Barry H. Cohen

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial:

Background: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. Methods: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. Results: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. Conclusions: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. Trial Registration: ClinicalTrials.gov Identifier: NCT00957359

Hyperdense middle cerebral artery sign: can it be used to select intra-arterial versus intravenous thrombolysis in acute ischemic stroke?

Background: Stroke patients with a hyperdense middle cerebral artery sign (HMCAS) may respond less favorably to intravenous (IV) thrombolysis. Objective: To compare outcomes of patients with and without early CT findings treated with IV versus intra-arterial (IA) recombinant tissue plasminogen activator (rtPA). Methods: Initial and 24-hour CT scans of the head were evaluated in 83 consecutive stroke patients (66 on IV rtPA, 17 on IA rtPA). Time permitting, a CT angiogram was performed immediately after the initial CT scan to ascertain major cerebral artery occlusion. Demographics and etiological stroke subtype, times to thrombolysis and CT scan, baseline (prethrombolysis) and 24-hour National Institutes of Health stroke scale (NIHSS) score, discharge NIHSS score and 90-day modified Rankin scale (mRS) were recorded. The initial CT of these patients was examined for early signs of stroke. The 24-hour scan was reviewed for the presence of infarct, hemorrhage and persistence of HCMAS. Results: A favorable outcome, indicated by a significant improvement in the discharge NIHSS score, was noted with IA rtPA, irrespective of the presence (p = 0.001) or absence (p = 0.01) of HCMAS. A less favorable outcome in discharge NIHSS score was noted with IV rtPA in patients with HCMAS (p = not significant) than those without the sign (p < 0.001). A similar proportion of patients with HCMAS exhibited a neurological improvement at 24 h as those without the sign in the IA rtPA group (p = 0.9). However, a smaller proportion of patients with HCMAS exhibited a neurological improvement at 24 h than those without the sign in the IV rtPA group (p = 0.005). The results were similar using 90-day mRS ≤1 as an indicator of significant persistent improvement (p = 1.0 for IA rtPA and 0.04 for IV rtPA group). Conclusions: In a small sample, patients with HMCAS appeared to respond better to IA than IV rtPA.

Muscle tension patterns during auditory attention

Although there is much evidence demonstrating muscle tension changes during mental work, there are few data concerning muscle tension patterns during effortful attention to simple sensory stimuli. In the present study, sensory attention was evoked by a pitch discrimination task at three levels of difficulty, with a digit retention task administered for comparison. Twenty-four females each performed both tasks at all levels of difficulty, while the EKG, and the corrugator supercilii, frontalis, lip, jaw, chin, and forearm area EMG were recorded. As expected, heart rate decreased significantly with increasing difficulty of the pitch task. A pattern of facial EMG responses accompanied the pitch task, which included significant increases in corrugator and frontalis, and decreases in the jaw as a function of difficulty, and time within trials. The tension pattern observed during sensory intake is discussed in terms of its relation to emotional expressions and motor theories of attention.

Evidence for image-scanning eye movements during transitive inference

Contrary to earlier work, recent studies have demonstrated a reduction in eye movements during the solution of tasks that seem to require visual imagery, relative to verbal tasks. The present study provides evidence that the nature of the visual imagery required by a task determines whether saccades are evoked and in which spatial pattern. In two experiments, subjects solved transitive inference problems with the relational terms left/right and above/below, while the horizontal and vertical EOG were recorded. Subjects made more horizontal and fewer vertical saccades while solving problems with the left/right terms than while solving identical problems with above/below. The results of silent counting tasks showed that the rate of subvocalization can also influence saccadic rate, especially in the horizontal plane, but cannot explain the eye-movement patterns observed during transitive inference. The results are discussed in terms of a motor theory of voluntary thinking.

Risk Factors for Progression of Aortic Atheroma in Stroke and Transient Ischemic Attack Patients

Background and Purpose— Aortic atheroma is an independent risk factor for stroke and undergoes temporal progression. Clinical and risk factor associations of such progression are unknown. Hyperhomocysteinemia has been linked with atherosclerosis, including that in the cerebral vasculature. This study investigated associations between elevated homocysteine levels and other stroke vascular risk factors and the risk of aortic atheroma progression in patients with cerebrovascular disease. Methods— Fifty-seven stroke and 21 transient ischemic attack patients underwent multiplanar transesophageal echocardiograms within 1 month of symptom onset and again at 9 months. Aortic atheroma was graded and stratified by use of existing criteria. Stroke risk factors; use of anticoagulant, antiplatelet, and hypolipidemic drugs; and clinical and etiological subtypes of stroke were recorded and compared in patients stratified for the presence or absence of aortic atheroma progression. Results— Of the 78, 29 (37%) progressed, 32 (41%) remained unchanged, and 17 (22%) regressed. Progression was most marked at the aortic arch (P =0.005), followed by the ascending segment (P <0.04). In nearly two thirds of the patients in whom aortic atheroma remained unchanged over 9 months, no atheroma was evident on baseline transesophageal echocardiogram. Only homocysteine levels ≥14.0 &mgr; mol/L (P =0.02), total anterior cerebral infarct (P =0.02), and large-artery atherosclerosis (P =0.005) significantly correlated with progression. Conclusions— Among vascular risk factors, elevated homocysteine levels are associated with aortic atheroma progression. Stroke and transient ischemic attack patients with aortic atheroma should undergo assessment of homocysteine levels, which, if elevated, may be treated with vitamins in an effort to arrest aortic atheroma progression.

Perceiver bias in the processing of human faces: neuropsychological mechanisms

Previous research has suggested that in face-to-face contexts perceivers are biased to judge the side of the posers face to their left as more similar to the full face than the side to their right. Traditional explanations of the perceiver bias have presumed that it is a visual field effect, with the side of the posers face falling within the perceivers left visual field dominating impressions of the full face. In this study, five experiments are reported. In the first experiment, the validity of the perceiver bias phenomenon was supported. The remaining experiments examined three alternative accounts of the neuropsychological processes that underlie the perceiver bias. No support was obtained for the visual field explanation, nor for an account of the bias as due to asymmetry in gaze patterns. Support was obtained for an account emphasizing a hemispatial bias in central processing. Despite equivalent intake of information from both sides of space, the brain may differentially weight information as a function of hemispatial origin. Practical and theoretical implications are discussed.

Anterior and posterior cingulate cortex volume in healthy adults: Effects of aging and gender differences

The cingulate cortex frequently shows gray matter loss with age as well as gender differences in structure and function, but little is known about whether individual cingulate Brodmann areas show gender-specific patterns of age-related volume decline. This study examined age-related changes, gender differences, and the interaction of age and gender in the relative volume of cingulate gray matter in areas 25, 24, 31, 23, and 29, over seven decades of adulthood. Participants included healthy, age-matched men and women, aged 20-87 (n=70). Main findings were as follows: (1) The whole cingulate showed significant age-related volume declines (averaging 5.54% decline between decades, 20s-80s). Each of the five cingulate areas also showed a significant decline with age, and individual areas showed different patterns of decline across the decades: Smaller volume with age was most evident in area 31, followed by 25 and 24. (2) Women had relatively larger cingulate gray matter volume than men overall and in area 24. (3) Men and women showed different patterns of age-related volume decline in area 31, at midlife and late in life. By delineating normal gender differences and age-related morphometric changes in the cingulate cortex over seven decades of adulthood, this study improves the baseline for comparison with structural irregularities in the cingulate cortex associated with psychopathology. The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function.

A preliminary look at the percentage of patients with Restless Legs Syndrome who also have Parkinson Disease, Essential Tremor or Tourette Syndrome in a single practice

Therapeutic studies, dopamine receptor blocking studies andPositronEmissionTomographic(PET)scanstudiesimplicatethe dopaminergic system in the pathogenesis of the RestlessLegsSyndrome(RLS)(Comella,2002;Eisensehret al.,2001;Michaud et al., 2002; Ruottinen et al., 2000; Staedt et al.,1993;Trenkwalderet al.,1999;Turjanskiet al.,1999;Walterset al.,1991).Itisthereforeofinteresttodeterminewhetherawell-proven dopaminergic disorder, Parkinson Disease (PD),predisposes to RLS, but results of such inquiries have beencontroversial (Krishnan et al., 2003; Ondo et al., 2002; Tanet al.,2002)andnotincompatiblewiththelargeprevalenceofRLSinthegeneralpopulation(Phillipset al.,2000).Therehavebeennopreviousstudieslookingatthereverseprevalence, i.e. the prevalence of PD in RLS. In the currentstudywetakeapreliminarylookatthepercentageofpatientswithRLSwhohavePDinasinglepractice.Tourette Syndrome (TS) is also responsive to eitherdopamineantagonistsoragonistsandRLShasbeenreportedinupto59%ofpatientswithTS(Lipinskiet al.,1997).Thesedata also suggest a dopaminergic hypothesis for RLS. Wethereforelookatthereverseprevalence,i.e.thatofTSinRLSintheaforementionedpractice.PreviousliteraturesuggestsanincreasedprevalenceofRLSin Essential Tremor (ET) (Larner and Allen, 1997) and asubset of patients with ET may be at increased risk for PD(Jankovic,2002).ThisindirectevidencealsosuggeststhatthedopaminesystemmayalsobeinvolvedinRLS.We,thereforealsoagainlookatthereverseprevalenceofETinRLSintheaforementionedpractice.Insummary,basedupontheaforementionedliterature,theproposedaimofthecurrentstudyistotakeapreliminarylookto see if RLS predisposes to other neurologic disordersinvolving the dopaminergic system. We want to emphasizethatthecurrentstudyisnotatrueprevalencestudysinceourpopulationis(a)small,(b)notpopulationbasedand(c)wedonothaveacontrolgroup.All RLS patients currently in the practice of a singleneurologist(ASW)withexpertiseinbothMovementandSleepDisorderswereexaminedforthepresenceofPD,TS,andETatthetimeofreferralforRLS.RLSwasdiagnosedbythefourcriteria established by the International Restless Legs Syn-dromeStudyGroup(Walters,1995).PDwasdiagnosedbythepresenceofbradykinesia,rigidity,restingtremor,andposturalinstability. TS was diagnosed by the presence of motor andvocal tics. ET was diagnosed by the presence of tremor thatwas predominantly a non-intention postural action type andthe absence of any features suggesting PD or cerebellar/spinocerebellardisease.OnlypatientswhowerereferredforRLSwereenteredintothestudy.RLSpatientswereexcludedwhowerereferredforPD,TS,orET.BecauseourdatasuggestedamildincreasedpercentageofPDinRLS,wealsoexcludedtwopatientswhowerereferredforRLSorsleepdisturbance,butwhohadPDatthe time of referral. This was done to exclude the possibilitythatapatientwithbothPDandRLSwouldbemorelikelytobereferredtousthanelsewhere,asweserveasareferralcenterfor both disorders. Patients with atypical parkinsonism werealso excluded. Two patients were also excluded when thediagnosis(PDorET)wasuncertain.Forpurposesofcalculation,thesurveywasconductedatasingle time point in November, 2001. For all three disordersstudied(PD,TS,andET),wecomparedthepercentagesofourRLSpatientswhohadthesedisorderstoprevalencesfromtheliteraturetakingageandsexintoaccount(Table1).Theexactbinomialtestwasusedforcomparison.Tourette’ssyndromeisofjuvenileonsetandtheprevalencerateisfairlystableacrossadultagegroups.Therefore,TSwasdeterminedforall118ofour adult RLS patients of any age in the study (Table1).Because of the tendency for PD to be of later onset andbecause most studies in the literature use an age base of>50years, we confined our survey for PD to our 85 RLSpatients>50yearsofage(Table1).Becauseofthetendencyfor ET to be of later onset and because most studies in theliterature use an age base of >60years, we confined oursurvey for ET to our 56 RLS patients >60years of age(Table1).After exclusion, four (three males, one female) or 4.7% ofour85(47females,38males)RLSpatients>50yearsofagedevelopedPDafterbeingreferredforRLS(Table1).Allhadat least stageII PD at the time of the survey indicating

Anxiety symptoms and disease severity in children and adolescents with Crohn disease.

Objectives: Children and adolescents diagnosed as having Crohn disease (CD), a type of inflammatory bowel disease (IBD), have increased vulnerability for anxiety symptoms that may be related to disease-related processes. The aims of this article are 3-fold: to report the proportion of pediatric patients with CD whose self-reported anxiety symptoms are indicative of distress, to describe the constellation of anxiety symptoms, and to examine the relation between anxiety and disease symptoms. Methods: Retrospective medical chart review was performed for 93 youths with CD (ages 9–18 years) who had completed the Screen for Child Anxiety Related Disorders during their gastroenterology visit. Medical records were reviewed for demographic and disease characteristics. the Harvey-Bradshaw Index (HBI) was used as a measure of CD activity. Results: Thirty percent of the youths reported experiencing elevated anxiety symptoms (Screen for Child Anxiety Related Disorder score >20), and 50% had scored above the cutoff in 1 or more anxiety domains, with school anxiety, general anxiety, and separation anxiety symptoms reported most frequently. Youth rated with moderate/severe disease activity on the HBI (n = 4) self-reported more anxiety symptoms compared with youth with inactive disease (n = 78, P = 0.03). Greater school anxiety was significantly associated with decreased well-being (P = 0.003), more abdominal pain (P < 0.001), and the number of loose stools (P = 0.01). Having extraintestinal symptoms was significantly associated with higher somatic/panic anxiety (P = 0.01). Conclusions: Implementing a brief anxiety screen in tertiary pediatric settings may be one approach to identify young patients with CD in distress. Health care providers should consider periodic assessment of school anxiety among youth with CD.

Dorso- and ventro-lateral prefrontal volume and spatial working memory in schizotypal personality disorder.

Schizotypal personality disorder (SPD) individuals and borderline personality disorder (BPD) individuals have been reported to show neuropsychological impairments and abnormalities in brain structure. However, relationships between neuropsychological function and brain structure in these groups are not well understood. This study compared visual-spatial working memory (SWM) and its associations with dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) gray matter volume in 18 unmedicated SPD patients with no BPD traits, 18 unmedicated BPD patients with no SPD traits, and 16 healthy controls (HC). Results showed impaired SWM in SPD but not BPD, compared with HC. Moreover, among the HC group, but not SPD patients, better SWM performance was associated with larger VLPFC (BA44/45) gray matter volume (Fishers Z p-values <0.05). Findings suggest spatial working memory impairments may be a core neuropsychological deficit specific to SPD patients and highlight the role of VLPFC subcomponents in normal and dysfunctional memory performance.