Global Mental Health and Immigrant Families.

There are few human tragedies that stir sympathy and concern more deeply than seeing children suffer secondary to war, displacement, and increasingly frequent epidemics of violence around the world. Falling witness or victim to acts of war and terrorism and subsequent fleeing of millions of children across the world stirs an array of powerful human emotions. Such circumstances by definition involve destruction, pain, and death. It is, paramount that we all work collaboratively, to provide psychological assistance, training, and education and work with various stakeholders to decrease the psychological impact of displacement secondary to war, terrorism, and other social factors.

Sexually Predatory Behavior in an Adolescent Female.

This report describes a rare case of an adolescent female with a history of unspecified depressive disorder, disinhibited social engagement disorder, and significant history of sexual trauma at an early age, who initially presented with suicidal ideation. During the initial evaluation, the patient was found to have engaged in sexually predatory behavior toward younger boys, including solicitation and inappropriate sexual behavior. This report discusses relevant literature on the prevalence, risk factors, and treatment for this behavior among female adolescent sexual predators, as sex offenders are primarily thought to be men. General recommendations for health care professionals caring for female sexual offenders are addressed as well as the importance of early treatment and appropriate training for professionals. The patient has been deidentified.

Psychotic symptoms and suicidal ideation in child and adolescent bipolar I disorder.

OBJECTIVES: The purpose of this study was to explore associations between specific types of hallucinations and delusions and suicidal ideation in a sample of children and adolescents with bipolar I disorder. METHODS: Participants (N = 379) were children and adolescents aged 6-15 years (M = 10.2, SD = 2.7) with DSM-IV diagnoses of bipolar I disorder, mixed or manic phase. The study sample was 53.8% female and primarily White (73.6% White, 17.9% Black, and 8.5% Other). Presence and nature of psychotic symptoms, suicidal ideation, and functioning level were assessed through clinician-administered measures. A series of logistic regressions was performed to assess the contribution of each subtype of psychotic symptom to the presence of suicidal ideation above and beyond age, sex, socio-economic status, age at bipolar disorder onset, and global level of functioning. RESULTS: Hallucinations overall, delusions of guilt, and number of different psychotic symptom types were uniquely associated with increased odds of suicidal ideation after accounting for covariates. Other forms of delusions (eg, grandiose) and specific types of hallucinations (eg, auditory) were not significantly uniquely associated with the presence of suicidal ideation. CONCLUSIONS: Findings of this study suggest the presence of hallucinations as a whole, delusions of guilt specifically, and having multiple concurrent types of psychotic symptoms are associated with the presence of suicidal ideation in children and adolescents with bipolar I disorder. Psychotic symptom subtypes, as opposed to psychosis as a whole, are an under-examined, potentially important, area for consideration regarding suicidal ideation in pediatric bipolar I disorder.

Editorial: Global mental health: challenges & opportunities.

There are few human tragedies that stir sympathy and concern more deeply than to see the suffering of children from around the world, often giving rise to spontaneous feelings and impulses of wanting to help. However, such impulses need to be harnessed in a productive manner. Knowledge and training in the psychopathology and phenomenology of mental illness is not enough. New, innovative, evidence-based treatments and interventions are equally important if we are to adequately address the needs of our youth who carry the burden of a psychiatric and/or behavioral condition. This edition of CAMH includes papers that address both the challenges and opportunities in terms of the way in which interventions underpinned by research can work to improve global mental health and how we can better understand the environmental, familial, cultural and societal underpinnings of global child mental health problems.

Comorbid sleep disorders and suicide risk among children and adolescents with bipolar disorder.

Children and adolescents with bipolar disorder are at increased risk for suicide. Sleep disturbances are common among youth with bipolar disorder and are also independently implicated in suicide risk; thus, comorbid sleep disorders may amplify suicide risk in this clinical population. This study examined the effects of comorbid sleep disorders on suicide risk among youth with bipolar disorder. We conducted secondary analyses of baseline data from the Treatment of Early Age Mania (TEAM) study, a randomized controlled trial of individuals aged 6-15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (N = 379). Sleep disorders (i.e., nightmare, sleep terror, and sleepwalking disorders) and suicide risk were assessed via the WASH-U-KSADS and the CDRS-R, respectively. We constructed uncontrolled logistic regression models as well as models controlling for trauma history, a generalized anxiety disorder (GAD) diagnosis, and depression symptoms. Participants with a current comorbid nightmare disorder versus those without were nearly twice as likely to screen positive for suicide risk in an uncontrolled model and models controlling for trauma history, a GAD diagnosis, and depression symptoms. Neither a current comorbid sleep terror disorder nor a sleepwalking disorder was significantly associated with suicide risk. This pattern of findings remained consistent for both current and lifetime sleep disorder diagnoses. Youth with bipolar I disorder and a comorbid nightmare disorder appear to be at heightened suicide risk. Implications for assessment and treatment are discussed.

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. RESULTS: GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. CONCLUSIONS: These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study.

OBJECTIVE: To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. METHOD: The Treatment of Early Age Mania (TEAM) study is a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15 years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. RESULTS: CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p = .03) or VAL (35.0%; p = .003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean = 4.72, 95% CI = 2.67, 6.78), and compared to LI (mean = 3.63, 95% CI = 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. CONCLUSION: Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov; NCT00057681.

Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment.

OBJECTIVE: The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively. METHOD: TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group. RESULTS: Response rate for children switched to risperidone (47.6%) was higher than for those switched to either lithium (12.8%; p = .005; number needed to treat [NNT] = 3; 95% CI = 1.71-9.09) or divalproex (17.2%; p = .03; NNT = 3; 95% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3%) was higher than for those who added divalproex (0%; p = .0002; NNT = 2; 95% CI = 1.27-3.56) and trended higher for lithium (26.7%; p = .07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5% significance level that the average weight gain was different by study medication for partial responders (p = .07, 1-way analysis of variance). CONCLUSION: Risperidone appears to be more useful than lithium or divalproex for children with bipolar I disorder and other comorbid conditions who are nonresponders or partial responders to an initial antimanic medication trial. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov/; NCT00057681.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. METHODS: DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. RESULTS: Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). CONCLUSIONS: These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder.

Partnering for the World's Children: Why Collaborations Are Important.

On a global scale, psychiatric disorders are among the most common of medical morbidity. Most psychiatric disorders have their onset in childhood and adolescence when prevention and early intervention can prevent a lifetime of suffering, disability, and stigma. Thus, we share in a global responsibility to transcend cultural and political boundaries to identify childhood-onset psychiatric illness as an international public health crisis that demands the attention and efforts of physicians and other clinicians, families, stakeholders, and policy makers around the world.

Displaced Children: The Psychological Implications.

Millions of people across the world have been displaced or live in exile and/or as refugees largely as a consequence of wars, acts of terrorism, and catastrophic natural disasters. There are serious psychological consequences as a result of these extremely difficult life circumstances. Adults often can express their needs and have them be heard, whereas children are unable to do so. The children may be provided food, shelter, and clothing and have their medical needs attended to, but their emotional and psychological needs go unrecognized and unmet, with dire and monumental long-term consequences.

Ask Suicide-Screening Questions (ASQ): a brief instrument for the pediatric emergency department.

OBJECTIVE: To develop a brief screening instrument to assess the risk for suicide in pediatric emergency department patients. DESIGN: A prospective, cross-sectional instrument-development study evaluated 17 candidate screening questions assessing suicide risk in young patients. The Suicidal Ideation Questionnaire served as the criterion standard. SETTING: Three urban, pediatric emergency departments associated with tertiary care teaching hospitals. PARTICIPANTS: A convenience sample of 524 patients aged 10 to 21 years who presented with either medical/surgical or psychiatric chief concerns to the emergency department between September 10, 2008, and January 5, 2011. MAIN EXPOSURES: Participants answered 17 candidate questions followed by the Suicidal Ideation Questionnaire. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values, likelihood ratios, and area under the receiver operating characteristic curves of the best-fitting combinations of screening questions for detecting elevated risk for suicide. RESULTS: A total of 524 patients were screened (344 medical/surgical and 180 psychiatric). Fourteen of the medical/surgical patients (4%) and 84 of the psychiatric patients (47%) were at elevated suicide risk on the Suicidal Ideation Questionnaire. Of the 17 candidate questions, the best-fitting model comprised 4 questions assessing current thoughts of being better off dead, current wish to die, current suicidal ideation, and past suicide attempt. This model had a sensitivity of 96.9% (95% CI, 91.3-99.4), specificity of 87.6% (95% CI, 84.0-90.5), and negative predictive values of 99.7% (95% CI, 98.2-99.9) for medical/surgical patients and 96.9% (95% CI, 89.3-99.6) for psychiatric patients. CONCLUSIONS: A 4-question screening instrument, the Ask Suicide-Screening Questions (ASQ), with high sensitivity and negative predictive value, can identify the risk for suicide in patients presenting to pediatric emergency departments.

Treatment moderators and predictors of outcome in the Treatment of Early Age Mania (TEAM) study.

OBJECTIVE: Both the diagnosis and treatment of bipolar disorder in youth remain the subject of debate. In the Treatment of Early Age Mania (TEAM) study, risperidone was more effective than lithium or divalproex in children diagnosed with bipolar mania and highly comorbid with attention-deficit/hyperactivity disorder (ADHD). We searched for treatment moderators and predictors of outcome. METHOD: TEAM was a multi-site, 8-week, randomized clinical trial of risperidone, lithium, or divalproex in 279 medication-naïve patients, aged 6 through 15 years, with a DSM-IV diagnosis of bipolar disorder currently in manic or mixed phase. Outcome measures included binary end-of-treatment responder status and change in the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (KMRS). Baseline demographics and clinical characteristics were tested as modifiers of treatment effect and as overall predictors of outcome. RESULTS: Moderator effects were detected for site, ADHD, and obesity. Across sites, the response ratio (RR) for risperidone versus lithium ranged from 1.2 (95% confidence interval [CI] = 0.8-1.7) to 8.3 (95% CI = 1.1-60.8), and for risperidone versus divalproex from 1.3 (95% CI = 0.8-2.2) to 10.5 (95% CI = 1.4-77.7). The RR for risperidone versus lithium was 2.1 for patients with ADHD, but 1.0 for those without ADHD, and 2.3 (95% CI = 1.6-3.3) for nonobese patients, but 1.1 (95% CI = 0.6-2.0) for obese ones. Older age and less severe ADHD symptoms were associated with greater improvement on the KMRS. CONCLUSIONS: Risperidone was more effective than lithium or divalproex across the demographics and clinical characteristics of the sample, but the magnitude of its effect was influenced by site-related characteristics and presence of ADHD. Clinical trial registration information--Treatment of Early Age Mania; http://clinicaltrials.gov/; NCT00057681.

A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents.

CONTEXT: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. OBJECTIVE: To investigate which medication to administer first to antimanic medication-naive subjects. DESIGN, SETTING, AND PARTICIPANTS: The Treatment of Early Age Mania (TEAM) study recruited 6- to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patient-choice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. INTERVENTIONS: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 µg/mL), and risperidone (4-6 mg). MAIN OUTCOME MEASURES: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents. RESULTS: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics: 100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) µg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; χ(2)(1) = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; χ(2)(1) = 28.3, P < .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (χ(2)(1) = 6.4, P = .011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F(1,212) = 45.5, P < .001; F(1,212) = 39.1, P < .001; and F(1,213) = 191.4, P < .001, respectively) and vs divalproex sodium (F(1,212) = 34.7, P < .001; F(1,212) = 45.3, P < .001; and F(1,213) = 209.4, P < .001, respectively). The thyrotropin level increased in subjects taking lithium (t(62) = 11.3, P < .001). CONCLUSIONS: Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00057681

Feasibility of screening patients with nonpsychiatric complaints for suicide risk in a pediatric emergency department: a good time to talk?

OBJECTIVE: Screening children for suicide risk when they present to the emergency department (ED) with nonpsychiatric complaints could lead to better identification and treatment of high-risk youth. Before suicide screening protocols can be implemented for nonpsychiatric patients in pediatric EDs, it is essential to determine whether such efforts are feasible. METHODS: As part of an instrument validation study, ED patients (10-21 years old) with both psychiatric and nonpsychiatric presenting complaints were recruited to take part in suicide screening. Clinically significant suicidal thoughts, as measured by the Suicidal Ideation Questionnaire, and suicidal behaviors were assessed, as well as patient opinions about suicide screening. Recruitment rates for the study as well as impact on length of stay were assessed. RESULTS: Of the 266 patients and parents approached for the study, 159 (60%) agreed to participate. For patients entering the ED for nonpsychiatric reasons (n = 106), 5.7% (n = 6) reported previous suicidal behavior, and 5.7% (n = 6) reported clinically significant suicidal ideation. There were no significant differences for mean length of stay in the ED for nonpsychiatric patients with positive triggers and those who screened negative (means, 382 [SD, 198] and 393 [SD, 166] minutes, respectively; P = 0.80). Ninety-six percent of participants agreed that suicide screening should occur in the ED. CONCLUSIONS: Suicide screening of nonpsychiatric patients in the ED is feasible in terms of acceptability to parents, prevalence of suicidal thoughts and behaviors, practicality to ED flow, and patient opinion. Future endeavors should address brief screening tools validated on nonpsychiatric populations.