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Supplemental material, sj-pptx-3-jop-10.1177_02698811231158232 for Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology by Jonathan P Rogers, Mark A Oldham, Gregory Fricchione, Georg Northoff, Jo Ellen Wilson, Stephan C Mann, Andrew Francis, Angelika Wieck, Lee Elizabeth Wachtel, Glyn Lewis, Sandeep Grover, Dusan Hirjak, Niraj Ahuja, Michael S Zandi, Allan Young, Kevin Fone, Simon Andrews, David Kessler, Tabish Saifee, Siobhan Gee, David S Baldwin and Anthony S David in Journal of Psychopharmacology

Supplemental material, sj-docx-2-jop-10.1177_02698811231158232 for Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology by Jonathan P Rogers, Mark A Oldham, Gregory Fricchione, Georg Northoff, Jo Ellen Wilson, Stephan C Mann, Andrew Francis, Angelika Wieck, Lee Elizabeth Wachtel, Glyn Lewis, Sandeep Grover, Dusan Hirjak, Niraj Ahuja, Michael S Zandi, Allan Young, Kevin Fone, Simon Andrews, David Kessler, Tabish Saifee, Siobhan Gee, David S Baldwin and Anthony S David in Journal of Psychopharmacology

This study will recruit 360 participants who self-report high symptoms of anxiety. Participants will be randomly assigned to one of 4 groups: one analog intervention of Imagery Rescripting (IR) for memories, an analog intervention of IR for future events, and analog intervention of Imaginal Exposure (IE) for memories, and an analog intervention of IE for future events. The primary objectives of this study are: first, to investigate the association between insight and the severity of anxiety symptoms, and second, to explore the relationship between insight and metacognition.

Supplemental material, sj-docx-1-jop-10.1177_02698811231158232 for Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology by Jonathan P Rogers, Mark A Oldham, Gregory Fricchione, Georg Northoff, Jo Ellen Wilson, Stephan C Mann, Andrew Francis, Angelika Wieck, Lee Elizabeth Wachtel, Glyn Lewis, Sandeep Grover, Dusan Hirjak, Niraj Ahuja, Michael S Zandi, Allan Young, Kevin Fone, Simon Andrews, David Kessler, Tabish Saifee, Siobhan Gee, David S Baldwin and Anthony S David in Journal of Psychopharmacology

IMPORTANCE: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. OBJECTIVE: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. DESIGN, SETTING, AND PARTICIPANTS: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. EXPOSURES: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. MAIN OUTCOMES AND MEASURES: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks. RESULTS: Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy. CONCLUSIONS AND RELEVANCE: In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p p p p p

Supplemental material, sj-pdf-2-isp-10.1177_00207640211036174 for Insight and equality: A systematic review and meta-analysis of socio-demographic associations by Kevin Ariyo, Alex Ruck Keene, Anthony S David and Gareth S Owen in International Journal of Social Psychiatry

Supplemental material, sj-pdf-2-isp-10.1177_00207640211036174 for Insight and equality: A systematic review and meta-analysis of socio-demographic associations by Kevin Ariyo, Alex Ruck Keene, Anthony S David and Gareth S Owen in International Journal of Social Psychiatry

Supplemental material, sj-pdf-1-isp-10.1177_00207640211036174 for Insight and equality: A systematic review and meta-analysis of socio-demographic associations by Kevin Ariyo, Alex Ruck Keene, Anthony S David and Gareth S Owen in International Journal of Social Psychiatry

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart – leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using “rule-in” examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Supplemental material, sj-pdf-1-isp-10.1177_00207640211036174 for Insight and equality: A systematic review and meta-analysis of socio-demographic associations by Kevin Ariyo, Alex Ruck Keene, Anthony S David and Gareth S Owen in International Journal of Social Psychiatry

Background Patients continue to suffer from medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS). General practitioners (GPs) play a key role in the management of PPS and require further training. Patients are often frustrated with the care they receive. This study aims to assess the acceptability of an ‘integrated GP care’ approach which consists of offering self-help materials to patients with PPS and offering their GPs training on how to utilise cognitive behavioural skills within their consultations, as well as assessing the feasibility of conducting a future trial in primary care to evaluate its benefit. Methods A feasibility cluster randomised controlled trial was conducted in primary care, South London, UK. GP practices (clusters) were randomly allocated to ‘integrated GP care plus treatment as usual’ or ‘treatment as usual’. Patients with PPS were recruited from participating GP practices before randomisation. Feasibility parameters, process variables and potential outcome measures were collected at pre-randomisation and at 12- and 24-weeks post-randomisation at cluster and individual participant level. Results Two thousand nine hundred seventy-eight patients were identified from 18 GP practices. Out of the 424 patients who responded with interest in the study, 164 fully met the eligibility criteria. One hundred sixty-one patients provided baseline data before cluster randomisation and therefore were able to participate in the study. Most feasibility parameters indicated that the intervention was acceptable and a future trial feasible. 50 GPs from 8 GP practices (randomised to intervention) attended the offer of training and provided positive feedback. Scores in GP knowledge and confidence increased post-training. Follow-up rate of patients at 24 weeks was 87%. However estimated effect sizes on potential clinical outcomes were small. Conclusions It was feasible to identify and recruit patients with PPS. Retention rates of participants up to 24 weeks were high. A wide range of health services were used. The intervention was relatively low cost and low risk. This complex intervention should be further developed to improve patients’/GPs’ utilisation of audio/visual and training resources before proceeding to a full trial evaluation. Trial registration NCT02444520 (ClinicalTrials.gov).

Nicola O’Connell,1 Abbeygail Jones,2 Trudie Chalder,2 Anthony S David3 1Department of Public Health and Primary Care, School of Medicine, Trinity College Dublin, Dublin, Ireland; 2Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 3UCL Institute of Mental Health, University College London, London, UKCorrespondence: Nicola O’ConnellDepartment of Public Health and Primary Care, Trinity College Dublin, Russell Centre, Tallaght Cross, Dublin 24, IrelandTel +353 1 896 3716Email noconne@tcd.ieIntroduction: A proportion of patients admitted to acute-stroke settings have not had a stroke, but have conditions mimicking a stroke. Approximately 25% of suspected stroke cases are “stroke mimics” and 2% are patients with functional symptoms — “functional stroke mimics”. This study aimed to explore experiences and illness perceptions of patients with functional symptoms admitted to hyperacute stroke wards.Methods: This study used mixed methods. Patients with functional stroke symptoms participated in semistructured qualitative interviews immediately after admission to one of two acute-stroke units in London and again 2 months after hospital discharge. Qualitative data were assessed using thematic analysis. The Brief Illness Perception Questionnaire (Brief-IPQ) measured illness perceptions at admission and at 2-month follow-up.Results: A total of 36 participants completed baseline interviews and 25 completed follow-up. Six themes emerged: physical symptom experience, emotional and coping responses, symptom causes, hospital experiences, views on the future, and uncertainty after hospital discharge. Mean Brief-IPQ score at admission was 49.3 (SD: 9.9), indicating a moderate–high level of perceived illness threat. Participants presented with a range of functional symptoms. At baseline, participants were highly concerned about their symptoms, but this had decreased at 2-month follow-up. Two months later, many were confused as to the cause of their admission.Conclusion: This is the first study to examine functional stroke patients’ experiences of acute-stroke admission. At admission, patients expressed confusion regarding their diagnosis, experienced high levels of emotional distress, and were concerned they were perceived as time wasting by stroke clinicians. While most participants experienced symptom recovery, there was a significant subgroup for whom symptoms persisted or worsened. A lack of care guidelines on the management of functional stroke patients may perpetuate functional symptoms.Keywords: functional stroke symptoms, stroke mimic, unexplained medical symptoms, qualitative research

International audience; Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.

BackgroundThe first episode of psychosis is a critical period in the emergence of cardiometabolic risk.AimsWe set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.MethodThis was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.ResultsRates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c(HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c>39 mmol/mol).ConclusionsUnhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a top-down approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging bottom-up or omics approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of bottom-up approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders.

Background Impulse‐control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug‐related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician‐rated severity scale for the assessment of syndromal and subsyndromal forms of impulse‐control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome). Methods The Parkinson's Impulse‐Control Scale (PICS), the first PD‐specific, semistructured interview to cover the full range of PD‐related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92). Results The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%–95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (Κ) values for clinician‐clinician rating of severity (Κ = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive‐behavioral therapy and medication adjustment (t[22] = 5.47; P < 0.001). Conclusions The PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD.

Objectives: Our aims were to confirm the relationship between lipid and lipoprotein concentrations and suicidal behaviour in first episode psychosis (FEP) patients. Methods: Suicidal behaviour was explored in a large FEP sample (N = 383). Baseline lipid profile was compared between those who attempted or completed suicide and those who not presented suicidal behaviour. Results: Low-density lipoprotein cholesterol (LDL-c) (OR = 0.99, 95% CI= 0.98-1.00) and depressive symptoms (OR = 1.15, 95% CI = 1.06-1.24) were significantly related with suicidal behaviour. Conclusions: Lipid profile test may be considered in the assessment of suicide risk in psychosis and LDL-c an important biological marker.

Background\ud \ud Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear.\ud \ud Methods\ud \ud Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed.\ud \ud Results\ud \ud GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology.\ud \ud Conclusions\ud \ud PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate.The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder.

BACKGROUND: The "jumping to conclusions" (JTC) data-gathering bias is implicated in the development and maintenance of psychosis but has only recently been studied in first episode psychosis (FEP). In this study, we set out to establish the relationship of JTC in FEP with delusions and neuropsychological functioning.METHODS: One hundred and eight FEP patients and 101 age-matched controls completed assessments of delusions, general intelligence (IQ), working memory (WM), and JTC (the probabilistic reasoning "beads" task).RESULTS: Half the FEP participants jumped to conclusions on at least 1 task, compared with 25% of controls (OR range 2.1 to 3.9; 95% CI range 1.5 to 8.0, P values ≤ .02). JTC was associated with clinical, but not nonclinical delusion severity, and with neuropsychological functioning, irrespective of clinical status. Both IQ and delusion severity, but not WM, were independently associated with JTC in the FEP group.CONCLUSIONS: JTC is present in FEP. The specific association of JTC with clinical delusions supports a state, maintaining role for the bias. The associations of JTC with neuropsychological functioning indicate a separable, trait aspect to the bias, which may confer vulnerability to psychosis. The work has potential to inform emerging interventions targeting reasoning biases in early psychosis.

Background: Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis. Methods: Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding. Results: Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders. Conclusions: These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis.

While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services.

Background:Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome). Methods:The Parkinson's Impulse-Control Scale (PICS), the first PD-specific, semistructured interview to cover the full range of PD-related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92). Results:The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%–95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (Κ) values for clinician-clinician rating of severity (Κ = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive-behavioral therapy and medication adjustment (t[22] = 5.47; P

Background and Objectives: Lack of insight is a cardinal feature of psycho - sis. Insight has been found to be a multidimensional concept, including awareness of having a mental illness, ability to relabel psychotic phenomena as abnormal and compliance with treatment., which can be measured with the Schedule for Assessment of Insight (SAI-E). The aim of this study was to validate the Spanish version of SAI-E. Methods: The SAI-E was translated into Spanish and back-translated into English, which was deemed appropriate by the original scale author. Next, the Spanish version of the SAI-E was administered to 39 patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) from a North Peruvian psychiatric hospital. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Scale of Unawareness of Mental Disorder (SUMD) were also administered. Specifically, internal consistency and convergent validity were assessed. Results: Internal consistency between the 11 items of the SAI-E was found to be good to excellent (α = 0.942). Compliance items did not contribute to internal consistency (A = 0.417, B = 572). Inter-rater reliability was excellent (ICC = 0.99). Regarding concurrent validity, the SAI-E total score correlated negatively with the lack of insight and judgement item of the PANNS (r = -0.91, p

Background and Objectives: Lack of insight is a cardinal feature of psycho­sis. Insight has been found to be a multidimensional concept, including awareness of having a mental illness, ability to relabel psychotic phenomena as abnormal and compliance with treatment., which can be measured with the Schedule for Assessment of Insight (SAI-E). The aim of this study was to validate the Spanish version of SAI-E. Methods: The SAI-E was translated into Spanish and back-translated into English, which was deemed appropriate by the original scale author. Next, the Spanish version of the SAI-E was administered to 39 patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) from a North Peruvian psychiatric hospital. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Scale of Unawareness of Mental Disorder (SUMD) were also administered. Specifically, internal consistency and convergent validity were assessed. Results: Internal consistency between the 11 items of the SAI-E was found to be good to excellent (α = 0.942). Compliance items did not contribute to internal consistency (A = 0.417, B = 572). Inter-rater reliability was excellent (ICC = 0.99). Regarding concurrent validity, the SAI-E total score correlated negatively with the lack of insight and judgement item of the PANNS (r = -0.91, p

Background Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. Methods Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. Results GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology. Conclusions PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder., Highlights • Differences in cortical R1 in young adults with psychotic experiences were found. • Implicates developmental processes related to myelination in psychotic illness. • The study utilises a large and well-controlled epidemiological cohort. • A novel approach to mapping microstructural parameters in cortex was employed.

Conversion disorders are a common cause of neurological disability, but the diagnosis remains controversial and the mechanism by which psychological stress can result in physical symptoms "unconsciously" is poorly understood. This review summarises research examining conversion disorder from a neurobiological perspective. Early observations suggesting a role for hemispheric specialization have not been replicated consistently. Patients with sensory conversion symptoms have normal evoked responses in primary and secondary somatosensory cortex but a reduction in the P300 potential, which is thought to reflect a lack of conscious processing of sensory stimuli. The emergence of functional imaging has provided the greatest opportunity for understanding the neural basis of conversion symptoms. Studies have been limited by small patient numbers and failure to control for confounding variables. The evidence available would suggest a broad hypothesis that frontal cortical and limbic activation associated with emotional stress may act via inhibitory basal ganglia-thalamocortical circuits to produce a deficit of conscious sensory or motor processing. The conceptual difficulties that have limited progress in this area are discussed. A better neuropsychiatric understanding of the mechanisms of conversion symptoms may improve our understanding of normal attention and volition and reduce the controversy surrounding this diagnosis.

Despite the general agreement that insight is a multidimensional phenomenon, the studies on the factorial structure of the scales for its assessment have yielded rather inconsistent results. The present study aimed to assess the internal structure of the Schedule for the Assessment of Insight (SAI-E). Seventy-two chronic patients with schizophrenia were assessed with SAI-E. Hierarchical cluster analysis and multidimensional scaling (MDS) were used to identify insight components and assess their inter-relationships. The associations of the extracted components with demographic, clinical and cognitive characteristics were also examined. The SAI-E demonstrated good psychometric properties. Three subscales of SAI-E were identified measuring awareness of illness, relabeling of symptoms, and treatment compliance. Moreover, the MDS disclosed two underlying dimensions - degree of ‘specificity’ and ‘spontaneity’ - within the insight construct. Treatment compliance was more strongly correlated with symptom relabeling than illness awareness. Excitement symptoms, global functioning and general intelligence were correlated with all the components of insight. Depressive symptoms were more strongly correlated with illness awareness. Impaired relabeling ability was linked to cognitive rigidity and greater severity of disorganization and positive symptoms. Education and severity of negative symptoms specifically affect treatment compliance. Our results support the hypothesis that insight is a multidimensional construct. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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.

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/amygdata volumes following anterior temporal tobectomy. 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 MR1 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 calcutated. 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 corretated 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. (C) 2008 Elsevier B.V. All rights reserved.

Objectives Firstly, to describe changes in the health of Gulf war veterans studied in a previous occupational cohort study and to compare outcome with comparable non-deployed military personnel. Secondly, to determine whether differences in prevalence between Gulf veterans and controls at follow up can be explained by greater persistence or greater incidence of disorders.

Background Emotional-processing inhibition has been suggested as a mechanism underlying some of the clinical features of depersonalization and/or derealization. In this study, we tested the prediction that autonomic response to emotional stimuli would be reduced in patients with depersonalization disorder. Methods The skin conductance responses of 15 patients with chronic depersonalization disorder according to DSM-IV, 15 controls, and 11 individuals with anxiety disorders according to DSM-IV, were recorded in response to nonspecific elicitors (an unexpected clap and taking a sigh) and in response to 15 randomized pictures with different emotional valences: 5 unpleasant, 5 pleasant, and 5 neutral. Results The skin conductance response to unpleasant pictures was significantly reduced in patients with depersonalization disorder (magnitude of 0.017 µsiemens in controls and 0.103 µsiemens in patients with anxiety disorders; P = .01). Also, the latency of response to these stimuli was significantly prolonged in the group with depersonalization disorder (3.01 seconds compared with 2.5 and 2.1 seconds in the control and anxiety groups, respectively; P = .02). In contrast, latency to nonspecific stimuli (clap and sigh) was significantly shorter in the depersonalization and anxiety groups (1.6 seconds) than in controls (2.3 seconds) (P = .03). Conclusions In depersonalization disorder, autonomic response to unpleasant stimuli is reduced. The fact that patients with depersonalization disorder respond earlier to a startling noise suggests that they are in a heightened state of alertness and that the reduced response to unpleasant stimuli is caused by a selective inhibitory mechanism on emotional processing.

Background Depersonalization disorder (DPD) is characterized by a subjective sense of unreality, disembodiment, emotional numbing and reduced psychogenic (sudomotor) sympathoexcitation. Aims Three related experiments utilized escalating physical and emotional challenges in 14 DPD participants and 16 controls aimed to elucidate (i) whether the cardiovascular sympathetic (SNS) and parasympathetic (PNS) nervous systems are implicated in DPD pathophysiology and (ii) if possible, to determine whether the blunted sympathoexcitation in DPD is peripherally or centrally mediated. Method Participants completed the Beck Anxiety Inventory (BAI), Dissociative Experience Scale (DES), and Cambridge Depersonalization Scale (CDS). Study I recorded heart rate (HR) and blood pressure (BP) during 5 min supine baseline, 3 min sustained handgrip (HG), 3 min cold pressor (CP) and 5 min 60° head-up tilt (HUT). In study II, HR, BP, and heart rate variability (HRV) were recorded during 5 min simultaneous 60° HUT and continuous presentation of unpleasant images (5 s per image). Study III examined HR and BP orienting responses (ORs) to simultaneous 60° HUT and pseudorandom presentation of unpleasant, neutral and pleasant images (5 s per image 3 min 25 s). OR data was grouped by image valence post hoc. Results DPD BAI (p = 0.0004), DES (p = 0.0002), and CDS (p ≤ 0.0001) scores were higher than controls. The DPD group produced diminished diastolic BP (DBP) (p = 0.045) increases to HG. Other indices were comparable between groups. DPD participants produced diminished systolic BP (SBP) (p = 0.003) and DBP (p = 0.002) increases, but greater (p = 0.004) HR increases to CP. In study II, DPD high frequency HRV (HF-HRV)—indicating parasympathetic vagal activity–was reduced (p = 0.029). In study III, DPD DBP was higher throughout the 5 s duration of HUT/pseudorandom unpleasant image presentation (1 s, p = 0.002, 2 s p = 0.033, 3 s p = 0.001, 4 s p = 0.009, 5 s p = 0.029). Conclusions Study I's BP pressor data supports previous findings of suppressed sympathoexcitation in DPD. The greater HR increases to CP, decreased HF-HRV in study II, and increased DBP during unpleasant ORs in study III implicates the SNS and PNS in DPD pathophysiology. These studies suggest the cardiovascular autonomic dysregulation in DPD is likely to be centrally-mediated.

BackgroundThe outcome of first episode psychosis (FEP) is highly variable and difficult to predict. Cognitive insight measured at illness onset has previously been found to predict psychopathology 12-months later. The aims of this study were to examine whether the prospective relationship between cognitive insight and symptom severity is evident at four-years following FEP and to examine some psychological correlates of cognitive insight.MethodsFEP participants (n = 90) completed the Beck Cognitive Insight Scale (BCIS) at illness onset, and associations between BCIS scores with symptom severity outcomes (4-years after FEP) were assessed. The BCIS scales (self-reflectiveness and self-certainty) were examined as a composite score, and individually compared to other cognitive measures (IQ and jumping to conclusions (JTC) bias).ResultsRegression analyses revealed that the cognitive insight composite did not predict 4-year symptom remission in this study while the self-reflection subscale of the BCIS predicted severity of symptoms at 4-years. Self-certainty items of the BCIS were not associated with symptom severity. Significant correlations between the JTC bias, self-certainty and IQ were found, but self-reflection did not correlate with these other cognitive measures.ConclusionsSelf-reflective capacity is a more relevant and independent cognitive construct than self-certainty for predicting prospective symptom severity in psychosis. Improving self-reflection may be a useful target for early intervention research.

BACKGROUND: Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related smallpox infection. METHODS: In this pre-registered (PROSPERO ID 336649) systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, AMED and the preprint server MedRxiv up to 31/05/2022. Any study design of humans infected with MPX that reported a neurological or psychiatric presentation was included. For eligible symptoms, we calculated a pooled prevalence using an inverse variance approach and corresponding 95% confidence intervals. The degree of variability that could be explained by between-study heterogeneity was assessed using the I 2 statistic. Risk of bias was assessed with the Newcastle Ottawa Scale and the Joanna Briggs Institute quality assessment tool. FINDINGS: From 1705 unique studies, we extracted data on 19 eligible studies (1512 participants, 1031 with confirmed infection using CDC criteria or PCR testing) most of which were cohort studies and case series with no control groups. Study quality was generally moderate. Three clinical features were eligible for meta-analysis: seizure 2.7% (95% CI 0.7-10.2%, I2 0%), confusion 2.4% (95% CI 1.1-5.2%, I2 0%) and encephalitis 2.0% (95% 0.5-8.2%, I2 55.8%). Other frequently reported symptoms included myalgia, headache and fatigue, where heterogeneity was too high for estimation of pooled prevalences, possibly as a result of differences in viral clades and study methodology. INTERPRETATION: There is preliminary evidence for a range of neuropsychiatric presentations including severe neurological complications (encephalitis and seizure) and nonspecific neurological features (confusion, headache and myalgia). There is less evidence regarding the psychiatric presentations or sequelae of MPX. This may warrant surveillance within the current MPX outbreak, with prospective longitudinal studies evaluating the mid- to long-term sequelae of the virus. Robust methods to evaluate the potential causality of MPX with these clinical features are required. More evidence is necessary to explain heterogeneity in prevalence estimates. FUNDING: UKRI/MRC (MR/V03605X/1), MRC-CSF (MR/V007181/1), MRC/AMED (MR/T028750/1) and the Wellcome Trust (102186/B/13/Z) and (102186/B/13/Z) and UCLH BRC.

Objective:Schizophrenia is associated with a marked cognitive impairment that is widely believed to remain stable after illness onset. Yet, to date, 10-year prospective studies of cognitive functioning following the first episode with good methodology are rare. The authors examined whether schizophrenia patients experience cognitive decline after the first episode, whether this decline is generalized or confined to individual neuropsychological functions, and whether decline is specific to schizophrenia.Methods:Participants were from a population-based case-control study of patients with first-episode psychosis who were followed prospectively up to 10 years after first admission. A neuropsychological battery was administered at index presentation and at follow-up to patients with a diagnosis of schizophrenia (N=65) or other psychoses (N=41) as well as to healthy comparison subjects (N=103).Results:The schizophrenia group exhibited declines in IQ and in measures of verbal knowledge and of memory, but not processing speed or executive functions. Processing speed and executive function impairments were already present at the first episode and remained stable thereafter. The magnitude of declines ranged between 0.28 and 0.66 standard deviations. Decline in measures of memory was not specific to schizophrenia and was also apparent in the group of patients with other psychoses. Healthy individuals with low IQ showed no evidence of decline, suggesting that a decline is specific to psychosis.Conclusions:Patients with schizophrenia and other psychoses experience cognitive decline after illness onset, but the magnitude of decline varies across cognitive functions. Distinct mechanisms consequent to the illness and/or psychosocial factors may underlie impairments across different cognitive functions.

Objectives: To investigate the role of risk assessment in predicting suicide in patients with schizophrenia spectrum disorders (SSDs) receiving secondary mental healthcare. We postulated that risk assessment plays a limited role in predicting suicide in these patients. Design: Retrospective case–control study. Setting: Anonymised electronic mental health record data from the South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) (London, UK) linked with national mortality data. Participants: In 242 227 SLaM service users up to 31 December 2013, 635 suicides were identified. 96 (15.1%) had a SSD diagnosis. Those who died before 1 January 2007 (n=25) were removed from the analyses. Thus, 71 participants with SSD who died from suicide over the study period (cases) were compared with 355 controls. Main outcome measure: Risk of suicide in relation to risk assessment ratings. Results: Cases were younger at first contact with services (mean±SD 34.5±12.6 vs 39.2±15.2) and with a higher preponderance of males (OR=2.07, 95% CI 1.18 to 3.65, p=0.01) than controls. Also, suicide occurred within 10 days after last contact with services in half of cases, with the most common suicide methods being hanging (14) and jumping (13). Cases were more likely to have the following ‘risk assessment’ items previously recorded: suicidal history (OR=4.42, 95% CI 2.01 to 9.65, p

Summary Background The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. Methods We applied adjusted logistic regression models to data from patients aged 18–65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. Findings Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52–3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81–11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17–31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. Interpretation The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. Funding UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).

Poor Insight is a common symptom of schizophrenia and it is conceptualised as having at least three principal components, namely unawareness of symptoms, unawareness of the need for treatment, and unawareness of the consequences of the disorder. These deficits have long been of clinical interest and have been shown to predict poorer treatment compliance, clinical outcome, social function, and response to vocational rehabilitation (Amador & David, 2004). Additionally, difficulties to establish and maintain social relationships are core features of schizophrenia, and there is evidence that these may to some extent stem from an alteration of the neural circuits that regulate social behaviour, and in particular deficits in Theory of Mind (ToM) (Lee et al., 2004). While deficits in insight in schizophrenia have been widely and consistently reported in the literature, evidence on the nature of the ToM dysfunction in this disorder is still controversial. This is mainly due to methodological differences across studies as well as limitations regarding the instruments used for ToM assessment. The first aim of this research consisted of clarifying some of these issues -whether a specific ToM dysfunction existed in schizophrenia and whether this most suitably fitted in the state or trait deficit views- trying to overcome previous methodological drawbacks. We did so by the use of a well matched control group, by controlling for important confounds and by the inclusion of ToM instruments of different nature (verbal and pictorial tasks). Results of this project were included in a first paper (Pousa et al., 2008a) and also led to the publication of a letter discussing part of the conclusions of a recent meta-analysis on ToM in schizophrenia (Pousa, Ruiz & David, 2008). Following this preliminary work and on the basis of a number of phenomenological parallelisms between insight and ToM dysfunctions that could be appreciated both clinically and in the literature, we decided to explore the relationship between insight and ToM. Given the scarcity of previous studies specifically focused on this issue, the nature of the study was mainly exploratory. The most relevant results of this investigation led to a second paper (Pousa et al., 2008b).Besides the mentioned publications, two complementary published works are added in the present thesis for their relevance to the project. The first is the manuscript of the Spanish adaptation of the SUMD (Ruiz et al., 2007). The second is a chapter of a book on mental disorders from an evolutionary perspective, titled "Theory of Mind as an evolutionary brain module". This chapter describes the concept of ToM, its measurement, as well as its neurobiological basis and philogenetic development, and was part of the literature review carried out while working on the design of the project (Obiols & Pousa, 2005). References:- Amador X & David A. Insight and Psychosis. Awareness of illness in schizophrenia and Related Disorders. (2nd Edition) (2004). Oxford University Press. - Lee KH; Farrow TFD; Spence SA & Woodruff PWR. (2004) Social cognition, brain networks and schizophrenia. Psychological Medicine 34: 391-400.- Obiols, JE; Pousa, E. (2005) La Teoría de la Mente como módulo cerebral evolutivo. En J Sanjuan y CJ Cela Conde (Eds) 2005, cap 6, pp105-119. La Profecia de Darwin. Ars Médica. ISBN: 84-9751-090-9- Pousa, E; Duñó, R; Brébion, G; David, AS; Ruiz, AI; Obiols, JE. (2008a) Theory of mind deficits in chronic schizophrenia: evidence for state dependence. Psychiatry Research, 158: 1-10.- Pousa, E; Duñó, R; Navarro, B; Ruiz, AI, Obiols, JE; David, AS. (2008b) Exploratory study of the association between insight and Theory of Mind (ToM) in stable schizophrenia patients. Cognitive Neuropsychiatry, 13, 210-232.- Pousa, E; Ruiz, AI; David, AS. (2008). Mentalising impairment as a trait marker of schizophrenia? Correspondence. British Journal of Psychiatry, 192, 312-315.- Ruiz, AI; Pousa, E; Duñó, R; Crosas, JM; Cuppa, S; Garcia-Ribera, C. (2008). Adaptación al español de la Escala de Valoración de la No Conciencia de Trastorno Mental SUMD. Actas Españolas de Psiquiatria, 36, 111-118.