Towards a therapeutic window of D2/3 occupancy for treatment of psychosis in Alzheimer's disease, with [18F]fallypride positron emission tomography.

OBJECTIVE: Dopamine D2/3 receptor positron emission tomography tracers have guided antipsychotic prescribing in young people with schizophrenia by establishing a 'therapeutic window' of striatal D2/3 receptor occupancy. Older people, particularly those with dementia, are highly susceptible to motor side effects and may benefit from the appropriate application of imaging techniques. The study aimed to adapt [18F]fallypride imaging for use in occupancy studies in Alzheimer's disease (AD) and to investigate whether data acquisition could be made more tolerable by piloting the protocol in a small sample. METHODS: Six participants with AD (three men; 85.0 ± 5.6 years old; MMSE = 16.0 ± 2.4) were recruited prior to commencing amisulpride for the treatment of psychosis and associated agitation. [18F]fallypride binding potential (BPND ) was determined using an interrupted scanning protocol at baseline (n = 6) and after 27.0 ± 6.1 days of amisulpride (25-50 mg) treatment (n = 4). D2/3 occupancy was calculated by percentage reduction in BPND between scanning sessions. Image data were re-analysed after reducing individual sampling times to 20 min. RESULTS: The protocol was tolerated well, apart from the final (40 min) session of the post-treatment scan in one participant. Higher occupancies were achieved in the striatum (caudate 47-70%, putamen 31-58%) and thalamus (54-76%) than in the inferior temporal gyrus (27-43%). There was high agreement between occupancy values derived using longer and shorter sampling times (mean absolute difference 6.1% in the inferior temporal gyrus; <2% all other regions). CONCLUSIONS: The protocol is feasible for use in AD and represents the first step towards establishing dose-occupancy relationships across older clinical populations.

Trends in use of electroconvulsive therapy in South London from 1949 to 2006.

OBJECTIVES: Electroconvulsive therapy (ECT) remains the most acutely effective treatment for severe depression, but its use has declined since its introduction more than 70 years ago. To provide some historical perspective on changes in ECT practice, the objective of the present study was to identify trends in ECT practice in selected teaching hospitals in South London, UK, between 1949 and 2006. METHODS: Annual rates of ECT for 1949-1970 were estimated from the contemporary hospital reports of the Maudsley and Bethlem Royal hospitals in South London, UK. Case notes were also retrospectively reviewed to calculate annual rates of ECT administration and extract demographic and clinical information for approximately every 5 years between 1987 and 2006. RESULTS: The annual rate of ECT peaked at 35% of total admission in 1956 and declined gradually thereafter to 10.8% by 1970 and fell below 2.2% from 1991 onward. Depressed and female patients were more likely to receive ECT. Compared to previous years, patients were more severely ill and treatment resistant in 2006, whereas ethnic minorities made up 30% of patients receiving ECT compared to approximately 14% in the preceding years. CONCLUSIONS: Currently, ECT seems to be provided increasingly late in more severe illness episodes. The ethnicity of patients receiving ECT in South London may be becoming more representative of the background population, but ECT is being used relatively more frequently for nonaffective disorders in ethnic minorities.

Comparison of electroconvulsive therapy practice between London and Bengaluru.

OBJECTIVE: To compare electroconvulsive therapy (ECT) practice between London in the United Kingdom and Bengaluru in India. METHODS: A retrospective case note study was conducted to compare patterns of referrals for ECT in university teaching hospitals in London (n = 46) and Bengaluru (n = 345) during a 1-year period. Further comparison of ECT practice was made for a consecutive series of depressed patients between London (n = 104) and Bengaluru (n = 125). RESULTS: The rates of ECT referral were 0.9% of total annual admissions at the London site and 8.2% at the Bengaluru site. At the Bengaluru site, a higher proportion of patients were referred for ECT with a diagnosis of schizophrenia (P < 0.0001). Compared to the Bengaluru sample, depressed patients treated with ECT in London (n = 104) were older with more treatment resistance (P < 0.0001), had longer inpatient stays, and were less responsive to ECT. CONCLUSIONS: The practice of ECT differed substantially between the London and Bengaluru sites. The relatively limited use of ECT in London reflects local treatment guidelines and may reflect the stigma associated with ECT. Electroconvulsive therapy is more widely used in Bengaluru with good outcomes. Further cross-cultural research is required to study the reasons for such contrasting practices and what constitutes the optimal practice of ECT for health systems in different countries.

Methohexitone, propofol and etomidate in electroconvulsive therapy for depression: a naturalistic comparison study.

BACKGROUND: Methohexitone has been the most widely used anaesthetic for electroconvulsive therapy (ECT). However, recent scarcity and erratic availability has led to use of other anaesthetics with differing effects upon ECT. We compared treatment parameters and response to ECT in patients anaesthetised with different anaesthetics in a routine clinical setting. METHODS: This was a naturalistic retrospective casenote analysis of 81 consecutive courses of ECT (total 659 treatments) for major depression. RESULTS: Three anaesthetics were compared: methohexitone (n=34), propofol (n=13) and etomidate (n=34). Mean seizure duration was lowest (p<0.0001) for propofol. However, mean stimulus charge was highest in the propofol group (p<0.0001) who required a greater increase in stimulus charge during the course of treatment and also experienced a greater proportion of failed seizures (

Capturing complexity: field-testing the use of 'structure from motion' derived virtual models to replicate standard measures of reef physical structure.

Reef structural complexity provides important refuge habitat for a range of marine organisms, and is a useful indicator of the health and resilience of reefs as a whole. Marine scientists have recently begun to use 'Structure from Motion' (SfM) photogrammetry in order to accurately and repeatably capture the 3D structure of physical objects underwater, including reefs. There has however been limited research on the comparability of this new method with existing analogue methods already used widely for measuring and monitoring 3D structure, such as 'tape and chain rugosity index (RI)' and graded visual assessments. Our findings show that analogue and SfM RI can be reliably converted over a standard 10-m reef section (SfM RI = 1.348 × chain RI-0.359, r 2 = 0.82; and Chain RI = 0.606 × SfM RI + 0.465) for RI values up to 2.0; however, SfM RI values above this number become increasingly divergent from traditional tape and chain measurements. Additionally, we found SfM RI correlates well with visual assessment grades of coral reefs over a 10 × 10 m area (SfM RI = 0.1461 × visual grade + 1.117; r 2 = 0.83). The SfM method is shown to be affordable and non-destructive whilst also allowing the data collected to be archival, less biased by the observer, and broader in its scope of applications than standard methods. This work allows researchers to easily transition from analogue to digital structural assessment techniques, facilitating continued long-term monitoring, whilst also improving the quality and additional research value of the data collected.

Cost-effectiveness of transcranial magnetic stimulation vs. electroconvulsive therapy for severe depression: a multi-centre randomised controlled trial.

BACKGROUND: Electroconvulsive therapy (ECT) has a long history of use in treating depression. Repetitive transcranial magnetic stimulation (rTMS) has been introduced more recently to the treatment spectrum. Its cost-effectiveness has not been explored. METHOD: Forty-six right-handed people with severe depressive episodes referred for ECT were randomised to receive either ECT twice weekly or rTMS on consecutive weekdays. Health and other service use were recorded for retrospective periods of 3 months prior to initiation of treatment and during the 6 months following the end of allocated treatment. Costs were calculated for the treatment period and the subsequent 6 months, and comparisons made between groups after adjustment for any baseline differences. Cost-effectiveness analysis was conducted with incremental change on the 17-item Hamilton Rating Scale for Depression (HRSD) as the primary outcome measure, and quality-adjusted life years (based on SF6D-generated utility scores with societal weights) as secondary outcome, cost-effectiveness acceptability curves plotted. RESULTS: Based on the HRSD scores and other outcome measures, rTMS was not as effective as ECT. The cost of a single session of rTMS was lower than the cost of a session of ECT, but overall there were no treatment cost differences. In the treatment and 6-month follow-up periods combined, health and other service costs were not significantly different between the two groups. Informal care costs were higher for the rTMS group. Total treatment, service and informal care costs were also higher for the rTMS group. The cost-effectiveness acceptability curves indicated a very small probability that decision-makers would view rTMS as more cost-effective than ECT. LIMITATIONS: Small sample size, some sample attrition and a relatively short follow-up period of 6 months for a chronic illness. Productivity losses could not be calculated. CONCLUSIONS: ECT is more cost-effective than rTMS in the treatment of severe depression.

A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been reported to be as effective as electroconvulsive therapy (ECT) for major depression. The authors conducted a multicenter randomized, controlled trial to test the equivalence of rTMS with ECT. METHOD: Forty-six patients with major depression referred for ECT were randomly assigned to either a 15-day course of rTMS of the left dorsolateral prefrontal cortex (N=24) or a standard course of ECT (N=22). The primary outcome measures were the score on the 17-item Hamilton Depression Rating Scale (HAM-D) and the proportion of patients with remissions (Hamilton score,

Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study.

BACKGROUND: Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication. Using repetitive transcranial magnetic stimulation (rTMS) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms. METHODS: We performed a double-blind randomized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia. 17 right-handed patients with prominent negative symptoms (PANSS negative subscore >or=20) were randomized to a 10 day course of real (n=8) or sham rTMS (n=9) applied to the left dorsolateral prefrontal cortex (20 trains per day, 10 s treatment at 10 Hz, 50 s inter-train interval, 110% of motor threshold). The primary outcome measure was PANSS negative symptom score. Secondary outcomes included mood, cognitive function and side-effects. Patients were followed-up two weeks afterwards. The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA. RESULTS: All subjects completed the treatment course. There was no significant difference between the two groups on PANSS negative symptom scores at either time point. At the end of treatment, no subjects in either group met the criterion for response (i.e. a 20% reduction in baseline PANSS negative symptom score). The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up. CONCLUSIONS: Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up.

Microplastic pollution identified in deep-sea water and ingested by benthic invertebrates in the Rockall Trough, North Atlantic Ocean.

Microplastics are widespread in the natural environment and present numerous ecological threats. While the ultimate fate of marine microplastics are not well known, it is hypothesized that the deep sea is the final sink for this anthropogenic contaminant. This study provides a quantification and characterisation of microplastic pollution ingested by benthic macroinvertebrates with different feeding modes (Ophiomusium lymani, Hymenaster pellucidus and Colus jeffreysianus) and in adjacent deep water > 2200 m, in the Rockall Trough, Northeast Atlantic Ocean. Despite the remote location, microplastic fibres were identified in deep-sea water at a concentration of 70.8 particles m-3, comparable to that in surface waters. Of the invertebrates examined (n = 66), 48% ingested microplastics with quantities enumerated comparable to coastal species. The number of ingested microplastics differed significantly between species and generalized linear modelling identified that the number of microplastics ingested for a given tissue mass was related to species and not organism feeding mode or the length or overall weight of the individual. Deep-sea microplastics were visually highly degraded with surface areas more than double that of pristine particles. The identification of synthetic polymers with densities greater and less than seawater along with comparable quantities to the upper ocean indicates processes of vertical re-distribution. This study presents the first snapshot of deep ocean microplastics and the quantification of microplastic pollution in the Rockall Trough. Additional sampling throughout the deep-sea is required to assess levels of microplastic pollution, vertical transportation and sequestration, which have the potential to impact the largest global ecosystem.

SCUBA divers as oceanographic samplers: The potential of dive computers to augment aquatic temperature monitoring.

Monitoring temperature of aquatic waters is of great importance, with modelled, satellite and in-situ data providing invaluable insights into long-term environmental change. However, there is often a lack of depth-resolved temperature measurements. Recreational dive computers routinely record temperature and depth, so could provide an alternate and highly novel source of oceanographic information to fill this data gap. In this study, a citizen science approach was used to obtain over 7,000 scuba diver temperature profiles. The accuracy, offset and lag of temperature records was assessed by comparing dive computers with scientific conductivity-temperature-depth instruments and existing surface temperature data. Our results show that, with processing, dive computers can provide a useful and novel tool with which to augment existing monitoring systems all over the globe, but especially in under-sampled or highly changeable coastal environments.

Effect of left prefrontal repetitive transcranial magnetic stimulation on food craving.

BACKGROUND: Dysfunction of the prefrontal cortex is implicated in craving for drugs and food. This study explores the effect of prefrontal cortex stimulation on food craving. METHODS: In a randomized double-blind parallel group study, 28 women, who reported frequent cravings for food were exposed to foods that typically elicit strong cravings before and after a single session of real or sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex at an intensity of 110% individual motor threshold. RESULTS: Self-reported food craving during exposure to the experimental foods remained stable before and after real stimulation compared with sham stimulation in which cravings increased over the experimental session. Consumption of snack foods within a 5-min period after stimulation did not differ between groups. CONCLUSIONS: Prefrontal stimulation inhibits the development of craving. A longer period of observation is necessary to establish whether there is an effect on food consumption.

Repetitive transcranial magnetic stimulation reduces cue-induced food craving in bulimic disorders.

BACKGROUND: Craving or the "urge to consume" is a characteristic of bulimic eating disorders and addictions. Dysfunction of the dorsolateral prefrontal cortex (DLPFC) is associated with craving. We investigated whether stimulation of the DLPFC reduces food craving in people with a bulimic-type eating disorder. METHODS: Thirty-eight people with bulimic-type eating disorders were randomly allocated to receive one session of real or sham high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC in a double-blind procedure. Outcome measures included self-reported food craving immediately after the stimulation session and frequency of bingeing over a 24-hour follow-up period. RESULTS: Compared with sham control, real rTMS was associated with decreased self-reported urge to eat and fewer binge-eating episodes over the 24 hours following stimulation. CONCLUSIONS: High-frequency rTMS of the left DLPFC lowers cue-induced food cravings in people with a bulimic eating disorder and may reduce binge eating. These results provide a rationale for exploring rTMS as a treatment for bulimic eating disorders.