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The objective of this study was to identify the predictive value of juvenile factors for adult suicidal behavior. We reviewed clinical records to compare factors identified in childhood and adolescence between adult suicidal versus nonsuicidal major affective disorder subjects. Suicide attempts occurred in 23.1% of subjects. Age-at-first-symptom was 14.2 vs. 20.2 years among suicidal versus nonsuicidal subjects (p

Objective: To investigate whether coronary artery disease alters vulnerability of hearts and myocytes to cardiac insults. To address this issue, we developed an experimental model of coronary artery disease. Design: Prospective, experimental study. Setting: University experimental research laboratories. Subjects: Apolipoprotein E knockout mice. Interventions: Male apolipoprotein E knockout mice, aged 8 wks, were fed either a normal or high-fat diet. Measurements and Main Results: High-fat feeding for 24 wks induced atherosclerosis in the coronary arteries, was associated with myocardial infarction, and produced evidence of myocardial metabolic anaerobic stress when compared with apolipoprotein E knockout mice fed normal diet. Myocytes and hearts from both groups had similar morphometric and hemodynamic characteristics. During global ischemia, hearts with coronary disease had shorter time to enter into rigor and developed greater ischemic contracture. They were markedly more resistant to reperfusion injury than nondiseased hearts, as shown by cardiac function, release of cardiac enzymes, and metabolic preservation. An increase in prosurvival signaling was detected in diseased hearts, as shown by a higher ratio of phospho-Akt/total Akt than in nondiseased hearts. Myocytes from diseased heart exposed to metabolic inhibition and reperfusion had fewer arrhythmias than myocytes from nondiseased heart. These differences are not due to high-fat feeding, as hearts of wild-type mice fed this diet were more, not less, vulnerable to cardiac insults. Conclusion: This work suggests that chronic partial ischemia associated with progression of coronary artery disease preconditions myocytes and hearts against subsequent acute cardiac insults.

Objectives: Early psychopathology in children diagnosed with Bipolar Disorder (BD) remains poorly characterized. Parental retrospective reports provide helpful details on the earliest manifestations and their evolution over time. These symptoms occur early in the course of BD, often before a formal diagnosis is made and/or treatment is implemented, and are of great importance to early recognition and prevention. Methods: Parents of pre-pubertal children and adolescents with DSM-IV diagnoses of BD attending an outpatient mood disorders clinic provided retrospective ratings of 37 symptoms of child psychopathology. Stability and comorbidity of diagnoses were evaluated, and severity of symptoms for each subject was assessed by identifying the earliest occurrence of the reported symptoms causing impairment. Results: Severe mood instability, temper tantrums, anxiety symptoms, sleep disturbances and aggression were among the most common signs of psychopathology reported in children diagnosed with BD before puberty. Symptoms were already apparent in the first three years in 28%, and formal diagnoses were made before the age of 8 y in the majority of cases. Conclusions: Retrospective parental reports of early symptoms of psychopathology in pre-pubertal children with BD revealed a very early occurrence of affective precursors (irritability and mood dysregulation) and clinical risk factors like impulsive aggression and anxiety that can precede the syndromal onset of mania by several years. These findings support previous reports suggesting a progression of symptoms from abnormal, non-specific presentations to sub-threshold and finally syndromal BD. The importance of early identification and intervention is discussed.

Background Distinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls. Methods Unmedicated youths (N = 155, 97 males, age 5–18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI). Results There were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%. Conclusions Objective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls.

Background: Pediatric bipolar disorder (BPD) can be misdiagnosed as a depressive, attention, conduct, or anxiety disorder and treatment with antidepressants and stimulants is common. Risk of adverse outcomes related to such treatment remains poorly defined. Methods: We analyzed clinical records of 82 children (mean age 10.6 years) meeting modified DSM-IV diagnostic criteria for BPD to evaluate risk and timing of operationally-defined treatment-emergent mania (TEM) or increased mood-cycling following pharmacological treatment. Results: Of 82 juvenile BPD patients, 57 (69%) had been given a mood-elevating agent at least once; 33/57 (58%) so-exposed met criteria for TEM, with median latency of 14 days; TEM was observed twice as often with antidepressants as stimulants (44% vs. 18%). TEM led to first-recognition of BPD in 14 cases (17%), and some drug-exposed children (4–9%) had prominent suicidal, homicidal or psychotic behavior. In addition to recent exposure to a mood-elevating agent, TEM was associated with early-onset anxiety and female gender. Limitations: Findings are retrospective in clinically diagnosed and treated outpatients, but involved otherwise unselected cases of juvenile BPD. Conclusions: TEM was reported in 58% of children with probable juvenile BPD within several weeks of new exposure to a mood-elevating agent.

Background: Specific features and diagnostic boundaries of childhood bipolar disorder (BD) remain controversial, and its differentiation from other disorders challenging, owing to high comorbidity with other common childhood disorders, and frequent lack of an episodic course typical of adult BD. Methods: We repeatedly examined children meeting DSM-IV criteria for BD (excluding episode-duration requirements) and analyzed their clinical records to evaluate age-at-onset, family history, symptoms, course, and comorbidity. Results: Of 82 juveniles (aged 10.6 ± 3.6 years) diagnosed with BD, 90% had a family history of mood or substance-use disorders, but only 10% of patients had been diagnosed with BD. In 74%, psychopathology was recognized before age 3, usually as mood and sleep disturbances, hyperactivity, aggression, and anxiety. At onset, dysphoric-manic and mixed presentations were most common (48%), euphoric mania less (35%), and depression least (17%). Subtype diagnoses were: BP-I (52%) > BP-II (40%) > cyclothymia (7%). DSM episode-duration criteria were met in 52% of cases, and frequent shifts of mood and energy were common. Limitations: Partly retrospective study of clinically diagnosed referred outpatients without a comparison group. Conclusions: Pediatric BD is often mis- or undiagnosed, although it often manifests with mood lability and sleep disturbances early in life. DSM BD criteria inconsistent with clinical findings require revision for pediatric application.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) are neurodevelopmental disorders with onset in childhood and early adolescence, and common persistence in adulthood. Both disorders are often undiagnosed, misdiagnosed, and sometimes over diagnosed, leading to high rates of morbidity and disability. The differentiation of these conditions is based on their clinical features, comorbidity, psychiatric family history course of illness, and response to treatment. We review recent relevant findings and highlight epidemiological, clinical, family history, course, and treatment-response differences that can aid the differential diagnosis of these conditions in an outpatient pediatric setting.

Objective To evaluate the presence of affective signs and symptoms as precursors of bipolar disorder in prospective studies, including assessment of their prevalence, duration, and predictive value. Data sources We followed PRISMA guidelines to search PubMed, CINAHL, PsycINFO, EMBASE, SCOPUS, and ISI Web of Science databases to May 31, 2013, using the terms bipolar disorder AND (antecedent* OR predict* OR prodrom* OR prospect*) AND (diagnosis OR development). Hand searching of identified reports led to additional relevant references. Study selection We included only English-language articles containing (1) prospective, longitudinal studies with at least 2 structured clinical assessments (intake and follow-up); (2) no previous DSM-III or DSM-IV diagnoses of bipolar I or bipolar II; and (3) diagnostic outcome of bipolar I or bipolar II. Studies of subjects at familial risk of bipolar disorder were excluded, as these have been reviewed elsewhere. Data extraction We tabulated details of study design, outcomes, precursors, and predictive value. Only studies reporting a positive predictive association were included. Results In 26 published reports meeting selection criteria, methods varied widely in terms of design, duration of follow-up, ages, and populations investigated. Despite such heterogeneity in methods, findings were notably consistent. Precursors of bipolar disorder include mood lability, subsyndromal and major depression, subsyndromal hypomanic symptoms with or without major depression, cyclothymia and bipolar not otherwise specified, major depression with psychotic features, and other psychotic disorders. Bipolar disorder was also predicted by juvenile onset of major depression as well as frequency and loading of hypomanic or depressive symptoms. Conclusions Despite the limitations of published reports, prospectively identified precursors of bipolar disorder typically arose years prior to syndromal onset, often with significant early morbidity and disability. Prospectively identified precursors of bipolar disorder are generally consistent with findings in retrospective and family-risk studies. Combining precursors and other risk factors may increase predictive value, support earlier diagnosis, improve treatment, and limit disability in bipolar disorder.

Multiple sclerosis (MS) is the most common inflammatory demyelinating brain disease. The occurrence of psychiatric disorders, especially for major depression, in the course of MS is high. Reports concerning bipolar disorder (BD) remain rather scarce although early descriptions were found in the old neurological literature. The purpose of this article is to provide a critical review of the epidemiology, comorbidity, and treatment findings regarding BD preceding the onset of MS.

Background Mixed states have been a fundamental part of Kraepelin׳s conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression. Methods We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos׳ first description of depressive mixed syndrome in 1992. Results The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture. Limitations Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos. Conclusions Koukopoulos׳ proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.

Velo-cardio-facial syndrome (VCFS) is the most common microdeletion syndrome in humans and is probably the most frequent genetic cause of psychosis currently known. Many psychiatric disorders have been reported to occur in people with VCFS including, but not limited to schizophrenia, unipolar and bipolar mood disorders (with or without psychotic features), schizoaffective disorder, psychosis NOS, social phobia, generalized and separation anxiety, obsessive-compulsive disorder, autism spectrum disorder, cognitive impairment, and ADHD. This report describes the psychiatric onset and development of catatonia in an adolescent female with VCFS that was undiagnosed until 15 years of age. Catatonia may be a relatively common presentation in people with VCFS with treatment-refractory psychiatric manifestations. © 2015 Wiley Periodicals, Inc.

Cardio-oncology is a relatively new discipline that focuses on the cardiovascular sequelae of anti-tumour drugs. As any other young adolescent discipline, cardio-oncology struggles to define its scientific boundaries and to identify best standards of care for cancer patients or survivors at risk of cardiovascular events. The International Colloquium on Cardio-Oncology was held in Rome, Italy, 12-14 March 2014, with the aim of illuminating controversial issues and unmet needs in modern cardio-oncology. This colloquium embraced contributions from different kind of disciplines (oncology and cardiology but also paediatrics, geriatrics, genetics, and translational research); in fact, cardio-oncology goes way beyond the merging of cardiology with oncology. Moreover, the colloquium programme did not review cardiovascular toxicity from one drug or the other, rather it looked at patients as we see them in their fight against cancer and eventually returning to everyday life. This represents the melting pot in which anti-cancer therapies, genetic backgrounds, and risk factors conspire in producing cardiovascular sequelae, and this calls for screening programmes and well-designed platforms of collaboration between one key professional figure and another. The International Colloquium on Cardio-Oncology was promoted by the Menarini International Foundation and co-chaired by Giorgio Minotti (Rome), Joseph R Carver (Philadelphia, Pennsylvania, United States), and Steven E Lipshultz (Detroit, Michigan, United States). The programme was split into five sessions of broad investigational and clinical relevance (what is cardiotoxicity?, cardiotoxicity in children, adolescents, and young adults, cardiotoxicity in adults, cardiotoxicity in special populations, and the future of cardio-oncology). Here, the colloquium chairs and all the session chairs briefly summarised what was said at the colloquium. Topics and controversies were reported on behalf of all members of the working group of the International Colloquium on Cardio-Oncology.

This study evaluated the quality and quantity of osseointegration of two thicknesses of hydroxyapatite coating on press-fit, porous-coated titanium implants in a canine hip model. In 12 dogs, titanium press-fit porous-coated prostheses were implanted. The stems had a 50-microm thickness hydroxyapatite coating, 100-microm thickness hydroxyapatite coating, or no hydroxyapatite coating. The animals were randomized into one of three groups and received one of the three implants. The implants were retrieved and examined 4 months after implantation. Direct juxtaposition of bone to the surface of the hydroxyapatite-coated implants with no intervening fibrous tissue layer was observed. There was no histologic evidence that hydroxyapatite initiated any foreign body reaction, nor was there any irregularity or resorption of the hydroxyapatite coating. There was a statistically significant greater degree of total bone apposition and bone ingrowth in the implants coated with hydroxyapatite at the level of the isthmus and the calcar. No statistical difference was found between the two groups with hydroxyapatite coatings in the degree of bone ingrowth or bone apposition.