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Summary Background Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5–36·0] of 129 patients), depressed mood (42 [32·6%; 24·7–40·9] of 129), anxiety (46 [35·7%; 27·6–44·2] of 129), impaired memory (44 [34·1%; 26·2–42·5] of 129), and insomnia (54 [41·9%; 22·5–50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5–14·1] of 332 patients), insomnia (34 [12·1%; 8·6–16·3] of 280), anxiety (21 [12·3%; 7·7–17·7] of 171), irritability (28 [12·8%; 8·7–17·6] of 218), memory impairment (44 [18·9%; 14·1–24·2] of 233), fatigue (61 [19·3%; 15·1–23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9–37·3] of 181) and sleep disorder (14 [100·0%; 88·0–100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

BACKGROUND: There is a paucity of longitudinal research investigating vitamin D in people with early psychosis.METHOD: Vitamin D levels were measured in 168 patients (64% (n = 108) male, mean age 29.3 (9.8) years) with first episode psychosis (FEP), along with measures of clinical state at baseline and at 12 months follow up. We assessed the a) cross sectional, and; b) longitudinal relationships between continuous and categorical 25-hydroxyvitamin D (25(OH)D) levels and clinical symptoms at first contact for psychosis and at 12 months.RESULTS: In FEP, 80% (n = 134) at baseline, and 76% at 12 months follow up, had suboptimal vitamin D levels (CONCLUSION: We identified a prospective association between higher baseline serum Vitamin D levels and lower total psychotic symptoms and negative symptoms of psychosis at 12 months after first contact for psychosis. The results of this study require replication in larger prospective studies, and highlight the need for large randomised trials to assess the effect of vitamin D supplementation on symptoms of psychosis in FEP.

BACKGROUND: Metabolic abnormalities and peripheral inflammation have been increasingly reported in patients at the onset of psychosis and associated with important physical health disorders and increased mortality. However, the impact of an abnormal metabolic-inflammatory status on the psychiatric outcome of these patients has not yet been investigated.OBJECTIVES: The aims of this study were 1) to explore whether, in a sample of patients at their first episode of psychosis (FEP), an overall metabolic-inflammatory status may be measured, by combining metabolic and inflammatory variables in metabolic-inflammatory factors; 2) to explore the association between these factors and clinical outcome at 1-year follow-up (FU), in terms of symptoms severity and treatment response.METHODS: In this longitudinal study we recruited 42 FEP patients and 46 healthy controls (HC) matched with patients for age, gender and ethnicity. At baseline (T1) we measured high sensitivity C-reactive protein (hsCRP) as biomarker of inflammation, and body mass index (BMI), lipid profile and gluco-metabolic parameters (glycated hemoglobin (HbA1c) and fasting glucose) as metabolic variables. A principal component analysis (PCA) was then used to reduce the dimensionality of the dataset accounting for both inflammation and metabolic status. In FEP patients, we assessed symptoms severity at T1 and at 1-year FU (T2) as well as treatment response to antipsychotics at T2.RESULTS: at T1, FEP showed higher HbA1c (p = 0.034), triglycerides (TG) (p = 0.045) and BMI (p = 0.026) than HC. PCA identified 3 factors: factor 1 accounting for hsCRP, TG and BMI, factor 2 accounting for LDL and cholesterol, and factor 3 accounting for fasting glucose and HbA1c. Factor 1 was associated with T1 negative symptoms severity (p = 0.021) and predicted T2 positive (p = 0.004) and overall symptoms severity (0.001), as well as general psychopathology (p CONCLUSION: In this sample of FEP patients, inflammation and metabolism, closely correlated at the onset of psychosis, proved to play a key role as predictors of the clinical course of psychosis when combined in a single factor. These findings offer an important potential target for early screening and interventions.

Neurological soft signs (NSS) are subtle abnormalities of motor and sensory function that are present in the absence of localized brain pathological lesions. In psychoses they have been consistently associated with a distinct pattern of cortical and subcortical brain structural alterations at the level of the heteromodal cortex and basal ganglia. However, a more specific and accurate evaluation of the cytoarchitecture of the cortical mantle could further advance our understanding of the neurobiological substrate of psychosis. We investigated the relationship between brain structure and NSS in a sample of 66 patients at their first episode of psychosis. We used the Neurological Evaluation Scale for neurological assessment and high-resolution MRI and Freesurfer to explore cortical thickness and surface area. Higher rates of NSS were associated with a reduction of cortical thickness in the precentral and postcentral gyri, inferior-parietal, superior temporal, and fusiform gyri. Higher rates of NSS were also associated with smaller surface areas of superior temporal gyrus and frontal regions (including middle frontal, superior and orbito-frontal gyri). Finally, more sensory integration signs were also associated with larger surface area of the latero-occipital region. We conclude that the presence of NSS in psychosis is associated with distinct but widespread changes in cortical thickness and surface area, in areas crucial for sensory-motor integration and for the fluid execution of movement. Studying these morphological correlates with advanced neuroimaging techniques can continue to improve our knowledge on the neurobiological substrate of these important functional correlates of psychosis.

There has been much recent debate concerning the relative clinical utility of symptom dimensions versus conventional diagnostic categories in patients with psychosis. We investigated whether symptom dimensions rated at presentation for first-episode psychosis (FEP) better predicted time to first remission than categorical diagnosis over a four-year follow-up. The sample comprised 193 FEP patients aged 18-65. years who presented to psychiatric services in South London, UK, between 2006 and 2010. Psychopathology was assessed at baseline with the Positive and Negative Syndrome Scale and five symptom dimensions were derived using Wallwork/Fortgang's model; baseline diagnoses were grouped using DSM-IV codes. Time to start of first remission was ascertained from clinical records. The Bayesian Information Criterion (BIC) was used to find the best fitting accelerated failure time model of dimensions, diagnoses and time to first remission. Sixty percent of patients remitted over the four years following first presentation to psychiatric services, and the average time to start of first remission was 18.3. weeks (SD = 26.0, median = 8). The positive (BIC = 166.26), excited (BIC = 167.30) and disorganised/concrete (BIC = 168.77) symptom dimensions, and a diagnosis of schizophrenia (BIC = 166.91) predicted time to first remission. However, a combination of the DSM-IV diagnosis of schizophrenia with all five symptom dimensions led to the best fitting model (BIC = 164.35). Combining categorical diagnosis with symptom dimension scores in FEP patients improved the accuracy of predicting time to first remission. Thus our data suggest that the decision to consign symptom dimensions to an annexe in DSM-5 should be reconsidered at the earliest opportunity.

Aims We aimed to test whether specific insight dimensions are associated with suicidality in patients with psychotic disorders. Methods 143 patients with schizophrenia spectrum disorders were recruited. Suicidality was assessed by item 8 of the Calgary Depression Scale for Schizophrenia (CDSS). Insight was measured by the Scale of Unawareness of Mental Disorder (SUMD) and the Markova and Berrios Insight Scale. Bivariate analyses and multivariable logistic regression models were conducted. Results Those subjects aware of having a mental illness and its social consequences had higher scores on suicidality than those with poor insight. Awareness of the need for treatment was not linked with suicidality. The Markova and Berrios Insight scale total score and two specific domains (awareness of “disturbed thinking and loss of control over the situation” and “having a vague feeling that something is wrong”) were related to suicidality. However, no insight dimensions survived the multivariable regression model, which found depression and previous suicidal behaviour to predict suicidality. Conclusions Suicidality in psychosis was linked with some insight dimensions: awareness of mental illness and awareness of social consequences, but not compliance. Depression and previous suicidal behaviour mediated the associations with insight; thus, predicting suicidality.

Background\ud Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses.\ud \ud Methods\ud The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis.\ud \ud Results\ud PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10−6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002).\ud \ud Conclusions\ud PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.

Evidence suggests there are two treatment-resistant schizophrenia subtypes (i.e. early treatment resistant (E-TR) and late-treatment resistant (L-TR)). We aimed to develop prediction models for estimating individual risk for these outcomes by employing advanced statistical shrinkage methods. 239 first-episode schizophrenia (FES) patients were followed-up for approximately 5 years after first presentation to psychiatric services; of these, n=56 (25.2%) were defined as E-TR and n=24 (12.6%) were defined as L-TR. Using known risk factors for poor schizophrenia outcomes, we developed prediction models for E-TR and L-TR using LASSO and RIDGE logistic regression models. Models' internal validation was performed employing Harrell's optimism-correction with repeated cross-validation; their predictive accuracy was assessed through discrimination and calibration. Both LASSO and RIDGE models had high discrimination, good calibration. While LASSO had moderate sensitivity for estimating an individual risk for E-TR and L-TR, sensitivity estimated for RIDGE model for these outcomes was extremely low, which was due to having a very large estimated optimism. Although it was possible to discriminate with sufficient accuracy who would meet criteria for E-TR and L-TR during the 5-year follow-up after first contact with mental health services for schizophrenia, further work is necessary to improve sensitivity for these models.

This study examined the reliability, validity and internal structure of the newly developed, interview-based Schedule for the Assessment of Insight in Eating Disorders (SAI-ED) and the relationships of insight with demographic and clinical characteristics in EDs. Ninety-four female patients - 44 with anorexia nervosa (AN) and 50 with bulimia nervosa (BN) - were assessed with SAI-ED. The Brown Assessment of Beliefs Scale was used to evaluate convergent validity of SAI-ED. Hierarchical cluster analysis and multidimensional scaling were used to identify insight components and assess their inter-relationships. The final 8-item SAI-ED demonstrated good psychometric properties. Inter-rater and test-retest reliabilities were high. Three subscales of SAI-ED were identified which measure major insight components: awareness of illness, awareness of symptoms, and treatment engagement. Patients with AN had significant lower score on SAI-ED than patients with BN. Impaired insight was associated with: (a) lower current and lowest lifetime BMI and more severe dietary restrain in AN, (b) illness duration, severity of overall ED symptoms, body-related concerns and obsessionality in BN. Insight is a multidimensional construct in EDs associated with different clinical aspects in AN and BN. The SAI-ED is a valid and reliable tool for the assessment of insight in EDs patients.

Purpose To compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. Methods Case–control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro-ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30 months (SD = 67 months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. Results Seventy-two percent (n = 36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n = 20), premorbid psychiatric (27%, n = 13) as well as functional (24%, n = 12) diagnoses and psychotropic medication usage (22%, n = 11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n = 9; 18%). Conclusions Medically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions.

Suicide is a major cause of premature death in psychosis. Earlier stages have been associated with higher risk. However, such risk periods have not been specifically determined and risk factors for suicidal behaviour may change over those periods, which may have crucial implications for suicide prevention. The aim of this study was to determine and characterize the highest risk period for suicide in a representative sample of first-episode psychosis (FEP) patients. Suicidal behaviour prior to first presentation of psychosis and during a 3-year follow-up was examined in a sample of 397 individuals. Risk factors for suicidal behaviour during specific time periods were investigated and compared. The greatest suicide risk was found during the month before and 2 months after first contact with psychiatric services (i.e., 'early' attempts). Severity of depressive symptoms and cannabis use emerged as predominant risk factors across time. 'Early' attempters were characterized as being male, living in urban areas, having poor premorbid adjustment, requiring hospitalization, scoring higher on anxiety measures and unusual thought content than non-attempters. Greater suspiciousness and more severe depressive symptoms distinguished the 'late' attempters. In conclusion, there is a specific high risk period for suicide in FEP around the time of the first presentation. Early intervention programmes targeting phase-specific risk factors, particularly psychotic symptoms management and secondary depression prevention strategies may be useful for suicide prevention in psychosis.

Background Substantial impairment in performance on the digit-symbol substitution task in patients with schizophrenia is well established, which has been widely interpreted as denoting a specific impairment in processing speed. However, other higher order cognitive functions might be more critical to performance on this task. To date, this idea has not been rigorously investigated in patients with schizophrenia. Methods Neuropsychological measures of processing speed, memory, and executive functioning were completed by 125 patients with schizophrenia and 272 control subjects. We implemented a series of confirmatory factor and structural regression modeling to build an integrated model of processing speed, memory, and executive function with which to deconstruct the digit-symbol substitution task and characterize discrepancies between patients with schizophrenia and control subjects. Results The overall structure of the processing speed, memory, and executive function model was the same across groups (χ 2 = 208.86, p > .05), but the contribution of the specific cognitive domains to coding task performance differed significantly. When completing the task, control subjects relied on executive function and, indirectly, on working memory ability, whereas patients with schizophrenia used an alternative set of cognitive operations whereby they relied on the same processes required to complete verbal fluency tasks. Conclusions Successful coding task performance relies predominantly on executive function, rather than processing speed or memory. Patients with schizophrenia perform poorly on this task because of an apparent lack of appropriate executive function input; they rely instead on an alternative cognitive pathway.

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations.

Metabolic abnormalities and peripheral inflammation have been increasingly reported in patients at their first episode of psychosis (FEP) and associated with increased mortality. However, the impact of an abnormal metabolic-inflammatory status on the psychiatric outcome of FEP is understudied. This study aimed 1) to combine metabolic and inflammatory variables in factors accounting for an overall metabolic-inflammatory status in FEP patients; 2) to explore the association between these factors and clinical outcome at 1 year. We recruited 43 FEP patients and 50 healthy controls (HC). At baseline (T1) we measured high sensitivity C-reactive protein (hsCRP) as inflammatory biomarker, and body mass index (BMI), lipid profile and gluco-metabolic parameters (glycated haemoglobin (HbA1c) and fasting glucose) as metabolic variables. Using a principal component analysis (PCA) we gathered all variables in factors accounting for both inflammation and metabolic status. In patients, we assessed symptoms severity at T1 and after 1-year (T2) as well as T2 treatment response. FEP showed higher HbA1c (p = 0.034), triglycerides (TG) (p = 0.044) and BMI (p = 0.023) than HC. PCA identified 3 factors. Factor 1, accounting for hsCRP, TG and BMI, was associated with T1 negative symptoms severity (p = 0.018) and predicted T2 positive symptoms severity (p = 0.003), overall symptoms severity (p = 0.004), general psychopathology (p = 0.001) and treatment response (p = 0.007). A combined inflammatory-metabolic factor proved to predict the clinical course of psychosis and offer an important target for early interventions.

Depersonalisation disorder (DPD) is characterised by a sense of unreality about the self and the world. Research suggests altered autonomic responsivity and dysfunction in prefrontal and temporal lobe areas in this condition. We report the first structural magnetic resonance imaging study of 20 patients with DPD and 21 controls using the FreeSurfer analysis tool employing both region-of-interest and vertex-based methods. DPD patients showed significantly lower cortical thickness in the right middle temporal region according to both methods of analysis. The vertex-based method revealed additional differences in bilateral temporal lobes, inferior frontal regions, the right posterior cingulate, and increased thickness in the right gyrus rectus and left precuneus. Clinical severity scores were negatively correlated with cortical thickness in middle and right inferior frontal regions. In sum, grey matter changes in the frontal, temporal, and parietal lobes are associated with DPD. Further research is required to specify the functional significance of the findings and whether they are vulnerability or disease markers.

Background The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome. Aims We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls. Method Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples. Results Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F = 5.5; df = 1,115; p = .02), physical (F = 4.7; df = 1, 118; p = .03) and sexual abuse (F = 5.4; df = 1,117; p = .02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β = − .30; p = .03) whereas sexual and/or physical abuse showed a trend (β = − .26; p = .06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls. Conclusion Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity.

Resume Introduction Le syndrome CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Skeletal anomalies) est un syndrome malformatif sporadique recemment decrit (mutation de PIK3CA), associant une hemi-hypertrophie corporelle, des hamartomes lipomateux du tronc et des malformations multiples. Observation Nous rapportons un cas de syndrome CLOVES initialement confondu avec un syndrome de Protee, revele par un episode de surinfection d’un hamartome lipomateux du dos. La patiente avait une hypertrophie et des malformations capillaires et veino-lymphatiques du membre inferieur droit, des malformations capillaires dorsales, une hemi-hypertrophie cervico-faciale gauche et un hamartome epidermique cervical, compatibles avec un syndrome de Protee. Le diagnostic de syndrome CLOVES etait pose plus tard, devant la mise en evidence par l’imagerie de l’hamartome lipomateux du dos associe aux malformations capillaires mais aussi a des malformations veino-lymphatiques sous-jacentes et a une syringomyelie. Discussion Plusieurs syndromes malformatifs peuvent etre evoques devant une hypertrophie tissulaire associee a des hamartomes et a des malformations vasculaires. Ainsi, le diagnostic de syndrome CLOVES peut etre retarde car ce syndrome est assez proche phenotypiquement du syndrome de Protee. Cependant, le pronostic et les complications sont differents. Il est important d’evoquer le diagnostic de syndrome CLOVES devant l’association d’hamartomes lipomateux du dos, d’une hemi-hypertrophie corporelle et d’un hamartome epidermique, afin de mettre en place un suivi adapte et une surveillance des complications propres a cette maladie.

Bulimia nervosa, binge-eating disorder, and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving. Transcranial direct current stimulation (tDCS) has been used to suppress food cravings, but there is insufficient evidence to support its application in clinical practice. Furthermore, the potential moderating role of impulsivity has not been considered. This study used a randomised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex (anode right/cathode left) would transiently modify food cravings and temporal discounting (TD; a measure of choice impulsivity) in 17 healthy women with frequent food cravings. Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored. Participants were exposed to food and a film of people eating, and food cravings and TD were assessed before and after active and sham stimulation. Craving for sweet but not savoury foods was reduced following real tDCS. Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour. No differences were seen in TD or food consumption after real versus sham tDCS. These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour.

A person's capacity to process advice is an important aspect of decision making in the real world. For example, in decisions about treatment, the way patients respond to the advice of family, friends and medical professionals may be used (intentionally or otherwise) as a marker of the “use or weigh” requirement of decision-making capacity. Here we explore neuroscientific research on decision-making to identify features of advice-taking that help conceptualize this requirement. We focus on studies of the neural and computational basis of decision-making in laboratory settings. These studies originally investigated simple perceptual decisions about ambiguous stimuli, but have more recently been extended to more complex “value-based” decisions involving the comparison of subjective preferences. Value-based decisions are a useful model system for capacity-related decision-making as they do not have an objectively ‘correct’ answer and are instead based on subjective preferences. In this context, advice-taking can be seen as a process in which new evidence for one or other option is integrated, leading to altered behaviour or choices. We use this framework to distinguish between different types of advice-taking: private compliance consists of updating one's privately held beliefs based on new evidence, whereas in the case of public compliance, people change their behaviour at a surface level without shifting their privately-held beliefs. Importantly, both types of advice-taking may lead to similar outcomes but rely on different decision processes. We suggest that understanding how multiple mechanisms drive advice-taking holds promise for targeting decision-making support and improving our understanding of the use and weigh requirement in cases of contested capacity.

The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self-regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants was shown 'control' feedback from another brain area. Pre- and post-training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF. In contrast to the controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and SCR to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI/control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed that the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate.

Introduction It has been proposed that theory of mind (ToM) deficits underlying difficulties in taking the perspective of others may substantially contribute to insight impairment in schizophrenia. The present study aimed to explore the effect of ToM deficits on insight impairment independently of co-existent neurocognitive deficits and symptom severity in chronic schizophrenia. Methods Fifty-eight chronic patients with schizophrenia and 56 matched healthy participants were assessed with the Schedule for the Assessment of Insight (SAI–E) along with a series of ToM tasks and a comprehensive battery of neuropsychological measures. Symptoms were measured with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Results ToM impairment explained a substantial proportion of variance in overall insight and its three major components: awareness of illness, relabelling of symptoms and treatment compliance. Moreover, the effect of ToM deficits on insight remained significant even after controlling for all neurocognitive factors and symptom ratings. Regression analysis showed that symptoms and cognitive deficits also contribute to impaired insight in schizophrenia. General intellectual ability was negatively associated with both overall insight and relabelling of symptoms. Executive functions were negatively associated with relabelling. Conclusion Our findings confirm that ToM deficits negatively affect insight independently of neurocognitive deficits and symptom severity in chronic schizophrenia. The effect of ToM deficits on insight should be further examined in the broader context of the failures in metacognition and their relationships with insight impairment in schizophrenia.

Background—Despite increasing evidence suggesting that childhood maltreatment is significantly associated with psychosis, the specific role of bullying in the onset of psychotic disorders is still unclear. This study aimed to examine whether bullying was more prevalent amongst individuals presenting to services for the first time with a psychotic disorder than in unaffected community controls. Methods—Data on exposure to bullying, psychotic symptoms, cannabis use and history of conduct disorder were collected cross-sectionally from 222 first-presentation psychosis cases and 215 geographically-matched controls. Bullying victimisation was assessed retrospectively as part of the Brief Life Events schedule. Logistic regression was used to examine associations between exposure to bullying and case-control status, while controlling for potential confounders. Results—Psychosis cases were approximately twice as likely to report bullying victimisation when compared to controls. No significant interactions between bullying and either gender or cannabis use were found. Controls reporting being a victim of bullying were approximately twice as likely to also report at least one psychosis-like symptom. Conclusions—Our results extend previous research by suggesting that bullying victimisation may contribute to vulnerability to develop a psychotic disorder in some individuals.

We attempted to explore whether lack of insight in patients with psychosis is related to their genuine inability to recognise symptoms of mental illness as opposed to denial. We addressed this by examining participants' judgments of illness in vignettes in which they were either the protagonist or were commenting on others' behaviour. We recruited 44 first episode psychosis patients and 23 healthy controls to make judgements of specially constructed vignettes describing psychotic symptoms. Insight, Theory of Mind (ToM) and IQ was also measured. Patients' and controls' rating of vignettes overall did not differ significantly with respect to their attribution of mental illness. Patients and controls rated 2nd person vignettes similarly; patients were less likely to attribute mental illness to a character described in the 3rd person. This effect correlated with insight scores. Vignette judgments were significantly correlated with ToM performance but this was moderated by IQ. In conclusion, patients with lower insight tend to make the same attributions to others as to themselves, whilst healthy controls tend to think of mental illness as something seen in other people. There was no support for a 'denial' explanation for lack of insight in these patients.

Recent research has identified impairment in processing speed, measured by the digit-symbol substitution task, as central to the cognitive deficit in schizophrenia. However, the underlying cognitive correlates of this impairment remain unknown.A sample of cases (N=125) meeting DSM-IV criteria for schizophrenia and a sample of community controls (N=272) from the same geographical area completed a set of putative measures of processing-speed ability to which we implemented confirmatory factor and structural regression modelling in order to elucidate the latent structure of processing speed. Next, we tested the degree to which the structural and relational portions of the model were equal across groups.Processing-speed ability was best defined, in both controls and cases (χ(2)=38.59(26), p=0.053), as a multidimensional cognitive ability consisting of three latent factors comprising: psychomotor speed, sequencing and shifting, and verbal fluency. However, cases exhibited dedifferentiation (i.e., markedly stronger inter-correlations between factors; χ(2)=59.94(29), p.01) and a reliance on an alternative ensemble of cognitive operations to controls when completing the digit-symbol substitution task.Dedifferentiation of processing-speed ability in schizophrenia and subsequent overreliance on alternative (and possibly less than optimal) cognitive operations underlies the marked deficit observed on the digit-symbol substitution task.

Purpose The purpose of this study was to test the psychometric properties of the Neurobehavior Inventory (NBI) in a group of temporal lobe epilepsy (TLE) patients from a tertiary care center, correlating its scores with the presence of psychiatric symptoms. Methods Clinical and sociodemographic data from ninety-six TLE outpatients were collected, and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured psychiatric interview (MINI-PLUS), Neurobehavior Inventory (NBI), and Hamilton Depression Rating Scale (HAM-D). Results Some traits evaluated by the NBI showed adequate internal consistency (mean inter-item correlation between 0.2 and 0.4) and were frequent, such as religiosity (74%) and repetitiveness (60.4%). Principal component analysis showed three factors, named here as emotions (Factor 1), hyposexuality (Factor 2), and unusual ideas (Factor 3). Depressive symptoms on HAM-D showed a strong association with emotions and hyposexuality factors. When patients with left TLE and right TLE were compared, the former exhibited more sadness (p = 0.017), and the latter, a greater tendency toward sense of personal destiny (p = 0.028). Conclusion Depression influences NBI scoring, mainly emotionality and hyposexuality traits. Neurobehavior Inventory subscales can be better interpreted with an appropriate evaluation of comorbid mood and anxiety disorders. Compromise in left temporal mesial structures is associated with increased tendency toward sad affect, whereas right temporal pathology is associated with increased beliefs in personal destiny.

Insight in psychosis is a multi-dimensional phenomenon, and has been hypothesised to have some sort of neuropsychological basis. It is unclear to what extent specific neuropsychological abilities are able to predict insight beyond the effect of generalised cognitive ability. We aimed to test this, alongside the relationship of insight with illness duration and diagnosis, in a sample of first episode psychosis patients. We recruited 102 patients experiencing their first episode of psychosis and assessed their insight, symptoms, diagnosis as well as administering a full neuropsychological battery. Low insight was related to worse performance in a variety of neuropsychological tasks. Regression analysis tested whether any specific tasks were related to insight (or dimensions of insight) beyond the effect of IQ. Verbal memory had an effect on total insight and all dimensions of insight (except compliance) beyond the effect of IQ. Insight appeared to vary with diagnosis, with those diagnosed with depressive affective psychoses having better insight than those with manic affective psychoses. There was no relationship between insight and DUP, but there was a relationship between time spent in treatment before assessment and insight, even after controlling for severity of symptoms. The results taken together suggest a model of insight in early psychosis with a significant neuropsychological component, particularly with verbal memory but also with generalised cognitive ability. There is likely to be a social component to insight affected by initial time spent in contact with treatment, helping patients to understand and come to terms with their illness.

Objective The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). Methods Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. Results A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures ( P = 0.012), current major depression ( P = 0.001), and motor impulsivity ( P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58–63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06–1.38, P = 0.005) to suicide risk. Conclusion Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.

Highlights ► First cortical imaging study of point-light signed language (SL). ► Distinguishes carrier and content in SL. ► Describes cortical circuitry for both carrier and content in SL., In this study, the first to explore the cortical correlates of signed language (SL) processing under point-light display conditions, the observer identified either a signer or a lexical sign from a display in which different signers were seen producing a number of different individual signs. Many of the regions activated by point-light under these conditions replicated those previously reported for full-image displays, including regions within the inferior temporal cortex that are specialised for face and body-part identification, although such body parts were invisible in the display. Right frontal regions were also recruited – a pattern not usually seen in full-image SL processing. This activation may reflect the recruitment of information about person identity from the reduced display. A direct comparison of identify-signer and identify-sign conditions showed these tasks relied to a different extent on the posterior inferior regions. Signer identification elicited greater activation than sign identification in (bilateral) inferior temporal gyri (BA 37/19), fusiform gyri (BA 37), middle and posterior portions of the middle temporal gyri (BAs 37 and 19), and superior temporal gyri (BA 22 and 42). Right inferior frontal cortex was a further focus of differential activation (signer > sign). These findings suggest that the neural systems supporting point-light displays for the processing of SL rely on a cortical network including areas of the inferior temporal cortex specialized for face and body identification. While this might be predicted from other studies of whole body point-light actions (Vaina, Solomon, Chowdhury, Sinha, & Belliveau, 2001) it is not predicted from the perspective of spoken language processing, where voice characteristics and speech content recruit distinct cortical regions (Stevens, 2004) in addition to a common network. In this respect, our findings contrast with studies of voice/speech recognition (Von Kriegstein, Kleinschmidt, Sterzer, & Giraud, 2005). Inferior temporal regions associated with the visual recognition of a person appear to be required during SL processing, for both carrier and content information.

Residential mobility among those with mental disorders is consistently associated with hospital admission. We studied 4485 psychiatric admissions in South London, aiming to describe the prevalence, timing and associations of residential moves occurring in association with admission. Moves tended to cluster around discharge; 15% of inpatients moved during admission or up to 28 days after discharge. The strongest associations were with younger age (especially 16–25 years) and homelessness. Unadjusted effects of gender, marital status and previous service use were mediated by homelessness. Possible mechanisms for the associations with homelessness and younger age are discussed.

Previous research has suggested that visual hallucinations in schizophrenia are associated with abnormal salience of visual mental images. Since visual imagery is used as a mnemonic strategy to learn lists of words, increased visual imagery might impede the other commonly used strategies of serial and semantic encoding. We had previously published data on the serial and semantic strategies implemented by patients when learning lists of concrete words with different levels of semantic organisation (Brébion et al., 2004). In this paper we present a re-analysis of these data, aiming at investigating the associations between learning strategies and visual hallucinations. Results show that the patients with visual hallucinations presented less serial clustering in the non-organisable list than the other patients. In the semantically organisable list with typical instances, they presented both less serial and less semantic clustering than the other patients. Thus, patients with visual hallucinations demonstrate reduced use of serial and semantic encoding in the lists made up of fairly familiar concrete words, which enable the formation of mental images. Although these results are preliminary, we propose that this different processing of the lists stems from the abnormal salience of the mental images such patients experience from the word stimuli.

Objective The purpose of this research was to evaluate the Brazilian-Portuguese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and to assess its psychometric properties. Methods This study involved 98 outpatients who underwent psychopathological evaluation with the Mini International Neuropsychiatric Interview—Plus Version, Hamilton Depression Scale (HAM-D), and a Portuguese version of the NDDI-E. Results The NDDI-E was easily understood and quickly administered to most of the patients. At a cutoff score > 15, NDDI-E had a sensitivity of 81.5%, a specificity of 83.1%, and a negative predictive value of 92.2% for diagnosis of major depression. Internal consistency reliability of the NDDI-E was 0.79, and there was also a positive correlation between the NDDI-E and the HAM-D (P Conclusion The Brazilian-Portuguese version of NDDI-E can be used as a practical screening tool to improve recognition of depression in Brazilian people with epilepsy.

Background: The associations of insight into illness and clinical and socio-demographic variables in schizophrenia have been examined, yet little attention has been given to premorbid functioning, insight change and outcomes. Objectives: We examined these associations in a large cohort of recent onset schizophrenia spectrum disorder patients. Methods: This was a prospective 6-month, open-label, multicentre, phase IV trial in 303 subjects with recent onset (≤2 years) schizophrenia treated with risperidone long-acting injection (RLAI). Insight (Schedule for the Assessment of Insight - Expanded), treatment efficacy (Positive and Negative Syndrome Scale, Clinical Global Impression) and quality of life (Short Form-36) were assessed at baseline and after 2, 4 and 6 months. The Premorbid Adjustment Scale was administered at baseline. Results: Insight was positively associated with better premorbid functioning, more education and schizoaffective disorder versus schizophrenia. Insight improved modestly, but significantly throughout treatment, particularly illness beliefs. Baseline insight was negatively correlated with quality of life and positive symptoms and positively correlated with anxiety/depression. It was not significantly associated with change in symptom severity or time in trial, but was positively associated with age. Conclusions: Insight, at least in this stable, comparatively high-insight sample, improved during treatment but this is not closely related to improvement in psychotic symptoms. Insight appears to have trait-like qualities demonstrated by association with premorbid factors. While insight is generally a favorable attribute and is associated with fewer psychotic symptoms, it is also associated with increased depression and lower perceived quality of life. Some components of insight are more amenable to improvement; particularly the ability to adopt less fixed illness attributions.

The COMT val(158) variant has been associated with impaired cognitive function compared to the Met(158) variant yet gene gene interactions are not well described. In this study we demonstrate an interaction between this COMT polymorphism and a deletion variant of ADRA2B, the gene encoding the alpha 2b-adrenergic receptor on episodic memory performance. Specifically, carriage of the ADRA2B deletion abolished the relative memory impairment in homozygous COMT val(158) carriers compared to Met(158) carriers.

Perception of fearful faces is associated with functional activation of cortico-limbic structures, which has been found altered in individuals with psychiatric disorders such as schizophrenia, autism and major depression. The objective of this study was to isolate the brain response to the features of standardized fearful faces by incorporating principal component analysis (PCA) into the analysis of neuroimaging data of healthy volunteers and individuals with schizophrenia. At the first stage, the visual characteristics of morphed fearful facial expressions (FEEST, Young et al., 2002) were classified with PCA, which produced seven orthogonal factors, with some of them related to emotionally salient facial features (eyes, mouth, brows) and others reflecting non-salient facial features. Subsequently, these PCA-based factors were included into the functional magnetic resonance imaging (fMRI) analysis of 63 healthy volunteers and 32 individuals with schizophrenia performing a task that involved implicit processing of FEEST stimuli. In healthy volunteers, significant neural response was found to visual characteristics of eyes, mouth or brows. In individuals with schizophrenia, PCA-based analysis enabled us to identify several significant clusters of activation that were not detected by the standard approach. These clusters were implicated in processing of visual and emotional information and were attributable to the perception of eyes and brows. PCA-based analysis could be useful in isolating brain response to salient facial features in psychiatric populations.

Background To correlate measures of insight for own psychopathology to structural and functional brain imaging findings in 21 patients with DSM-IV bipolar I disorder. Methods Insight was assessed using the Scale to Assess Unawareness of Mental Disorder (SUMD). Resting single photon emission computed tomography (SPECT) and computed tomography (CT) was conducted in patients and 21 normal comparison subjects matched for age, gender and handedness. Results Reduced general insight and symptom awareness, but not symptom attribution, were significantly related to cortical and subcortical atrophy, respectively. No correlations between SPECT and insight measures were identified. Limitations Limited sample size and the use of resting state SPECT. Conclusions General and symptom awareness were related to measures of brain atrophy but not to neurofunctioning as measured by SPECT. Future research should consider the structure and function of specific cortical regions, including the frontal and parietal cortices.

Summary Purpose Patients with temporal lobe epilepsy (TLE) often present mood disturbances, which may either exacerbate or remit following surgery. The objective of the study was to investigate the relationship between post-operative depressive/anxiety symptoms and hippocampal/amygdala volumes following anterior temporal lobectomy. Methods Thirty-five patients operated for TLE were assessed for mood disturbances by the Beck depression inventory (BDI) and Beck anxiety inventory (BAI). Post-operative MRI data were collected and volumetric analysis of the hippocampi (HV) and amygdala (AV) was performed. Correlations between volumetric data, measures of mood, and demographic and clinical data were calculated. Results BDI scores significantly correlated with the intact HV ( p =0.029) as well as the absolute difference between the intact and remnant HV ( p =0.021). This was evident in left-side resections ( p =0.049); in right-side resections the correlation was marginally non- significant ( p =0.057). Depressed patients also had smaller remnant AV ( p =0.002). Furthermore, BAI was negatively correlated with the HV remnant in left-side resections ( p =0.038). No other significant associations between post-operative mood disturbances and various demographic and clinical variables were observed. Conclusion The severity of depressive symptomatology in operated epilepsy patients correlates with the extent of hippocampal and amygdala resection; this association appears to be more evident in left-side resections.

There is evidence that people with schizophrenia show specific deficits in theory of mind (ToM). However, it is a matter of debate whether these are trait or state dependent, and the nature of the relationship between ToM deficits and particular symptoms is controversial. This study aimed to shed further light on these issues by (1) examining ToM abilities in 61 individuals with chronic schizophrenia during a stable phase as compared with 51 healthy controls matched by gender, age, educational level and current IQ, and (2) exploring the relationship between ToM and symptoms. Second order verbal stories and a non-verbal picture-sequencing task were used as ToM measures. Results showed no differences in ToM performance between patients and controls on either measure. Subsequent subgrouping of patients into remitted and non-remitted showed a worse performance of non-remitted patients only on second order ToM tasks. Specific ToM deficits were found associated with delusions. Association with negative symptoms was found to be less specific and accounted for by illness chronicity and general cognitive impairment. The results from the present study are in line with models which hypothesise that specific ToM deficits in schizophrenia are state dependent and associated with delusions. Such associations may also be task specific.

Medication adherence is crucial in psychiatry, especially for chronic disorders. Both clinician and patient share responsibilities for adherence, which is rarely an all-or-none phenomenon. Non-adherence explains much of the difference between drug efficacy and effectiveness, as demonstrated by higher relapse in non-adherent patient groups, and has a profoundly impact on clinical and economic burden for health services. During clinical assessment, predictive factors of non-adherence should be considered, including: cognitive deficit a prior history of non-adherence and comorbid alcohol or substance misuse. Dose strength and frequency, drug formulation and route of administration, polypharmacy and side-effects, the doctor-patient relationship and family support also effect adherent behaviour. Psychoeducational interventions aiming to enhance adherence focus primarily on imparting knowledge have proved largely ineffective. Individual psychological interventions are more effective as they specifically target the patient's beliefs and attitudes concerning the illness and medication by using cognitive therapy, behavioural modification approaches and/or motivational interviewing techniques. Compliance therapy combines all of these. All clinicians should routinely use simple adherence-enhancing techniques and patients should be given the opportunity to voice their individual perspectives.

Schizophrenia patients show a disconnection in amygdala-medial prefrontal cortex and autonomic arousal systems for processing fear. Concurrent functional magnetic resonance imaging [fMRI] and skin conductance recording were used to determine whether these disturbances are specific to fear, or present in response to other signals of danger. We also examined whether these disturbances distinguish a specific symptom profile. During scanning, 27 schizophrenia (13 paranoid, 14 nonparanoid) and 22 matched healthy control subjects viewed standardized facial expressions of fear, anger and disgust (versus neutral). Skin conductance responses [SCRs]were acquired simultaneously to assess phasic increases in arousal. 'With-arousal' versus 'without-arousal' responses were analysed using non-parametric methods. For controls, 'with-arousal' responses were associated with emotion-specific activity for fear (amygdala), disgust (insula) and anger (anterior cingulate), together with common medial prefrontal cortex [MPFC] engagement, as predicted. Schizophrenia patients displayed abnormally increased phasic arousal, with concomitant reductions in emotion-specific regions and MPFC. These findings may reflect a general disconnection between central and autonomic systems for processing signals of danger. This disjunction was most apparent in patients with a profile of paranoia, coupled with poor social function and insight. Heightened autonomic sensitivity to signals of fear, threat or contamination, without effective neural mechanisms for appraisal, may underlie paranoid delusions which concern threat and contamination, and associated social and interpersonal difficulties.

In fingerspelling, different hand configurations are used to represent the different letters of the alphabet. Signers use this method of representing written language to fill lexical gaps in a signed language. Using fMRI, we compared cortical networks supporting the perception of fingerspelled, signed, written, and pictorial stimuli in deaf native signers of British Sign Language (BSL). In order to examine the effects of linguistic knowledge, hearing participants who knew neither fingerspelling nor a signed language were also tested. All input forms activated a left fronto-temporal network, including portions of left inferior temporal and mid-fusiform gyri, in both groups. To examine the extent to which activation in this region was influenced by orthographic structure, two contrasts of orthographic and non-orthographic stimuli were made: one using static stimuli (text vs. pictures), the other using dynamic stimuli (fingerspelling vs. signed language). Greater activation in left and right inferior temporal and mid-fusiform gyri was found for pictures than text in both deaf and hearing groups. In the fingerspelling vs. signed language contrast, a significant interaction indicated locations within the left and right mid-fusiform gyri. This showed greater activation for fingerspelling than signed language in deaf but not hearing participants. These results are discussed in light of recent proposals that the mid-fusiform gyrus may act as an integration region, mediating between visual input and higher-order stimulus properties. © 2007 Elsevier Inc. All rights reserved.

Background A deficit in remembering the temporal context of events (a type of source memory) has been observed in schizophrenia, and suggested to be associated with positive symptoms. Methods In order to investigate memory for temporal context, we administered a list discrimination task to a sample of schizophrenia patients and a sample of healthy controls. Participants were required to learn two lists of mixed high- and low-frequency words separated by 10 min, then to remember whether each word had been presented in the first or in the second list. Results The number of misattributions to the wrong list was significantly higher in patients than in healthy controls. However, the group difference was eliminated when recall efficiency was covaried. The number of list misattributions was higher in patients with auditory hallucinations than in the other patients, independently of verbal recall efficiency. By contrast, affective flattening and anhedonia were associated with fewer list misattributions of the high-frequency words. Conclusions It is suggested that auditory hallucinations are associated with deficit in processing or remembering the temporal context. Conversely, certain negative symptoms are associated with reduced temporal context errors. The possible neural mechanisms involved in temporal context deficit as well as in these specific clinical symptoms are discussed.

Abnormalities in social functioning are a significant feature of schizophrenia. One critical aspect of these abnormalities is the difficulty these individuals have with the recognition of facial emotions, particularly negative expressions such as fear. The present work focuses on fear perception and its relationship to the paranoid symptoms of schizophrenia, specifically, how underlying limbic system structures (i.e. the amygdala) react when probed with dynamic fearful facial expressions. Seven paranoid and eight non-paranoid subjects (all males) with a diagnosis of schizophrenia took part in functional magnetic resonance imaging study (1.5T) examining neural responses to emerging fearful expressions contrasted with dissipating fearful expressions. Subjects viewed emerging and dissipating expressions while completing a gender discrimination task. Their brain activation was compared to that of 10 healthy male subjects. Increased hippocampal activation was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae were observed only in the paranoid individuals. These patterns may represent trait-related hippocampal dysfunction, coupled with state (specifically paranoia) related amygdala abnormalities. The findings are discussed in light of models of paranoia in schizophrenia.

Nineteen patients evaluated facial emotional expressions and performed 'theory of mind' reasoning tasks before and after a temporal lobectomy for medically intractable epilepsy, and results were compared with the performance of 19 healthy controls. Following operation, which in all cases resulted in excision of the entire amygdala, there was no change in the ability to reason about the mental states of others, in line with the suggestion that the anterior temporal lobe is not necessary for theory of mind reasoning. However, following a left anterior temporal lobectomy, patients evaluated fearful facial expressions in a more normative manner. This may reflect the excision of a 'hyper-excitable' amygdala which pre-operatively misinterprets fearful expressions as containing blends of other emotions. Alternatively the results may represent an improvement in function of the right amygdala following the excision of a noxious inhibitory epileptogenic focus on the left. The finding complements earlier demonstrations that damage to the right amygdala is associated with impaired processing of fear; amelioration of right amygdala function may conversely be associated with an improvement.