Psychotherapies for Panic Disorder: A Tale of Two Sites.

OBJECTIVE: To compare cognitive-behavioral therapy (CBT), panic-focused psychodynamic psychotherapy (PFPP), and applied relaxation training (ART) for primary DSM-IV panic disorder with and without agoraphobia in a 2-site randomized controlled trial. METHOD: 201 patients were stratified for site and DSM-IV agoraphobia and depression and were randomized to CBT, PFPP, or ART (19-24 sessions) over 12 weeks in a 2:2:1 ratio at Weill Cornell Medical College (New York, New York) and University of Pennsylvania ("Penn"; Philadelphia, Pennsylvania). Any medication was held constant. RESULTS: Attrition rates were ART, 41%; CBT, 25%; and PFPP, 22%. The most symptomatic patients were more likely to drop out of ART than CBT or PFPP (P = .013). Outcome analyses revealed site-by-treatment interactions in speed of Panic Disorder Severity Scale (PDSS) change over time (P = .013). At Cornell, no differences emerged on improvement on the primary outcome, estimated speed of change over time on the PDSS; at Penn, ART (P = .025) and CBT (P = .009) showed greater improvement at treatment termination than PFPP. A site-by-treatment interaction (P = .016) for a priori-defined response (40% PDSS reduction) showed significant differences at Cornell: ART 30%, CBT 65%, PFPP 71% (P = .007), but not at Penn: ART 63%, CBT 60%, PFPP 48% (P = .37). Penn patients were more symptomatic, differed demographically from Cornell patients, had a 7.2-fold greater likelihood of taking medication, and had a 28-fold greater likelihood of taking benzodiazepines. However, these differences did not explain site-by-treatment interactions. CONCLUSIONS: All treatments substantially improved panic disorder with or without agoraphobia, but patients, particularly the most severely ill, found ART less acceptable. CBT showed the most consistent performance across sites; however, the results for PFPP showed the promise of psychodynamic psychotherapy for this disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00353470.

Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of oxytocin as a putative biomarker or mediator of SA response. These pilot data generate testable hypotheses supporting an attachment domain underlying treatment-resistant anxiety, and new treatment strategies.

A golden experience: Fifty years of experience managing the frontal sinus.

OBJECTIVES/HYPOTHESIS: The frontal sinus is one of the most anatomically complex and inaccessible of the paranasal sinuses. As a result, surgeons have continually tried to improve surgical management of the frontal sinus. The senior author (c.w.g.) shares 50 years of experience managing the frontal sinus. DATA SOURCES: PubMed literature search. REVIEW METHODS: Review of the literature regarding landmark innovations in frontal sinus surgery. RESULTS: Open approaches established that the frontal sinus is accessible, and in certain circumstances, such as with large osteoma or papilloma, are still required. The endoscope changed the surgical landscape and allowed for greater finesse and decreased morbidity. Sinus balloon dilation is the newest change in frontal sinus management and shows promise in properly selected cases. CONCLUSION: Surgery of the frontal sinus continues to evolve and improve. Although there are new techniques, the older techniques are still pertinent.

Scientific Misconduct.

Scientific misconduct has been defined as fabrication, falsification, and plagiarism. Scientific misconduct has occurred throughout the history of science. The US government began to take systematic interest in such misconduct in the 1980s. Since then, a number of studies have examined how frequently individual scientists have observed scientific misconduct or were involved in it. Although the studies vary considerably in their methodology and in the nature and size of their samples, in most studies at least 10% of the scientists sampled reported having observed scientific misconduct. In addition to studies of the incidence of scientific misconduct, this review considers the recent increase in paper retractions, the role of social media in scientific ethics, several instructional examples of egregious scientific misconduct, and potential methods to reduce research misconduct.

Some revolutions in neuroscience.

In the long history of the study of the nervous system, there have been a number of major developments that involved radical and permanent changes in fundamental beliefs and assumptions about the nervous system and in tactics and strategies for studying it. These may be termed Revolutions in Neuroscience. This essay considers eight of these, ranging from the 6th century BCE to the end of the 20th century.

Alfred Russell Wallace and the evolution of the human mind.

Today the fame of Alfred Russell Wallace is as the independent codiscoverer with Charles Darwin of the origin of species by natural selection. Although they were on very amiable terms all their lives, 11 years after announcing their discovery, Wallace and Darwin had a major disagreement on the evolution of human cognition. The author considers how this divergence and other disagreements, particularly on the role of instinct, are related to the differences in their class backgrounds, education, experience with non-European cultures, and views on socialism, phrenology, mesmerism, and spiritualism.

Pediatric septoplasty.

This article discusses the importance of obtaining the correct anatomic location of a nasal obstruction in the pediatric patient, the relative and absolute indications for septoplasty, and surgical techniques. Because disruption of the developing nasal septum can alter craniofacial growth patterns, the current understanding of the effect of septoplasty on craniofacial growth is also discussed.

Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.

Three before their time: neuroscientists whose ideas were ignored by their contemporaries.

I discuss three examples of neuroscientists whose ideas were ignored by their contemporaries but were accepted as major insights decades or even centuries later. The first is Emanuel Swedenborg (1688-1772) whose ideas on the functions of the cerebral cortex were amazingly prescient. The second is Claude Bernard (1813-1878) whose maxim that the constancy of the internal environment is the condition for the free life was not understood for about 50 years when it came to dominate the development of modern physiology. The third is Joseph Altman (1925-) who overturned the traditional dogma that no new neurons are made in the adult mammalian brain and was vindicated several decades later.

Single neuron studies of inferior temporal cortex.

This paper reviews our experiments on the response properties of single neurons in inferior temporal (IT) cortex in the monkey that were carried out starting in 1965. It describes situational factors that led us to find neurons sensitive to images of faces and hands and summarizes the basic sensory properties of IT neurons. Subsequent developments on the cognitive properties of IT neurons and on imaging the responses of human temporal cortex to facial images are outlined. Finally, this paper summarizes recent results on fMRI imaging of the responses of temporal cortex to facial images.

Endoscopic localization of the anterior and posterior ethmoid arteries.

OBJECTIVES: Understanding the endoscopic locations of the anterior and posterior ethmoid arteries is important during endoscopic sinus or endoscopic skull base procedures so that these arteries can be avoided. Therefore, the objective of this study was to define the endoscopic locations of the ethmoid arteries. METHODS: Twenty-four cadaver heads were used to identify the endoscopic location of the ethmoid arteries via an external incision. An image guidance system was used to record the locations of these arteries. The anterior ethmoid artery was referenced to the axilla of the middle turbinate, and the posterior ethmoid artery to the anterior wall of the sphenoid sinus. The closest lamella to these arteries was identified. RESULTS: Forty-eight nasal cavities were dissected. The mean distance from the axilla to the anterior ethmoid artery was 17.5 mm. The anterior ethmoid artery was located immediately anterior to (31%), at (36%), or immediately posterior to (33%) the superior attachment of the basal lamella. The mean distance from the posterior ethmoid artery to the anterior ethmoid artery was 14.9 mm. The mean distance from the posterior ethmoid artery to the anterior wall of the sphenoid sinus was 8.1 mm. The posterior ethmoid artery was either anterior to (98%) or at (2%) the anterior face of the sphenoid sinus. CONCLUSIONS: Specific endoscopic anatomic relationships and measurements have been presented for the anterior and posterior ethmoid arteries.

Diminished adult neurogenesis in the marmoset brain precedes old age.

With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging. To investigate this possibility, young to middle aged adult common marmosets (Callithrix jacchus) were injected with BrdU and perfused 3 weeks later. The number of newly generated cells in the subgranular zone/granule cell layer of the dentate gyrus was significantly lower in older animals and decreased linearly with age. A similar age-related decline in new cells was observed in the subventricular zone but not in the hilar region of the dentate gyrus. These data demonstrate that a substantial decrease in neurogenesis occurs before the onset of old age in the adult marmoset brain, suggesting the possibility that similar alterations occur in the human brain.

Risk factors for recurrent sinus surgery in cystic fibrosis: review of a decade of experience.

BACKGROUND: Patients with cystic fibrosis (CF) who undergo endoscopic sinus surgery often require multiple revision procedures. Our objective was to identify risk factors for revision sinus surgery in patients with CF, to better identify this subset of patients who might be better suited for alternative interventions at their initial procedure. METHODS: Patients with CF who presented to our academic tertiary care sinus clinic between 1994 and 2003 were reviewed. Data were collected from CT scans using the Lund-Mackay scale. Data are collected on demographics, comorbidities, CF genotype, number and type of sinus surgeries, and pulmonary function tests. RESULTS: Eighty-one patients met inclusion criteria. Fifty patients were <18 years old at presentation. Forty-one patients were A508 homozygotes, 32 patients were A508 heterozygotes, and 5 patients were non-A508 heterozygotes. Respiratory comorbidities were asthma alone (28%) and aspirin triad (5%). Eighteen (22%) patients either smoked or lived with smokers. The mean Lund-Mackay score before the initial surgery was 16. Twenty patients were treated with medication only; 35 patients underwent 1 surgery; 14 patients underwent 2 surgeries; 8 patients underwent 3 surgeries; 2 patients underwent 4 surgeries; and 2 patients underwent 5 surgeries. Patients with higher Lund-Mackay scores at their initial CT were more likely to undergo repeat surgeries (p < 0.05). CONCLUSION: CF patients with high Lund-Mackay scores at their initial surgery are more likely to undergo several revision surgeries. These patients should be considered for more alternative initial management of their sinuses.

Suicide tourism in Manhattan, New York City, 1990-2004.

Suicide accounts for over 30,000 deaths per year in the United States and is associated with psychiatric illness and substance abuse. Research suggests a strong relationship between method of suicide and the lethal means that are readily available in one's community of residence. However, certain individuals may also seek the opportunity for suicide outside their proximal environment, often in well-known places. Whereas prevention efforts have been aimed at certain repeatedly used sites for suicide (i.e., Golden Gate Bridge), little research has studied "suicide tourism," the phenomenon of out of town accompanied by suicide. We collected data on all suicide deaths in New York City (NYC) between 1990 and 2004 from the Office of the Chief Medical Examiner of NYC. We examined trends and correlates of out-of-town residents who committed suicide in NYC. Manhattan accounted for 274 of the 407 nonresident suicides in NYC, which represented over 10% of all suicides committed in Manhattan. The most common methods of suicide for the Manhattan nonresidents were long fall, hanging, overdose, drowning, and firearms; the most common locations included hotels and commercial buildings, followed by outside locations such as bridges, parks, and streets. Nonresident victims tended to be younger, more often white and Asian and less often black and Hispanic than their residential counterparts. An analysis of nonresident suicides in Manhattan revealed that it is a location where individuals travel and take their lives, often by similar means and in similar locations. A comparison with residential suicide implied that a different type of individual is at risk for nonresidential suicide, and further research and prevention efforts should be considered.

The discovery of motor cortex and its background.

In 1870 Gustav Fritsch and Edvard Hitzig showed that electrical stimulation of the cerebral cortex of a dog produced movements. This was a crucial event in the development of modern neuroscience because it was the first good experimental evidence for a) cerebral cortex involvement in motor function, b) the electrical excitability of the cortex, c) topographic representation in the brain, and d) localization of function in different regions of the cerebral cortex. This paper discusses their experiment and some developments in the previous two centuries that led to it including the ideas of Thomas Willis and Emanuel Swedenborg, the widespread interest in electricity and the localizations of function of Franz Joseph Gall, John Hughlings Jackson, and Paul Broca. We also consider the subsequent study of the motor cortex by David Ferrier and others.

Initial surgical treatment for chronic frontal sinusitis: a pilot study.

OBJECTIVES: The initial surgical treatment for chronic frontal sinusitis is not well defined. Our objective was to determine the effectiveness of anterior ethmoidectomy for chronic frontal sinusitis. METHODS: Patients with chronic frontal sinusitis who underwent anterior ethmoidectomy as initial surgical treatment were reviewed. Data were collected from computed tomography scans with use of the Lund-Mackay scale. Data on demographics, comorbidities, management, postoperative recovery, and follow-up were collected. RESULTS: Seventy-seven patients representing 121 diseased frontal sinuses met the inclusion criteria. The respiratory comorbidities were asthma alone (8.3%), asthma and polyps (6.6%), aspirin triad (5.8%), and cystic fibrosis (0.8%). Nineteen of 121 frontal sinuses (15.7%) belonged to smokers. Fourteen of 121 frontal sinuses (11.5%) exhibited postoperative evidence of disease. Of these 14 frontal sinuses, 10 (8.3%) underwent revision surgery. Frontal sinuses of patients with aspirin triad, with both nasal polyposis and asthma, or with inter-frontal sinus septal cells were more likely to fail Draf I surgery (p < .05). CONCLUSIONS: Anterior ethmoidectomy for drainage of frontal sinuses appears to be effective initial surgical treatment for chronic frontal sinusitis. Patients with aspirin triad, both asthma and polyposis, or inter-frontal sinus septal cells are more likely to fail this procedure.

Cocaine- and opiate-related fatal overdose in New York City, 1990-2000.

BACKGROUND: In New York City (NYC), the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990-2000. METHODS: Data were collected from the NYC Office of the Chief Medical Examiner (OCME) on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000 (n = 8,774) and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. RESULTS: Overall, among decedents ages 15-64, 2,392 (27.3%) were attributed to cocaine only and 2,825 (32.2%) were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62-0.82), Black (OR = 4.73, 95% CI 4.08-5.49) or Hispanic (OR = 1.51, 95% CI 1.29-1.76), an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06-1.68), having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44-0.56) and older age (55-64) (OR = 2.53 95% CI 1.70-3.75)). CONCLUSION: As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical.

Steroid injection for sinonasal polyps: the University of Virginia experience.

BACKGROUND: Sinonasal polyps are treated with topical steroids, systemic oral steroids, surgical excision, and intrapolyp steroid injection. Use of steroid injection is not widespread because of reported complications. The objective of this study was to evaluate the complications of intrapolyp steroid injections and compare it to the complications of surgical removal of polyps. METHODS: All patients seen between 1994 and 2003 with a diagnosis of nasal polyps were reviewed retrospectively. Demographics, complications, follow-up, and comorbidities were collected. Frequency of each treatment modality used and complications of each treatment were compared. RESULTS: Three hundred fifty-eight patients were in the study with a mean follow-up of 30 months. Respiratory comorbidities were asthma alone (35%), aspirin triad (16%), and cystic fibrosis (15%). Other comorbidities were smokers (21%). Treatment modalities were medical treatment alone (14%); medical treatment and steroid injections (19%); medical treatment and surgery (33%); and medical treatment, injections, and surgery (34%). Patients who underwent injection had fewer surgeries (p < 0.001). There was 1 minor complication associated with 1495 injections and 11 major and 16 minor complications associated with the 310 surgeries. The differences in complication rates were statistically significant (p < 0.001). There was no significant difference in demographics, follow-up, or comorbidities between patients who received injections and patients who underwent surgery. CONCLUSION: Intrapolyp steroid injection is associated with a significantly lower rate of complication than is surgical excision of sinonasal polyps. Steroid injection also may decrease the need for further surgical intervention of polyps.