Search

This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury. The GFT system was trained using one-week total PCSS scores, 48 volumetric magnetic resonance imaging inputs, and 192 DTI inputs per participant over 225 training runs. Each training run contained a randomly selected 80% of the total sample followed by a 20% validation run. Over a different randomly selected sample distribution, GFT was also compared with six common classification methods. The cascading GFT structure controlled an effectively infinite solution space that classified participants as recovered or not recovered significantly better than chance. It demonstrated 100% and 62% classification accuracy in training and validation, respectively, better than any of the six comparison methods. Recovery sensitivity and specificity were 59% and 65% in the GFT validation set, respectively. These results provide initial evidence for the effectiveness of a GFT system to make clinical predictions of trauma symptom recovery using objective brain measures. Although clinical and research applications will necessitate additional optimization of the system, these results highlight the future promise of AI in acute care.

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.

OBJECTIVES: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, were previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after eight weeks of treatment compared to those that did not. METHODS: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received eight weeks of treatment. Twenty-one remitted following treatment. Participants completed fMRI scans, at baseline and following eight weeks of treatment, while performing a continuous performance task with emotional and neutral distractors. A healthy comparison group (n=41) received fMRI evaluations at the same intervals. Differences in functional connectivity of the amygdala and caudate with the rostral anterior cingulate and ventrolateral prefrontal cortices at baseline (and changes in functional connectivity following treatment) were modeled between groups. RESULTS: At baseline, non-remitters showed an increase in positive connectivity between right anterior cingulate and caudate and a loss of negative connectivity between right anterior cingulate and amygdala, compared to healthy participants. Individuals who remitted following treatment showed an increase in negative connectivity between amygdala and left anterior cingulate eight weeks following treatment. CONCLUSIONS: Results provide evidence of alterations in anterior cingulate-amygdala and caudate functional connectivity in bipolar disorder non-remitters during a first manic episode and changes in anterior cingulate functional connectivity associated with remission suggesting targets to predict treatment response. Registered at ClinicalTrials.Gov; Functional and Neurochemical Brain Changes in First-episode Bipolar Mania. NCT00609193. URL: https://clinicaltrials.gov/ct2/show/NCT00609193?term=strakowski&rank=1

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime, and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. Here, we studied the neuroanatomical basis for suicide attempt history in bipolar disorder by measuring gray matter volumes (GMV) to identify differences in brain-volumes in 121 participants with bipolar disorder type I, and healthy participants (n=40). The bipolar group consisted of individuals with suicide attempt history (n=23) and no suicide attempt history (n=58). All participants completed behavioral/diagnostic assessments and MRI measures of GMV. We focused on a predefined frontolimbic circuitry in bipolar disorder versus (vs.) healthy to first identify diagnostic GMV markers and to specifically identify markers for suicide attempt history. We found reduced GMV markers for bipolar diagnosis (i.e., bipolarHighlightsSuicide is a major health problem especially in bipolar disorder but the neurobiological basis for suicide attempts remains obscure. We identified an anterior cingulate and dorsolateral prefrontal cortical volume correlate for suicide attempt history and suicidal ideation and thereby demonstrates a convergent brain marker for suicidal behaviors.

OBJECTIVE To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. DESIGN Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. SETTING Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. PARTICIPANTS Eleven former football players and 10 demographically similar track-and-field athletes. MAIN OUTCOME MEASURES Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. RESULTS Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. CONCLUSIONS These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.

Lateral and medial epicondylitis are common pathologic conditions and can be debilitating problems for athletes. Lateral epicondylitis occurs much more commonly than medial epicondylitis but both can create significant and persistent symptoms that limit performance. Nonoperative management is the mainstay of treatment for both conditions with more invasive treatments, including surgical intervention, reserved for recalcitrant cases. Both pathological entities can be operatively managed by using either percutaneous, formal open, or arthroscopic surgical techniques.

Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

Background Clinical remission is widely accepted as the primary target outcome for juvenile idiopathic arthritis (JIA). PR-COIN is a quality improvement collaborative that serves as a sample of pediatric rheumatology centers in North America. By measuring disease activity in practice using the ACR provisional criteria for Clinical Inactive Disease (CID), variation in patient outcomes has been previously observed between centers. Objectives The objective of this study was to evaluate differences in patient-level factors that may be driving center-level variation in JIA outcomes. Methods This study used cross-sectional data provided by PR-COIN that was collected by PR-COIN centers from March 2015 to May 2016. For each patient, sociodemographic, clinical, patient-reported, disease activity, and medication variables were extracted from the most recent encounter. Patients with disease duration less than 9 months were excluded. Patients were grouped by CID status (inactive vs active disease) and then compared using descriptive statistics, chi-square for categorical variables, and independent t-tests for continuous variables. Missing data were excluded with each analysis. Analyses were performed using R software. Results There were 2751 patients eligible for analysis from 14 centers, with 33 to 394 patients per center. We identified 1249 patients with inactive disease (47%) and 1428 patients with active disease (53%). Patients with inactive disease were younger (12 vs 13 years), more likely to have persistent oligoarticular subtype (33% vs 23%), and less likely to have enthesitis related arthritis (9% vs 14%). Patients with active disease had higher patient-reported measures of global assessment of disease activity, pain, and functional disability, as well as disease activity measures per definition. More medication usage was observed in patients with active disease compared to inactive disease across multiple categories, including both non-biologic DMARDs (45% vs. 32%) and biologic DMARDs (48% vs 35%). Conclusion This study demonstrates differences in sociodemographic, clinical, and medication factors between patients with inactive and active JIA. Further analysis is needed to adjust center-level measures of JIA disease activity using the observed differences in patient case-mix. By using population data to identify predictors of inactive disease in JIA, there is potential to develop and implement targeted clinical interventions to directly impact care and improve outcomes. Disclosure of Interests: Emily A. Smitherman: None declared, Bin Huang: None declared, Ronald Laxer Consultant for: Eli Lilly Canada, Alexion, Sanofi, C. April Bingham: None declared, Cagri Yildirim-Toruner: None declared, Beth Gottlieb: None declared, Jennifer E. Weiss: None declared, Tzielan Lee: None declared, Sheetal Vora: None declared, Jon (Sandy) Burnham: None declared, Julia G. Harris: None declared, Judyann C. Olson: None declared, Mileka Gilbert: None declared, Michelle Batthish Speakers bureau: Novartis, Abbvie, Michael Shishov: None declared, Dustin Fleck: None declared, Esi Morgan: None declared

Objectives We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize – i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers. Methods Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response. Results ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors. Conclusions These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

1. Dustin E. Fleck, MD* 2. Mark F. Hoeltzel, MD* 1. *Division of Pediatric Rheumatology, Department of Pediatrics, University of Michigan, Ann Arbor, MI * ADHD: : attention-deficit/hyperactivity disorder ANA: : antinuclear antibody POTS: : postural tachycardia syndrome Primary care clinicians are challenged to evaluate an array of different hand and foot color changes in kids, as treatment may range from reassurance of a benign, self-limited condition to further diagnostic evaluation and treatment with vasodilator pharmacotherapy. The most common and well-known causes of these color changes are Raynaud phenomenon, acrocyanosis, and the more rare but serious erythromelalgia. Clinicians should be aware of the clinical presentation, symptoms, etiologic origins, diagnostic evaluation, treatment, and potential complications of Raynaud phenomenon, acrocyanosis, and erythromelalgia in children. After completing this article, readers should be able to: 1. Identify the various causes of hand and foot color change in children and adolescents. 2. Recognize the differences in signs and symptoms of acrocyanosis, erythromelalgia, and Raynaud phenomenon. 3. Recognize complications associated with acrocyanosis, erythromelalgia, and Raynaud phenomenon. 4. Describe current treatments for acrocyanosis, erythromelalgia, and Raynaud phenomenon. ### Clinical Presentation Acrocyanosis is a clinically benign process that is known to cause alarm in patients and their parents. Acrocyanosis typically presents as symmetrical blue and/or purple discoloration in the peripheral extremities, usually either the hands or the feet (Figs 1, 2, 3, 4). In infants, acrocyanosis also includes the perioral area but not the lips or tongue, where central cyanosis becomes a concern. It is often seen after bathing, after feeding, or in a cool environment. It is evanescent and benign. The bluish discoloration in acrocyanosis is often asymptomatic, without clear demarcation of color change. Acrocyanosis episodes can be either precipitated or exacerbated by external factors, such as cold temperatures. Acrocyanosis may also be a process secondary to an underlying systemic disease or a side effect of certain medications. Figure 1. Teenage …

Objective: To examine the effect of cost, a traditionally “inactive” trait of intervention, as contributor to the response to therapeutic interventions. Methods: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a “cheap” or “expensive” subcutaneous “novel injectable dopamine agonist” placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the “practically defined off” state, before and after each intervention, included the Unified Parkinson9s Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. Results: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. Conclusion: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. Classification of evidence: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.

Pathologic changes to the biceps tendon including subluxation are frequently encountered in patients with subscapularis tears. Operatively managing these combined lesions can be difficult depending on the status of the subscapularis tendon and the degree of biceps medialization. The presented technique is an effective and relatively simple method that simultaneously and efficiently provides for secure tenodesis of the biceps and fixation of subscapularis tendon detachment.

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodynamics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased. All these parameters, including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang II occurred with quinapril 20 mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.

Objectives Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. Methods We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. Results LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. Conclusions The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem—namely, prediction of the lithium response—in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.

Objectives Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization. Methods Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery–Asberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11. Results Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables. Conclusions Better trait impulse control may be associated with better treatment responsiveness among adults with bipolar disorder.

Heffner JL, Fleck DE, DelBello MP, Adler CM, Strakowski SM. Cigarette smoking and impulsivity in bipolar disorder. Bipolar Disord 2012: 14: 735–742. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: There is a high prevalence of smoking among individuals with bipolar disorder, yet there have been few efforts to identify potential contributing factors as a means of improving prevention and treatment approaches. The goal of this study was to examine the association between impulsivity and the initiation or maintenance of smoking in bipolar disorder. Methods: Participants comprised 97 adolescents and adults, ages 16–50, with bipolar I disorder who were experiencing a mixed or manic episode at the time of study enrollment. Participants completed the Barratt Impulsiveness Scale-11 (BIS-11) as a self-report indicator of trait impulsivity, and the Logan Stop-Signal Task (SST), Delayed Reward Task (DRT), and Degraded Stimulus Continuous Performance Task (DSCPT) as behavioral measures of impulsivity. Results: Current smokers (34%) and former smokers (23%) generally reported higher trait impulsivity on the BIS-11 than never smokers (43%), with minimal evidence for differences among the two ever-smoking groups. No differences in impulsivity by smoking status emerged on the behavioral measures. Conclusions: Trait impulsivity is associated with the initiation, but not necessarily the maintenance, of cigarette smoking in adolescents and adults with bipolar disorder. Our findings provide no evidence that smoking is associated with impulsive responding on cognitive tasks during a symptomatic period during which impulsivity is elevated.

Bipolar I disorder is defined by the occurrence of mania and exhibits a dynamic course of symptoms that alternate among affective extremes. The specific neurophysiological basis of bipolar disorder is unknown, but neuroimaging studies suggest impairments in corticolimbic regions responsible for regulating emotion that have been termed the anterior limbic network (1–5). In subjects with bipolar I disorder, abnormal brain activation has been shown in the amygdala, anterior cingulate gyrus (ACC), ventrolateral prefrontal cortex (VLPFC), insula, and medial prefrontal cortex (1, 3). The amygdala seems to play a central role in this network and is responsible for the appraisal of emotional stimuli (6–8). Other regions in the anterior limbic network, including the VLPFC and insula, interact with the amygdala to provide cortical modulation of the appraisal process (3). Patients with bipolar I disorder spend significantly more time in depression than mania (9). Yet few studies have specifically examined the neurophysiology of the depressed phase of bipolar I disorder, and it is not clear which corticolimbic regions are involved in the generation of the syndrome of depression or involved in the switch from mania to depression. One approach to answer these questions is to use imaging to examine patients with bipolar I disorder across different mood states. However, there are few longitudinal imaging studies of bipolar I disorder across mood states (3). Comparing the same patients across manic and depressive episodes may lead to a better understanding of the how corticolimbic networks generate mood states (10). The current study was designed to understand the role of the amygdala during the course of bipolar I disorder. Using amygdala as the primary seed region in a functional connectivity analysis allowed us to identify altered connections with other brain regions in mania and depression. Subjects with bipolar I disorder were assessed during an initial manic or mixed episode and then followed for up to one year and re-assessed if they developed a depressive episode. Subjects received an fMRI scan at each assessment while performing a modified continuous performance task with emotional distracters (5). The task was designed to discriminate between ventral emotional and dorsal cognitive brain networks and their interaction and requires effective regulation of emotion to complete successfully (5). We predicted that subjects with bipolar I disorder would show different patterns of amygdala connectivity in mania versus depression. Given previous findings of decreased prefrontal modulation of limbic regions in mania, we predicted that when subjects no longer had manic symptoms (i.e., they switched to being in a depressive episode) activation in these brain regions would normalize to more closely resemble healthy comparison subjects (HC) (5, 11–13). Therefore we predicted that during depression subjects would show increased amygdala connectivity with ventral and dorsal prefrontal regions.

Objectives Cigarette smoking is highly prevalent among individuals with bipolar disorder (BD) and may adversely affect symptoms of the disorder as well as co-occurrence of other substance use disorders. However, anecdotal reports suggesting that smoking cessation caused a worsening of mood in smokers with BD have raised concerns about quitting. In this study, we prospectively evaluated the course of BD, alcohol use disorders, and cannabis use disorders in relation to smoking and examined the relationship between smoking abstinence and changes in mood.

Treating septic arthritis of the hip with coexisting advanced degenerative disease is challenging. The use of primary total hip arthroplasty (THA) has led to postoperative infection rates as high as 22%. Insertion of antibiotic spacers with subsequent reimplantation of a THA controls infection and improves pain and function in patients with periprosthetic infections.We asked whether two-stage exchange for patients with degenerative joint disease (DJD) and coexisting septic arthritis would control infection and improve pain relief and function both during the period after insertion of the spacer and after conversion to THA.We retrospectively reviewed 14 patients with severe DJD and either active or recent septic arthritis treated with débridement and insertion of a primary antibiotic-loaded cement spacer between 1996 and 2008. Ten patients underwent subsequent exchange to a permanent hip arthroplasty. Four patients did not undergo exchange to a permanent THA: two died from unrelated causes and two elected not to proceed with exchange because their spacer provided adequate function. We obtained a modified Harris hip score. The minimum clinical followup was 7 months (average, 28 months; range, 7-65 months) after insertion of the spacer.Mean pain scores improved from 6 to 34, and overall Harris hip scores improved from 11 to 67 at last followup with the spacer. Those who underwent definitive THA had further improvement in their mean Harris hip scores to 93.Articulating antibiotic spacers offer acceptable pain relief and function while the infection is treated in this unique group of patients.Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

To compare the type and degree of impulsivity among adolescents with bipolar disorder (BD), adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy comparison subjects using the Barratt Impulsiveness Scale, Version 11 (BIS-11).Manic adolescents with BD (n=31), adolescents with ADHD (n=30), and healthy subjects (n=25) completed the BIS-11, a 30-item, self-report scale with three subscales (cognitive, motor, and nonplanning). The BIS-11 total and subscale scores were compared among groups. We also examined associations among the BIS-11, Young Mania Rating Scale and co-occurring disruptive behavioral disorders (DBDs) within the BD group.Total and each subscale scores were significantly higher for the BD group than for the healthy controls (p0.05). The total scores and the cognitive and motor subscale scores were significantly higher for the ADHD group than for the healthy control group (p0.05). However, there was no statistically significant difference between the nonplanning subscale scores of the ADHD group and the healthy control group (p0.05). There were no significant differences between the BD and ADHD groups or between the BD groups with and without ADHD. The BD patients with DBDs (i.e., oppositional defiant disorder or conduct disorder) scored significantly higher on the motor subscale than did BD patients without DBDs. There were no statistically significant associations between the Young Mania Rating Scale and BIS-11 scores within the BD group.Our findings suggest that impulsivity is elevated in adolescents with BD as well as adolescents with ADHD, except for nonplanning impulsivity, which was not significantly different between adolescents with ADHD and the healthy comparison group. This may suggest that nonplanning impulsivity is relatively specific to adolescents with BD. Additionally, our data indicate that elevations in impulsivity, as measured by the BIS-11, may be independent of symptoms severity and, therefore, may be a stable, trait-related component of BD.

Lisy ME, Jarvis KB, DelBello MP, Mills NP, Weber WA, Fleck D, Strakowski SM, Adler CM. Progressive neurostructural changes in adolescent and adult patients with bipolar disorder. Bipolar Disord 2011: 13: 396–405. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. Methods: A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3–34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. Results: We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Conclusions: Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age.

Background There is substantial inconsistency in results of brain structural magnetic resonance imaging studies in adult bipolar disorder. This is likely consequent upon limited statistical power of studies together with their clinical and methodological heterogeneity. The current study was undertaken to perform an international collaborative mega-analysis of regional volumetric measurements of individual patient and healthy subject data, to optimize statistical power, detect case-control differences, assess the association of psychotropic medication usage with brain structural variation, and detect other possible sources of heterogeneity. Methods Eleven international research groups contributed published and unpublished data on 321 individuals with bipolar disorder I and 442 healthy subjects. We used linear mixed effects regression models to evaluate differences in brain structure between patient groups. Results Individuals with bipolar disorder had increased right lateral ventricular, left temporal lobe, and right putamen volumes. Bipolar patients taking lithium displayed significantly increased hippocampal and amygdala volume compared with patients not treated with lithium and healthy comparison subjects. Cerebral volume reduction was significantly associated with illness duration in bipolar individuals. Conclusions The application of mega-analysis to bipolar disorder imaging identified lithium use and illness duration as substantial and consistent sources of heterogeneity, with lithium use associated with regionally specific increased brain volume.

Aim: To identify differential patterns of brain activation between adolescents with bipolar disorder and adolescents with attention-deficit hyperactivity disorder (ADHD) to better understand the neurophysiology of both disorders. We hypothesized that subjects with ADHD would show altered activation in brain regions involved in executive and sustained attention. In contrast, we hypothesized that bipolar subjects would show altered brain activation in regions responsible for emotionally homeostasis, including the striatum and amygdala. Methods: Functional magnetic resonance imaging was performed during a continuous performance task with a response inhibition component in 11 adolescents with bipolar disorder during a manic episode, 10 adolescents with ADHD, and 13 healthy adolescents. Results: There were no differences in behavioural performance among the three groups. Compared with bipolar subjects, subjects with ADHD showed increased activation in the superior temporal lobe during successful response inhibition. Although bipolar subjects did not show activation differences in the striatum or amygdala compared with ADHD subjects, increased left parahippocampal activation in the bipolar group was associated with increased manic symptoms. Conclusions: The patterns of brain activation observed in the current study support divergent patterns of neurophysiological dysfunction in individuals with bipolar disorder as compared with those with ADHD. Therefore, the impulsive behaviour seen in both disorders may be the consequence of dysfunction in different brain regions, and further research may help identify neurobiological markers that are specific to each condition.

Objective: To determine whether specific aspects of impulsivity (response disinhibition, inability to delay gratification, inattention) differ between healthy and bipolar manic subjects, and whether these aspects of impulsivity were associated with each other and severity of affective symptoms. Methods: Performance of 70 bipolar I manic or mixed patients was compared to that of 34 healthy subjects on three tasks specifically designed to study response inhibition, ability to delay gratification, and attention; namely, a stop signal task, a delayed reward task, and a continuous performance task, respectively. Correlations among tasks and with symptom ratings were also performed. Results: Bipolar subjects demonstrated significant deficits on all three tasks as compared to healthy subjects. Performance on the three tasks was largely independent. Task performance was not significantly associated with the severity of affective symptom ratings. However, measures of response inhibition and attention were sensitive to medication effects. Differences in the delayed reward task were independent of medication effects or symptom ratings. During the delayed reward task, although bipolar patients made their choices more slowly than healthy subjects, they were significantly more likely to choose a smaller, but more quickly obtained reward. Moreover, performance on this task was not associated with performance on the other impulsivity measures. Manic patients showed more impulsive responding than mixed patients. Conclusions: Bipolar I manic patients demonstrate deficits on tests of various aspects of impulsivity as compared to healthy subjects. Some of these differences between groups may be mediated by medication effects. Findings suggested that inability to delay gratification (i.e., delayed reward task) was not simply a result of the speed of decision making or inattention, but rather that it reflected differences between bipolar and healthy subjects in the valuation of reward relative to delay.

Although advances in the clinical criteria of various axis I psychiatric disorders are continually being made, there is still considerable overlap in the clinical features, and diagnosis is often challenging. As a result, there has been substantial interest in using morphometric magnetic resonance imaging to better characterize these diseases and inform diagnosis. Region of interest and voxel-based morphometry studies are reviewed herein to examine the extent to which these goals are being met across various psychiatric disorders. It is concluded based on the studies reviewed that specific patterns of regional loss, although present in certain axis I disorders, are not, as yet, diagnostically useful. However, advances in outcome and treatment monitoring show considerably more promise for rapid application in psychiatry.

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.

Objectives: Bipolar disorder (BD) is recognized as a significant psychiatric condition worldwide, yet little is known about cross-national differences in the course of illness. This information might clarify features of the disorder that are illness versus culturally specific. Therefore, the aim of this study was to identify differential and shared outcome predictors in first-episode manic bipolar patients in Cincinnati, OH, USA and Taipei, Taiwan. Methods: DSM-IV bipolar patients were identified at the time of their first manic or mixed episode and were prospectively followed in a naturalistic, longitudinal study for one year. Patients were recruited from a first psychiatric hospitalization at university-affiliated, urban hospitals in Taipei and Cincinnati. The primary outcome measures were remission, recovery, recurrence and percent of follow-up spent with affective symptoms and syndromes. Treatment adherence was also assessed, as were a number of possible mediator variables. Results: The two patient groups showed a number of significant differences in index clinical presentation on characteristics previously associated with outcome in other studies (e.g., substance abuse). The patients in Taipei showed significantly better outcome on virtually all measures. Some of these findings reflected differences in index (mediator) variables, whereas others persisted after controlling for potential baseline confounds. Conclusions: The early course of BD varies between Chinese and American patients. Some of this variance results from demographic and clinical cross-national differences in premorbid variables. Other sources of variance remain to be identified.

Die chronische koronare Herzkrankheit mit dem Hauptsymptom der stabilen Angina Pectoris ist eine der haufigsten Erkrankungen der Industrienationen. Ziel der Behandlung der chronischen koronaren Herzerkrankung ist primar eine Verbesserung der Prognose, jedoch ist die Steigerung der krankheitsbedingt eingeschrankten Lebensqualitat bei gleichzeitig niedriger Komplikationsrate der Therapiemasnahme fur den Patienten ebenfalls von entscheidender Bedeutung. Als Behandlungsoptionen stehen neben Lebensstilanderungen und der medikamentosen Therapie seit Ende der 60er-Jahre auch die aortokoronare Bypassoperation sowie seit 1977 die perkutane transluminale Koronarangioplastie bzw. perkutane Koronarintervention zur Verfugung. Sowohl die operativen als auch die interventionellen Revaskularisationsverfahren sind seitdem kontinuierlich weiterentwickelt und verbessert worden. Parallel dazu sind auch bei der medikamentosen Therapie grose Fortschritte erzielt worden, sodass diese 3 Therapieoptionen je nach Befundkonstellation um das beste Behandlungskonzept wetteifern.

Barzman DH, DelBello MP, Fleck DE, Lehmkuhl H, Strakowski SM. Rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder. Bipolar Disord 2007: 9: 339-344. © Blackwell Munksgaard, 2007 Objectives: To examine the rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder (BD). Methods: Adolescents (n = 80), between the ages of 12 and 21 years (mean = 15.6, standard deviation - 2.3), hospitalized for their initial manic or mixed episode of BD, were evaluated for the incidence of prior juvenile offending (i.e., legal charges). We examined potential psychosocial correlates associated with legal charges using chi-square, (t-tests, and discriminant function analyses to determine if there were differences between adolescents who did and did not offend prior to their first manic episode. Results: Juvenile antisocial behaviors were common (55%) for adolescents with newly diagnosed BD. Discriminant function analysis revealed that older age at first treatment (p < 0.01), sexual activity over the previous month (p < 0.05), therapeutic use of stimulants (p < 0.05), and anxiety disorders were the most significant factors to differentiate between bipolar adolescents who offended and those who did not (Wilks' lambda = 0.80, p < 0.005). Conclusions: Our findings indicate that there are identifiable psychosocial correlates associated with antisocial behaviors in adolescents with newly diagnosed BD that may improve our understanding of juvenile antisocial behaviors.

Durch Senkung des kardiovaskularen Risikofaktors Cholesterins mittels HMG-CoA-Reduktasehemmer („Statine“) konnen das Herzinfarkt- und Schlaganfallrisiko sowie die Sterblichkeit reduziert werden. Die absolute Risikoreduktion hangt von dem individuellen Risiko des Patienten, von der Hohe des LDL-Cholesterins vor Therapie und der erzielten absoluten LDL-Cholesterinsenkung ab. Dieser Tatsache wird durch die nach Risiko abgestuften Zielwerte der aktuellen Leitlinien Rechnung getragen. Das Prinzip der Ausrichtung einer Statintherapie an Lipidzielwerten betont die Bedeutung von Lebensstilmasnahmen (Ernahrung, korperliche Aktivitat) fur alle Patienten und auf jeder Stufe der Therapie. Statine sind fur die grose Mehrheit der Patienten nebenwirkungs- und risikoarm. Aktuell gibt es keinen eindeutigen klinischen Beleg fur differenzielle „pleiotrope“ Effekte zwischen verschiedenen Statinen. In Zusammenschau der vorliegenden Studien gibt es bei Einsatz von Dosierungen mit gleicher LDL-Senkung bislang keinen Beleg fur eine unterschiedliche Wirksamkeit verschiedener Statine in Bezug auf kardiovaskulare Endpunkte. Fur alle Patienten mit koronarer Herzerkrankung wird eine Senkung des LDL-Cholesterins unter 100 mg/dl durch ein Statin empfohlen.

Previous research has shown that performance on cognitive tasks administered in the scanner can be altered by the scanner environment. There are no previous studies that have investigated the impact of scanner noise using a well-validated measure of affective change. The goal of this study was to determine whether performance on an affective attentional task or emotional response to the task would change in the presence of distracting acoustic noise, such as that encountered in a magnetic resonance imaging (MRI) environment.Thirty-four young adults with no self-reported history of neurologic disorder or mental illness completed three blocks of the affective Posner task outside of the scanner. The task was meant to induce frustration through monetary contingencies and rigged feedback. Participants completed a Self-Assessment Manikin at the end of each block to rate their mood, arousal level, and sense of dominance. During the task, half of the participants heard noise (recorded from a 4T MRI system), and half heard no noise.The affective Posner task led to significant reductions in mood and increases in arousal in healthy participants. The presence of scanner noise did not impact task performance; however, individuals in the noise group did report significantly poorer mood throughout the task.The results of the present study suggest that the acoustic qualities of MRI enhance frustration effects on an affective attentional task and that scanner noise may influence mood during similar functional magnetic resonance imaging (fMRI) tasks.

Objectives: Alcohol use disorders (AUDs) are common co-occurring conditions in patients with bipolar disorder (BD), but it is unclear whether or not AUD and BD symptoms are temporally correlated. The primary aim of this analysis was to examine concurrent symptom tracking and how the relative onsets of AUD and BD influence the concurrent tracking of symptoms. Methods: Participants met DSM-IV criteria for bipolar I disorder, manic or mixed, with no prior hospitalizations and minimal treatment. Patients were rated for alcohol use and bipolar symptom severity on a weekly basis for up to 7 years. For analysis purposes, patients were placed into groups with no AUD (BD Only; n = 21), onset of AUD either concurrent with or after the onset of bipolar symptoms (BD First; n = 32), and onset of AUD at least 1 year before the onset of bipolar symptoms (AUD First; n = 18). Results: None of the patient groups demonstrate consistent positive or negative temporal correlations between alcohol use and affective symptoms. However, there were significant between-group differences on the relationship of symptom tracking and age of BD onset. For the AUD First group, the correlation between age of BD onset and symptom tracking was positive 0.41. However, for the BD First and BD Only groups the correlations were negative (−0.32 and −0.41, respectively). Moreover, for patients whose BD onset was ≤18 years old, the correlation between age of onset and tracking was −0.47. Conclusions: These findings suggest that although there is no direct temporal correlation of AUD and BD symptoms in subgroups of BD patients, age at illness onset contributes to the complex relationship between BD and AUD. For younger patients there may be a greater likelihood that alcohol use and bipolar symptoms increase or decrease in unison.

Die Begriffe „Vernetzung“ und „integrierte Versorgung“ sind neben „Kostenreduktion“ die derzeit am haufigsten diskutierten Begriffe im Bereich der Gesundheitsversorgung. Leider ist die Vorstellung uber deren Inhalte sehr heterogen. Die integrierte Versorgung im Sinne einer Zusammenarbeit zwischen ambulanter und stationarer Versorgung wird schon lange betrieben. Uber die klassischen Kommunikationswege entsteht jedoch ein Informationsverlust. Dieser fuhrt zu erhohten Kosten und, noch wesentlicher, zu direkten Beeintrachtigungen im Heilungs- und Genesungsprozess des einzelnen Patienten. Eine computergestutzte Vernetzung der Arztpraxen untereinander und mit Kliniken konnte diesen Informationsverlust verhindern und den Informationsfluss insgesamt beschleunigen. Mit der Umsetzung der Vernetzung wurde bereits von mehreren Seiten begonnen. Da es jedoch unterschiedliche Interessen gibt, mussen diese zusammengefuhrt werden. Diese Aufgabe hat der Gesetzgeber erkannt und ubernommen. Damit dieses Projekt auch aus medizinischer Sicht ein Erfolg wird, sind bestimmte Voraussetzungen zu erfullen, die in dieser Schrift benannt werden. Einigkeit besteht daruber, dass alle Anstrengungen am Ende der Allgemeinheit zugute kommen sollen. Die Erlauterung der medizinischen Notwendigkeiten und der diesbezuglichen Grunde ist Inhalt dieses Beitrages. Es wird hier bei besonders die Notwendigkeit der Nutzung der Datentechnik in der Zusammenarbeit von Medizinern betont.

Background African American patients may be less likely than white patients to adhere to maintenance pharmacotherapy for bipolar disorder. The purpose of this study was to examine rates of medication nonadherence, self-perceived reasons for nonadherence, and attitudes associated with non-adherence in these ethnic groups. Method 20 African American and 30 white subjects with DSM-IV bipolar I disorder participated in this study. At a single follow-up visit with patients at least 4 months after their first hospitalization for acute mania, we assessed demographics, symptom severity, degrees of adherence, reasons for non-adherence, and self-perceptions regarding factors previously associated with nonadherence using a visual analog scale (VAS). The cross-sectional data that are the subject of this report were obtained from July 1, 2002, through June 30, 2004. Results Over 50% of participants in each group were currently either fully or partially nonadherent with medications. Greater than 20% of participants in each group denied having bipolar disorder and described physical side effects from medications as contributing to nonadherence. In principal components analysis of the VAS, 2 components were identified. The first component contained patient-related factors associated with nonadherence, while the second contained a combination of illness- and medication-related factors. African American participants were more likely to endorse patient-related factors associated with nonadherence relative to white participants. Specifically, African Americans self-endorsed a fear of becoming addicted to medications and feeling that medications were symbols of mental illness. Conclusion Findings suggest that both African American and white patients with bipolar disorder demonstrate poor medication adherence that they attribute to illness/medication-related factors (denial of illness, physical side effects). However, patient-related factors (fear of addiction, medication as a symbol of illness) accounted for ethnic differences on self-perceived ratings of nonadherence factors. Differences in the reasons for nonadherence relative to culturally biased self-perceptions may help explain nonadherence behaviors in the African American community.

The aim of this retrospective chart review was to evaluate the effectiveness and tolerability of aripiprazole for the treatment of children and adolescents with bipolar disorders.The medical charts of all children and adolescents with a DSM-IV diagnosis of bipolar disorder, type I, type II, not otherwise specified (NOS), or schizoaffective disorder, bipolar type, and who were treated with aripiprazole were reviewed by two child and adolescent psychiatrists who independently confirmed their DSM-IV diagnoses, severity, and the improvement of illness using the Clinical Global Impression (CGI) Severity and Improvement scores for bipolar disorder (CGI-BP) and the Clinical Global Assessment Scale (CGAS).Thirty patients who were treated with aripiprazole were identified (mean starting dose=9 +/- 4 mg/day, mean final dose=10 +/- 3 mg/day). The overall response rate, defined by a CGI-Improvement score ofor = 2 at endpoint, was 67%. There was a statistically significant improvement in CGAS scores (48 +/- 11 to 65 +/- 11, signed rank = 191, p0.0001) and CGI-S scores (4.2 +/- 0.8 to 2.8 +/- 1.0, signed rank=-172, p0.0001, effect size=1.90) from baseline to endpoint. No serious adverse events were identified. Common side effects were sedation (n=10, 33%), akathisia (n=7, 23%), and gastrointestinal disturbances (n=2, 7%). Baseline and endpoint weights were available for 14 (47%) of the patients. Change in weight ranged from +5 to -21 kg and 12 (86%) of 14 patients lost weight (mean weight loss was 3 +/- 6 kg).This retrospective chart review suggests that aripiprazole may be effective and well tolerated for children and adolescents with bipolar disorders. Controlled studies of aripiprazole for the treatment of pediatric bipolar disorder are necessary.

A standardized documentation of echocardiographic studies is necessary to provide comparability of data and to realize software-based documentation and electronic communication, both essential for quality management in echocardiography. Therefore, the subgroup on "Standardization and LV function" of the working group on cardiovascular ultrasound of the German Cardiac Society developed a consensus report for documentation of echocardiographic studies, which was first published in 2000. This report represents the current update of the standardized documentation for echocardiography; its impact for quality management in conjunction with the "guidelines echocardiography" is discussed.

Objectives: Manic patients exhibit impaired verbal learning and memory, particularly following longstanding illness. However, it is unclear whether recognition and recall performance are differentially influenced by a manic mood state. Methods: To examine this issue, we administered the California Verbal Learning Test and symptom-rating scales to inpatients with pure or mixed mania, euthymic outpatients, and healthy comparison subjects. Results: An overall performance difference was identified between groups. Manic and euthymic patients performed more poorly than healthy subjects on recall. However, manic patients performed more poorly than euthymic patients and healthy subjects on recognition. Conclusions: These results suggest that verbal retrieval deficits are stable vulnerability indicators in bipolar disorder, whereas verbal encoding deficits are manic episode indicators. The known subcortical dysfunction in this disorder may produce stable retrieval deficits while acute mood symptoms attenuate encoding during affective episodes only.

The effects of dietary saturated fatty acids and polyunsaturated fatty acids (PUFA) of then-3 andn-6 series on weight gain, body composition and substrate oxidation were investigated in broiler chickens. At 3 weeks of age three groups of chickens (n30; ten birds per group) were fed the fat-enriched experimental diets for 5 weeks. These diets were isonitrogenous, isoenergetic and contained 208 g protein/kg and 80 g edible tallow, fish oil or sunflower oil/kg; the dietary fatty acid profiles were thus dominated by saturated fatty acids,n-3 PUFA orn-6 PUFA respectively. Resting RQ was measured in five birds from each treatment group during weeks 4 and 5 of the experiment. There were no significant differences between treatments in total feed intake or final body mass. Birds fed the PUFA diets had lower RQ and significantly reduced abdominal fat pad weights (PPn-3 andn-6 PUFA groups). In addition, the PUFA-rich diets lowered plasma concentrations of serum triacylglycerols and cholesterol. The findings indicate that dietary fatty acid profile influences nutrient partitioning in broiler chickens.

Reports of normal Continuous Performance Test (CPT) accuracy in patients with temporal lobe epilepsy (TLE) stand in contrast to a demonstration of nonspecific absolute reaction time (RT) deficits in this population. In this study, we examined CPT data from a TLE sample for potential RT deficits across three consecutive blocks of time during the vigil. Seventeen patients with medically intractable epilepsy of temporal lobe origin and 17 healthy volunteers participated. The Conners CPT was used to assess sustained attention over a 14-min vigil. There were no significant group differences in accuracy. There was, however, a significant interaction between groups and time intervals, with disproportionate RT increases for patients at the end of the vigil. These findings are consistent with a report of nonspecific RT deficits in TLE despite normal accuracy scores, and further indicate impaired RT performance over time.

Objectives Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood. Methods Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans. Results At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p

Objective Adolescents with bipolar disorder (BD) are more likely to develop substance use disorders (SUDs) than adolescents without psychiatric disorders; however, to our knowledge, specific risk factors underlying this relationship have not been prospectively examined. The purpose of this study was to identify predictors of developing SUDs after a first manic episode. Method Participants aged 12 to 20 years and hospitalized with their first manic episode associated with bipolar I disorder (BP-I) were recruited as part of the University of Cincinnati First-Episode Mania Study and prospectively evaluated for patterns of substance use. Follow-up ranged between 17 and 283 weeks (mean = 113 weeks, SD = 71.9 weeks). Demographic and clinical variables were compared between adolescents with and without SUDs. Results Of the 103 adolescents with BD, 49 (48%) either had a SUD at baseline or developed one during follow-up. Of the 71 participants who did not have a SUD at study entry, 17 (24%) developed one during follow-up (median = 40 weeks). Later onset of BD, manic (versus mixed) mood episode, and comorbid disruptive behavior disorders were associated with an increased risk of developing a SUD in univariate analyses. Adolescents treated with psychostimulant treatment before their first manic episode were significantly less likely to develop a SUD independent of attention-deficit/hyperactivity disorder (ADHD) diagnosis. Comorbid posttraumatic stress disorder (PTSD) and psychotic symptoms were the strongest predictors of SUD development. Conclusion Our results confirm high rates of SUD in adolescents with BD. In addition, our findings identify potential risk factors associated with SUDs in adolescents with BD. These data are preliminary in nature and should be explored further in future studies.