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.

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.

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.

Ethical issues in local, national, and international disaster psychiatry.

The world as we know it is plagued with conflict, yet little attention is paid to the inherent ethical issues and challenges related to trauma work. It is important to be aware of these issues because they are bound to raise questions about how medical practitioners confer neutrality in the face of political agendas and war on one hand and maintain a commitment to a person's well-being on the other. When engaged in local, national, or international trauma work, cultural, ethnic, and political literacy is crucial, and an acknowledgment of one's subjectivity is paramount. There are contradictory points of view about practicing value-free psychiatry. Psychosocial programs should examine the long-term political consequences of their work as well as the short- and long-term humanitarian impact.

Innovations: child & adolescent psychiatry: Training in developmental responses to trauma for child service providers.

Youths most at risk of exposure to community violence are often those who are least likely to receive the attention of mental health professionals. The column describes the development and testing of training about trauma for school personnel and other community providers of children's services. The curriculum was developed with input from focus groups of school nurses. The one-day training sessions address nine areas: normal responses to stress, abnormal responses to stress, posttraumatic stress disorder and acute stress disorder, stage theories of loss and grief, risk and protective factors, crisis and disaster planning, resilience, mental health referral sources, and self-care techniques.

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.

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.

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.

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.

Consequences of child exposure to war and terrorism.

Acts of war and terrorism are increasingly prevalent in contemporary society. Throughout history, weaponry has become more efficient, accurate, and powerful, resulting in more devastation and loss of human life. Children are often overlooked as victims of such violence. Around the world, children are exposed to violence in multiple forms, frequently developing traumatic stress reactions. Such reactions are best understood within the context of social-emotional and cognitive development, as children respond differently to the stress of violence depending on their developmental level. Furthermore, the violence of war and terrorism often results in a multitiered cascade of negative life events including loss of loved ones, displacement, lack of educational structure, and drastic changes in daily routine and community values. These numerous losses, challenges, and stresses affect children's brains, minds, and bodies in an orchestrated whole-organism response. This paper describes these effects, synthesizing the current state of research on childhood traumatic stress reactions from the fields of neuroscience, clinical psychology, and pediatric diagnostic epidemiology.