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Bipolar disorder is a highly heritable illness, with genetic influences explaining 60–85% of risk variance (1). However, specific susceptibility genes or neurobiological markers remain unknown. In recent years, genetic and behavioral neuroscience has attempted to define endophenotypes that encompass deficits that are heritable, state-independent, and cosegregated with illness, as well as those which occur at higher rates in unaffected relatives than the general population (2, 3). Plausible endophenotype candidates in bipolar disorder include impairments in specific neurocognitive domains. Cognitive impairments in individuals with bipolar disorder were traditionally thought of as mild and limited to acute mood episodes; however, a growing body of evidence challenges this assumption. At least three recent meta-analyses in euthymic adults with bipolar disorder (4–6) and two in youths with bipolar disorder have identified several cognitive impairments, particularly in attention, processing speed, and other aspects of executive function (7, 8). Some studies have suggested that medication exposure has an effect on cognition in both adult (9) and pediatric bipolar disorder subjects (10), while others have suggested no neurocognitive differences in euthymic unmedicated pediatric bipolar disorder subjects (11). Thus, studies of cognitive impairment in youths and adults with bipolar disorder cannot fully dissociate possible effects of illness chronicity and medication exposure. Studying youth at familial risk for developing bipolar disorder (i.e., with a parent who has bipolar disorder) could facilitate identifying cognitive endophenotypes, yet few studies have examined neurocognitive function in this population. Nonetheless, recent studies suggest that children of bipolar disorder patients demonstrate specific deficits in executive function, particularly in tasks assessing cognitive interference and flexibility (12, 13). Cognitive interference occurs when task-irrelevant background information impedes processing task-relevant information that forms the current focus of attention (14). Cognitive conflict may be best described as a special instance of cognitive interference in which task-irrelevant information induces incongruent or incompatible mental representations (15). Given this theoretical approach, selecting task-relevant over task-irrelevant information may be thought of as a core process in the resolution of cognitive interference, and the main goal of conflict monitoring (16). Similarly, changes in processing speed with shifting levels of conflict represent a measure of conflict-driven adaptation (17). In the current study, we examined conflict monitoring and conflict-driven adaptation in youths at risk for bipolar disorder using an arrow version of the Eriksen Flanker Task (EFT). We hypothesized that youths at risk for bipolar disorder would exhibit deficits in conflict monitoring and conflict-driven adaptation. Additionally, we predicted that youths at risk for developing bipolar disorder would be more susceptible to interference, exhibit increased behavioral inconsistencies as measured by increased variability of response time, and show less flexible cognitive adaptation to shifting levels of conflict than healthy controls.

The purpose of this study was to explore the correlates of online health information-seeking behaviors among Hispanic residents of a low-income urban neighborhood.Data were collected with a community survey from 1045 unique participants at ambulatory care clinics in a largely Hispanic immigrant community in northern Manhattan, New York. A descriptive correlational analysis was conducted using logistic regression.A majority of the participants were born outside the United States (85.7%), and half (50.3%) had completed high school. A logistic regression revealed that five independent variables were significantly correlated with online health information-seeking behaviors: age, education, marital status, primary language, and health literacy. Age and Spanish as preferred language were negatively associated with online health information-seeking (OR = 0.93 and 0.50), whereas education and health literacy were positively associated with online health information-seeking (OR = 4.28 and 1.28).The findings have implications for designing online health information resources and interventions appropriate for the populations they are likely to reach. Furthermore, the findings highlight the need for special efforts to ensure access to reliable health information for immigrant populations and those with low health literacy.

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.

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.

Impulsivity is a frequent component of the course and presentation of bipolar disorder; it has therefore been proposed to represent a core feature of the illness that persists across different affective states (1–8). However, impulsivity is a multi-faceted construct that cannot be defined by a single behavior. For example, based on studies with the Barratt Impulsiveness Scale (BIS), Barratt and colleagues suggested that impulsivity consists of three independent behavioral factors (9,10). These factors include: 1) Non-planning Impulsiveness, which refers to a present orientation or failure to consider the future; 2) Motor Impulsiveness, i.e., acting without thinking; and 3) Attentional Impulsiveness, which is a tendency to shift attention quickly, causing inappropriately rapid decisions. This work and that of others (e.g., 11–13) suggests that impulsivity is comprised of three components: 1) an inability to delay gratification, i.e., an inability to delay response for an immediate reward in order to gain a larger reward or prevent a negative consequence; 2) disinhibition, i.e., an inability to inhibit a prepotent response in favor of a better response; and 3) inattention, i.e., an inability to maintain attention to complete a particular task rather than being distracted to an alternative task (4). These three behavioral components of impulsivity appear to be independent and may be mediated by semi-independent neural systems (12). We recently examined these three aspects of impulsivity during the manic phase of bipolar disorder (4). In order to assess these behaviors we employed a stop-signal task, delayed reward task, and a continuous performance task, respectively. We found that these three aspects of impulsivity were largely independent, were elevated in mania as compared with healthy subjects, and did not correlate with affective symptoms (4). These findings supported the proposal that impulsivity may represent a core trait of bipolar disorder that is independent of symptom severity (1–4). However, we also found that manic patients were more impulsive on the delayed reward task than mixed patients (4), suggesting that impulsivity may instead be related to affective state. In the absence of longitudinal measures within individual subjects, we could not resolve this apparent contradiction. Moreover, to our knowledge, no previous studies have longitudinally examined impulsivity in bipolar disorder, leaving the state or trait nature of these behaviors uncertain. With these considerations in mind, the aim of the present study was to determine whether impulsivity observed during mania persists across phases of bipolar illness, in order to clarify whether impulsivity is independent of affective state. To achieve this aim, we administered the previously described tasks (4) and the Barratt Impulsiveness Scale (BIS-11)(9) to 108 bipolar subjects during an acute manic or mixed episode and then again as these subjects developed depression and achieved euthymia. We predicted that elevated ratings on the BIS-11 and impulsive responding on the behavioral tasks would longitudinally persist during depression and euthymia, consistent with the hypothesis that impulsivity is core trait of bipolar disorder.

Aims: To examine the prevalence of trauma exposure as well as the rates and effects of post-traumatic stress disorder (PTSD) in adolescents with bipolar disorder following a first manic episode. Methods: Adolescents (12–18 years) with DSM-IV bipolar I disorder and experiencing their first manic or mixed episode were recruited. Participants underwent structured diagnostic interviews, completed the Trauma Symptom Checklist for Children (TSCC), and were prospectively evaluated using diagnostic, symptomatic and functional assessments over the course of 12 months. Results: Seventy-six adolescents (14.9 ± 1.7 years) completed the TSCC and 66% (50 individuals) reported exposure to traumatic events. Two (3%) subjects met DSM-IV criteria for PTSD, 11 (14%) had post-traumatic stress t-scores ≥65, the threshold for clinically significant symptoms. Subjects with and without post-traumatic stress t-scores ≥65 did not differ in demographic characteristics. When compared by t-score, TSCC subscores of the first episode bipolar adolescents were similar to normative data. Regression models incorporating TSCC subcomponents, did not predict syndromic recovery or recurrence or symptomatic recovery. Conclusions: Rates of PTSD were lower in this sample of bipolar adolescents at the time of their first hospitalization compared with rates in samples of bipolar adults. These differences coupled with the low incidence of PTSD and trauma symptoms in this young sample suggests that bipolar disorder may be a risk factor for the development of PTSD later in the course of illness or following recurrent affective episodes.

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.

Aims: Impulsivity is common in bipolar disorder, especially during mania. Understanding the functional neuroanatomy of response inhibition, one component of impulsivity, might clarify the neural substrate of bipolar disorder. Methods: Sixteen DSM-IV first-episode, manic bipolar patients and 16 matched healthy subjects were examined during a first manic episode using functional magnetic resonance imaging while performing a response inhibition task. All subjects were studied using a 4.0 Tesla Varian Unity INOVA Whole Body MRI/MRS system. The response inhibition task was presented using non-ferromagnetic goggles, and task performance was recorded during scan acquisition. Imaging data were analysed using analysis of functional neuroimages. Group contrasts were made for the specific response inhibition measure. Results: The groups performed the task similarly, although both demonstrated relatively poor rates of target response, but high rates of successful ‘stops’. Despite similar behavioural results, the groups showed significantly different patterns of functional magnetic resonance imaging brain activation. Specifically, during response inhibition, the healthy subjects exhibited significantly greater activation in anterior and posterior cingulate, medial dorsal thalamus, middle temporal gyrus, and precuneus. The bipolar patients exhibited prefrontal activation (BA 10) that was not observed in healthy subjects. Conclusions: Bipolar and healthy subjects exhibit different patterns of brain activation to response inhibition; these differences may reflect different functional neuroanatomic approaches to response inhibition between the two groups.

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.

The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [(99m)Tc]-conjugated AP39 ([(99m)Tc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice.Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [(99m)Tc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry.In vivo [(99m)Tc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236 ± 40.646 cpm/cm³) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468 ± 4.976 cpm/cm³) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P0.01).[(99m)Tc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.

This work continues the development of an ultrasonic sensor system for in-line measurement of the physical properties of fluid foods. The test system was a semi-batch evaporator in which juice from three varieties of processing tomatoes was concentrated from 5 to 24 Brix. The physical properties of the tomato concentrates were measured and correlated to ultrasound properties. Speed of sound was linearly correlated with density, soluble solids content and total solids content of the tomato concentrates. Shear viscosity of the tomato concentrates flowing in viscometric pipe flow was evaluated using ultrasonic Doppler velocimetry (UDV). The UDV technique combines a fluid velocity profile and a simultaneous pressure drop to create a rheogram. Simple shear viscosity was modeled as power law behavior for tomato concentrates as a function of solids content for the three processing varieties. Off-line measurements of apparent viscosity were well correlated to the in-line measurements.

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.

The present study was conducted to determine the pattern of incorporation of dietary EPA and docosahexaenoic acid (DHA) into milk, and to evaluate consequent changes in milk fat composition and sensory characteristics. Fourteen multiparous cows in early lactation were divided into two groups and were offered supplements for 10 d. While individual stalls after each morning milking, one group was offered a mixture of rumen-protected tuna oil (RPTO)–soyabean supplement (2 kg; 30:70, w/w; +RPTO) and the second group was offered the basal ration without RPTO (−RPTO). Both groups grazed together on a spring pasture after supplementation. Feeding supplemental RPTO increased the concentrations of EPA and DHA in milk fat from undetectable levels in −RPTO cows to 6·9 and 10·1 g/kg milk fat respectively. Total n-3 PUFA concentration in milk fat was increased three- to fourfold by tuna-oil supplementation (8·4 to 32·0 g/kg milk fat). There were no significant effects on milk production (35·4 v. 33·9 l/d), milk protein (28·2 v. 30·1 g/kg) or milk fat (36·2 v. 40·4 g/kg for −RPTO and +RPTO respectively). The concentration of total saturated fatty acids in milk fat was significantly reduced (568 v. 520 g/kg total fatty acids) and there was a 17 % reduction in the atherosclerotic index of milk after tuna-oil supplementation. Untrained consumer panellists (n 61) rated milk from both groups of cows similarly for taste and smell. We conclude that it is possible to enrich milk with n-3 PUFA without deleterious effects on yield, milk composition or sensory characteristics.

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 diets high inn-3 polyunsaturated fatty acids (PUFA; provided by fish oil),n-6 PUFA (sunflower oil) or in more-saturated fatty acids (tallow) on the distribution of subclasses of choline phospholipids (PC) and ethanolamine phospholipids (PE) from the breast muscle of broiler chickens were examined. Supplementation with the different fatty acids had no effect on the distribution of phospholipid subclasses. Feeding sunflower oil or tallow gave a molecular-species profile similar in both fatty acid subtype and proportion. In the diacyl PC phospholipids, 16: 0–18: 1n-9 and 16: 0–18: 2n-6 accounted for approximately 60 % of the total molecular species, whereas for the alkylenyl PC the predominant species were 16: 0–18: 1n-9 and 16: 0–20: 4n-6. Of the diacyl PE the dominant species was 18: 0–20: 4n-6 which accounted for 50 % of the molecular species, and of the alkylenyl PE the dominant species were 16: 0–18: 1n-9, 16: 0–20: 4n-6 and 18: 0–20: 4n-6. Supplementation with fish oil significantly increased levels of both eicosapentaenoic acid (20: 5n-3) and docosahexaenoic acid (22: 6n-3) in PC and PE when compared with either sunflower oil or tallow supplementation. The increase in then-3 PUFA incorporation was associated with a corresponding decrease in the proportion of arachidonic acid (20: 4n-6) in both PC and PE. Different dietary fats induce different patterns of fatty acid incorporation and substitution in thesn-2 position of the diacyl and alkylenyl PC and PE of avian breast muscle, and this finding is indicative of selective acyl remodelling in these two phospholipids.

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