Cannabis use in patients with early psychosis is associated with alterations in putamen and thalamic shape.

Around half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP - C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C - C = 22) cannabis use. We undertook vertex-based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p < .05. We adjusted analyses for age, sex, tobacco and alcohol use. The putamen (bilaterally) and the right thalamus showed regional enlargement in PwP + C versus PwP - C. There were no areas of regional deflation. There were no significant differences between C + C and C - C. Cannabis use in participants with psychosis is associated with morphological alterations in subcortical structures. Putamen and thalamic enlargement may be related to compulsivity in patients with a history of cannabis use.

Abnormal Bodily Phenomena in First Episode Psychosis: A Preliminary Exploratory Cohort Study.

Schizophrenia patients frequently display an array of abnormal bodily phenomena (ABPs). There is literature to suggest that the presence of ABPs may be representative of a fundamental disruption of the embodied and prereflexive state of selfhood and hence be relevant for the development of schizophrenia spectrum disorders. ABPs have been considered as trait features of vulnerability to psychosis and may have value as potential markers for early detection, target symptoms for prevention and predictors of clinical outcomes. This longitudinal cohort study aimed to explore: (1) the prevalence of ABPs in first episode psychosis, (2) their longitudinal stability, (3) how ABPs compare with data from patients with enduring psychosis, and (4) how aspects of disorders of self-experience (DSEs) and ABPs and the corresponding instruments relate to each other. Sixteen patients were recruited from an early intervention in psychosis service. They were assessed with a series of structured and semi-structured interviews at point of entry, after 6 months and 12 months of follow-up. A variety of ABPs and DSEs were displayed in all study subjects, associated with high levels of core psychotic symptoms and reduced with treatment over time. Compared with findings of both acute and chronic schizophrenia patients, the prevalence of ABPs seems to be representative of severity and acuteness of the illness. Two factors were identified with stable trait characteristics and might be of predictive value for the course of the illness. Further studies with bigger samples are needed to further test the value of ABPs as early markers of detection and predictors of clinical course. The association between DSEs and ABPs warrants further investigation.

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.

Eye movements in patients in early psychosis with and without a history of cannabis use.

It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p < 0.001), patient effect (χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76-0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.

Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis.

The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.

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.