Objective-To examine abnormal patterns of frontal cortical-subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait-like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities.Method-We analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to mild and intense happy, fearful and neutral faces.Results-Relative to healthy individuals, bipolar subjects had significantly increased left striatal activity in response to mild happy faces (p < 0.05, corrected), decreased right dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild and intense happy faces, and decreased left DLPFC activity in response to neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and healthy individuals did not differ in amygdala activity in response to either emotion. In bipolar individuals, there was no significant association between medication load and abnormal activity in these regions, but a negative relationship between age of illness onset and amygdala activity in response to mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar individuals with comorbidities showed a trend increase in left striatal activity in response to mild happy faces.Conclusions-Abnormally increased striatal activity in response to potentially rewarding stimuli and decreased DLPFC activity in response to other emotionally salient stimuli may underlie mood instabilities in euthymic bipolar individuals, and are more apparent in those with comorbid diagnoses. No relationship between medication load and abnormal neural activity in bipolar individuals suggests that our findings may reflect pathophysiologic mechanisms of the illness rather than medication confounds. Future studies should examine whether this pattern of abnormal neural activity could distinguish bipolar from unipolar depression. Bipolar disorder is one of the most debilitating illnesses worldwide (1). Bipolar disorder type I, in particular, is characterized by abnormalities in psychosocial and cognitive function as well as emotion and mood regulation that can persist outside of episodes of mania and depression, during remission (2-6), and likely reflect pathophysiologic mechanisms of the illness (7) that are not mood state dependant. The research agenda for DSM-V emphasizes a need to translate basic and clinical neuroscience findings into a new classification system for all psychiatric disorders based upon pathophysiologic and etiological processes (8,9). Examining neural system abnormalities in euthymic individuals with bipolar disorder type I during paradigms specifically designed to measure emotion processing is therefore a first stage toward identifying biomarkers of bipolar disorder that reflect pathophysiologic neural mechanisms of the disorder (10). These, in turn, can then be included in future diagnostic cl...

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Our findings support the conclusion that CT specifically designed for relapse prevention in bipolar affective disorder is a useful tool in conjunction with mood stabilizers.

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation, including ventral/orbital medial prefrontal cortex (OMPFC) GMV decreases and, more inconsistently, amygdala GMV increases. We aimed to examine OMPFC and amygdala GMV in bipolar disorder, type 1 patients (BPI) versus healthy control participants (HC), and examine potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age-and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry to first examine main effects of diagnostic group and gender upon whole brain (WB) GMV. Post hoc analyses were subsequently performed to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions demonstrated by the above VBM analyses. Here, SPPSS was used to examine the effects of these variables on magnitude of GMV in these a priori and nona priori regions in BPI versus HC. BPI showed reduced GMV in two regions established a priori: bilateral posteromedial rectal gyrus (PMRG), but no amygdala GMV abnormalities. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low trait anxiety BPI versus male low trait anxiety HC, and in high versus low trait anxiety male BPI. Our findings show in BPI significant effects of male gender and high trait anxiety on GMV reduction in left PMRG, part of the OMPFC medial prefrontal network implicated in visceromotor and emotion regulation.

Combination of cognitive therapy and mood stabilizers was superior to mood stabilizers alone in terms of clinical outcome and cost-effectiveness for those with frequent relapses of bipolar disorder.

Our findings suggest that both BP and MDD patients demonstrate impaired performance on neutral and emotionally salient attentionally demanding tasks. The finding of impaired performance in all patients on baseline conditions in each task, however, indicates the need for inclusion of additional baseline conditions in these tasks in order to elucidate the nature of attentional impairments specific to these patient populations.

ABSTRACT. Objective. Child abuse occurs in 1% of children in the United States every year; 10% of the traumatic injuries suffered by children under 5 years old are nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid characterization of the injury as nonaccidental is of considerable benefit to child protection workers and police investigators seeking to safeguard the child care environment and apprehend and prosecute those who have committed the crime of child abuse. Physically abused children present with a variety of well-described injuries that are usually easily identifiable. In some cases, however, particularly those involving children with the shaken baby syndrome, obvious signs of physical injury may not exist. Although external signs of such an injury are infrequent, the rapid acceleration-deceleration forces involved often cause subdural hematomas and retinal hemorrhages, hallmarks of the syndrome. Frequently, retinal hemorrhages may be the only presenting sign that child abuse has occurred. Complicating the interpretation of the finding of retinal hemorrhages is the belief by some physicians that retinal hemorrhages may be the result of chest compressions given during resuscitative efforts. The objective of this study is to determine the prevalence of retinal hemorrhages after inpatient cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for nontraumatic illnesses in an intensive care unit.Design. Prospective clinical study. Setting. Pediatric intensive care unit. Patients. Forty-three pediatric patients receiving at least 1 minute of chest compressions as inpatients and surviving long enough for a retinal examination. Patients were excluded if they were admitted with evidence of trauma, documented retinal hemorrhages before the arrest, suspicion of child abuse, or diagnosis of neardrowning or seizures. All of the precipitating events leading to cardiopulmonary arrest occurred in our intensive care unit, eliminating the possibility of physical abuse as an etiology.Interventions. None. Measurements. Examination of the retina was performed by one of two pediatric ophthalmologists within 96 hours of CPR. The chart was reviewed for pertinent demographic information; the platelet count, prothrombin time, and partial thromboplastin time proximate to the CPR were recorded if they had been determined.Results. A total of 43 pediatric patients hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR. The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the patients were under 2 years old. The majority of the patients (44%) were admitted to the intensive care unit after surgery for congenital heart disease, and another 21% were admitted for respiratory failure. The mean duration of chest compressions was 16.4 minutes ؎ 17 minutes with 58% lasting between 1 and 10 minutes. Five patients had chest compressions lasting >40 minutes, and two patients had open chest cardiac massage. All patients survived their resuscitative efforts. Nin...

The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation.