To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Executive and mnemonic impairments have been well documented in the high-risk states for development of psychosis and have been pinpointed as a possible core neuropsychological dysfunction. However, their neurofunctional correlates are still not clear.
fMRI was used in 17 patients at risk for developing psychosis (ARMS, “at risk mental state”), 10 patients with a first episode of psychosis (FEP) and 15 age-matched healthy comparison subjects to examine neural responses to increasing difficulty of mnemonic engagement in an object–location paired associate memory task. Groups were matched in terms of age, IQ, gender, and psychopathology ratings. Accuracy and reaction time were recorded during the scan.
As the mnemonic load increased, response latency increased and response accuracy decreased in an approximately linear fashion. No main effect for group was observed. However, a trend towards decreased accuracy in FEP subjects, as compared with controls, was evident. As the task difficulty increased, increased brain activity was observed in the medial frontal cortex and in the medial posterior parietal cortex. Between-groups differences in activation were observed in a cluster spanning the MFG, SFG and SMA and in the right precuneus. However, these neurofunctional abnormalities were more evident in the most demanding level of the task than in the easy level, with the ARMS groups showing less activation than controls and higher activation than FEP.
Abnormal neural activity in medial frontal cortex and posterior parietal cortex during paired associate learning task may represent a neurofunctional substrates of vulnerability to psychosis.
Previous DTI studies in schizophrenia have all found decreased white matter integrity in the patients, though the location of these differences has varied. This may be due to the use of region-of-interest methods and underpowered studies. We used voxel-based DTI to examine a much larger sample of patients with schizophrenia and controls.
Seventy-six patients with DSM-IV schizophrenia and 76 controls matched for age, gender, handedness, IQ, and education were scanned with an optimized DTI sequence at 1.5T. FA maps were co-registered using SPM2 and group differences calculated using non-parametric XBAM_v3.4. Mean FA was extracted from each significant cluster and correlated with illness duration in the patients. Cluster FA was compared between the 15 patients with a few days exposure to antipsychotics and 30 matched patients who had been treated for over a year.
At thresholds of <1 false positive (voxel p<0.01, cluster p<0.0005), there were widespread reductions in FA in the patient group. These areas included bilateral cingulum, superior & inferior longitudinal fasciculus, left uncinate and the genu of the corpus callosum. There were no areas of increased FA in patients relative to controls. In our secondary analyses, there were no significant correlations between the mean FA extracted from any of these clusters and duration of illness, and no significant differences between the briefly medicated and chronically medicated groups.
Schizophrenia is associated with FA reductions distributed widely in white matter, but these differences do not correlate with duration of illness, and do not segregate with medication.
Inhibitory dysfunction is the key behavioural and cognitive phenotype of Attention Deficit Hyperactivity Disorder (ADHD) and of obsessive-compulsive-disorder (OCD). Both disorders show deficits in tasks of response inhibition and cognitive flexibility as well as fronto-striatal brain dysfunctions during task performance. The goal of this research was to investigate differences and commonalities in functional neural networks mediating inhibitory control between adolescents with ADHD and those with OCD to identify disorder-specific neurofunctional biomarkers.
Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation of 18/12 boys (Stop/Switch task) with clinical ADHD, 10 boys with clinical OCD and 20 healthy comparison boys during a tracking Stop task measuring motor response inhibition and its failure and a switching task measuring cognitive flexibility. Non-parametric permutation analyses were used for fMRI analysis (XBAM). Functional connectivity analyses investigating group differences in fronto-striatal connections will be presented at the conference.
Both patient groups shared brain dysfunction compared to controls in right orbitofrontal, left dorsolateral (Stop task) and left inferior prefrontal cortices (Switch task). Right inferior prefrontal under-activation, however, was specific to ADHD during both tasks. Under-activation in left caudate and anterior cingulate was also specific to ADHD during the Switch task.
Patients with ADHD appear to have both common and distinct dysfunctions during inhibitory control compared to OCD patients. The most consistent fMRI finding in ADHD of a dysfunction in right inferior prefrontal cortex during inhibitory control appears to be disorder-specific when compared to OCD, and may be a specific neurofunctional biomarker of ADHD.
Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence.
Data came from four prospective twin cohorts – Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study – who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9–10; 12; 14–15 and 16–18.
MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression.
Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents’ aggressive behaviour.
Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population.
We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants’ facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES).
While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = −2.33, p = 0.02) and at trend level in healthy controls (Z = −1.87, p = 0.06).
These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.
The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown.
We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses.
The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive–compulsive disorder symptoms.
Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.
Cannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms.
Clinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points – at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded.
Level of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up.
Effective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.
Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.
We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.
At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.
These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
The antimalarial drug artemisinin (ART) is commercially extracted from the medicinal plant Artemisia annua L. Here, we report the screening of 70 A. annua plants representing 14 diverse germplasm accessions sourced from around the world, and identify lines containing >2% ART. These extremely high-yielding individuals have been maintained as vegetative clones, and they represent promising germplasm resources for future A. annua breeding programmes.
Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia.
fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load.
In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS.
Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.
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.
The pattern of brain morphological changes at the early stages of schizophrenia may depend on the age at onset of illness; in children and adolescents with schizophrenia, grey matter deficits are seen in the parietal lobe whereas in individuals with adult onset these are more widespread.
To examine whether white matter is similarly affected.
Diffusion tensor imaging was used to compare fractional anisotropy measures in individuals with adolescent-onset (n = 17) and adult-onset schizophrenia (n = 17) with those in age- and gender-matched controls.
Compared with their respective controls, individuals with adolescent-onset schizophrenia showed fractional anisotropy decrease in parietal regions; individuals with adult onset showed additional fractional anisotropy reductions in frontal, temporal and cerebellar regions. A differential effect of age at onset (adolescent v. adult) was noted bilaterally in medial prefrontal white matter.
White matter abnormalities in frontal regions in schizophrenia may depend on developmental stage at the time of illness onset.
Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis.
The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model.
Over the initial 12 months from presentation, the costs of the OASIS intervention were £1872 higher than CAU. However, after 24 months they were £961 less than CAU.
This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving.
People with prodromal symptoms have a very high risk of developing psychosis.
To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability.
Cross-sectional comparison of regional activation in individuals with an ‘at-risk mental state’ (at-risk group: n=17), patients with first-episode schizophreniform psychosis (psychosis group: n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task and an N-back working memory task.
A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during the N-back task.
The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.
Cognitive models propose that faulty appraisal of anomalous experiences
is critical in developing psychosis, particularly delusions. A data
gathering bias may be fundamental to abnormal appraisal
To examine whether there is a data gathering bias in people at high risk
of developing psychosis
Individuals with an at-risk mental state (n=35) were
compared with a matched group of healthy volunteers
(n=23). Participants were tested using a modified
version of the ‘beads’ reasoning task with different levels of task
When task demands were high, the at-risk group made judgements on the
basis of less information than the control group (P <
0.05). Within both groups, jumping to conclusions was directly correlated
with the severity of abnormal beliefs and intolerance of uncertainty
(P<0.05). In the at-risk group it was also
associated with impaired working memory (P<0.05),
whereas in the control group poor working memory was associated with a
more conservative response style (P<0.05)
People with an at-risk mental state display a jumping to conclusions
reasoning style, associated with impaired working memory and intolerance
of uncertainty. This may underlie a tendency to develop abnormal beliefs
and a vulnerability to psychosis
In the UK, older people who are resident in care homes because of their needs for social support and personal care receive their health care from primary health care. Although there is increasing input from district nurses in care homes (Audit Commission, 1999), there is little knowledge or recognition of the primary care nursing contribution. This paper reviews two types of research literature: studies that consider the health care needs of older people in residential care homes that could inform nursing support and interventions in care homes, and research that describes the nursing involvement with these settings. The paper argues that on the basis of the research reviewed many of the health problems older people in care homes experience could be avoided or improved by primary care nursing support and intervention. A reassessment is needed of how the interface between community and residential care is managed so that older people in care homes have access to appropriate health care support.
Objective: To audit sore throat management in adults, introduce proforma-based guidelines and to reaudit clinical practice.
Setting: Adult emergency department of an inner city teaching hospital.
Methods: A literature search was carried out to identify relevant guidelines. In stage one, patients presenting to the emergency department with sore throat were identified retrospectively from the emergency department attendance register. Proformas were completed retrospectively. In stage two, new guidelines were introduced and staff educated about the guidelines. In stage three, patients presenting with sore throat were identified at triage and proformas were completed at time of consultation.
Outcome Measures: (1) appropriate clinical assessment of the likelihood of bacterial infection using the clinical scoring system, (2) appropriateness of antibiotic prescription, (3) recommendation of supportive treatments to patients.
Results: Introduction of a clinical scoring system reduced the inappropriate prescribing of antibiotics from 44 per cent to 11 per cent. Correct antibiotic prescription rose from 60 per cent to 100 per cent. Although the variety of advice given about supportive treatment increased, the actual number of patients receiving documented supportive advice fell from 67.8 per cent in stage one to 58 per cent in stage three.
Conclusion: The introduction of clinically based guidelines for the diagnosis and management of sore throat in adults can reduce inappropriate antibiotic prescribing.
The introduction of a fifth amphibole group, the Na-Ca-Mg-Fe-Mn-Li group, defined by 0.50 < B(Mg,Fe2+,Mn2+,Li) < 1.50 and 0.50 ≤ B(Ca,Na) ≤ 1.50 a.f.p.u. (atoms per formula unit), with members whittakerite and ottoliniite, has been required by recent discoveries of B(LiNa) amphiboles. This, and other new discoveries, such as sodicpedrizite (which, here, is changed slightly, but significantly, from the original idealized formula), necessitate amendments to the IMA 1997 definitions of the Mg-Fe-Mn-Li, calcic, sodic-calcic and sodic groups. The discovery of obertiite and the finding of an incompatibility in the IMA 1997 subdivision of the sodic group, requires further amendments within the sodic group. All these changes, which have IMA approval, are summarized.