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Several studies have independently suggested that patients with schizophrenia are more likely to have an enlarged cavum septum pellucidum (CSP) and an absent adhesio interthalamica (AI), respectively. However, neither finding has been consistently replicated and it is unclear whether there is an association between these two midline brain abnormalities. Thus, we compared the prevalence of absent AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia and 38 healthy controls using magnetic resonance imaging (MRI). There were no between group differences in the presence or volume of CSP; however, an enlarged CSP was commoner among patients than controls. There was also a positive correlation between CSP ratings and volumes. No differences in the presence or absence of the AI were found between patients and controls; however, an absent AI was commoner in male patients with schizophrenia than females. There was absolutely no overlap between the presence of a large CSP and an absence of AI. In conclusion, our findings are in line with several case series and other MRI investigations that have shown a higher incidence of putatively developmental brain abnormalities in patients with schizophrenia, particularly in males, and support the neurodevelopmental model of this disorder.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
The study sought to examine the neurophysiological effects of cannabidiol (CBD) on the emotional processing using functional Magnetic Resonance Imaging (fMRI).
Fifteen healthy male participants (age range 18-35) with a lifetime exposure to cannabis of 15 times or less were recruited in a double blind event-related fMRI design. Prior to each scanning session, participants were given an oral dose of either 600mg CBD or a placebo. The blood levels of drugs were monitored via an intravenous line, while systolic and diastolic blood pressure and heart rate (beats per minute) were recorded manually. During the scan, subjects were presented with 10 different facial identities, each identity expressing 50% or 100% intensities of fear or a neutral expression. Neuropsychological performance and symptoms ratings were recorded at baseline, immediately before scanning (1 hr), immediately after scanning (2 hr), and one hour post scanning (3 hr).
CBD had no significant effect on the gender discrimination task. Reaction times were significantly faster when processing 100% fearful faces than compared to 50% fearful and neutral faces. CBD had a significant effect on brain activation in response to faces with emotional expressions, decreasing activation in the right posterior cingulate gyrus and in the right cerebellum, when compared to placebo. Furthermore, a significant interaction effect was observed. In the right cingulate gyrus CBD attenuated activation during the processing of intense fearful faces but had no effect of neural response to neutral or mild fearful faces.
CBD significantly modulates the neurophysiological response associated with anxiety.
This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.
Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.
Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.
These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.
While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear.
To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor.
Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months.
People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year.
It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.
In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear.
To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis.
Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist–hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients.
A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. β = 0.36, P = 0.01), higher leptin levels (Std. β = 0.34, P = 0.02), higher waist–hip ratio (Std. β = 0.32, P = 0.04) and lower testosterone levels (Std. β = −0.44, P = 0.002). In contrast, in females, SFQ scores were not associated with any of these factors.
While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist–hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.
Total laryngectomy is considered the primary treatment modality for advanced laryngeal carcinoma. This study assessed the quality of life in patients after total laryngectomy, and ascertained whether quality of life is affected by socioeconomic status.
Forty-seven patients (20 state- and 27 private-sector) who underwent total laryngectomy between 1998 and 2014 responded to the University of Washington Quality of Life Questionnaire, the Voice-Related Quality of Life Questionnaire and the Brief Illness Perception Questionnaire.
Significant differences were found in socioeconomic status between state- and private-sector patients (p < 0.001). There was no significant difference in overall quality of life between groups (p = 0.210). State-sector patients scored significantly higher Voice-Related Quality of Life Questionnaire scores (p = 0.043). Perception of illness did not differ significantly between groups.
Overall quality of life after total laryngectomy appears to be similar in patients from different socioeconomic backgrounds. However, patients from lower socioeconomic circumstances have better voice-related quality of life. The results illustrate the importance of including socioeconomic status when reporting voice outcomes in total laryngectomy patients.
Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.
We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22).
Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC.
These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.
Introduction: Recent studies have shown that point of care ultrasound is a valuable tool in the assessment and management of shock in the Emergency Department (ED). Despite proven utility, data is limited on the current utilization and quality assurance of POCUS in ED management of shock. The aim of this study was to determine the rate of POCUS use, characterize data collection methods and determine rate of quality assurance in both the ED and Intensive Care Unit (ICU) of a tertiary care academic center. Methods: The study included all patients who visited the ED from Jan-Jun 2015 that were transferred to the ICU, and were in shock, as determined by sBP <90, diagnostic code or vasopressor use. Patient charts, as well as wirelessly archived ultrasound studies were reviewed to determine which patients had POCUS performed, and how the results were recorded. By reviewing formal worksheets archived online, it could be determined if a management change was recommended, if studies were over-read for quality assurance and if improvement was recommended to image acquisition or interpretation. Results: Both departments used POCUS in roughly half of patients presenting in shock (53% ED, 41% ICU) with no statistical difference in usage (Δ12, 95% CI −0.01 to 0.25; p=0.06). Most ED studies (87%), had some form of documentation either on paper or online, however few (9%) had a formal worksheet completed. In comparison 71% of ICU studies had a worksheet. There was no difference in the number of performed scans that were saved electronically (66% ED vs 71% ICU; Δ5%, 95%CI −0.13 to 0.21; p=0.60).In the ICU the majority (77%) of the formal reports recommended a management change as a direct result of scan findings. Furthermore, of worksheets submitted for quality assurance (88%), over half the reviews (55%) suggested an improvement in image acquisition or interpretation. Conclusion: To our knowledge, our study is the first to demonstrate that POCUS is only utilized in about half of the shock cases in ED and ICU. Given that the majority of the formally reported studies in the ICU that were over-read for quality assurance found areas for potential improvement and given that the majority of ED studies were reported informally, it stands to reason that POCUS operators in the ED could benefit from a formalized quality assurance program. Future studies should explore potential barriers to implementation of such a program.
The majority of older adults with dementia live in low- and middle-income countries (LMICs). Illiteracy and low educational background are common in older LMIC populations, particularly in rural areas, and cognitive screening tools developed for this setting must reflect this. This study aimed to review published validation studies of cognitive screening tools for dementia in low-literacy settings in order to determine the most appropriate tools for use.
A systematic search of major databases was conducted according to PRISMA guidelines. Validation studies of brief cognitive screening tests including illiterate participants or those with elementary education were eligible. Studies were quality assessed using the QUADAS-2 tool. Good or fair quality studies were included in a bivariate random-effects meta-analysis and a hierarchical summary receiver operating characteristic (HSROC) curve constructed.
Forty-five eligible studies were quality assessed. A significant proportion utilized a case–control design, resulting in spectrum bias. The area under the ROC (AUROC) curve was 0.937 for community/low prevalence studies, 0.881 for clinic based/higher prevalence studies, and 0.869 for illiterate populations. For the Mini-Mental State Examination (MMSE) (and adaptations), the AUROC curve was 0.853.
Numerous tools for assessment of cognitive impairment in low-literacy settings have been developed, and tools developed for use in high-income countries have also been validated in low-literacy settings. Most tools have been inadequately validated, with only MMSE, cognitive abilities screening instrument (CASI), Eurotest, and Fototest having more than one published good or fair quality study in an illiterate or low-literate setting. At present no screening test can be recommended.
Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.
This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.
SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.
Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population.
To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis.
We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode.
The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment.
Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes.
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.
What determines inter-individual variability to impairments in behavioural control that may underlie road-traffic accidents, and impulsive and violent behaviours occurring under the influence of cannabis, the most widely used illicit drug worldwide?
Employing a double-blind, repeated-measures design, we investigated the genetic and neural basis of variable sensitivity to cannabis-induced behavioural dyscontrol in healthy occasional cannabis users. Acute oral challenge with placebo or Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, was combined with functional magnetic resonance imaging, while participants performed a response inhibition task that involved inhibiting a pre-potent motor response. They were genotyped for rs1130233 single nucleotide polymorphisms (SNPs) of the protein kinase B (AKT1) gene.
Errors of inhibition were significantly (p = 0.008) increased following administration of THC in carriers of the A allele, but not in G allele homozygotes of the AKT1 rs1130233 SNP. The A allele carriers also displayed attenuation of left inferior frontal response with THC evident in the sample as a whole, while there was a modest enhancement of inferior frontal activation in the G homozygotes. There was a direct relationship (r = − 0.327, p = 0.045) between the behavioural effect of THC and its physiological effect in the inferior frontal gyrus, where AKT1 genotype modulated the effect of THC.
These results require independent replication and show that differing vulnerability to acute psychomotor impairments induced by cannabis depends on variation in a gene that influences dopamine function, and is mediated through modulation of the effect of cannabis on the inferior frontal cortex, that is rich in dopaminergic innervation and critical for psychomotor control.
Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.
Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.
Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).
In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.
Although translational medicine has become a priority for medical science, advances in neuroscience have failed to be translated for the benefit of patients. In populations at high risk of psychosis, neuroimaging could stratify those mostly likely to develop psychosis. This is an example of potentially translatable psychiatry.