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Aim. The aim of the study was to assess concentrations of the following neuropeptides: phoenixin, spexin and kisspeptin in venous blood serum of children and adolescents suffering from bipolar disorder, and by this their predictive efficiency in this disorder. Material. The study included 75 individuals with a mean age of 15.26 years (95% CI: 14.86-15.67), of which the study group comprised 57 individuals diagnosed with bipolar affective disorder and the control group - 18 individuals with no psychiatric diagnosis and no pharmacological treatment. Method. Phoenixin, spexin and kisspeptin levels were determined in the peripheral venous blood serum. Neuropeptide concentrations were measured with the enzyme-linked immunosorbent assay (ELISA). Results. The mean phoenixin concentration in the studied group equalled 1.57 ng/ml (95% CI: 1.35-1.79), while in the control group - 2.69 ng/ml (95% CI: 2.38-3; U Mann-Whitney test p-value < 0.05). For spexin, these results were 639.65 pg/ml (95% CI: 558.86-720.44) in the studied group, and 354.28 pg/ml (95% CI: 310.33-398.22; U Mann-Whitney test p-value < 0.05) in the control group. The observed differences were statistically significant. The mean concentration of kisspeptin levels in the studied group was 126.02 pg/ml (95% CI: 39.82-212.23; median: 59.85), while in the control group - 54.83 pg/ml (95% CI: 39.23-70.43; median: 51.3; U Mann-Whitney test p-value = 0.29), and the observed difference was not statistically significant. Conclusions. The occurrence of bipolar disorder symptoms is statistically significantly linked with a decreased phoenixin concentration and to a small degree - with an increased spexin concentration in blood serum of patients. However, it is not linked with the kisspeptin concentration. [ABSTRACT FROM AUTHOR]

Family-focused therapy (FFT) is an emerging psychotherapy treatment option for pediatric bipolar disorder. This paper will provide an in-depth analysis of FFT, its effectiveness in treating pediatric bipolar disorder, and its use in conjunction with pharmacological treatments. Although the current literature surrounding pediatric bipolar disorder is minimal, it is apparent that the disorder can cause significant impairments in multiple domains of function. Thus, an effective and safe treatment option for children with bipolar disorder is in dire need. The main goal of FFT is to address familial functioning, attitudes, and coping strategies which are often impaired in the greater context of this disorder. To address these impairments, FFT encompasses three phases: psychoeducation, communication enhancement training, and problem-solving skills training. While a recognized limitation is the therapy's adaptability, studies have found that early administration of FFT is key to success and many trials demonstrated significant improvements in depressive and manic symptoms of pediatric bipolar disorder. Additionally, compared to other psychosocial treatments for pediatric bipolar disorder, FFT is the most evidence-based approach available within the current literature. However, it is generally agreed upon that an effective treatment modality consists of a combination of FFT and pharmacotherapy. While FFT is a promising treatment option, further research is required to assess its effectiveness and to ensure its feasibility for pediatric bipolar disorder. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BPD) is a psychiatric condition driving frequent mood swings between periodic extremes of happiness and depression in patients. In this study, a source-based morphometry (SBM) and voxel-based morphometry (VBM) analysis was utilized to measure the differences in the white matter (WM) and grey matter (GM) between euthymic children with BPD and typically developing (TD) children. We adapted both multivariate (SBM) and univariate (VBM) analysis in 20 children with BPD euthymia /remission and compared to the same number of TD age-matched children. The VBM did not reveal any increase in GM and WM voxel values in children with BPD. However, a decrease in the GM voxel values in the bilateral middle frontal and WM voxels in the left hippocampus, left caudate, left orbitofrontal and right inferior parietal cortices was identified. Conversely, SBM analysis in BPD displayed a high GM value in bilateral angular gyrus, bilateral inferior temporal, left supplementary motor area and left middle temporal region, while a low value was observed in left inferior and middle occipital, cerebellum, thalamus, left premotor area and left lingual gyrus. These findings suggested a crucial GM and WM alteration in multiple neural regions in BPD children even during sustained and substantial remission. [ABSTRACT FROM AUTHOR]

Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness. [ABSTRACT FROM AUTHOR]

Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08–2.36) and olanzapine (OR = 1.68, CI: 1.03–2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69–1.54) or risperidone (OR = 1.02, CI: 0.68–1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08–2.38) and olanzapine (OR = 1.73, CI: 1.06–2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68–1.54) or risperidone (OR = 1.01, CI: 0.67–1.51) was not. In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone. [ABSTRACT FROM AUTHOR]

The article discusses the question of diagnosing disruptive mood dysregulation disorder (DMDD). It mentions the increase in the diagnosis of bipolar disorder in children and teenagers, the overlap of symptoms of DMDD with other disorders, and questions the need for this specific disorder.

Attention deficits are considered one of the potential endophenotypic markers of Bipolar Disorder (BD). Pediatric bipolar disorder (PBD) likely has stronger genetic underpinnings than adult onset BD; therefore, demonstrating attention deficits in PBD can be both strategic and convincing in attesting their status as one of the potential endophenotypic markers of BD. However, unlike adult literature, uncertainty exists regarding the magnitude of attention deficits in PBD. In this regard, one key unresolved question is the potential impact of attention deficit hyperactivity disorder (ADHD). The main goal of the study was to examine attention deficits in a comorbidity-free sample of euthymic PBD patients. Thirty (21 boys, 9 girls) remitted PBD patients without co-morbidity and thirty age (<17 years), sex, handedness, and Full-Scale IQ matched control subjects were compared on performance on attention tasks. Working memory (WM), which might potentially confound with the attention task performances, was also examined. Compared to controls, PBD patients performed poorly on various tests of attention, but not on any WM tasks. Further, it was found that observed attention deficits were independent of residual mood symptoms, medication effect or illness characteristics. Such attention deficits in this comorbidity-free PBD sample further endorses its status as an endophenotypic marker of bipolar disorders and establishes continuity with deficits found in adult bipolar patients. [ABSTRACT FROM AUTHOR]

Background: Impulsivity is a core feature of the attention-deficit/hyperactivity disorder (ADHD) and is one of the DSM-V diagnostic criteria for borderline personality disorder (BPD). Impulsivity is also present in bipolar disorder (BD). Impulsivity has been linked to adverse behavior (suicidality,…) and to traumatic childhood experiences. Our study explored impulsivity in BPD, BD, ADHD and healthy controls (CTRL) and investigated the impact of early trauma on impulsivity.Methods: 744 patients with BD (n = 276), BPD (n = 168), ADHD (n = 173) or a combination (BPD_BD, n = 29; BPD_ADHD, n = 94, BD_BPD_ADHD n = 13) and 47 controls were included. All subjects were completed the Baratt Impulsivity Scale (BIS-10) and the Childhood Trauma Questionnaire (CTQ).Results: BD reported the same levels of impulsiveness as CTRL. When BPD and BD are co-morbid, impulsivity increased to reach the level of BPD. Impulsiveness was significantly associated to traumatic childhood event for BD and CTRL, not for BPD and AHDH.Limitations: Impulsivity was assessed on the basis of a self-report questionnaire and not by the mean of an objective measure such as a neuropsychological test. Moreover, we don't know what treatment our pathological subjects were receiving. But, ADHD and BPD, despite the probable treatment, were more impulsive than healthy CTRLs who did not take medications.Conclusions: Impulsivity is probably not a feature of BD but is associated with the presence of traumatic childhood experiences, especially for euthymic patients, unlike BPD and ADHD. So, it seems essential to assess the presence of early trauma to reduce the impulsivity and improve the evolution of BD. [ABSTRACT FROM AUTHOR]

Background: Childhood adversity has been shown to exert profound effects on basic psychological processes well into adulthood. Some of these processes, such as those related to reward and emotion, play critical roles in moral decision-making. As a population with high rates of childhood trauma as well as heterogenous clinical presentation, individuals with bipolar disorder (BD) constitute an enriched group in which to examine the correlates of trauma and other clinical variables with moral cognition.Methods: 62 euthymic BD patients and 27 controls responded to moral dilemma scenarios and completed the Childhood Trauma Questionnaire.Results: Results revealed a main effect of diagnosis on moral decision-making only when both personal force and an intention were required, indicating a more utilitarian style in BD patients relative to controls. Several interesting patterns also emerged regardless of diagnostic status. Higher ratings of physical neglect were significantly associated with higher ratings of acceptability (a utilitarian tendency) across dilemma types, and a similar pattern was observed at the trend level for experiences of emotional neglect. Significant main effects on moral decision-making were also observed for sex, illness duration, and history of psychotic features in the BD sample.Limitations: The present study is limited by the self-reported nature of the CTQ and by the small number of trials of moral dilemmas. In addition, practical and clinical implications of the moral dilemmas paradigm are limited due to its abstract nature.Conclusions: Our results indicate that certain clinical features as well as childhood maltreatment (in particular neglect) may significantly impact moral decision making in adult life. Surprisingly, childhood trauma was associated with a more utilitarian style, which is in the opposite direction from previous effects shown in PTSD. Although speculative, our results suggest that there may be a protective quality associated with utilitarian moral decision-making tendencies. [ABSTRACT FROM AUTHOR]

Background: Paediatric bipolar disorder (BD) has gained validity, and substantial research in the last 20 years has dissipated the controversy surrounding it. However, data on the prevalence, prodromes, phenomenology, and longitudinal stability of paediatric BD are still required.Methods: We reviewed the medical records of all patients (n = 72) with DSM-IV BD evaluated over a 15-year period. We assessed the most frequently present symptoms prior to and at the time of diagnosis, the diagnostic stability of the disorder and its subtypes (I, II and NOS).Results: Patients [75% boys, median age (interquartile range, IQR) at diagnosis 12.6 (9.6-15.7) years] underwent follow up for a median period of 3.86 (1.8-5.9) years. There was a median delay from symptom onset to diagnosis of 2.3 (1.2-4.8) years. At the time of diagnosis, 37.5% had BD-I, 8.3% BD-II, and 54.2% BD-NOS. At follow-up, 62.5% had BD-I, 8.3% had BD-II, and 23.6% had BD-NOS, whereas 4.2% no longer met the DSM-IV criteria for BD.Limitations: Our sample size limited the BD subtype analyses. Some of information was collected retrospectively.Conclusion: 95.8% of our sample retained a BD diagnosis after a median follow-up period of 3.86 years. BD-I patients maintained their diagnosis and subtype of BD. Half of all patients with baseline BD-NOS maintained their BD subtype, but most of the other half showed conversion to BP-I at follow up. Only 4.2% of the sample (all with BD-NOS at baseline) did not meet criteria for BD at follow up, and these patients were stable. [ABSTRACT FROM AUTHOR]

Caregivers of psychiatrically impaired children experience considerable parenting stress. However, no research has evaluated parenting stress within the context of pediatric bipolar spectrum disorders (BPSD). Thus, the aim of this investigation was to identify predictors and moderators of stress among caregivers in the Longitudinal Assessment of Manic Symptoms study. Participants included 640 children and their caregivers in the Longitudinal Assessment of Manic Symptoms cohort. Children had a mean age of 9.4 ± 1.9 years (68% male, 23% BPSD); parents had a mean age of 36.5 ± 8.3 years (84% mothers). Children with BPSD had more service utilization, psychiatric diagnoses, mood and anxiety symptoms, and functional impairment but fewer disruptive behavior disorders. Caregivers of children with BPSD were more likely than caregivers of children without BPSD to have a partner, elevated depressive symptoms, antisocial tendencies, and parenting stress (Cohen's d = .49). For the whole sample, higher child IQ, mania, anxiety, disruptive behavior, and caregiver depression predicted increased parenting stress; maternal conduct disorder predicted lower stress. Child anxiety and disruptive behavior were associated with elevated caregiver stress only for non-BPSD children. Caregivers of children with BPSD experience significant burden and thus require specialized, family-focused interventions. As stress was also elevated, to a lesser degree, among depressed caregivers of children with higher IQ, mania, anxiety, and disruptive behavior, these families may need additional supports as well. Although parents with conduct/antisocial problems evidenced lower stress, these difficulties should be monitored. Thus, parenting stress should be evaluated and addressed in the treatment of childhood mental health problems, especially BPSD. [ABSTRACT FROM AUTHOR]

Background: To assess whether the course of pediatric bipolar-I (BP-I) disorder impacts the course of conduct disorder (CD)/antisocial personality disorder (ASPD). We hypothesized that remission of manic symptoms in BP-I youth will be associated with remission of CD/ASPD.Methods: We used data from four longitudinal datasets of carefully characterized and comprehensively assessed youth with structured diagnostic interview based diagnoses of BP-I disorder and CD/ASPD assessed at baseline in childhood and at follow-up onto adolescent years. The baseline sample consisted of 240 subjects with full BP-I disorder. The average follow-up time was 6.6 ± 2.4 years.Results: Subjects with remitting BP-I disorder in adolescent years had a significantly lower one-year prevalence of CD or ASPD compared to those with persistent BP-I disorder (χ2 = 10.35, p = 0.001).Limitations: Our inferences were derived from the examination of naturalistic longitudinal follow-up data and not results of a clinical trial.Conclusions: Results indicate that remission of manic symptoms at the adolescent follow up in youth with BP-I disorder were associated with a significant decrease in rates of CD/ASPD. These results suggest that targeting manic symptoms in youth with BP-I disorder could mitigate the course of CD/ASPD in youth. Considering the high morbidity and disability associated CD/ASPD in youth and the limited treatment options available to address it, if replicated, these findings would have very important clinical and public health significance. [ABSTRACT FROM AUTHOR]

Family-based psychosocial treatments have been developed to address the significant impairments in psychosocial functioning among youth with pediatric bipolar disorder (PBD), yet factors impacting engagement in these treatments have yet to be extensively studied. Early termination from treatment may lead to negative outcomes among youth with PBD. Thus, the primary aim of this exploratory study was to identify predictors and moderators of treatment dropout in PBD. Drawing from the child attrition literature, this study examined characteristics likely to be associated with dropout in families affected by PBD, including potential targets of treatment. Using Cox proportional hazards regressions, we explored the impact of modifiable parent, child, and family characteristics (i.e., parent stress, family coping, child symptoms) and stable demographic characteristics (i.e., family income, ethnic minority status) on dropout among 59 youth aged 7 to 13 who participated in a randomized clinical trial comparing a manualized psychotherapy for PBD (child- and family-focused cognitive behavioral therapy; CFF-CBT) versus treatment as usual (TAU). Specifically, we explored whether dropout was related to baseline levels and changes in these characteristics over the course of treatment in CFF-CBT versus TAU. Findings provide preliminary support for high parental stress as a predictor of dropout across treatments and low baseline parent coping as a predictor of retention in CFF-CBT specifically. Worsening of child depression symptoms over treatment predicted greater likelihood of dropout in CFF-CBT. Finally, improvement in children’s global functioning was associated with reduced dropout across treatments. Results have important implications for tailoring interventions for PBD. [ABSTRACT FROM AUTHOR]

Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatment in bipolar disorder patients. The neural effects of VPA in pediatric bipolar disorder (PBD) have yet to be established. This preliminary study explored the effects of VPA on brain structure in PBD. Fourteen PBD patients (10 males; mean = 13.43 ± 3.05 years old) underwent a structural MRI before and after a 6-week VPA treatment period. Bayesian linear mixed modeling explored seven brain region volumes as a function of dichotomous pre/post time. Results showed a decrease in amygdala volume over time. These findings need to be confirmed by large-scale, longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: Patient characteristics and disease progression may affect response to pharmacologic intervention in bipolar I disorder. Asenapine is approved for acute treatment of manic/mixed episodes of bipolar I disorder in patients 10–17 years old. Post hoc analyses assessed asenapine efficacy in pediatric patients by current manic or mixed episode, number of lifetime episodes, and baseline body mass index (BMI). Patients and methods: Data were obtained from a 3-week, randomized, double-blind, placebo-controlled, parallel-group trial of asenapine 2.5, 5.0, or 10.0 mg twice daily (BID) in male or female patients (10–17 years) with bipolar I disorder (NCT01244815). Patients were stratified by current episode type (Diagnostic and Statistical Manual of Mental Disorders, fourth edition – defined mixed/manic), number of lifetime episodes (<3, 3–5, >5), and baseline BMI tertile. Changes from baseline to day 21 in Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions Scale for use in Bipolar Illness (CGI-BP) were assessed in asenapine subgroups vs placebo. Results: In patients with mixed episodes, differences in YMRS and CGI-BP scores were statistically significant for each asenapine dose vs placebo (P<0.001) at day 21; in patients with manic episodes, significant differences vs placebo were seen in all groups (P<0.05) except 2.5 mg BID on the YMRS. In patients with <3 previous mixed/manic episodes, significant differences in YMRS and CGI-BP scores were observed for all asenapine doses vs placebo (P<0.05). In patients with 3–5 or >5 previous episodes, asenapine 10 mg BID was significantly different than placebo (P<0.05) on both scales; differences vs placebo varied for lower doses. Baseline body weight or BMI did not appear to influence the efficacy of asenapine. Conclusion: Asenapine was effective in the treatment of pediatric patients with bipolar I disorder. Efficacy did not appear to be influenced by the type of current episode, stage of disease progression, or baseline body weight/BMI. [ABSTRACT FROM AUTHOR]

Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental illnesses, including schizophrenia, bipolar disorder, and autism. Prenatal interventions to ameliorate that risk have yet to be established for clinical use. A systematic review of prenatal nutrients and childhood emotional development and later mental illness was performed. Randomized trials of folic acid, phosphatidylcholine, and omega-3 fatty acid supplements assess effects of doses beyond those adequate to remedy deficiencies to promote normal fetal development despite genetic and environmental risks. Folic acid to prevent neural tube defects is an example. Vitamins A and D are currently recommended at maximum levels, but women's incomplete compliance permits observational studies of their effects. Folic acid and phosphatidylcholine supplements have shown evidence for improving childhood emotional development associated with later mental illnesses. Vitamins A and D decreased the risk for schizophrenia and autism in retrospective observations. Omega-3 fatty acid supplementation during early pregnancy increased the risk for schizophrenia and increased symptoms of attention deficit hyperactivity disorder, but in later pregnancy it decreased childhood wheezing and premature birth. Studies are complicated by the length of time between birth and the emergence of mental illnesses like schizophrenia, compared with anomalies like facial clefts identified at birth. As part of comprehensive maternal and fetal care, prenatal nutrient interventions should be further considered as uniquely effective first steps in decreasing risk for future psychiatric and other illnesses in newborn children. [AJP at 175: Remembering Our Past As We Envision Our Future July 1959: Longitudinal Observations of Biological Deviations in a Schizophrenic Infant Barbara Fish described the course of an infant born with fluctuating motor problems who developed schizophrenia. (Am J Psychiatry 1959; 116:25-31 )]. [ABSTRACT FROM AUTHOR]

The offspring of parents with bipolar disorder (OBD) are at high risk for developing mental disorders. In addition to genetic factors, environmental risk is purported to be associated with these negative outcomes. However, few studies have examined this relation. Using concurrent and longitudinal data, we examined if support, structure, and control provided by parents in middle childhood mediated the relation between having a parent with or without bipolar disorder, and offspring mental health. The sample included 145 offspring (77 OBD, 68 controls) aged 4 to 14 years and their parents. Parent and teacher ratings of child behavior were collected, and diagnostic assessments were conducted in offspring 12 years later (n = 101). Bootstrapping analyses showed that low levels of structure mediated the relation between having a parent with bipolar disorder and elevated internalizing and externalizing difficulties during middle childhood. For the longitudinal outcomes, parental control emerged as the strongest mediator of the relation between parents’ bipolar disorder and offspring psychopathology. Suboptimal childrearing may have different immediate and enduring consequences on mental health outcomes in the OBD. Parental structure has robust effects on emotional and behavioral problems in middle childhood, while levels of control promote psychological adjustment in the OBD as they mature. [ABSTRACT FROM AUTHOR]

Non-suicidal self-injury (NSSI) in childhood is not well documented, especially among youth with pediatric bipolar disorder (PBD). The current study evaluated prevalence and correlates of NSSI, and its impact on intervention response, in a randomized trial of Child- and Family-Focused Cognitive-Behavioral Therapy (CFF-CBT) versus Treatment As Usual (TAU), adjunctive to pharmacotherapy. This study included 72 children ages 7-13 (58% male) with PBD. NSSI and correlates were assessed at baseline; mood and psychiatric severity were measured longitudinally. NSSI was common: 31% endorsed NSSI behaviors; 10% reported thoughts of NSSI, in the absence of behaviors. Children engaging in NSSI reported higher depression, psychosis, suicidality, and hopelessness; lower self-esteem; and reduced family help-seeking in univariate analyses. In a multivariate logistic regression, high child depression and psychosis, and low family help-seeking, remained significantly associated with baseline NSSI. In mixed-effects regression models, presence of NSSI at baseline did not influence the response of depressive symptoms to treatment. Children who endorsed NSSI experienced steeper response trajectories for psychiatric severity, regardless of treatment group. Youth who denied NSSI showed poorer response to TAU for manic symptoms; mania trajectories in CFF-CBT were similar across youth. Thus, NSSI in PBD is common and associated with impairment. As children might engage in NSSI for different reasons, the function of NSSI should be considered in treatment. Since children without NSSI fared worse in TAU, it may be important to ensure that youth with PBD receive structured, intensive interventions. CFF-CBT was efficacious regardless of NSSI, and thus shows promise for high-risk children with PBD. [ABSTRACT FROM AUTHOR]

This study investigates multimodal structural MR imaging biomarkers of development trajectories in pediatric bipolar disorder. T1-weighted and diffusion-weighted MR imaging was conducted to investigate cross-sectional group differences with age between typically developing controls ( N = 26) and youths diagnosed with bipolar disorder ( N = 26). Region-based analysis was used to examine cortical thickness of gray matter and diffusion tensor parameters in superficial white matter, and tractography-based analysis was used to examine deep white matter fiber bundles. Patients and controls showed significantly different maturation trajectories across brain areas; however, the magnitude of differences varied by region. The rate of cortical thinning with age was greater in patients than controls in the left frontal pole. While controls showed increasing fractional anisotropy (FA) and axial diffusivity (AD) with age, patients showed an opposite trend of decreasing FA and AD with age in fronto-temporal-striatal regions located in both superficial and deep white matter. The findings support fronto-temporal-striatal alterations in the developmental trajectories of youths diagnosed with bipolar disorder, and further, show the value of multimodal computational techniques in the assessment of neuropsychiatric disorders. These preliminary results warrant further investigation into longitudinal changes and the effects of treatment in the brain areas identified in this study. [ABSTRACT FROM AUTHOR]

Child mental illness impacts the entire family, and previous research has consistently found that parenting children with mental health disorders is psychologically distressing. The study’s purpose was to delineate the stressors for which parents request advice and the online interactions in which often isolated parents engage. We coded the content of 146 posts written by parents of 77 daughters and 69 sons ages 5 to 18 years with AD/HD, bipolar disorder, and depressive and anxiety disorders (M age = 10) on four publicly accessible internet forums. Most posters were mothers, most wrote to seek information or advice, and most received advice from other women. Parents posted on a wide range of parental concerns, most frequently the effects of children’s illness on themselves, specifically feelings of helplessness, their need for advice on their own coping, and the stress of child discipline. Parents frequently also expressed concern about child symptoms, especially poor academic performance, and had questions about efficacy, side effects of, and noncompliance with medication. Parents’ concerns did not differ by child diagnosis, gender, or age. However, parents of children with AD/HD only were significantly less likely to describe parent-child verbal or physical conflict than other forum parents. Future research should create empirically based recommendations for effective discipline and medication management that reflects parents’ concerns. [ABSTRACT FROM AUTHOR]

MR imaging studies in paediatric bipolar disorder have particularly focused on the amygdala and hippocampus, subcortical structures, and to a lesser extent on the thalamus. The purpose of this study was to perform structural analysis of the regions of interest (ROI) associated with mood regulation. In this study 18 children (between the ages of 12–18) were matched according to their age and sex and were divided into three groups. These were: a paediatric bipolar disorder group, risk group and a healthy control group. The structured diagnostic interviews were performed with children and their parents. T1 weighted MR images in the sagittal plane with a thickness of 1 mm were taken from the subjects. Automatic structural brain analysis was performed, and the volume and volume fraction (VF) of the ROIs were obtained. Brain size in the patients with paediatric bipolar disorder (742.4 ± 110.1 cm 3 ) was significantly smaller than the healthy control group (880.7 ± 73.8 cm 3 ) (p≤0.05). MRI analysis between the paediatric bipolar disorder, risk group and healthy control group revealed no difference between them in terms of amygdala, thalamus or hippocampal volumes. In this study, there was no difference between the volumes of amygdala, thalamus or hippocampus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression.Method: Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change from baseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures analysis.Results: A total of 347 patients were randomized and received at least 1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (-21.0 versus -15.3; p < .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters.Conclusion: In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters. Clinical trial registration information-Lurasidone Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding of the symptomatic development of bipolar disorder from childhood to early adulthood.Aims: We assessed whether borderline personality disorder traits, ADHD, and emotional, behavioural and social difficulties during childhood were associated with hypomania assessed in young adulthood.Method: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine associations between measures of childhood psychopathology and lifetime hypomanic features assessed at age 22-23 years using the Hypomania Checklist-32 (HCL-32; n = 3372). We also conducted a factor analysis of the HCL to identify latent constructs underlying hypomania, and the extent to which childhood psychopathology was associated with these.Results: We identified two factors of the HCL corresponding to energy/mood and risk-taking/irritability. There was evidence of association between childhood borderline personality disorder traits and both hypomania factors, with evidence that the association was stronger with the risk-taking/irritability factor. All individual borderline traits, with the exception of fear of abandonment, were associated with hypomania. There was also evidence of association between most other measures of childhood psychopathology (ADHD, hyperactivity, conduct problems, peer relationship problems and reduced prosocial behaviour) and the risk-taking/irritability factor, but much less consistent evidence of association with the energy/mood factor.Limitations: The HCL cannot diagnose bipolar disorder and may be subject to reporting bias.Conclusions: A broad range of childhood psychopathologies may represent early markers of risk for hypomania. Further studies are required to understand the mechanisms underlying these associations, and to inform earlier detection of bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: We examined the efficacy of olanzapine/fluoxetine combination (OFC) in improving health-related quality of life (QoL) in the treatment of bipolar depression in children and adolescents. Methods: Patients aged 10-17 years with bipolar I disorder, depressed episode, baseline children's depression rating scale-revised (CDRS-R) total score ≥40, Young Mania Rating Scale (YMRS) total score ≤15, and YMRS-item 1 ≤ 2 were randomized to OFC (6/25-12/50 mg/day olanzapine/fluoxetine; n = 170) or placebo (n = 85) for up to 8 weeks of double-blind treatment. Patients and parents completed the revised KINDL questionnaire for measuring healthrelated QoL in children and adolescents (KINDL-R) at baseline and endpoint. The mean change in CDRS-R total and item scores were used to compare improvement in symptomatology in patients taking OFC and placebo. Tests were 2-sided using a Type I error cutoff of 0.05, and no adjustments for multiple comparisons were made. Results: Baseline QoL as measured by the KINDL-R was substantially impaired relative to published norms for a healthy school-based sample. OFC-treated patients demonstrated an improvement over placebo at endpoint with respect to mean change from baseline in the patient-rated KINDL-R Self-esteem subscale score (p = 0.028), and in the parent KINDL-R ratings of emotional well-being (p = 0.020), Self-esteem (p = 0.030), and Family (p = 0.006). At endpoint, OFC-treated patients still had a lower QoL compared to the normative population. OFC showed significant improvement (p ≤ 0.05) versus placebo on the CDRS-R total score and on 7 of the 17 CDRS-R items. Conclusions: Patients aged 10-17 years with an acute episode of bipolar depression and their parents reported greater improvements (parents noticed improvements in more areas than did their offspring) on some aspects of QoL when treated with OFC compared with placebo. However, after 8 weeks of treatment, KINDL-R endpoint scores remained lower than those of the, presumably healthy, control population. [ABSTRACT FROM AUTHOR]

A case of psychotropic-resistant pediatric bipolar disorder is presented. Both awareness and proper treatment of previously unrecognized infections and their effects on the immune system were very important in stabilizing the patient's psychiatric symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the last few decades, a noticeable increase in the diagnosis of bipolar disorder (BD) in youth has raised concerns, particularly because of a consequent increase in the use of psychotropic medications with adverse side effects. After observing the development of those youth into adulthood, clinicians and researchers have questioned the notion of expanding the diagnostic boundaries of BD to encapsulate these youth. METHODS: Our research is aimed at gleaning further information on disruptive mood dysregulation disorder (DMDD) and to observe whether its introduction has affected the rates of BD in children and adolescents. In a retrospective study, we calculated the frequencies of patients with BD admitted to a pediatric psychiatric hospital both before and after the introduction of DSM-5. We also observed age, sex, comorbid disorders, and management of DMDD. RESULTS: We found a decrease in the diagnosis of BD with the introduction of DMDD in DSM-5, without much change in treatment interventions utilized. CONCLUSIONS: Research on DMDD is limited so far. Further studies are needed to put together evidence-based guidelines and practice parameters for its management. [ABSTRACT FROM AUTHOR]

Objectives To examine the validity of subthreshold pediatric bipolar I disorder ( BP-I), we compared the familial risk for BP-I in the child probands who had either full BP-I, subthreshold BP-I, ADHD, or were controls that neither had ADHD nor bipolar disorder. Methods BP-I probands were youth aged 6−17 years meeting criteria for BP-I, full (N=239) or subthreshold (N=43), and also included were their first-degree relatives (N=687 and N=120, respectively). Comparators were youth with ADHD (N=162), controls without ADHD or bipolar disorder (N=136), and their first-degree relatives (N=511 and N=411, respectively). We randomly selected 162 non-bipolar ADHD probands and 136 non-bipolar, non- ADHD control probands of similar age and sex distribution to the BP-I probands from our case−control ADHD family studies. Psychiatric assessments were made by trained psychometricians using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Epidemiological Version ( KSADS-E) and Structured Clinical Interview for DSM-IV ( SCID) structured diagnostic interviews. We analyzed rates of bipolar disorder using multinomial logistic regression. Results Rates of full BP-I significantly differed between the four groups (χ23=32.72, P<.001): relatives of full BP-I probands and relatives of subthreshold BP-I probands had significantly higher rates of full BP-I than relatives of ADHD probands and relatives of control probands. Relatives of full BP-I, subthreshold BP-I, and ADHD probands also had significantly higher rates of major depressive disorder compared to relatives of control probands. Conclusions Our results showed that youth with subthreshold BP-I had similarly elevated risk for BP-I and major depressive disorder in first-degree relatives as youth with full BP-I. These findings support the diagnostic continuity between subsyndromal and fully syndromatic states of pediatric BP-I disorder. [ABSTRACT FROM AUTHOR]

Background: Prior studies have suggested that inhibited temperament may be associated with an increased risk for developing anxiety or mood disorder, including bipolar disorder. However, the neurobiological basis for this increased risk is unknown. The aim of this study was to examine temperament in symptomatic and asymptomatic child offspring of parents with bipolar disorder (OBD) and to investigate whether inhibited temperament is associated with aberrant hippocampal volumes compared with healthy control (HC) youth.Methods: The OBD group consisted of 45 youth, 24 of whom had current psychiatric symptoms (OBD+s) and 21 without any psychiatric symptoms (OBD-s), and were compared with 24 HC youth. Temperament characteristics were measured by using the Revised Dimensions of Temperament Survey. Magnetic resonance imaging was used to measure hippocampal volumes. The association between temperament and hippocampal volumes was tested by using multiple regression analysis.Results: Compared with the OBD-s group, the OBD+s group had significantly more inhibited temperament traits, less flexibility, more negative mood, and less regular rhythm in their daily routines. In contrast, the OBD-s group was more likely to approach novel situations compared with OBD+s or HC groups. Within the OBD+s group, a more inhibited temperament was associated with smaller right hippocampal volumes.Conclusions: In this study, symptomatic OBD were characterized by an inhibited temperament that was inversely correlated with hippocampal volume. Additional longitudinal studies are needed to determine whether inverse correlations between hippocampal volume and inhibited temperament represent early markers of risk for later developing bipolar disorder. [ABSTRACT FROM AUTHOR]

Evidence of a high or increasing incidence of childhood onset bipolar disorder in the United States (US) has been viewed skeptically. Here we review evidence that childhood onsets of bipolar disorder are more common in the US than in Europe, treatment delays are longer, and illness course is more adverse and difficult. Epidemiological data and studies of offspring at high risk also support these findings. In our cohort of outpatients with bipolar disorder, two of the major vulnerability factors for early onset − genetics and environmental adversity in childhood − were also greater in the US than in Europe. An increased familial loading for multiple psychiatric disorders was apparent in 4 generations of the family members of the patients from the US, and that familial burden was linked to early onset bipolar disorder. Since both early onset and treatment delay are risk factors for a poor outcome in adulthood, new clinical, research, and public health initiatives are needed to begin to address and ameliorate this ongoing and potentially devastating clinical situation. [ABSTRACT FROM AUTHOR]

Background: In the last two decades, there has been a significant increase in the diagnosis of Bipolar Disorder (BD) in children. The notion of prepubertal onsets of BD is not without controversy, with researchers debating whether paediatric cases have a distinct symptom profile or follow a different illness trajectory from other forms of BD. The latter issue is difficult to address without long-term prospective follow-up studies. However, in the interim, it is useful to consider the phenomenology observed in groups of cases with different ages of onset and particularly to compare manic symptoms in children diagnosed with BD compared to cases presenting with BD in adolescence and adulthood. This review systematically explores the phenomenology of manic or hypomanic episodes in groups defined by age at onset of BD (children, adolescents and adults; or combined age groups e.g. children and adolescents versus adults). Methods: Literature reviews of PubMed and Scopus were conducted to identify publications which directly compared the frequency or severity of manic symptoms in individuals with BD presenting with a first episode of mania in childhood, adolescence or adulthood. Results: Of 304 studies identified, 55 texts warranted detailed review, but only nine studies met eligibility criteria for inclusion. Comparison of manic symptoms across age groups suggested that irritability is a key feature of BD with an onset in childhood, activity is the most prominent in adolescent-onset BD and pressure of speech is more characteristic of adult-onset BD. However, none of the eligible studies made a direct comparison of phenomenology in children versus adults. Assessment procedures varied in quality and undermined the reliability of cross-study comparisons. Other limitations were: the scarcity of comparative studies, the geographic bias (most studies originated in the USA), the failure to fully consider the impact of psychiatric comorbidities on recorded symptoms and methodological heterogeneity. Conclusions: Despite frequent discussion of similarities and differences in phenomenology of mania presenting in different age groups, systematic research is lacking and studies are still required to reliably establish whether the frequency and severity of manic symptoms varies. Such information has implications for clinical practice and the classification of mental disorders. [ABSTRACT FROM AUTHOR]

Objective Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder. Method The sample was derived from two previously conducted longitudinal case-control family studies of psychiatrically and pediatrically referred youth and their families. For this study, probands were stratified based on the presence or absence of a parental mood disorder. Results Subsyndromal scores on the CBCL Anxiety/Depression scale significantly separated the children at high risk for pediatric MDD from those at low risk in a variety of functional areas, including social and academic functioning. Additionally, children at genetic risk without elevated CBCL Anxiety/Depression scale scores were largely indistinguishable from controls. Conclusion These results suggest that the CBCL Anxiety/Depression scale can help identify children at highest risk for pediatric MDD. If implemented clinically, this scale would cost-effectively screen children and identify those most in need of early intervention resources to impede the progression of depression. [ABSTRACT FROM AUTHOR]

Introduction. Decreased need for sleep has been proposed as a core symptom of mania and it has been associated with the pathogenesis of Bipolar Disorder. The emergence of Disruptive Mood Dysregulation Disorder (DMDD) as a new diagnostic has been controversial and much has been speculated about its relationship with the bipolar spectrum. REM sleep fragmentation could be a biomarker of affective disorders and it would help us to differentiate them from other disorders. Method. Polysomnographic cross-sectional study of children with DMDD, bipolar disorder and Attention Deficit Hyperactivity Disorder (ADHD). All participants underwent a psychiatric semi-structured interview to obtain the diagnosis, comorbidities and primary sleep disorders. DMDD's sample was performed following DSM5 criteria. Goals. Perform polysomnography in a sample of bipolar, DMDD and ADHD children and compare their profiles to provide more evidence about the differences or similarities between bipolar disorder and DMDD. Results. Bipolar group had the highest REM density values while ADHD had the lowest. REM density was not statiscally different between bipolar phenotypes. REM density was associated with antidepressant treatment, episodes of REM and their interaction. REM latency was associated with antipsychotic treatment and school performance. Bipolar patients had higher scores on the depression scale than DMDD and ADHD groups. ++++++++++++++++Conclusions. No significant differences between the two compared affective disorders were found. However there were differences in REM density between bipolar and ADHD groups. REM sleep study could provide a new theoretical framework to better understand the pathogenesis of pediatric bipolar disorder. [ABSTRACT FROM AUTHOR]