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Cannabis is the world's most commonly used illicit substance. Whilst its effects on perception are well documented, little is known about the neural basis of these effects and how they are modulated by two of cannabis sativa's most abundant active ingredients, Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).
We used fMRI to assess the effects of THC and CBD on brain activation during a simple visual and auditory stimulation paradigm in healthy volunteers.
Fourteen right handed male subjects were scanned on 3 occasions. Identical 10mg THC, 600mg CBD and placebo capsules were allocated in a balanced double blinded pseudorandomised crossover design.
Ingestion of THC and CBD led to reliable increases in plasma levels of each substance and for THC concomitant increases in anxiety, intoxication and positive psychotic symptoms; CBD and placebo caused no significant symptoms. Visual and auditory stimulation led to robust activations in occipital and temporal cortices respectively under placebo conditions. Administration of THC led to decreased activation in primary sensory cortices relative to placebo whilst CBD led to an increase in activation in right temporal regions during auditory stimulation and right striate cortex activation during visual stimulation. THC mediated reduction of activation in this area during auditory stimulation correlated with a concomitant rise in psychotic symptoms.
These data indicate that the different psychoactive constituents of cannabis have dissociable effects on sensory processing, often in opposite directions
Medication adherence is a matter of relevance for early treatment of psychotic disorder.
To understand pattern of medication adherence in this population and factors influencing.
To understand the antipsychotic adherence pattern in early stages of psychotic disorder and to identify factors that influence.
Natural observation study of 136 patients of first-episode psychosis presenting to Early intervention service in multicultural South London. Data derived from case notes and interviews using standard rating scales for first 18 months.
Only 39% of patients (n=50) were 100% time adherent with antipsychotic medication in the first month (rest were 83%). Patients using illicit substances were less likely 100% adherent (Pearson χ2= 13.1, df=1,p=0.001). Caucasian patients were more likely to be fully adherent in the first month than Ethnic minority patients (Pearson χ2= 7.5, df=1, p=0.009). During the follow-up period about 57% patients had weeks of not taking antipsychotic, mostly after recovery from first episode. Ethnicity (Pearson χ2=4.5, df=1, p=0.05) and experience of extrapyramidal side-effect (Pearson χ2= 5.6, df=1, p=0.02) were associated with this gap. Involvement of a carer in treatment was associated with better (100%) adherence during follow-up (Pearson χ2= 4.9, df=1,p=0.03).
Interventions in early stages of psychosis should focus on therapies involving carers/ families and giving attention to illicit substances use and delivered in way relevant to the local ethnic population. Also antipsychotics chosen carefully, using a lower dose and actively looking for emergence of side-effects.
Current guidelines on management of first-episode mania recommend augmenting with Valproate or other mood-stabilisers if antipsychotic proves ineffective.
To study if timing of starting mood-stabiliser augmentation would influence recovery outcomes in first-episode mania with psychosis.
To study how ‘time to start augmentation’ is related to ‘time to recovery’ and ‘hospital stay’
11 patients with first-episode mania with psychosis (FEM-P) presenting to a specialist early-intervention service in South London, part of naturalistic study of 150 cases of first-episode psychosis. Patients interviewed using the standard rating scales. Other details of treatment obtained from systematic review of case-notes covering 18 months. Operational criteria defined recovery. Correlation and regression analysis carried out to test hypotheses using SPSS-19. Set of predictor variables such as age, DUP, type of antipsychotic, substance misuse used in regression.
All 11 patients started on atypical-antipsychotic (Olanzapine 5, Risperidone 6). 9 patients required augmentation with Valproate, with a mean time of 74 days (s.d.=91) to start augmentation. The mean time to first recovery was 86 days (s.d.=39). Regression analysis with ‘time to recovery’ as dependant variable and ‘time to start augmentation’ as covariate with other predictor variables yielded significant relationship (F=9.2, t=3.1, p=0.02, CI 0.07-0.56). Also time to ‘start augmentation’ showed correlation at trend-level with ‘hospital stay’ (mean= 40, s.d.= 40.3) (Pearson correlation =0.57, p=0.09).
When there is insufficient response with antipsychotic in treatment of FEM-P, augmentation with mood-stabiliser such as Valproate without delay can shorten time to recovery and hospital stay.
Discontinuation of antipsychotic medication occurs in 40-55% of patients following first episode psychosis. It is only recently that the impacts of short periods of nonadherence in first episode psychosis are being understood.
To study the impact of short periods of interruptions in antipsychotic treatment in first episode psychosis.
127 consecutive cases of first episode non-affective psychosis (F20-29 ICD-10) presenting to a specialist first episode psychosis service in South East London. Patients were interviewed at baseline by a researcher using the PANSS and other symptom scales at the start and at 18 months. Clinical notes were analysed using operational criteria set for recovery, exacerbation and relapse. Medication utilisation assessed using patient report and clinical notes to identify interruptions of ≥ 1 month in treatment.
58% (n = 73) patients had a treatment break due to non-adherence in the follow up period. 18 patients had treatment break before first recovery and their time to recovery was significantly prolonged than those without a break (mean 210 days Vs 127 days, t = 2.9, P = 0.01). The odds of relapse was 5.4 for those with treatment break (≥ 1 month) compared to those without break (p = 0.0001, CI 2.1–11). About 40% relapses occurred in first month of treatment break and mean time to relapse was 3 months.
Antipsychotic treatment should be uninterrupted in the early stages of psychosis and periods of even short breaks in treatment carries risk of adverse outcome like longer time to recover and high risk of immediate relapse.
The definition of ultra-high risk (UHR) for psychosis was derived from community-based help-seeking populations. Prisoners have high rates of psychosis and other severe mental health (MH) problems. They also have high rates of risk factors for psychiatric morbidity and yet they are among the populations who are less likely to seek help in the community. Despite a policy of equivalence of care for individuals in prison there are no early intervention services for psychosis in prisons in the UK. This was a study exploring feasibility of introducing such a service into a local London prison. This paper discusses the differences in MH profile of prisoners who met criteria for at-risk mental state compared with those who did not.
A two-stage procedure was used. Participants in a local London prison were routinely screened in the first week of arrival in prison with the Prodrome Questionnaire – Brief Version (PQ-B; Loewy et al. 2011). Those that screened positive as well as a small sample of those who screened negative underwent a further semi-structured assessment to see whether they met criteria for UHR state. Data on self-harm and suicide attempt, family psychiatric history, and anxiety and depression was also collected.
A total of 891 prisoners were screened, 44% of whom screened positive. A total of 354 underwent second stage assessment, 60 of whom had screened negative. Four groups were identified: those that had no MH problems, a group experiencing First Episode Psychosis, those at UHR of psychosis and a group with other MH problems. The UHR state and Psychotic groups had very similar MH profiles of symptoms and distress. Prisoners with no MH problems were at the other end of the spectrum with few symptoms and little distress. The Other group fell in between this group and the psychotic spectrum group in terms of symptomology and distress.
This study is the first to examine risk for psychosis in an adult male prison population. We identified a broad spectrum of MH disorder for which there is little current service provision in prisons. Screening early in the custodial process has the potential to identify unmet MH need and has implications for keeping individuals safe in custody. A long-term strategic approach is required to address MH need in prisons.
Cognitive models suggest that auditory verbal hallucinations arise through defective self-monitoring and the external attribution of inner speech. We used a paradigm that engages verbal self-monitoring (VSM) to examine whether this process is impaired in people experiencing prodromal symptoms, who have a very high risk of developing psychosis.
We tested 31 individuals with an At-Risk Mental State (ARMS) and 31 healthy volunteers. Participants read single adjectives aloud while the source and pitch of the online auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard (Self/Other/Unsure). Response choice and reaction time were recorded.
When reading aloud with distorted feedback of their own voice, ARMS participants made more errors than controls (misidentifications and unsure responses). ARMS participants misidentified the source of their speech as ‘Other’ when the level of acoustic distortion was severe, and misidentification errors were inversely related to reaction times.
Impaired VSM is evident in people with an ARMS, although the deficit seems to be less marked than in patients with schizophrenia. Follow-up of these participants may clarify the extent to which the severity of this impairment predicts the subsequent onset of psychosis and development of positive symptoms.
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