and NCT01507753.

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., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objective: 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., Methods: A literature review was conducted, including guidelines and recommendations, with case presentations including case and control liver histology biopsy photographs., Results: 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., Conclusions: 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.

Objectives: 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., Methods: 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., Results: Augmentation over a 2 year period was notable for clinically significant and sustained improvement in depressive, manic, and psychotic symptoms., Conclusion: 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.

Background: Vitamin D deficiency is a re-emerging epidemic, especially in minority populations. Vitamin D is crucial not only for bone health but for proper brain development and functioning. Low levels of vitamin D are associated with depression, seasonal affective disorder, and schizophrenia in adults, but little is known about vitamin D and mental health in the pediatric population., Methods: One hundred four adolescents presenting for acute mental health treatment over a 16-month period were assessed for vitamin D status and the relationship of 25-OH vitamin D levels to severity of illness, defined by presence of psychotic features., Results: Vitamin D deficiency (25-OH D levels <20 ng/ml) was present in 34%; vitamin D insufficiency (25-OH D levels 20-30 ng/ml) was present in 38%, with a remaining 28% in the normal range. Adolescents with psychotic features had lower vitamin D levels (20.4 ng/ml vs. 24.7 ng/ml; p=0.04, 1 df). The association for vitamin D deficiency and psychotic features was substantial (OR 3.5; 95% CI 1.4-8.9; p <0.009). Race was independently associated with vitamin D deficiency and independently associated with psychosis for those who were Asian or biracial vs. white (OR=3.8; 95% CI 1.1‒13.4; p<0.04). Race was no longer associated with psychosis when the results were adjusted for vitamin D level., Conclusions: Vitamin D deficiency and insufficiency are both highly prevalent in adolescents with severe mental illness. The preliminary associations between vitamin D deficiency and presence of psychotic features warrant further investigation as to whether vitamin D deficiency is a mediator of illness severity, result of illness severity, or both. Higher prevalence of vitamin D deficiency but no greater risk of psychosis in African Americans, if confirmed, may have special implications for health disparity and treatment outcome research.

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., ((c) Copyright 2010 Physicians Postgraduate Press, Inc.)

Objectives: This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder., Methods: Children and adolescents aged 6-17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses., Results: There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %alpha-LNA (r = -0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = -0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms., Conclusions: Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.

Objective: To examine the short-term efficacy of methylphenidate in the treatment of youths with bipolar disorder (BD) and comorbid attention deficit/hyperactivity disorder (ADHD)., Method: A 4-week double-blind, placebo-controlled trial in youths ages 5 to 17 years was conducted. Subjects met DSM-IV criteria for bipolar disorder and ADHD, were currently receiving a stable dose of at least one thymoleptic, and while euthymic continued to have clinically significant symptoms of ADHD. Patients received 1 week each of placebo, methylphenidate 5 mg twice daily, methylphenidate 10 mg twice daily, and methylphenidate 15 mg twice daily using a crossover design. Subjects were randomly assigned to receive one of six possible dosing orders. At study's end, and before the blind being broken, a "best dose week" for each subject was determined. The primary outcome measure was the total score on the parent-completed ADHD Rating Scale-IV., Results: Sixteen patients, with a mean age of 10.43 (SD 3.14) years completed the trial. Lower scores during best dose treatment compared to the week of placebo treatment were found on the ADHD Rating Scale-IV (p < .05), suggesting a therapeutic benefit. A large effect size (Cohen's d = 0.90) was found for methylphenidate. Treatment was generally well tolerated., Conclusions: Euthymic youths with bipolar disorder and ADHD may benefit from short-term concomitant treatment with methylphenidate.

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 dival-proex 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 < .002). One patient, from the placebo group, ended study participation due to an adverse event., Conclusion: These results suggest that, although well tolerated, divalproex sodium does not produce clinically meaningful improvements in the treatment of symptomatic youths suffering from either bipolar NOS or cyclothymia who are at genetic risk for developing bipolar disorder.

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: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of re-stabilization after the resumption of lithium (Li) plus divalproex (DVPX) following relapse on either agent as monotherapy., Method: This is a prospective, 8-week, open-label outpatient Li/DVPX combination therapy trial. Patients ages 5 to 17 years with bipolar disorder type I or II, who had achieved symptom remission with Li/DVPX combination therapy and subsequently relapsed during treatment with Li or DVPX monotherapy were enrolled between January 1999 and January 2003., Results: Thirty-eight patients with a mean age of 10.5 years entered the study. Thirty-four (89.5%) patients responded to treatment with Li/DVPX mood stabilizer therapy alone, but four patients required adjunctive antipsychotic treatment to address residual symptomatology. Overall, reinitiation of Li/DVPX combination therapy was well tolerated with no subjects discontinuing because of a medication-related adverse event., Conclusions: It appears that most youths with bipolar disorder who stabilize on combination Li/DVPX therapy and subsequently relapse during monotherapy can safely and effectively be re-stabilized with the reinitiation of Li/DVPX combination treatment.

Objective: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy., Method: Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures., Results: Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72)., Conclusions: DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy.

Objective: To compare weight loss after birth in women who took the antidepressants nortriptyline or sertraline or placebo in 2 clinical studies designed to prevent recurrent postpartum major depression., Method: Data were collected from 1995 to 2001. All subjects had at least 1 prior episode of Research Diagnostic Criteria- or DSM-IV-defined major depressive disorder. Data on weight were available for 467 weeks from 60 women who were weighed 8 times from 2 to 17 weeks postpartum. The dependent measures were weight at weeks 11 and 17 and weight change from weeks 2 to 17 postpartum., Results: At week 17, the women's weights ranged from 109 to 268 lb. Their weight change ranged from +14 to -19 lb over the 15-week postpartum period (mean = -1.8, SD = 5.1 lb). After controlling for week 2 weights, the mean weights at week 17 for the women treated with nortriptyline, sertraline, or placebo were not significantly different. Of 60 women with 3 or more weight assessments, those who were randomly assigned to nortriptyline lost weight more rapidly than the other 2 groups; however, the mean weight change across all groups was only -1.8 lb (SD = 5.1 lb)., Conclusions: Weight loss was not compromised by antidepressant pharmacotherapy. Postpartum weight retention occurred in this group of nondepressed women with previous histories of major depression independent of drug treatment.

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., (Copyright 2004 American Academy of Child and Adolescent Psychiatry)

Objective: The aim of this study was to examine the effectiveness of quetiapine in adolescents suffering from autistic disorder (AD)., Methods: 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., Results: 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., Conclusions: 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.

Objective: 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., Method: 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., Results: 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)., Conclusions: 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 /=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.

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.

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 (alpha =.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.

Objective: The purpose of this study was to explore whether amantadine would slow or reverse significant weight gain in children and adolescents treated with antipsychotics and/or mood stabilizers that may promote increases in weight., Methods: Eight boys and one girl ages 9-16 years and their parents consented to an open trial of amantadine 100 mg po bid or tid for weight gain in children. Side effects and body mass index were determined at baseline and during amantadine treatment., Results: A mean weight gain of 10.5 kg (19.9% mean increase in body weight) occurred from baseline to the beginning of amantadine treatment. Amantadine trial length averaged 14.5 weeks (range 4-33 weeks). A planned comparison using repeated measures analysis of variance demonstrated strong support for a "slowing weight gain" mechanism (p = 0.001) for weight gain and body mass. Weight loss was strongly correlated with length of amantadine treatment (p = < 0.05). One child experienced orthostatic hypotension with concomitant stimulant medication. No other side effects or exacerbation of psychiatric symptoms was reported., Conclusions: Amantadine appears to stabilize weight gain related to psychotropic medications. Decreased weight and body mass index may occur with continued amantadine usage. Controlled trials of amantadine in children and adolescents taking weight-gain-inducing psychotropics are warranted.

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.

Introduction: There are no definitively established acute or maintenance treatments for juvenile bipolar disorder., Method: Two randomized, blind, maintenance clinical trials in children and adolescents with bipolar disorders are ongoing at the University Hospitals of Cleveland/Case Western Reserve University Stanley Clinical Research Center for bipolar disorder. The first is comparing the safety and effectiveness of lithium carbonate (Li+) to divalproex sodium (VPA) for up to 76 weeks in youths with stabilized bipolar illness (type 1 or 2). The second study is designed to compare the efficacy of VPA to placebo in the acute management of subsyndromal symptoms of bipolar disorder ('cyclotaxia') and the prevention of the full syndrome in children at risk. Both studies use the prospective life-chart method as an outcome measure., Results: Sixty-six youths have received study medication as part of the trial that is comparing Li+ to VPA as a maintenance therapy. In addition, 32 youths have received blinded treatment as part of the 'cyclotaxia' prevention study. Combination Li+A/PA treatment appears generally well tolerated and seems to have robust anti-manic and antidepressant effects., Discussion: Since the blind has not been broken on either of these clinical trials, conclusions about the maintenance effectiveness of either VPA or Li+ in youths with bipolar disorder type 1 or 2 cannot be made yet. Similarly, it is unclear whether VPA is superior to placebo in genetically high-risk youths with cyclotaxia. The final results of these trials should provide valuable information about the treatment of juvenile bipolar disorders.

Antipsychotics are commonly prescribed to children and adolescents. With the relatively recent availability of the atypical antipsychotics, physicians have begun prescribing these agents to young people in the hope of finding safe, effective alternatives to the typical antipsychotics. This report reviews what is currently known about the use of the atypical antipsychotics in young people. Most of the currently available data are based on case reports and case series. The results of only a handful of prospective trials pertaining to the use of the atypical antipsychotics in youths have been reported. Based on the available information, it appears that clozapine has a role in juvenile treatment resistant schizophrenia. When considered as a group, the 'first-line' atypical antipsychotics risperidone, olanzapine and quetiapine appear to have promise as treatments for several neuropsychiatric disorders in young people. These conditions include psychotic, mood, disruptive, movement and pervasive developmental disorders. Unfortunately, as has historically been the case, the demand to address the clinical needs of young patients with neuropsychiatric disorders has outpaced empirically based information. This is particularly important because significant side effects can occur when children or adolescents are treated with atypical antipsychotics. Since there is a paucity of short-term and almost no long-term safety data pertaining to these agents in young people, careful consideration must be made prior to initiating atypical antipsychotic treatment for a child or teenager. Based upon what is known about these agents, a rational approach to the use of these drugs in juveniles is offered.

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.