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Internal jugular vein (IJV) compression influences not only intracranial but also intracochlear physiology and has demonstrated preclinical effectiveness in reducing acute audiological injury in a rodent blast model. However, the long-term effects in this model are unknown.Blast wave-induced audiological injury from an improvised explosive device is a leading cause of morbidity among service members in theater but there are limitations to the current protective measures.For this study, we exposed 20 Sprague Dawley rats to a 16.8 ± 0.3 PSI (195.3 dB SPL) right-sided shock wave in which 10 had application of a custom IJV compression collar in place at the time of injury.IJV compression at the time of injury was shown acutely to significantly reduce the incidence of tympanic membrane rupture and the initial temporary threshold shift on otoacoustic emissions in both the right and left ears of animals who had collar application immediately after and 7 days post injury. At 28 days from injury, collared animals demonstrated a return to baseline of otoacoustic emission values while the noncollared animals had persistent threshold shifts, signifying the presence of a permanent threshold shift only in those animals without collar application. IJV compression was also found to significantly reduce hair cell loss at the base of the cochlea secondary to mechanical trauma from the blast wind.Previously observed acute protective effects of IJV compression are sustained at chronic time points. IJV compression can potentially be used to reduce long-term permanent morbidity from blast-induced audiological trauma.

HYPOTHESIS Internal jugular vein (IJV) compression before blast injury will lead to reduced risk of traumatic hearing injury following exposure to a blast injury. BACKGROUND IJV compression and its effects on not only intracranial, but also intracochlear pressure may potentiate blast induced hearing injury, therefore, precluding its use as a prophylactic therapy for blast induced traumatic brain injury. METHODS Twenty Sprague Dawley rats were exposed to a 17.9 ± 0.4 PSI (195.8 dB SPL) right sided shock wave in which 10 had application of a custom IJV compression collar before injury. All rodents received baseline and post blast injury otoacoustic emission (OAE) and auditory brainstem response (ABR) testing followed by cochlear histology. RESULTS IJV compression was shown to significantly reduce ABR and OAE threshold shifts in comparison to the non-intervention group by: 14.9 ± 4.8 dB (right ear ABR 0.5 kHz Day 1 post blast, p = 0.01), 13.1 ± 4.9 dB (right ear ABR 4 kHz Day 1 post blast, p = 0.04), 16.5 ± 4.5 dB (right ear ABR click Day 1 post blast, p = 0.003), 12.1 ± 4.6 dB (right ear ABR click Day 6 post blast, p = 0.04), and 14.0 ± 3.2 dB (both ears OAE 3.2-10 kHz, p

To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU).Randomized, double-masked, placebo-controlled, phase 2 study.Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis.Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo.The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis.At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 μm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] μm (P = 0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients).Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Objective The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of >100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT). Methods A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight. Results Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight. Conclusion Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs. © 2013 John Wiley & Sons, Ltd.

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations.

To assess the long-term safety and vision change in patients who received intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration in an extension study after completing VIEW 1 trial.Prospective, open-label, multicenter, extension study.Three hundred twenty-three patients.In VIEW 1, 1217 patients were randomized to receive fixed dosing of 0.5 mg IAI every 4 weeks (0.5q4), 2 mg IAI every 4 weeks (2q4), 2 mg IAI every 8 weeks after 3 initial monthly dosing (2q8), or 0.5 mg ranibizumab every 4 weeks (Rq4) from baseline through week 52, followed by modified quarterly injections of the same dose of anti-vascular endothelial growth factor agent from weeks 52 to 96. After completing VIEW 1 at week 96, patients (n = 323) enrolled in an extension study and received 2 mg IAI on a modified quarterly injection schedule followed by at least an every 8-week dosing through week 212.Long-term safety and vision change in patients followed for a median duration of 116 weeks in the extension study (total follow-up time of 212 weeks from the VIEW 1 baseline).Patients enrolled in the extension study gained a mean of 10.2 letters from the VIEW 1 baseline at week 96. These patients largely maintained vision over the extension study with a mean gain of 7.1 letters from the VIEW 1 baseline to week 212. The proportion of patients who lost ≥15 letters from the VIEW 1 extension baseline was 8.2% at week 212. Mean number of injections was 12.9 (range, 1-41) in the extension study. The most common serious ocular adverse event was endophthalmitis (0.9%). The overall incidence of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events was 6.2%.Vision gains achieved with anti-vascular endothelial growth factor therapy in VIEW 1 were largely maintained by continued treatment with IAI 2 mg in the extension study. Anti-vascular endothelial growth factor injections (including 4 years of IAI 2 mg) were well-tolerated with no new safety signals compared with the known profile of IAI.

Objective To assess the frequency of surgical techniques at cesarean delivery (CD) among U.S. obstetricians. Methods Members of the American College of Obstetrician Gynecologists were randomly selected and e-mailed an online survey that assessed surgical closure techniques, demographics, and reasons. Data were analyzed using SPSS (IBM Corp., Armonk, New York, United States), descriptive statistics, and analysis of variance. Results Our response rate was 53%, and 247 surveys were analyzed. A similar number of respondents either “always or usually” versus “rarely or never” reapproximate the rectus muscles (38.4% versus 43.3%, p = 0.39), and close parietal peritoneum (42.5% versus 46.9%, p = 0.46). The most frequently used techniques were double-layer hysterotomy closure among women planning future children (73.3%) and suturing versus stapling skin (67.6%); the least frequent technique was closure of visceral peritoneum (12.2%). Surgeons who perform double-layer hysterotomy closure had fewer years in practice (15.0 versus 18.7 years, p = 0.021); surgeons who close visceral peritoneum were older (55.5 versus 46.4 years old, p Conclusion Similar numbers of obstetricians either reapproximate or leave open the rectus muscles and parietal peritoneum at CD, suggesting that wide variation in practice exists. Surgeon demographics and safety concerns play a role in some techniques.

Objective To survey generalist obstetrician-gynecologists about their satisfaction with and patterns of referral to maternal–fetal medicine (MFM) specialists. Study Design A survey was sent three times to 1030 randomly selected American Congress of Obstetricians and Gynecologists members across the country, and results were tabulated. Results A total of 516 surveys (50%) were returned; 68% of respondents were satisfied (S) with available MFM services and 31% were not satisfied (Not S). S and Not S respondents were similar with respect to age, gender, years in practice, type of practice, hours worked per week, proximity to MFM specialists, number of deliveries per year, and level of nursery in their hospital. Reasons for dissatisfaction included: MFM specialist not readily available (49%), during the day (26%), at night (35%), or on weekends (36%); MFM specialist unwilling to take care of hospitalized patients (26%); or MFM specialist does only ultrasound, chorionic villus sampling, and amniocentesis (32%). Although some generalists do not consult MFM specialists frequently, the majority of both S and Not S respondents would request an MFM consult or comanagement for 26 of 38 specific maternal, fetal, and obstetric diagnoses/complications. Conclusion The majority of obstetrician-gynecologists are satisfied with their MFM support. The dissatisfaction expressed by 31% of generalists might be ameliorated if individual MFM specialists increased their availability and/or broadened their scope of practice.

BackgroundMajor depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall.MethodParticipants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings.ResultsBehavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (pversus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD.ConclusionsWe replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.

Preterm (PT) birth is an established risk factor for high mortality and morbidity rates. Infants and school-aged children have been well-studied, but few have described neuropsychological and behavioral outcomes at preschool age. We compared a 2004-2006 preterm/extremely low birth weight (ELBW) cohort (PT/ELBW; N = 60) born ≤ 33 weeks gestation and

Objective: Motor impairments are prevalent in children born at extremely low birth weight (ELBW; < 1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. Method: We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. Results: ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born

Objective: The spatial location memory of preschool-aged children born preterm has rarely been studied primarily due to an absence of developmentally sensitive measures. This study aimed to address this gap in the literature. Method: We administered a modification of the Hopkins Board to 135 children at age 3 who were born extremely low birth weight (ELBW) (n = 20), late-preterm (LPT) (n = 75), or at term (TERM) (n = 40). Five measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, and delayed location recall. Results: ANCOVA indicated that the groups differed in naming (p = .019), errors-to-criterion (p = .002), and delayed item recall (p = .025). For these measures, ELBW performed worse than TERM and LPT, but LPT did not differ from TERM. Corrected age and sociodemographic factors did not eliminate the deficit in spatial location learning for ELBW participants. A MANCOVA found a significant difference in learning, with post hoc tests indicating significant learning across trials in the LPT and TERM groups, but not in the ELBW group. Conclusions: ELBW is a significant risk factor for developmental delay or impairment of spatial location learning. These findings suggest that the modified Hopkins Board identifies at-risk premature children. This modification may be more broadly useful to assess preschoolers' neurodevelopmental maturation.

Background Late-preterm children constitute a majority of all preterm deliveries (75%). Their immature brain development at birth has been associated with an increased risk for morbidities. Data have been sparse regarding neuropsychological outcomes in the preschool years. Aim To examine general cognition, attention/working memory, language, manual coordination/motor dexterity, visuomotor, visuospatial, and executive functions in preschoolers born late-preterm (LPT; 34–36 gestational weeks) who required NICU admission compared to term-born participants. Design Single-center retrospective cohort study of 95 three-year-old children; 60 born LPT in 2004–2005 and admitted to the NICU compared to 35 healthy term-born participants born ≥ 37 gestational weeks and ≥ 2500 g. Results LPT birth was associated with visuospatial (p = .005), visuomotor (p = .012), and executive function (noun [p = .018] and action-verb [p = .026] fluency) relative deficits, but not attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficit. Conclusions Late-preterm birth is likely to be associated with negative neuropsychological sequelae, although subtle and selective compared to effects reported for children born at an earlier gestational age. Visuospatial function appears to be especially vulnerable to disruption even at preschool age, and verbal fluency may be useful as an early predictor of executive dysfunction in childhood. Routine preschool neuropsychological evaluation is recommended to identify delay or deficit in LPT children preparing for school entry, and may highlight underlying vulnerable neural networks in LPT children.

Extremely low birth weight (ELBW) is an established risk factor for poor neurocognitive outcome, particularly when severe intraventricular hemorrhage (IVH) complicates the neonatal course. Those born26 weeks gestational age (GA) are at greatest risk, their outcomes poorer than later born ELBW children. Outcomes of GA subgroups of ELBW uncomplicated by severe IVH have not been well described.To compare neurocognitive and behavioral outcomes of those bornandor=26 weeks for an ELBW cohort treated in a single center with extremely low IVH incidence.Single center retrospective observational cohort study ofor=1000 g survivors born between 1998-2000, using standardized tests of cognition, academic achievement, executive function, attention, language, memory, motor/visual-motor skill, parent and teacher behavioral questionnaires.ELBW participants (mean age: 6.85+/-0.79) had a mean General Cognitive Ability of 101.4+/-13.05; no significant differences found between26 weeks (98.19+/-12.48) andor=26 weeks (102.97+/-13.21) subgroups. No neurocognitive, achievement, or behavioral score was impaired (or=2 SDs below the normative mean). Subgroup comparisons were nonsignificant after controlling for BW and maternal education, except foror=26 week advantage for phoneme analysis. Poorer, but low average, performances were found for motor dexterity/coordination, spatial working memory, and selective attention.Age-appropriate neurocognitive and behavioral function of ELBW survivors suggests outcome may be predicted based on IVH incidence as opposed to birth weight or GA. Factors leading to decreased IVH incidence deserve further study, via single- and cross-center methodologies, to enhance decision-making regarding resuscitation and care of these highly at-risk neonates.

Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects.Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable.With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory.Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.

Background Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. Few studies have directly compared depressed subjects with major depressive disorder (MDD) and bipolar disorder (BD), and many are confounded by medication status across subjects. In this study, we compared the performance of unmedicated currently depressed MDD and BD groups on a battery of neuropsychological tests that included measures of risk taking and reflection impulsivity. Methods Twenty-two MDD, seventeen BDII, and 25 healthy control subjects (HC), matched for age and IQ, were assessed on a battery of neuropsychological tests. Results The depressed groups showed comparable ratings of depression severity and age of illness onset. The MDD group was impaired on tests of spatial working memory and attentional shifting, sampled less information on a test of reflection impulsivity, and was oversensitive to loss trials on a decision-making test. The BDII subjects were generally intact and did not differ significantly from control subjects on any test. Conclusions These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.

Summary Summary/objectives In accordance with the Joint Committee on Infant Hearing's (JCIH, 2000) position statement regarding Universal Newborn Hearing Screenings (UNHS), the state of Illinois enacted legislation requiring all birthing hospitals to conduct UNHS by 31 December 2002. Currently 100% of birthing facilities in the state of Illinois perform newborn infant hearing screenings using otoacoustic emissions (OAEs) and/or automated auditory brainstem response (AABR) measures. This study is an attempt to document current practices in hospital-based UNHS programs, as reported by program personnel, in the state of Illinois. The goal is to compare these reported practices to the recommended standards and identify factors that could lead to further refinement of the process. Methods A modified version of the Newborn Hearing Screening Survey from the Marion Downs National Center for Infant Hearing was used to gather practice- and protocol-related data for the 2004 calendar year via the World Wide Web. Data presented here are extracted from the online survey as reported by hospital staff presumably associated with the UNHS program. Results Fifty-nine of the 140 hospitals with UNHS programs responded to the Web-based survey. Nursing staff, followed by technicians, were most commonly reported to perform initial hearing screenings in both the well-baby nursery (WBN) and the neonatal intensive care unit (NICU). Audiologists appeared to participate in re-screenings at a greater number of the facilities. Automated ABR was the most common screening tool (80%) followed by Distortion Product OAEs (32%) and Transient Evoked OAEs (5%). Eighty-six percent reported referral rates that were less than 5%, with 32% reporting a referral rate less than 1%. Conclusions At the beginning of 2004, 99% of all infants born in Illinois were being screened for hearing loss. Personnel involvement and screening measures employed were comparable to the few reports available from other states. The audiologist's role was found to be fairly limited in screening, re-screening, or managing UNHS programs. Referral rates were consistent with national standards (∼1%). Management of UNHS programs in small, rural facilities, tracking/monitoring high-risk infants, and other services provided to families emerged as areas with room for improvement.

The purpose was to assess practicing obstetrician-gynecologists' knowledge about the prenatal diagnosis and postnatal prognosis of spina bifida. Written questionnaires designed to assess practicing obstetrician-gynecologists' knowledge of spina bifida were mailed to 1000 randomly selected American College of Obstetricians and Gynecologists Fellows. More than 50% did not identify many of the sonographic features indicative of an open neural tube defect in the fetus and more than one third overestimated the risks of stillbirth, whereas more than two thirds overestimated the risk for premature delivery in a pregnancy complicated by fetal spina bifida. Just more than 50% correctly estimated the 1-year survival rate and just less than 50% correctly estimated survival at 6 years. Sixty-six percent overestimated the incidence of mental retardation associated with spina bifida. Maternal-fetal medicine specialists returning the survey exhibited a much better understanding of the prenatal issues and prognostic and outcome factors related to spina bifida. There are gaps in obstetrician-gynecologists' knowledge about the diagnostic features of and prognosis for fetal spina bifida. It is important for them to take advantage of continuing medical education opportunities to learn more about the management of pregnancies complicated by fetal spina bifida and about the prognosis for affected individuals.

The present study examined the effects of glucocorticoid administration on emotional memory and on corticotropin-releasing hormone (CRH) mRNA expression in the central nucleus of the amygdala (CeA) and the paraventricular nucleus of the hypothalamus (PVN). This was tested by administering repeated corticosterone (CORT) within a contextual fear conditioning paradigm. Rats received 2.5 mg/kg (s.c.) CORT or placebo twice a day for five and a half days and, 2 h after the last injection, rats were given one-trial contextual fear conditioning. When tested for retention of conditioned fear 6 days later, the CORT-treated rats displayed more fear-conditioned freezing in the retention test than vehicle-treated rats, which was not accounted for by an increase in footshock responsivity nor elevated plasma CORT. Another group of rats was fear conditioned prior to CORT administration, followed 24 h later by the five and a half days of CORT, and tested 6 days later; conditioned fear was not enhanced in these rats. Finally, CORT administration produced an increase of CRH mRNA in the CeA and a decrease in the PVN. The data suggest that repeated administration of CORT given before fear conditioning facilitates the acquisition of emotional memory, whereas CORT given after consolidation does not increase emotional memory.

Facial expressions are one example of emotional behavior that illustrate the importance of emotions to both basic survival and social interaction. Basic facial responses to stimuli such as sweet and bitter taste are important for species fitness and governed by simple rules. Even at this basic level, facial responses have communicative value to other species members. During evolution simple facial responses were extended for use in more complex nonverbal communications; the responses are labile. The perception and production of facial expressions are cognitive processes and numerous subcortical and cortical areas contribute to these operations. We suggest that no specific emotion center exists over and above cognitive systems in the brain, and that emotion should not be divorced from cognition.

The glucocorticoid hormone cortisol is essential for many forms of regulatory physiology and for cognitive appraisal. Cortisol, while associated with fear and stress response, is also the hormone of energy metabolism and it coordinates behavioral adaptation to the environmental and internal conditions through the regulation of many neurotransmitters and neural circuits. Cortisol has diverse effects on many neuropeptide and neurotransmitter systems thus affecting functional brain systems. As a result, cortisol affects numerous cognitive domains including attention, perception, memory, and emotional processing. When certain pathological emotional states are present, cortisol may have a role in differential activation of brain regions, particularly suppression of hippocampal activation, enhancement of amygdala activity, and dendritic reshaping in these regions as well as in the ventral prefrontal cortex. The coordinated actions of glucocorticoid regulation on various brain systems such as those implicated in emotional processing can lead to perceptual and cognitive adaptations and distortions of events that may be relevant for understanding mood disorders.

To assess practicing obstetricians' knowledge of the etiology and pathophysiology of neonatal encephalopathy and its relationship to cerebral palsy.A questionnaire designed to test both knowledge and practice patterns was mailed to 413 members of the Collaborative Ambulatory Research Network of The American College of Obstetricians and Gynecologists (ACOG), as well as 600 randomly selected non-Network ACOG Fellows. The questionnaire was composed of 15 knowledge questions and three clinical scenarios containing seven knowledge questions. Six of the questions directly assessed knowledge of cerebral palsy.Of those who returned the questionnaire, 351 practiced obstetrics and were included in the statistical analyses. For the majority of questions, "Don't know" was the most frequent response. The next most frequent response for 8/13 questions was the correct answer. Performance was strongest as regarded actual clinical practice and relatively weak regarding the antecedents of neonatal encephalopathy and cerebral palsy. The physicians' actual knowledge scores showed a significant correlation with their self-assessments of knowledge (r =.41, P.001). The majority of physicians rated their training on this topic in medical school, residency, and through continuing medical education as marginal or inadequate.The results of this survey identified large knowledge gaps in this area, suggesting a need to develop educational projects to address these deficits by both professional organizations and individual teachers.

To compare the efficacy and safety of intravitreal aflibercept injection (IAI) with macular grid laser photocoagulation for the treatment of macular edema after branch retinal vein occlusion (BRVO).The VIBRANT study was a double-masked, active-controlled, randomized, phase III trial.Treatment-naïve eyes with macular edema after BRVO were included in the study if the occlusion occurred within 12 months and best-corrected visual acuity (BCVA) was between ≤73 and ≥24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40-20/320 Snellen equivalent).Eyes (1 eye per patient) received either IAI 2 mg every 4 weeks (n=91) from baseline to week 20 or grid laser (n=92) at baseline with a single grid laser rescue treatment, if needed, from weeks 12 through 20.The primary outcome measure was the proportion of eyes that gained ≥15 ETDRS letters from baseline BCVA at week 24. Secondary end points included mean change from baseline BCVA and central retinal thickness (CRT) at week 24.The proportion of eyes that gained ≥15 ETDRS letters from baseline at week 24 was 52.7% in the IAI group compared with 26.7% in the laser group (P=0.0003). The mean improvement from baseline BCVA at week 24 was 17.0 ETDRS letters in the IAI group and 6.9 ETDRS letters in the laser group (P0.0001). The mean reduction in CRT from baseline at week 24 was 280.5 μm in the IAI group and 128.0 μm in the laser group (P0.0001). Traumatic cataract in an IAI patient was the only ocular serious adverse event (SAE) that occurred. There were no cases of intraocular inflammation or endophthalmitis. The incidence of nonocular SAEs was 8.8% in the IAI group and 9.8% in the laser group. One Anti-Platelet Trialists' Collaboration-defined event of nonfatal stroke (1.1%) and 1 death (1.1%) due to pneumonia occurred during the 24 weeks of the study, both in patients in the laser group.Monthly IAI provided significantly greater visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes with macular edema after BRVO.

Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child's functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.

UNLABELLED Historically, obstetrics and gynecology has been a medical/surgical specialty focusing on women's health and reproductive concerns during the childbearing years. Newer responsibilities-for example, in primary care, gerontology, and genetics-require Ob-Gyns to draw upon a base of medical knowledge that traditionally was not considered germane to their practices. Ob-Gyns are increasingly providing more primary care services to their patients; consequently, the field has expanded considerably. The Collaborative Ambulatory Research Network (CARN) was created in 1990 as a vehicle for investigating issues pertinent to women's health and to the practice of obstetrics and gynecology in the outpatient setting. This article summarizes the findings of CARN studies from 1995 to 2000, covering a range of topics related to women's health across the life cycle, including, but not limited to perinatal care. Topics include nutrition, infectious disease, hormone replacement therapy, psychosocial issues, and genetic testing in obstetric and gynecologic practice. Each study produced a picture of current practice patterns and knowledge of the physicians surveyed. Findings on knowledge, attitudes, and practices varied widely. Overall, Ob-Gyns were knowledgeable and consistent in more traditional areas of practice. Conversely, inconsistencies were observed in newer areas. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES After completion of this article, the reader will be able to define what the Collaborative Ambulatory Research Network (CARN) involves, describe how CARN obtains its data, and summarize some of the findings of CARN from the years 1995 to 2000.

Increased CRH secretion by the placenta of pregnant women has been associated with preterm birth. Certain indices of risk, both medical and psychosocial in nature, have been linked to preterm delivery. Levels of total, bound, and free CRH, CRH-binding protein (CRH-BP), and cortisol were measured prospectively in a large sample of pregnant Danish women who delivered preterm and term infants. Measures of maternal serum hormones were taken at 7--23 and 27--37 weeks gestation and, for those who delivered at term, at 37--43 weeks gestation. At 7--23 weeks gestation, maternal levels of total CRH (P = 0.01), bound CRH (P = 0.03), and CRH-BP (P = 0.01) were higher in the preterm than in the term group. At 27--37 weeks gestation, levels of total CRH (P < 0.0001), bound CRH (P < 0.0001), free CRH (P < 0.0001), and cortisol (P < 0.0001) were all higher in the preterm than the term group, whereas levels of CRH-BP (P < 0.0001) were lower in the preterm than in the term group. The best medical and behavioral factors associated with preterm delivery were, respectively, previous preterm delivery (P < 0.0001) and engagement in certain risk-taking behaviors (P = 0.008). The positive relations between preterm delivery and various adverse medical and socioeconomic variables with increases in placental secretion of CRH suggest that the latter may participate in the pathophysiology of preterm delivery.

To characterize the clinical decisions, knowledge, opinions, and education of obstetricians and gynecologists about antenatal corticosteroids.Questionnaires mailed to 1020 ACOG Fellows included items on demographics, knowledge, clinical practice patterns, and educational background regarding antenatal corticosteroids.The survey response rate was 47.8%. Almost all respondents (94%) reported administering antenatal corticosteroids, with reduction of respiratory distress syndrome (82%) as the primary reason for antenatal corticosteroid administration. Most (59.2%) were unaware of newly recognized associations between multiple administrations of corticosteroids and fetal growth restriction. In hypothetical clinical situations, responses by physicians who completed their residency training before 1970 indicated less likelihood to administer corticosteroids when administration is relatively indicated per National Institutes of Health (NIH) and ACOG guidelines than those trained later (P.001). Only 8% of the entire sample rated their knowledge of antenatal corticosteroids as comprehensive; most (68%) rated it as adequate. Respondents rated residency training as a much better source of antenatal corticosteroid knowledge than medical school.Most obstetrician-gynecologists reported using antenatal corticosteroids; however, in general, many were not aware of more recent information regarding potential risks. This survey suggests that a multipronged educational approach is warranted to update obstetrician-gynecologists about antenatal corticosteroids.

Our objective was to describe gynecologists' current practice patterns and opinions on genetic screening and their perceived importance of genetic screening within individual practices. A questionnaire survey was sent to 1248 American College of Obstetrics and Gynecology (ACOG) Fellows, of whom 564 (45%) responded. Results from the 428 respondents providing genetic screening for heritable diseases or disorders are reported. Forty-four percent of respondents believe advances in the treatment of genetic diseases are likely in the next 10 years. Currently, however, genetics in gynecological practice receives infrequent attention. Twenty-four percent of respondents do not routinely review family histories at gynecological visits, 39% rate genetic issues as last among priorities in the office, and only 14% obtain consent for the DNA tests that they initiate. Although 21.3% identified themselves as sole providers of genetic information and counseling to their patients, most (65.4%) note they are not confident of their knowledge of genetics, particularly concerning breast and ovarian cancer. For obstetrician-gynecologists to keep pace with the rapid changes in genetics, further education and assimilation of genetics into the routine office practice will need to occur. Not currently viewed as a priority among practitioners, issues of genetic knowledge, ethics, and test interpretation will soon need attention. National organizations, continuing medical education, and existing genetic centers will need to meet these recognized demands.

Although delayed umbilical cord clamping has been demonstrated to reduce the incidence of intraventricular hemorrhage and neonatal sepsis, and decrease the need for neonatal transfusions (without affecting cord pH, Apgar scores or the need for phototherapy), the extent to which this practice is being employed is unknown. We conducted a survey of US obstetricians to assess their attitudes and beliefs about cord clamping.Questionnaires were randomly mailed to members of the American College of Obstetricians and Gynecologists (ACOG), and the Collaborative Ambulatory Research Network (CARN). The data were analyzed using Chi-square and Student t tests.The response rates for the CARN and other ACOG members were 47% and 21%, respectively. Most (88%) responders reported their hospital had no umbilical cord clamping policy. The most frequent response for optimal timing of umbilical cord clamping, regardless of gestational age, was "don't know". Potential for neonatal red blood cell transfusion was the only concern cited as a reason for being somewhat or very inclined to delay umbilical cord clamping (51%). Delayed neonatal resuscitation (76%) was listed as a reason to clamp the cord immediately, despite the paucity of literature to support immediate cord clamping in this cohort.Despite substantial evidence supporting the practice of delayed cord clamping, few institutions have policies regarding this practice. Moreover, obstetricians' beliefs about the appropriate timing for umbilical cord clamping are not consistent with the evidence that demonstrates its beneficial impact on neonatal outcomes.

The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT).A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight.Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight.Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs.

Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories. The current study goal was to assess whether emotionally valenced cue words led to memories of similar emotional valence and whether this pattern differed between 12 unmedicated MDD and 14 healthy control participants. Both groups recalled autobiographical memories in response to positive, negative, and neutral cue words. Positive and neutral cues prompted recall of positive memories less often in the MDD group than in the controls. MDD participants recalled fewer specific and more categorical memories than controls; however, the proportion of specific memories didn't differ across memory valences. The MDD group had fewer specific memories in response to positive and neutral cues than the controls. These results suggest that the MDD participants may process positive stimuli differently than healthy controls and that their recall of specific autobiographical memories is impaired, regardless of the affective valence of those memories.

Attention is a limited resource, and in order to improve processing of the attended information, competing processes must be suppressed. Although it is well established that an experimentally induced change in mood state comprises one type of competing process that can impair performance on a subsequent task, no study has investigated whether an emotionally valenced autobiographical memory (AM) also can alter performance on a subsequent task. We therefore examined the effects of AM recall on cognitive performance. Healthy participants (n = 20 per experiment) recalled AMs in response to positive, negative, and neutral cue words. Following each AM participants completed a simple perceptual task (Experiment 1) or solved moderately difficult subtraction problems (Experiment 2). In Experiment 1 participants performed less accurately following exposure to positive or negative versus neutral cue words (ps < 0.001), and also were less accurate following negative versus positive cue words (p < 0.001). In Experiment 2, in contrast, no difference in accuracy or response times reached statistical significance. Performance accuracy even trended toward being higher following exposure to negative versus neutral cue words (p = 0.08). The results of Experiment 1 suggested that recalling emotionally salient AMs reduces the attention directed toward a simple continuous performance task administered immediately following the AM task, conceivably due to persistent contemplation of the AM. The negative results of Experiment 2 suggested that the effect of AMs on attention was attenuated, however, by increasing the difficulty of the subsequent task. Our results have implications for patients with major depressive disorder (MDD), as performing cognitively demanding tasks may allow them to attenuate the impairing effects of negative rumination on cognition.

Epinephrine increased outflow facility and cyclic AMP in the in vitro perfused human anterior segment with a maximal facility increase of 44% occurring at approximately 2 x 10(-5) M. Cyclic AMP measured in the perfusate from anterior segments increased by 12-14 fold after administration of 10(-5) M epinephrine. Both the facility increase and cyclic AMP rise were blocked by the beta-2 selective antagonist, ICI118,551. While there was a correlation between the facility increase and elevation in cyclic AMP levels, the rise in cyclic AMP preceded the facility increase by about 1 hour, suggesting that the ultimate effect of epinephrine involved a rather slow event such as synthesis and release of prostaglandins or protein synthesis. Subsequent perfusion studies showed that very large concentrations of indomethacin were necessary to block the outflow facility effect of epinephrine, suggesting that prostaglandin synthesis did not underlie the facility effect in this system. However, 5 x 10(-5) M cyclohexamide blocked the effect on outflow facility of both epinephrine and forskolin, but did not block the rise in cyclic AMP. These studies suggest that protein synthesis may play a role in the epinephrine-induced facility increase at some point beyond the second messenger level.

Spatial location memory has rarely been assessed in young children due to a scarcity of developmentally appropriate tests. This study sought to compare nonverbal learning and recall in children born extremely low birth weight (ELBW;1000 g) and less than 33 gestational weeks (GW) with term-born children at early school age using a recently developed and adapted test. We administered a modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35 born26 GW; 49 born 26-33 GW) and 126 term-born. Six measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed location recall, and percent retention. After age correction, ELBW children had worse general cognition, item naming, delayed item recall, delayed location recall, and percent retention than term-born children. Delayed item recall and percent retention performances of ELBW children remained worse after correction for general cognition. ELBW groups (26 GW and 26-33 GW) groups performed worse than term-born children in naming and delayed item recall with chronological age as covariate. Those born before 26 GW, but not 26-33 GW, performed worse than term-born children in delayed location recall and percent retention. Differences remained significant after controlling for gender, maternal education, and delivery type. All three groups' performance declined from final learning trial to delayed location recall, with a decline greater for less than 26 GW than term-born children. Extreme prematurity (26 GW) and ELBW are significant risk factors for spatial location memory deficit. The modified Hopkins Board discriminated high-risk preterm and term-born children at early school age and appears to be a useful test to measure this rarely studied cognitive capacity.

The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = .04), increased the percent of categorical (nonspecific) memories recalled (p < .001), and slowed response times for categorical memories (p < .001), compared with placebo performance. Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories.

To study postnatal dexamethasone treatment effects on cognitive, neuropsychological and behavioral functioning at early school age in preterm children.We recruited 222 children born between 1998 and 2003: 114 extremely low birth weight (1000 g; 60 dexamethasone-treated; 54 untreated) and 108 term-born. Data were analyzed using multivariate methods.Preterm performed below term-born on all measures. Dexamethasone-treated performed below dexamethasone-untreated in immediate visual memory, visual-motor integration, mathematical skill and motor dexterity. However, stepwise regression indicated that medical and sociodemographic factors other than dexamethasone contributed to preterm group differences.Dexamethasone alone does not explain neurocognitive impairment in preterm children. Medical and sociodemographic factors (illness severity, male gender and parental education) are influential. Prospective longitudinal neuropsychological and behavioral study from preschool to school age that considers medical and sociodemographic variables will best address effects of dexamethasone exposure.

late-preterm (LPT) birth accounts for a majority of preterm deliveries and until recently was considered low risk for poor cognitive outcome. Previously, we reported deficits in complicated LPT (cLPT) preschoolers (neonatal intensive care unit [NICU]-admitted).to extend our prior study by comparing cognitive outcome in cLPT and uncomplicated LPT (uLPT; NICU non-admitted) preschoolers.single center retrospective cohort study of 118 LPT children born in 2004-2006 at 35-36 weeks of gestation; 90 cLPT and 28 uLPT, compared with 100 term-born (≥ 37 weeks of gestation and ≥ 2500 g) participants.a well-standardized measure of general conceptual ability (GCA), the Differential Ability Scales, Second Edition.cLPT participants had average mean performances but significantly poorer GCA, Nonverbal Reasoning, and Spatial scores than term-born children, and higher rates of Nonverbal Reasoning and Spatial impairment; uLPT did not differ from TERM. Combined LPT males were at eightfold greater risk than term-born males for nonverbal deficit, and at sevenfold greater risk for GCA impairment than LPT females.finding greater risk of cognitive deficit in those NICU-admitted due to clinical instability or birth weight2 kg compared with non-admitted preschoolers indicates that neonatal morbidities contribute to subtle cognitive deficits detectable at young age, with male gender an additive risk factor. LPT gestational age alone is an insufficient predictor of long-term neurocognitive outcome. Further study should elucidate salient etiologies for early emerging cognitive weaknesses and suggest appropriate interventions to prepare at-risk LPT preschoolers for elementary school entry.

Genetic variation in the cholinergic muscarinic-2 (M-2) receptor gene (CHRM2) has been associated with the risk for developing depression. We previously reported that M-2-receptor distribution volume (V-T) was reduced in depressed subjects with bipolar disorder (BD) relative to depressed subjects with major depressive disorder (MDD) and healthy controls (HCs). In this study, we investigated the effects of six single-nucleotide polymorphisms (SNPs) for CHRM2 on M-2-receptor binding to test the hypotheses that genetic variation in CHRM2 influences M-2-receptor binding and that a CHRM2 polymorphism underlies the deficits in M-2-receptor V-T observed in BD. The M-2-receptor V-T was measured using positron emission tomography and [F-18]FP-TZTP in unmedicated, depressed subjects with BD (n = 16) or MDD (n = 24) and HCs (n = 25), and the effect of genotype on V-T was assessed. In the controls, one SNP (with identifier rs324650, in which the ancestral allele adenine (A) is replaced with one or two copies of thymine (T), showed a significant allelic effect on V-T in the pregenual and subgenual anterior cingulate cortices in the direction AA < AT < TT. In contrast, in BD subjects with the TT genotype, V-T was significantly lower than in BD subjects with the AT genotype in these regions. The BD subjects homozygous for the T -allele also showed markedly lower V-T (by 27 to 37% across regions) than HCs of the same genotype. Post hoc analyses suggested that T homozygosity was associated with a more severe illness course, as manifested by lower socioeconomic function, poorer spatial recognition memory and a greater likelihood of having attempted suicide. These data represent novel preliminary evidence that reduced M-2-receptor V-T in BD is associated with genetic variation within CHRM2. The differential impact of the M-2-receptor polymorphism at rs324650 in the BD and HC samples suggests interactive effects with an unidentified vulnerability factor for BD. Molecular Psychiatry (2011) 16, 407-418; doi:10.1038/mp.2010.24; published online 30 March 2010

To determine obstetrician-gynecologists' practice patterns of cesarean delivery on maternal request (CDMR) following the 2006 National Institutes of Health (NIH) State-of-the-Science conference on this topic, and compare them with those in their practice prior to the conference.Questionnaires were mailed to 612 American College of Obstetricians and Gynecologists fellows who participated in a 2006 preconference survey, with 59% responding. The survey assessed demographic characteristics, practice, attitudes, knowledge regarding potential risks and benefits, counseling practices, and department policies with regards to CDMR.The majority of obstetrician-gynecologists in our sample continues to believe that a woman has the right to CDMR, but fewer than in 2006 would agree to perform this procedure. In general, obstetrician-gynecologists associate more risks and fewer benefits with CDMR than in 2006.Some physicians have shifted their perception of CDMR risks and benefits since the NIH State-of-the-Science conference; however, practice patterns have not changed significantly.

Objectives: Neuropsychological studies in subjects with bipolar disorder (BD) have reported deficits on a variety of cognitive measures. However, because the majority of subjects were medicated at the time of testing in previous studies, it is currently unclear whether the pattern of deficits reported is related to BD itself or to psychotropic medication. We addressed this issue by examining cognitive performance in a group of unmedicated, currently depressed subjects with BD. Methods: Forty-nine unmedicated subjects who met DSM-IV criteria for BD, depressed phase, and 55 control subjects participated in this study. Most patients were diagnosed with bipolar II disorder. Performance on emotion-dependent, or ‘hot’, and emotion-independent, or ‘cold’, cognitive tasks was assessed using tests from the Cambridge Neuropsychological Test Automated Battery. Results: The groups were well matched with respect to general intelligence and demographic variables. Deficits in the unmedicated depressed BD group were apparent on tests tapping ‘hot’ cognitive processing, for example the Cambridge Gamble task and the Probabilistic Reversal Learning task. However, other than a deficit on the Spatial Span test in the depressed BD subjects, the groups performed equivalently on most measures of ‘cold’ cognitive processing, for example visual memory, attention, and working memory. Conclusions: These data suggest that deficits on tests involving reward processing, short-term spatial memory storage, and sensitivity to negative feedback in depressed BD subjects represent an effect of the illness itself and not mood-stabilizing medication.

Introduction The dopamine-type-1 receptor has been implicated in major depressive disorder (MDD) by clinical and preclinical evidence from neuroimaging, post-mortem and behavioral studies. To date, however, selective in vivo assessment of D1-receptors has been limited to the striatum in MDD-samples manifesting anger attacks. We employed the PET radioligand, [11C]NNC-112, to selectively assess D1-receptor binding in extrastriatal and striatal regions in a more generalized sample of MDD-subjects. Methods The [11C]NNC-112 nondisplaceable binding-potential (BPND) was assessed using PET in 18 unmedicated, currently-depressed subjects with MDD and 19 healthy controls, and compared between groups using MRI-based region-of-interest analysis. Results The mean D1-receptor BPND was reduced (14%) in the left middle caudate of the MDD group relative to control group (p

Neuropsychological studies of major depressive disorder have described attentional biases for affectively laden stimuli, but these reports were based on measures obtained from medicated subjects. This study investigated performance of unmedicated depressed patients on the Affective Go/No-Go Task.Twenty depressed patients and 20 healthy comparison subjects, matched for age, gender, and IQ, performed the Affective Go/No-Go Task as well as tests of attention and memory for nonaffective stimuli.Depressed patients did not differ from healthy subjects on memory task performance, but they made more omission errors on the attention task. On the Affective Go/No-Go Task, depressed patients made more omission errors during happy than sad word blocks and required more time to respond to happy than to sad words. In contrast, healthy subjects required more time to respond to sad than to happy words.Unmedicated depressed patients do not show a pattern of generalized cognitive impairment but, rather, specifically display an attentional deficit and a mood-congruent bias toward salient stimuli.

Background Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Methods Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Results Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. Limitations The sample size was limited, however, all patients were drug-free at the time of testing. Conclusions The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.